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Sample records for a-lipoic acid prevents

  1. Potential administration of lipoic acid and coenzyme Q against ...

    African Journals Online (AJOL)

    Potential administration of lipoic acid and coenzyme Q against adipogensis: target for weight reduction. ... prevents its accumulation in visceral tissues. Further studies should be carried out to examine the mechanistic signals of these nutrients that helps in weight = management. Keywords: lipolysis, obesity, lipoic acid, Co-Q ...

  2. Lipoic Acid

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    Ramazan Tetikcok

    2015-09-01

    Full Text Available Lipoic acid, which is defined as a miralce antioxidan, is used by many departments. Eventhough clinical using data are very limited , it is used in treatment of diabetic neuropathy, physical therapy and rehabilitation clinic, dermatology clinic, geriatric clinics. It has usage area for cosmetic purposes. Although there are reports there are the direction of the effectiveness in these areas, the works done are not enough. Today lipoic acid , used in many areas ,is evaluated as universal antioxidant [J Contemp Med 2015; 5(3.000: 206-209

  3. The Effects of α-Lipoic Acid against Testicular Ischemia-Reperfusion Injury in Rats

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    Seda Ozbal

    2012-01-01

    Full Text Available Testicular torsion is one of the urologic emergencies occurring frequently in neonatal and adolescent period. Testis is sensitive to ischemia-reperfusion injury, and, therefore, ischemia and consecutive reperfusion cause an enhanced formation of reactive oxygen species that result in testicular cell damage and apoptosis. α-lipoic acid is a free radical scavenger and a biological antioxidant. It is widely used in the prevention of oxidative stress and cellular damage. We aimed to investigate the protective effect of α-lipoic acid on testicular damage in rats subjected to testicular ischemia-reperfusion injury. 35 rats were randomly divided into 5 groups: control, sham operated, ischemia, ischemia-reperfusion, and ischemia-reperfusion +lipoic acid groups, 2 h torsion and 2 h detorsion of the testis were performed. Testicular cell damage was examined by H-E staining. TUNEL and active caspase-3 immunostaining were used to detect germ cell apoptosis. GPx , SOD activity, and MDA levels were evaluated. Histological evaluation showed that α-lipoic acid pretreatment reduced testicular cell damage and decreased TUNEL and caspase-3-positive cells. Additionally, α-lipoic acid administration decreased the GPx and SOD activity and increased the MDA levels. The present results suggest that LA is a potentially beneficial agent in protecting testicular I/R in rats.

  4. THE COMBINATION OF α-LIPOIC ACID INTAKE WITH ECCENTRIC EXERCISE MODULATES ERYTHROPOIETIN RELEASE

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    B. Morawin

    2014-08-01

    Full Text Available The generation of reactive nitrogen/oxygen species (RN/OS represents an important mechanism in erythropoietin (EPO expression and skeletal muscle adaptation to physical and metabolic stress. RN/OS generation can be modulated by intense exercise and nutrition supplements such as α-lipoic acid, which demonstrates both anti- and pro-oxidative action. The study was designed to show the changes in the haematological response through the combination of α-lipoic acid intake with running eccentric exercise. Sixteen healthy young males participated in the randomised and placebo-controlled study. The exercise trial involved a 90-min run followed by a 15-min eccentric phase at 65% VO2max (-10% gradient. It significantly increased serum concentrations of nitric oxide (NO, hydrogen peroxide (H2O2 and pro-oxidative products such as 8-isoprostanes (8-iso, lipid peroxides (LPO and protein carbonyls (PC. α-Lipoic acid intake (Thiogamma: 1200 mg daily for 10 days prior to exercise resulted in a 2-fold elevation of serum H2O2 concentration before exercise, but it prevented the generation of NO, 8-iso, LPO and PC at 20 min, 24 h, and 48 h after exercise. α-Lipoic acid also elevated serum EPO level, which highly correlated with NO/H2O2 ratio (r=0.718, P<0.01. Serum total creatine kinase (CK activity, as a marker of muscle damage, reached a peak at 24 h after exercise (placebo 732 ± 207 IU · L-1, α-lipoic acid 481 ± 103 IU · L-1, and correlated with EPO (r = 0.478, P<0.01 in the α-lipoic acid group. In conclusion, the intake of high α-lipoic acid modulates RN/OS generation, enhances EPO release and reduces muscle damage after running eccentric exercise.

  5. Lipoic Acid Treatment after Brain Injury: Study of the Glial Reaction

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    Brenda Rocamonde

    2013-01-01

    Full Text Available After trauma brain injury, oxidative substances released to the medium provoke an enlargement of the initial lesion, increasing glial cell activation and, occasionally, an influx of immune cells into the central nervous system, developing the secondary damage. In response to these stimuli, microglia are activated to perform upregulation of intracellular enzymes and cell surface markers to propagate the immune response and phagocytosis of cellular debris. The phagocytosis of debris and dead cells is essential to limit the inflammatory reaction and potentially prevent extension of the damage to noninjured regions. Lipoic acid has been reported as a neuroprotectant by acting as an antioxidant and anti-inflammatory agent. Furthermore, angiogenic effect promoted by lipoic acid has been recently shown by our group as a crucial process for neural regeneration after brain injury. In this work, we focus our attention on the lipoic acid effect on astroglial and microglial response after brain injury.

  6. Role of catalase and superoxide dismutase activities on oxidative stress in the brain of a phenylketonuria animal model and the effect of lipoic acid.

    Science.gov (United States)

    Moraes, Tarsila Barros; Jacques, Carlos Eduardo Diaz; Rosa, Andrea Pereira; Dalazen, Giovana Reche; Terra, Melaine; Coelho, Juliana Gonzalez; Dutra-Filho, Carlos Severo

    2013-03-01

    Phenylketonuria (PKU) is an inherited metabolic disorder caused by deficiency of phenylalanine hydroxylase which leads to accumulation of phenylalanine and its metabolites in tissues of patients with severe neurological involvement. Recently, many studies in animal models or patients have reported the role of oxidative stress in PKU. In the present work we studied the effect of lipoic acid against oxidative stress in rat brain provoked by an animal model of hyperphenylalaninemia (HPA), induced by repetitive injections of phenylalanine and α-methylphenylalanine (a phenylalanine hydroxylase inhibitor) for 7 days, on some oxidative stress parameters. Lipoic acid prevented alterations on catalase (CAT) and superoxide dismutase (SOD), and the oxidative damage of lipids, proteins, and DNA observed in HPA rats. In addition, lipoic acid diminished reactive species generation compared to HPA group which was positively correlated to SOD/CAT ratio. We also observed that in vitro Phe inhibited CAT activity while phenyllactic and phenylacetic acids stimulated superoxide dismutase activity. These results demonstrate the efficacy of lipoic acid to prevent oxidative stress induced by HPA model in rats. The possible benefits of lipoic acid administration to PKU patients should be considered.

  7. The effect of systemic lipoic acid on hearing preservation after cochlear implantation via the round window approach: A guinea pig model.

    Science.gov (United States)

    Chang, Mun Young; Gwon, Tae Mok; Lee, Ho Sun; Lee, Jun Ho; Oh, Seung Ha; Kim, Sung June; Park, Min-Hyun

    2017-03-15

    The present study aimed to evaluate the effects of systemic lipoic acid on hearing preservation after cochlear implantation. Twelve Dunkin-Hartley guinea pigs were randomly divided into two groups: the control group and the lipoic acid group. Animals in the lipoic acid group received lipoic acid intraperitoneally for 4 weeks. A sterilised silicone electrode-dummy was inserted through the round window to a depth of approximately 5 mm. The hearing level was measured using auditory brainstem responses (ABRs) prior to electrode-dummy insertion, and at 4 days and 1, 2, 3 and 4 weeks after electrode-dummy insertion. The threshold shift was defined as the difference between the pre-operative threshold and each of the post-operative thresholds. The cochleae were examined histologically 4 weeks after electrode-dummy insertion. Threshold shifts changed with frequency but not time. At 2kHz, ABR threshold shifts were statistically significantly lower in the lipoic acid group than the control group. At 8, 16 and 32kHz, there was no significant difference in the ABR threshold shift between the two groups. Histologic review revealed less intracochlear fibrosis along the electrode-dummy insertion site in the lipoic acid group than in the control group. The spiral ganglion cell densities of the basal, middle and apical turns were significantly higher in the lipoic acid group compared with the control group. Therefore, systemic lipoic acid administration appears to effectively preserve hearing at low frequencies in patients undergoing cochlear implantation. These effects may be attributed to the protection of spiral ganglion cells and prevention of intracochlear fibrosis. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. THE COMBINATION OF α-LIPOIC ACID INTAKE WITH ECCENTRIC EXERCISE MODULATES ERYTHROPOIETIN RELEASE.

    Science.gov (United States)

    Morawin, B; Turowski, D; Naczk, M; Siatkowski, I; Zembron-Lacny, A

    2014-08-01

    The generation of reactive nitrogen/oxygen species (RN/OS) represents an important mechanism in erythropoietin (EPO) expression and skeletal muscle adaptation to physical and metabolic stress. RN/OS generation can be modulated by intense exercise and nutrition supplements such as α-lipoic acid, which demonstrates both anti- and pro-oxidative action. The study was designed to show the changes in the haematological response through the combination of α-lipoic acid intake with running eccentric exercise. Sixteen healthy young males participated in the randomised and placebo-controlled study. The exercise trial involved a 90-min run followed by a 15-min eccentric phase at 65% VO2max (-10% gradient). It significantly increased serum concentrations of nitric oxide (NO), hydrogen peroxide (H2O2) and pro-oxidative products such as 8-isoprostanes (8-iso), lipid peroxides (LPO) and protein carbonyls (PC). α-Lipoic acid intake (Thiogamma: 1200 mg daily for 10 days prior to exercise) resulted in a 2-fold elevation of serum H2O2 concentration before exercise, but it prevented the generation of NO, 8-iso, LPO and PC at 20 min, 24 h, and 48 h after exercise. α-Lipoic acid also elevated serum EPO level, which highly correlated with NO/H2O2 ratio (r = 0.718, P exercise (placebo 732 ± 207 IU · L(-1), α-lipoic acid 481 ± 103 IU · L(-1)), and correlated with EPO (r = 0.478, P release and reduces muscle damage after running eccentric exercise.

  9. Physiological and Histopathological Investigations on the Effects of -Lipoic Acid in Rats Exposed to Malathion

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    Atef M. Al-Attar

    2010-01-01

    Full Text Available The present study was designed to evaluate the influence of -lipoic acid treatment in rats exposed to malathion. Forty adult male rats were used in this study and distributed into four groups. Animals of group 1 were untreated and served as control. Rats of group 2 were orally given malathion at a dose level of 100 mg/kg body weight (BW for a period of one month. Experimental animals of group 3 were orally given -lipoic acid at a dose level of 20 mg/kg BW and after 3 hours exposed to malathion at the same dose given to group 2. Rats of group 4 were supplemented with -lipoic acid at the same dose given to group 3. The activities of serum glutamic oxaloacetic acid transaminase (GOT, glutamic pyruvic acid transaminase (GPT, alkaline phosphatase (ALP, and acid phosphatase (ACP, and the values of creatinine, urea, and uric acid were statistically increased, while the values of total protein and total albumin were significantly decreased in rats exposed to malathion. Moreover, administration of malathion for one month resulted in damage of liver and kidney structures. Administration of -lipoic acid before malathion exposure to rat can prevent severe alterations of hematobiochemical parameters and disruptions of liver and kidney structures. In conclusion, this study obviously demonstrated that pretreatment with -lipoic acid significantly attenuated the physiological and histopathological alterations induced by malathion. Also, the present study identifies new areas of research for development of better therapeutic agents for liver, kidney, and other organs' dysfunctions and diseases.

  10. α-Lipoic acid prevents lipotoxic cardiomyopathy in acyl CoA-synthase transgenic mice

    International Nuclear Information System (INIS)

    Lee, Young; Naseem, R. Haris; Park, Byung-Hyun; Garry, Daniel J.; Richardson, James A.; Schaffer, Jean E.; Unger, Roger H.

    2006-01-01

    α-Lipoic acid (α-LA) mimics the hypothalamic actions of leptin on food intake, energy expenditure, and activation of AMP-activated protein kinase (AMPK). To determine if, like leptin, α-LA protects against cardiac lipotoxicity, α-LA was fed to transgenic mice with cardiomyocyte-specific overexpression of the acyl CoA synthase (ACS) gene. Untreated ACS-transgenic mice died prematurely with increased triacylglycerol content and dilated cardiomyopathy, impaired systolic function and myofiber disorganization, apoptosis, and interstitial fibrosis on microscopy. In α-LA-treated ACS-transgenic mice heart size, echocardiogram and TG content were normal. Plasma TG fell 50%, hepatic-activated phospho-AMPK rose 6-fold, sterol regulatory element-binding protein-1c declined 50%, and peroxisome proliferator-activated receptor-γ cofactor-1α mRNA rose 4-fold. Since food restriction did not prevent lipotoxicity, we conclude that α-LA treatment, like hyperleptinemia, protects the heart of ACS-transgenic mice from lipotoxicity

  11. Analysis of Reaction between α-Lipoic Acid and 2-Chloro-1-methylquinolinium Tetrafluoroborate Used as a Precolumn Derivatization Technique in Chromatographic Determination of α-Lipoic Acid

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    Magdalena Godlewska

    2015-01-01

    Full Text Available The present study offers results of analysis concerning the course of reaction between reduced α-lipoic acid (LA and 2-chloro-1-methylquinolinium tetrafluoroborate (CMQT. In water environments, the reaction between CMQT and hydrophilic thiols proceeds very rapidly and the resultant products are stable. For the described analysis, optimum reaction conditions, such as concentration of the reducing agent, environment pH, and concentration of the reagent were carefully selected. The spectrophotometric assay was carried out measuring absorbance at λ=348 nm (i.e., the spectral band of the obtained reaction product. Furthermore, the calibration curve of lipoic acid was registered. It was concluded that the Lambert-Beer law was observed within the range 1–10 μmol L−1. Later, the reaction between LA and CMQT was used as precolumn derivatization in a chromatographic determination of the lipoic acid in the range 2.5–50 μmol L−1. Practical applicability of the designed methods was evaluated by determining lipoic acid in Revitanerv pharmaceutical preparation which contains 300 mg LA in a single capsule. The error of the determination did not exceed 0.5% in relation to the declared value.

  12. Oxidative modification of lipoic acid by HNE in Alzheimer disease brain

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    Sarita S. Hardas

    2013-01-01

    Full Text Available Alzheimer disease (AD is an age-related neurodegenerative disease characterized by the presence of three pathological hallmarks: synapse loss, extracellular senile plaques (SP and intracellular neurofibrillary tangles (NFTs. The major component of SP is amyloid β-peptide (Aβ, which has been shown to induce oxidative stress. The AD brain shows increased levels of lipid peroxidation products, including 4-hydroxy-2-nonenal (HNE. HNE can react covalently with Cys, His, or Lys residues on proteins, altering structure and function of the latter. In the present study we measured the levels of the HNE-modified lipoic acid in brain of subjects with AD and age-matched controls. Lipoic acid is a key co-factor for a number of proteins including pyruvate dehydrogenase and α-ketoglutarate dehydrogenase, key complexes for cellular energetics. We observed a significant decrease in the levels of HNE-lipoic acid in the AD brain compared to that of age-matched controls. To investigate this phenomenon further, the levels and activity of lipoamide dehydrogenase (LADH were measured in AD and control brains. Additionally, LADH activities were measured after in-vitro HNE-treatment to mice brains. Both LADH levels and activities were found to be significantly reduced in AD brain compared to age-matched control. HNE-treatment also reduced the LADH activity in mice brain. These data are consistent with a two-hit hypothesis of AD: oxidative stress leads to lipid peroxidation that, in turn, causes oxidative dysfunction of key energy-related complexes in mitochondria, triggering neurodegeneration. This study is consonant with the notion that lipoic acid supplementation could be a potential treatment for the observed loss of cellular energetics in AD and potentiate the antioxidant defense system to prevent or delay the oxidative stress in and progression of this devastating dementing disorder.

  13. Effects of two antioxidants; α-lipoic acid and fisetin against diabetic cataract in mice.

    Science.gov (United States)

    Kan, Emrah; Kiliçkan, Elif; Ayar, Ahmet; Çolak, Ramis

    2015-02-01

    The purpose of this study was to determine whether α-lipoic acid and fisetin have protective effects against cataract in a streptozotocin-induced experimental cataract model. Twenty-eight male BALB/C mice were made diabetic by the intraperitoneal administration of streptozotocin (200 mg/kg). Three weeks after induction of diabetes, mice were divided randomly into 4 groups in which each group contained 7 mice; fisetin-treated group (group 1), α-lipoic acid-treated group (group 2), fisetin placebo group (group 3), α-lipoic acid placebo group (group 4). Fisetin and α-lipoic acid were administered intraperitoneally weekly for 5 weeks. Cataract development was assessed at the end of 8 weeks by slit lamp examination, and cataract formation was graded using a scale. All groups developed at least grade 1 cataract formation. In the fisetin-treated group, the cataract stages were significantly lower than in the placebo group (p = 0.02). In the α-lipoic acid-treated group, the cataract stages were lower than in the placebo group but it did not reach to a significant value. Both fisetin and α-lipoic acid had a protective effect on cataract development in a streptozotocin-induced experimental cataract model. The protective effect of fisetin appears as though more effective than α-lipoic acid.

  14. Behavioral and Neurochemical Effects of Alpha-Lipoic Acid in the Model of Parkinson’s Disease Induced by Unilateral Stereotaxic Injection of 6-Ohda in Rat

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    Dayane Pessoa de Araújo

    2013-01-01

    Full Text Available This study aimed to investigate behavioral and neurochemical effects of α-lipoic acid (100 mg/kg or 200 mg/kg alone or associated with L-DOPA using an animal model of Parkinson’s disease induced by stereotaxic injection of 6-hydroxydopamine (6-OHDA in rat striatum. Motor behavior was assessed by monitoring body rotations induced by apomorphine, open field test and cylinder test. Oxidative stress was accessed by determination of lipid peroxidation using the TBARS method, concentration of nitrite and evaluation of catalase activity. α-Lipoic acid decreased body rotations induced by apomorphine, as well as caused an improvement in motor performance by increasing locomotor activity in the open field test and use of contralateral paw (in the opposite side of the lesion produced by 6-OHDA at cylinder test. α-lipoic acid showed antioxidant effects, decreasing lipid peroxidation and nitrite levels and interacting with antioxidant system by decreasing of endogenous catalase activity. Therefore, α-lipoic acid prevented the damage induced by 6-OHDA or by chronic use of L-DOPA in dopaminergic neurons, suggesting that α-lipoic could be a new therapeutic target for Parkinson's disease prevention and treatment.

  15. Ambazone-lipoic acid salt: Structural and thermal characterization

    Energy Technology Data Exchange (ETDEWEB)

    Kacso, Irina [National Institute for Research and Development of Isotopic and Molecular Technologies, 65-103 Donath street, 400293 Cluj-Napoca (Romania); Racz, Csaba-Pal; Santa, Szabolcs [Babes-Bolyai' University, Faculty of Chemistry, 11 Arany Janos street, Cluj-Napoca (Romania); Rus, Lucia [' Iuliu Hatieganu' University of Medicine and Pharmacy, Faculty of Pharmacy, 6 Louis Pasteur street, 400349 Cluj-Napoca (Romania); Dadarlat, Dorin; Borodi, Gheorghe [National Institute for Research and Development of Isotopic and Molecular Technologies, 65-103 Donath street, 400293 Cluj-Napoca (Romania); Bratu, Ioan, E-mail: ibratu@gmail.com [National Institute for Research and Development of Isotopic and Molecular Technologies, 65-103 Donath street, 400293 Cluj-Napoca (Romania)

    2012-12-20

    Highlights: Black-Right-Pointing-Pointer Salt of Ambazone with lipoic acid obtained by solvent-drop grinding. Black-Right-Pointing-Pointer Ambazone lipoate salt crystallizes in monoclinic system. Black-Right-Pointing-Pointer FTIR data suggest the deprotonation of the lipoic acid. Black-Right-Pointing-Pointer Thermal behaviour different of ambazone salt as compared to the starting compounds. - Abstract: A suitable method for increasing the solubility, dissolution rate and consequently the bioavailability of poor soluble acidic or basic drugs is their salt formation. The aim of this study is to investigate the structural and thermal properties of the compound obtained by solvent drop grinding (SDG) method at room temperature, starting from the 1:1 molar ratios of ambazone (AMB) and {alpha}-lipoic acid (LA). The structural characterization was performed with X-ray powder diffraction (XRPD) and infrared spectroscopy (FTIR). The thermal behaviour of the obtained compound (AMB{center_dot}LA) was investigated by differential scanning calorimetry (DSC) and thermogravimetry (TG). The photopyroelectric calorimetry, in front detection configuration (FPPE), was applied to measure and compare the room temperature values of one dynamic thermal parameter (thermal effusivity) for starting and resulting compounds. Both structural and supporting calorimetric techniques pointed out a salt structure for AMB{center_dot}LA compound as compared to those of the starting materials.

  16. Physicochemical Profiling of α-Lipoic Acid and Related Compounds.

    Science.gov (United States)

    Mirzahosseini, Arash; Szilvay, András; Noszál, Béla

    2016-07-01

    Lipoic acid, the biomolecule of vital importance following glycolysis, shows diversity in its thiol/disulfide equilibria and also in its eight different protonation forms of the reduced molecule. In this paper, lipoic acid, lipoamide, and their dihydro derivatives were studied to quantify their solubility, acid-base, and lipophilicity properties at a submolecular level. The acid-base properties are characterized in terms of six macroscopic, 12 microscopic protonation constants, and three interactivity parameters. The species-specific basicities, the pH-dependent distribution of the microspecies, and lipophilicity parameters are interpreted by various intramolecular effects, and contribute to understanding the antioxidant, chelate-forming, and enzyme cofactor behavior of the molecules observed. © 2016 Wiley-VHCA AG, Zürich.

  17. Effect of the Antioxidant Lipoic Acid in Aortic Phenotype in a Marfan Syndrome Mouse Model

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    Maria C. Guido

    2018-01-01

    Full Text Available Marfan syndrome (MFS cardiovascular manifestations such as aortic aneurysms and cardiomyopathy carry substantial morbidity/mortality. We investigated the effects of lipoic acid, an antioxidant, on ROS production and aortic remodeling in a MFS mgΔloxPneo mouse model. MFS and WT (wild-type 1-month-old mice were allocated to 3 groups: untreated, treated with losartan, and treated with lipoic acid. At 6 months old, echocardiography, ROS production, and morphological analysis of aortas were performed. Aortic ROS generation in 6-month-old MFS animals was higher at advanced stages of disease in MFS. An unprecedented finding in MFS mice analyzed by OCT was the occurrence of focal inhomogeneous regions in the aortic arch, either collagen-rich extremely thickened or collagen-poor hypotrophic regions. MFS animals treated with lipoic acid showed markedly reduced ROS production and lower ERK1/2 phosphorylation; meanwhile, aortic dilation and elastic fiber breakdown were unaltered. Of note, lipoic acid treatment associated with the absence of focal inhomogeneous regions in MFS animals. Losartan reduced aortic dilation and elastic fiber breakdown despite no change in ROS generation. In conclusion, oxidant generation by itself seems neutral with respect to aneurysm progression in MFS; however, lipoic acid-mediated reduction of inhomogeneous regions may potentially associate with less anisotropy and reduced chance of dissection/rupture.

  18. [Use of alpha-lipoic acid and omega-3 in postpartum pain treatment].

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    Costantino, D; Guaraldi, C; Costantino, M; Bounous, V E

    2015-10-01

    Postpartum pain is a frequent condition that negatively affects women's quality of life, interferring with everyday life. Analgesic drugs and surgery are often contraindicated in pregnancy and during breast feeding. This review of the literature aims to evaluate the rational of the association of lipoic acid and omega-3 employ in the management of postpartum pain. Lipoic acid is a cofactor essential in mitochondrial metabolism with antioxidant and anti-inflammatory activity. Lipoic acid has been shown to be effective in neuropatic pain treatment in patients with sciatica, carpal tunnel syndrome and diabetic neuropathy. Omega-3 are known for their anti-inflammatory and neurotrophic activity. The peripheral and central activity of both substances allows to act on neuroinflammation mechanisms thus reducing cronicization of pain and also determining a potential improvement of women's emotional status. The preliminary data here presented confirm the positive effect of this association on the treatment of postpartum perineal pain. The supplementation of lipoic acid in association with omega-3 seems effective and safe for the treatment of chronic postpartum pain, allowing a pathogenetic approach to neuroinflammation, thus reducing the consumption of analgesic drugs, often contraindicated during breast-feeding.

  19. Benfotiamine and Alpha-Lipoic Acid in the Treatment of Diabetic Cardiovascular Autonomic Neuropathy (Review of Literature and Own Researches

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    V.O. Sergiyenko

    2014-04-01

    Full Text Available The analysis of current views on the mechanisms of fat-soluble form of vitamin B1 (benfotiamine and α-lipoic acid action, in particular features of their impact on carbohydrate and lipid metabolism, endothelial function, hemodynamics, vessel stiffness in cardiovascular diseases, cardiovascular autonomic neuropathy in type 2 diabetes mellitus, was perfomed. The results of experimental, randomized and own studies confirmed the value of the combined administration of benfotiamine and α-lipoic acid for the prevention and treatment of cardiovascular diseases, in particular cardiovascular autonomic neuropathy in patients with type 2 diabetes mellitus.

  20. The Effect of Alpha-Lipoic Acid on Learning and Memory Deficit in a Rat Model of Temporal Lobe Epilepsy

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    Narges Karimi

    2012-07-01

    Full Text Available Introduction : Epilepsy is a chronic neurological disorder in which patients experience spontaneous recurrent seizures and deficiency in learning and memory. Although the most commonly recommended therapy is drug treatment, some patients do not achieve adequate control of their seizures on existing drugs. New medications with novel mechanisms of action are needed to help those patients whose seizures are resistant to currently-available drugs. While alpha-lipoic acid as a antioxidant has some neuroprotective properties, but this action has not been investigated in models of epilepsy. Therefore, the protective effect of pretreatment with alpha-lipoic acid was evaluated in experimental model of temporal lobe epilepsy in male rats. Methods: In the present study, Wistar male rats were injected intrahippocampally with 0.9% saline(Sham-operated group, kainic acid(4 μg alone, or α-lipoic acid (25mg and 50mg/kg in association with kainic acid(4μg. We performed behavior monitoring(spontaneous seizure, learning and memory by Y-maze and passive avoidance test, intracranial electroencepholography (iEEG recording, histological analysis, to evaluate the anti- epilepsy effect of α-lipoic acid in kainate-induced epileptic rats.   Results: Behavior data showed that the kainate rats exhibit spontaneous seizures, lower spontaneous alternation score inY-maze tasks (p<0.01, impaired retention and recall capability in the passive avoidance test (p<0.05. Administration of alpha-lipoic acid, in both doses, significantly decrease the number of spontaneous seizures, improved alternation score in Y-maze task (p<0.005 and impaired retention and recall capability in the passive avoidance test (p<0.01 in kainite rats. Moreover, lipoic acid could improve the lipid peroxidation and nitrite level and superoxid dismutase activity.Conclusion: This study indicates that lipoic acid pretreatment attenuates kainic acid-induced impairment of short-term spatial memory in rats

  1. The Effect of Alpha-Lipoic Acid on Learning and Memory Deficit in a Rat Model of Temporal Lobe Epilepsy

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    Tourandokht Baluchnejadmojarad

    2012-07-01

    Full Text Available Introduction: Epilepsy is a chronic neurological disorder in which patients experience spontaneous recurrent seizures and deficiency in learning and memory. Although the most commonly recommended therapy is drug treatment, some patients do not achieve adequate control of their seizures on existing drugs. New medications with novel mechanisms of action are needed to help those patients whose seizures are resistant to currently-available drugs. While alpha-lipoic acid as a antioxidant has some neuroprotective properties, but this action has not been investigated in models of epilepsy. Therefore, the protective effect of pretreatment with alpha-lipoic acid was evaluated in experimental model of temporal lobe epilepsy in male rats. Methods: In the present study, Wistar male rats were injected intrahippocampally with 0.9% saline(Sham-operated group, kainic acid(4 μg alone, or α-lipoic acid (25mg and 50mg/kg in association with kainic acid(4μg. We performed behavior monitoring(spontaneous seizure, learning and memory by Y-maze and passive avoidance test, intracranial electroencepholography (iEEG recording, histological analysis, to evaluate the anti- epilepsy effect of α-lipoic acid in kainate-induced epileptic rats. Results: Behavior data showed that the kainate rats exhibit spontaneous seizures, lower spontaneous alternation score inY-maze tasks (p<0.01, impaired retention and recall capability in the passive avoidance test (p<0.05. Administration of alpha-lipoic acid, in both doses, significantly decrease the number of spontaneous seizures, improved alternation score in Y-maze task (p<0.005 and impaired retention and recall capability in the passive avoidance test (p<0.01 in kainite rats. Moreover, lipoic acid could improve the lipid peroxidation and nitrite level and superoxid dismutase activity. Discussion: This study indicates that lipoic acid pretreatment attenuates kainic acid-induced impairment of short-term spatial memory in rats

  2. NMR studies of inclusion complexes formed by (R)-α-lipoic acid with α-, β-, and γ-cyclodextrins

    International Nuclear Information System (INIS)

    Ikeda, Hiroshi; Ikuta, Naoko; Nakata, Daisuke; Ishida, Yoshiyuki; Terao, Keiji

    2015-01-01

    The structures of inclusion complexes of (R)-α-lipoic acid with α-, β-, and γ-cyclodextrin (CD) were constructed using restraints derived from ROESY spectra and MMFF94 molecular mechanics calculations. (R)-α-lipoic acid and α-CD generate a single stable inclusion complex, in which the 1,2-dithiolane ring of the (R)-α-lipoic acid is oriented toward the secondary hydroxy side of the α-CD. NMR data suggests that β-CD produces two kinds of inclusion complexes with α-lipoic acid. Finally, γ-CD yields 1:1 and 1:2 host/guest complexes with (R)-α-lipoic acid. The estimated structure of the 1:1 γ-CD inclusion complex has the 1,2-dithiolane ring oriented toward the primary hydroxy side of the γ-CD. (author)

  3. Synergistic Effect of Quercetin and α-Lipoic Acid on Aluminium Chloride Induced Neurotoxicity in Rats

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    Sooad Saud Al-Otaibi

    2018-01-01

    Full Text Available Objectives. The present study was carried out to study the protective effects of quercetin and α-lipoic acid alone and in combination against aluminum chloride induced neurotoxicity in rats. Materials and Methods. The study consisted of eight groups, namely, Group 1: control rats, Group 2: rats receiving aluminium chloride 7 mg/kg body weight intraperitoneal route (i.p for two weeks, Group 3: rats receiving quercetin 50 mg/kg body weight i.p. for two weeks, Group 4: rats receiving quercetin 50 mg/kg body weight followed by aluminium chloride 7 mg/kg body weight i.p. for two weeks, Group 5: rats receiving α-lipoic acid 20 mg/kg body weight i.p. for two weeks, Group 6: rats receiving lipoic acid 20 mg/kg body weight followed by aluminium chloride 7 mg/kg body weight i.p. for two weeks, Group 7: rats receiving α-lipoic acid 20 mg/kg body weight and quercetin 50 mg/kg body weight i.p. for two weeks, and Group 8: rats receiving α-lipoic acid 20 mg/kg body weight and quercetin 50 mg/kg body weight followed by aluminium chloride 7 mg/kg body weight i.p. for two weeks. The animals were killed after 24 hours of the last dose by cervical dislocation. Results. Aluminium chloride treatment of rats resulted in significant increases in lipid peroxidation, protein carbonyl levels, and acetylcholine esterase activity in the brain. This was accompanied with significant decreases in reduced glutathione, activities of the glutathione reductase, and superoxide dismutase. Pretreatment of AlCl3 exposed rats to either quercetin or α-lipoic acid also restored altered lipid peroxidation and superoxide dismutase to near normal levels. Quercetin or α-lipoic acid pretreatment of AlCl3 exposed rats improved the protein carbonyl and reduced glutathione, glutathione reductase, and acetylcholine esterase activities in rat brains towards normal levels. Combined pretreatment of AlCl3 exposed rats with quercetin and α-lipoic acid resulted in a

  4. A Clinical Trial about a Food Supplement Containing α-Lipoic Acid on Oxidative Stress Markers in Type 2 Diabetic Patients.

    Science.gov (United States)

    Derosa, Giuseppe; D'Angelo, Angela; Romano, Davide; Maffioli, Pamela

    2016-10-28

    The aim of this study was to evaluate the effect of a food supplement containing α-lipoic acid and of a placebo on glyco-metabolic control and on oxidative stress markers in type 2 diabetics. We randomized 105 diabetics to either a supplementation containing 600 mg of α-lipoic acid, 165 mg of L -carnosin, 7.5 mg of zinc, and vitamins of group B, or a placebo, for three months. We evaluated body mass index, fasting plasma glucose (FPG), post-prandial-glucose (PPG), glycated hemoglobin (HbA 1c ), fasting plasma insulin (FPI), HOMA-index (HOMA-IR), lipid profile, high sensitivity C-reactive protein (Hs-CRP), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA). There was a reduction of FPG, PPG, and HbA 1c with the food supplement containing α-lipoic acid compared with a baseline, and with the placebo. Concerning lipid profile, we observed a reduction of LDL-C, and Tg with the food supplement, compared with both the baseline, and the placebo. There was a reduction of Hs-CRP with the food supplement containing α-lipoic acid, both compared with the baseline and the placebo. An increase of SOD, and GSH-Px, and a decrease of MDA were reached by the food supplement containing α-lipoic acid, both compared with the baseline and the placebo. We can conclude that the food supplement containing α-lipoic acid, L -carnosin, zinc, and vitamins of group B improved glycemic control, lipid profile, and anti-oxidative stress markers.

  5. A Clinical Trial about a Food Supplement Containing α-Lipoic Acid on Oxidative Stress Markers in Type 2 Diabetic Patients

    Directory of Open Access Journals (Sweden)

    Giuseppe Derosa

    2016-10-01

    Full Text Available The aim of this study was to evaluate the effect of a food supplement containing α-lipoic acid and of a placebo on glyco-metabolic control and on oxidative stress markers in type 2 diabetics. We randomized 105 diabetics to either a supplementation containing 600 mg of α-lipoic acid, 165 mg of L-carnosin, 7.5 mg of zinc, and vitamins of group B, or a placebo, for three months. We evaluated body mass index, fasting plasma glucose (FPG, post-prandial-glucose (PPG, glycated hemoglobin (HbA1c, fasting plasma insulin (FPI, HOMA-index (HOMA-IR, lipid profile, high sensitivity C-reactive protein (Hs-CRP, superoxide dismutase (SOD, glutathione peroxidase (GSH-Px, malondialdehyde (MDA. There was a reduction of FPG, PPG, and HbA1c with the food supplement containing α-lipoic acid compared with a baseline, and with the placebo. Concerning lipid profile, we observed a reduction of LDL-C, and Tg with the food supplement, compared with both the baseline, and the placebo. There was a reduction of Hs-CRP with the food supplement containing α-lipoic acid, both compared with the baseline and the placebo. An increase of SOD, and GSH-Px, and a decrease of MDA were reached by the food supplement containing α-lipoic acid, both compared with the baseline and the placebo. We can conclude that the food supplement containing α-lipoic acid, L-carnosin, zinc, and vitamins of group B improved glycemic control, lipid profile, and anti-oxidative stress markers.

  6. Co-administration of α-lipoic acid and cyclosporine aggravates colon ulceration of acetic acid-induced ulcerative colitis via facilitation of NO/COX-2/miR-210 cascade

    Energy Technology Data Exchange (ETDEWEB)

    El-Gowelli, Hanan M., E-mail: dr_Hanan_el_gowali@hotmail.com; Saad, Evan I.; Abdel-Galil, Abdel-Galil A.; Ibrahim, Einas R.

    2015-11-01

    In this work, α-lipoic acid and cyclosporine demonstrated significant protection against acetic acid-induced ulcerative colitis in rats. We proposed that α-lipoic acid and cyclosporine co-administration might modulate their individual effects. Induction of ulcerative colitis in rats was performed by intra-rectal acetic acid (5% v/v) administration for 3 consecutive days. Effects of individual or combined used of α-lipoic acid (35 mg/kg ip) or cyclosporine (5 mg/kg sc) for 6 days starting 2 days prior to acetic acid were assessed. Acetic acid caused colon ulceration, bloody diarrhea and weight loss. Histologically, there was mucosal atrophy and inflammatory cells infiltration in submucosa, associated with depletion of colon reduced glutathione, superoxide dismutase and catalase activities and elevated colon malondialdehyde, serum C-reactive protein (C-RP) and tumor necrosis factor-α (TNF-α). Colon gene expression of cyclooxygenase-2 and miR-210 was also elevated. These devastating effects of acetic acid were abolished upon concurrent administration of α-lipoic acid. Alternatively, cyclosporine caused partial protection against acetic acid-induced ulcerative colitis. Cyclosporine did not restore colon reduced glutathione, catalase activity, serum C-RP or TNF-α. Unexpectedly, co-administration of α-lipoic acid and cyclosporine aggravated colon ulceration. Concomitant use of α-lipoic acid and cyclosporine significantly increased nitric oxide production, cyclooxygenase-2 and miR-210 gene expression compared to all other studied groups. The current findings suggest that facilitation of nitric oxide/cyclooxygenase-2/miR-210 cascade constitutes, at least partially, the cellular mechanism by which concurrent use of α-lipoic acid and cyclosporine aggravates colon damage. Collectively, the present work highlights the probable risk of using α-lipoic acid/cyclosporine combination in ulcerative colitis patients. - Highlights: • Lipoic acid is more effective than

  7. A Comparative Study of Effects of Omega‑3 Fatty Acids, Alpha Lipoic ...

    African Journals Online (AJOL)

    Background: Diabetes Mellitus is a metabolic disorder characterized by abnormal lipid and glucose metabolism. Various modes of adjuvant therapy have been advocated to ameliorate insulin resistance. Aim: This study was intended to assess the effects of antioxidants; alpha lipoic acid (ALA), omega 3 fatty acid and vitamin ...

  8. Multilayer emulsions as a strategy for linseed oil and α-lipoic acid micro-encapsulation: study on preparation and in vitro characterization.

    Science.gov (United States)

    Huang, Juan; Wang, Qiang; Li, Tong; Xia, Nan; Xia, Qiang

    2018-01-04

    Linseed oil and α-lipoic acid are bioactive ingredients, which play an important role in human nutrition and health. However, their application in functional foods is limited because of their instabilities and poor solubilities in hydrophilic matrices. Multilayer emulsions are particularly useful to protect encapsulated bioactive ingredients. The aim of this study was to fabricate multilayer emulsions by a high-pressure homogenization method to encapsulate linseed oil and α-lipoic acid simultaneously. Tween 20 and lecithin were used as surfactants to stabilize the oil droplets of primary emulsions. Multilayer emulsions were produced by using an electrostatic layer-by-layer deposition process of lecithin-chitosan membranes. Thermal treatment exhibited that chitosan encapsulation could improve the thermal stability of primary emulsions. During in vitro digestion, it was found that chitosan encapsulation had little effect on the lipolysis of linseed oil and bioaccessibility of α-lipoic acid. The oxidation stability of linseed oil in multilayer emulsions was improved effectively by chitosan encapsulation and α-lipoic acid. Chitosan encapsulation could inhibit the degradation of α-lipoic acid. A physical stability study indicated that multilayer emulsions had good centrifugal, dilution and storage stabilities. Multilayer emulsion is an effective delivery system to incorporate linseed oil and α-lipoic acid into functional foods and beverages. © 2018 Society of Chemical Industry. © 2018 Society of Chemical Industry.

  9. Physiological activities of the combination of fish oil and α-lipoic acid affecting hepatic lipogenesis and parameters related to oxidative stress in rats.

    Science.gov (United States)

    Ide, Takashi

    2018-06-01

    We studied the combined effect of fish oil and α-lipoic acid on hepatic lipogenesis and fatty acid oxidation and parameters of oxidative stress in rats fed lipogenic diets high in sucrose. A control diet contained a saturated fat (palm oil) that gives high rate of hepatic lipogenesis. Male Sprague-Dawley rats were fed diets supplemented with 0 or 2.5 g/kg α-lipoic acid and containing 0, 20, or 100 g/kg fish oil, for 21 days. α-Lipoic acid significantly reduced food intake during 0-8 days but not the later period of the experiment. Fish oil and α-lipoic acid decreased serum lipid concentrations and their combination further decreased the parameters in an additive fashion. The combination of fish oil and α-lipoic acid decreased the activity and mRNA levels of hepatic lipogenic enzymes in an additive fashion. Fish oil increased the parameters of hepatic fatty acid oxidation enzymes. α-Lipoic acid appeared to antagonize the stimulating effects of fish oil of fatty acid oxidation through reductions in the activity of some fatty acid oxidation enzymes. α-Lipoic acid attenuated fish oil-dependent increases in serum and liver malondialdehyde levels, and this compound also reduced the serum 8-hydroxy-2'-deoxyguanosine level. α-Lipoic acid affected various parameters related to the antioxidant system; fish oil also affected some of the parameters. The combination of fish oil and α-lipoic acid effectively reduced serum lipid levels through the additive down-regulation of hepatic lipogenesis. α-Lipoic acid was effective in attenuating fish oil-mediated oxidative stress.

  10. Effect of saponified high fat sunflower oilcake and lipoic acid ...

    African Journals Online (AJOL)

    unsaturated fatty acids (PUFA) are toxic to cellulolytic bacteria and are also saturated in the rumen. Stabilization of residual oil in sunflower oilcake by conversion into calcium salts would be advantageous. Alpha lipoic acid acts as an anti-oxidant to ...

  11. Alpha-lipoic acid reduces body weight and regulates triglycerides in obese patients with diabetes mellitus.

    Science.gov (United States)

    Okanović, Azra; Prnjavorac, Besim; Jusufović, Edin; Sejdinović, Rifat

    2015-08-01

    To determine an influence of alpha-lipoic acid to reduction of body weight and regulation of total cholesterol concentration, triglycerides and glucose serum levels in obese patients with diabetes mellitus type 2. A prospective study includes two groups of obese patients with diabetes mellitus and signs of peripheral polyneuropathia: examined group (30 patients; 15 females and 15 males), and control group (30 patients; 12 females and 18 males). All were treated with metformin (850-1700 mg/day). Examined patients were additionally treated with alpha-lipoic acid 600 mg/day during 20 weeks. Body mass index and concentrations of total cholesterol, triglycerides and glucose in serum were compared before and after the treatment. The group treated with 600 mg alpha-lipoic acid lost significantly more weight, and had lower triglyceride level than the control group. There were no significant differences in total cholesterol and glucose serum levels between the groups. Alpha-lipoic acid of 600 mg/day treatment have influenced weight and triglycerides loss in obese patients with diabetes mellitus type 2. It should be considered as an important additive therapy in obese patients with diabetes mellitus type 2. Copyright© by the Medical Assotiation of Zenica-Doboj Canton.

  12. Alpha lipoic acid efficacy in burning mouth syndrome. A controlled clinical trial

    Science.gov (United States)

    Palacios-Sánchez, Begoña; Cerero-Lapiedra, Rocío; Llamas-Martínez, Silvia; Esparza-Gómez, Germán

    2015-01-01

    Background A double-blind placebo-controlled trial was conducted in order to evaluate the efficacy of alpha lipoic acid (ALA) and determine the statistical significance of the outcome variables. Burning mouth syndrome (BMS) is defined as an oral burning sensation in the absence of clinical signs which could justify the syndrome. Recent studies suggest the existence of neurological factors as a possible cause of the disease. Material and Methods 60 patients with BMS, in two groups: case group with 600 mg/day and placebo as control group; with follow up of 2 months. Results 64% of ALA patients reported some level of improvement, with a level of maintenance of 68.75% one month after treatment. 27.6% of the placebo group also demonstrated some reduction in BMS symptoms. Conclusions Long-term evolution and the intensity of symptoms are variables that reduce the probability of improvement with ALA treatment. Key words: Burning mouth syndrome, neuropathy, alpha lipoic acid. PMID:26034927

  13. Protective effects of lipoic acid against oxidative stress induced by lead acetate and gamma-irradiation in the kidney and lung in albino rats

    International Nuclear Information System (INIS)

    Rezk, R.G.; Abdel-Rahman, N.A.

    2013-01-01

    Lipoic acid is widely used as antioxidant that protects tissues against a range of oxidative stress. The present study was designed to determine the protective effect of lipoic acid against oxidative organ damage induced by lead intoxication and/or gamma-irradiation. Rats were treated daily intrapritonealy (i. p.) with lipoic acid( 200 mg/kg/b.w.) for 15 consecutive days before lead acetate injection(30 mg/kg/b.w) i.p. for 5 days and/ or whole body. gamma-irradiation (3 Gy). Animals were sacrificed on the 3rd day post the last treatment. Histological examination of kidney and lung tissues through light microscope showed that lead acetate injection and/or exposure to gamma radiation has provoked severe architectural damage in both tissues as necrotic lesions, atrophoid glomerulei and degenerated proximal and distal convoluted tubules, severe bronchiole fibrosis, decreased ciliated bronchioles and dilated and widened pulmonary artery. Histological damage was associated with significant biochemical. changes as increase in lead, copper, iron, zinc and calcium levels in both kidney and lung tissues. Kidney and lung of rats treated with lipoic acid before lead intoxication and/or gamma-irradiation showed significant regenerated glomerulei structure, well-defined structure of proximal and distal convoluted tubules, regenerated ciliated bronchiole structure and improved pulmonary artery. Tissue regeneration was associated with significant decrease in Pb, Cu, Fe, Zn, and Ca levels in kidney and lung and prevented the accumulation of metals in these organs. It could be concluded that lipoic acid administration before lead and/or whole body gamma-irradiation might be capable to attenuate lead and/or gamma radiation induced organ injury and organ metals disruption

  14. Effect of alpha-lipoic acid on the removal of arsenic from arsenic-loaded isolated liver tissues of rat

    Directory of Open Access Journals (Sweden)

    Noor-E-Tabassum

    2006-06-01

    Full Text Available The patient of chronic arsenic toxicity shows oxidative stress. To overcome the oxidative stress, several antioxidants such as beta-carotene, ascorbic acid, α-tocopherol, zinc and selenium had been suggested in the treatment of chronic arsenic toxicity. In the present study universal antioxidant (both water and lipid soluble antioxidant α-lipoic acid was used to examine the effectiveness of reducing the amount of arsenic from arsenic-loaded isolated liver tissues of rat. Isolated liver tissues of Long Evans Norwegian rats were cut into small pieces and incubated first in presence or absence of arsenic and then with different concentrations of α-lipoic acid during the second incubation. α-Lipoic acid decreases the amount of arsenic and malondialdehyde (MDA in liver tissues as well as increases the reduced glutathione (GSH level in dose dependent manner. These results suggest that α-lipoic acid remove arsenic from arsenic-loaded isolated liver tissues of rat.

  15. Therapy of Primary Hypothyroidism with α-Lipoic Acid Review of Studies Results

    Directory of Open Access Journals (Sweden)

    A.V. Savustyanenko

    2016-05-01

    Full Text Available Primary hypothyroidism occurs in the general population with an incidence of 0.5–1 %, and includes congenital and acquired (due to autoimmune thyroiditis, after surgical removal of the thyroid gland or treatment with radioactive iodine forms. The basic treatment of primary hypothyroidism is replacement therapy with L-thyroxine. Combined administration of L-thyroxine and α-lipoic acid resulted in more marked decrease of oxidative stress, hyperlipidemia, hyperactivity of the immune system, endothelial dysfunction and neurological disorders, observed in patients with primary hypothyroidism, as compared to monotherapy with L-thyroxine. α-lipoic acid use was effective in adults and children, in case of parenteral and/or oral administration.

  16. Age-dependent modulation of synaptic plasticity and insulin mimetic effect of lipoic acid on a mouse model of Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Harsh Sancheti

    Full Text Available Alzheimer's disease is a progressive neurodegenerative disease that entails impairments of memory, thinking and behavior and culminates into brain atrophy. Impaired glucose uptake (accumulating into energy deficits and synaptic plasticity have been shown to be affected in the early stages of Alzheimer's disease. This study examines the ability of lipoic acid to increase brain glucose uptake and lead to improvements in synaptic plasticity on a triple transgenic mouse model of Alzheimer's disease (3xTg-AD that shows progression of pathology as a function of age; two age groups: 6 months (young and 12 months (old were used in this study. 3xTg-AD mice fed 0.23% w/v lipoic acid in drinking water for 4 weeks showed an insulin mimetic effect that consisted of increased brain glucose uptake, activation of the insulin receptor substrate and of the PI3K/Akt signaling pathway. Lipoic acid supplementation led to important changes in synaptic function as shown by increased input/output (I/O and long term potentiation (LTP (measured by electrophysiology. Lipoic acid was more effective in stimulating an insulin-like effect and reversing the impaired synaptic plasticity in the old mice, wherein the impairment of insulin signaling and synaptic plasticity was more pronounced than those in young mice.

  17. The Protective Effects of Alpha-Lipoic Acid and Coenzyme Q10 Combination on Ovarian Ischemia-Reperfusion Injury: An Experimental Study

    Directory of Open Access Journals (Sweden)

    Ahmet Ali Tuncer

    2016-01-01

    Full Text Available Objective. This study aims to evaluate whether alpha-lipoic acid and/or coenzyme Q10 can protect the prepubertal ovarian tissue from ischemia-reperfusion injury in an experimental rat model of ovarian torsion. Materials and Methods. Forty-two female preadolescent Wistar-Albino rats were divided into 6 equal groups randomly. The sham group had laparotomy without torsion; the other groups had torsion/detorsion procedure. After undergoing torsion, group 2 received saline, group 3 received olive oil, group 4 received alpha-lipoic acid, group 5 received coenzyme Q10, and group 6 received both alpha-lipoic acid and coenzyme Q10 orally. The oxidant-antioxidant statuses of these groups were compared using biochemical measurement of oxidized/reduced glutathione, glutathione peroxidase and malondialdehyde, pathological evaluation of damage and apoptosis within the ovarian tissue, and immunohistochemical assessment of nitric oxide synthase. Results. The left ovaries of the alpha-lipoic acid + coenzyme Q10 group had significantly lower apoptosis scores and significantly higher nitric oxide synthase content than the left ovaries of the control groups. The alpha-lipoic acid + coenzyme Q10 group had significantly higher glutathione peroxidase levels and serum malondialdehyde concentrations than the sham group. Conclusions. The combination of alpha-lipoic acid and coenzyme Q10 has beneficial effects on oxidative stress induced by ischemia-reperfusion injury related to ovarian torsion.

  18. Effects of alpha-lipoic acids on sperm membrane integrity during liquid storage of boar semen

    Directory of Open Access Journals (Sweden)

    Laura Parlapan

    2015-05-01

    Full Text Available Preliminary studies have shown that sperm membrane from swine shows high sensitivity to cryopreservation process, causing a dramatic reduction in sperm quality. This has been attributed to the production of reactive oxygen species, that cause lipid peroxidation in sperm membranes. The aim of the present study was to minimize the oxidative attack by adding different concentration of alpha-lipoic acid into the sperm liquid storage at 17ºC for 7 days. Freshly ejaculated boar semen was diluted with Beltsville Thawing Solution (BTS and supplemented with 5 levels of alpha-lipoic  acid (0.015, 0.02, 0.05, 0.1, 0.15 mmol/ml. The membrane integrity was evaluated at days 0, 1, 3, 5 and 7 of liquid preservation, using flow cytometer FACSCanto II (BD Biociencias systems. The experiment indicate that supplementation of alpha-lipoic  acid to the semen liquid storage extender improve sperm membrane

  19. Neuroprotective effects of α-lipoic acid against hypoxic– ischemic ...

    African Journals Online (AJOL)

    Purpose: To explore the neuroprotective efficacy of α-lipoic acid (ALA) against hypoxic-ischemic encephalopathy (HIE) in neonatal rats. Methods: Forty-eight rats (P7-pups) were randomly assigned to one of four groups: group I received saline; group II (HI) underwent unilateral carotid artery ligation and hypoxia (92 % N2 ...

  20. In Vivo Roles of Fatty Acid Biosynthesis Enzymes in Biosynthesis of Biotin and α-Lipoic Acid in Corynebacterium glutamicum.

    Science.gov (United States)

    Ikeda, Masato; Nagashima, Takashi; Nakamura, Eri; Kato, Ryosuke; Ohshita, Masakazu; Hayashi, Mikiro; Takeno, Seiki

    2017-10-01

    For fatty acid biosynthesis, Corynebacterium glutamicum uses two type I fatty acid synthases (FAS-I), FasA and FasB, in addition to acetyl-coenzyme A (CoA) carboxylase (ACC) consisting of AccBC, AccD1, and AccE. The in vivo roles of the enzymes in supplying precursors for biotin and α-lipoic acid remain unclear. Here, we report genetic evidence demonstrating that the biosynthesis of these cofactors is linked to fatty acid biosynthesis through the FAS-I pathway. For this study, we used wild-type C. glutamicum and its derived biotin vitamer producer BFI-5, which was engineered to express Escherichia coli bioBF and Bacillus subtilis bioI Disruption of either fasA or fasB in strain BFI-5 led to decreased production of biotin vitamers, whereas its amplification contributed to increased production, with a larger impact of fasA in both cases. Double disruptions of fasA and fasB resulted in no biotin vitamer production. The acc genes showed a positive effect on production when amplified simultaneously. Augmented fatty acid biosynthesis was also reflected in pimelic acid production when carbon flow was blocked at the BioF reaction. These results indicate that carbon flow down the FAS-I pathway is destined for channeling into the biotin biosynthesis pathway, and that FasA in particular has a significant impact on precursor supply. In contrast, fasB disruption resulted in auxotrophy for lipoic acid or its precursor octanoic acid in both wild-type and BFI-5 strains. The phenotypes were fully complemented by plasmid-mediated expression of fasB but not fasA These results reveal that FasB plays a specific physiological role in lipoic acid biosynthesis in C. glutamicum IMPORTANCE For the de novo biosynthesis of fatty acids, C. glutamicum exceptionally uses a eukaryotic multifunctional type I fatty acid synthase (FAS-I) system comprising FasA and FasB, in contrast to most bacteria, such as E. coli and B. subtilis , which use an individual nonaggregating type II fatty acid synthase

  1. Effects of dietary supplementation with EPA and/or α-lipoic acid on adipose tissue transcriptomic profile of healthy overweight/obese women following a hypocaloric diet.

    Science.gov (United States)

    Huerta, Ana E; Prieto-Hontoria, Pedro L; Fernández-Galilea, Marta; Escoté, Xavier; Martínez, J Alfredo; Moreno-Aliaga, María J

    2017-01-02

    In obesity, the increment of adiposity levels disrupts the whole body homeostasis, promoting an over production of oxidants and inflammatory mediators. The current study aimed to characterize the transcriptomic changes promoted by supplementation with eicosapentaenoic acid (EPA, 1.3 g/day), α-lipoic acid (0.3 g/day), or both (EPA + α-lipoic acid, 1.3 g/day + 0.3 g/day) in subcutaneous abdominal adipose tissue from overweight/obese healthy women, who followed a hypocaloric diet (30% of total energy expenditure) during ten weeks, by using a microarray approach. At the end of the intervention, a total of 33,297 genes were analyzed using Affymetrix GeneChip arrays. EPA promoted changes in extracellular matrix remodeling gene expression, besides a rise of genes associated with either chemotaxis or wound repair. α-Lipoic acid decreased expression of genes related with cell adhesion and inflammation. Furthermore, α-lipoic acid, especially in combination with EPA, upregulated the expression of genes associated with lipid catabolism while downregulated genes involved in lipids storage. Together, all these data suggest that some of the metabolic effects of EPA and α-lipoic acid could be related to their regulatory actions on adipose tissue metabolism. © 2016 BioFactors, 43(1):117-131, 2017. © 2016 International Union of Biochemistry and Molecular Biology.

  2. Apicoplast lipoic acid protein ligase B is not essential for Plasmodium falciparum.

    Directory of Open Access Journals (Sweden)

    Svenja Günther

    2007-12-01

    Full Text Available Lipoic acid (LA is an essential cofactor of alpha-keto acid dehydrogenase complexes (KADHs and the glycine cleavage system. In Plasmodium, LA is attached to the KADHs by organelle-specific lipoylation pathways. Biosynthesis of LA exclusively occurs in the apicoplast, comprising octanoyl-[acyl carrier protein]: protein N-octanoyltransferase (LipB and LA synthase. Salvage of LA is mitochondrial and scavenged LA is ligated to the KADHs by LA protein ligase 1 (LplA1. Both pathways are entirely independent, suggesting that both are likely to be essential for parasite survival. However, disruption of the LipB gene did not negatively affect parasite growth despite a drastic loss of LA (>90%. Surprisingly, the sole, apicoplast-located pyruvate dehydrogenase still showed lipoylation, suggesting that an alternative lipoylation pathway exists in this organelle. We provide evidence that this residual lipoylation is attributable to the dual targeted, functional lipoate protein ligase 2 (LplA2. Localisation studies show that LplA2 is present in both mitochondrion and apicoplast suggesting redundancy between the lipoic acid protein ligases in the erythrocytic stages of P. falciparum.

  3. Alpha-lipoic acid protects oxidative stress, changes in cholinergic system and tissue histopathology during co-exposure to arsenic-dichlorvos in rats.

    Science.gov (United States)

    Dwivedi, Nidhi; Flora, Govinder; Kushwaha, Pramod; Flora, Swaran J S

    2014-01-01

    We investigated protective efficacy of α-lipoic acid (LA), an antioxidant against arsenic and DDVP co-exposed rats. Biochemical variables suggestive of oxidative stress, neurological dysfunction, and tissue histopathological alterations were determined. Male rats were exposed either to 50 ppm sodium arsenite in drinking water or in combination with DDVP (4 mg/kg, subcutaneously) for 10 weeks. α-Lipoic acid (50mg/kg, pos) was also co-administered in above groups. Arsenic exposure led to significant oxidative stress along, hepatotoxicity, hematotoxicity and altered brain biogenic amines levels accompanied by increased arsenic accumulation in blood and tissues. These altered biochemical variables were supported by histopathological examinations leading to oxidative stress and cell death. These biochemical alterations were significantly restored by co-administration of α-lipoic acid with arsenic and DDVP alone and concomitantly. The results indicate that arsenic and DDVP induced oxidative stress and cholinergic dysfunction can be significantly protected by the supplementation of α-lipoic acid. Copyright © 2013 Elsevier B.V. All rights reserved.

  4. Research and Application of Lipoic Acid in Plants

    Science.gov (United States)

    Xiao, Renjie; Wang, Xiran; Jiang, Leiyu; Tang, Haoru

    2018-01-01

    Lipoic acid is a kind of small molecular compound with strong oxidizing properties. It has been widely used in medicine and has achieved good results since its discovery. However, it is less used in plants, and the biosynthetic pathway is not clear. The content in the plant is mainly measured by high-performance liquid chromatography(HPLC). At present, it is mainly used as an additive to the culture medium for plant tissue culture and Agrobacterium-mediated plant genetic transformation, in order to reduce the browning rate of explants, improve Agrobacterium-mediated genetic transformation efficiency.

  5. [EFFECT OF α-LIPOIC ACID IN INHIBITING OXIDATIVE STRESS AND PROMOTING DIABETIC WOUND HEALING BY SUPPRESSING EXPRESSION OF miR-29b IN MICE].

    Science.gov (United States)

    Wu, Jun; Tang, Huiqin; Liu, Qun; Gan, Dingyun; Zhou, Man

    2016-08-08

    To investigate the effect of α-lipoic acid on the oxidative stress of wound tissues and diabetic wound healing in mice with diabetic feet. Sixty male C57BL/6J mice weighting 200-300 g were randomly divided into model group (control group, n =15), α-lipoic acid-treated model group ( n =15), miR-29b mimic group ( n =15), and miR-29b mimic negative control group (NC group, n =15). All animals received intraperitoneal injection of streptozocin to establish the diabetic model. Then, a full thickness wound of 5 mm×2 mm in size was created at 4 weeks after modeling. All mice were administrated with high-sugar-fat-diet. At the same day after modeling, α-lipoic acid-treated model group was continuously given intravenous injection of 100 mg/(kg·d) α-lipoic acid for 14 days; miR-29b mimic group and NC group received the tail intravenous injection of lentiviral vector for miR-29b mimic and miR-29b mimic negative control (a total of 2×10 7 TU), respectively, with the treatment of α-lipoic acid. The wound healing was observed and wound area was measured at 7 and 14 days. The wound tissues were harvested to detect the levels of superoxide dismutase (SOD) and glutathione (GSH) using xanthine oxidase method and 5, 5-dithiobis-2-nitrobenzoic acid staining method at 14 days. At the same day, 7, and 14 days after modeling, the relative miR-29b expression in wound tissues from control and α-lipoic acid-treated model groups was detected by real-time fluorescence quantitative PCR. All mice survived to the experiment end. The wound healing was faster in α-lipoic acid-treated group than control group. At 7 and 14 days, the relative wound area and miR-29b expression level were significantly lower, while the contents of SOD and GSH were significantly higher in α-lipoic acid-treated group than control group ( P diabetic wound healing by suppressing expression of miR-29b in mice.

  6. Site-Specific Protein Labeling Utilizing Lipoic Acid Ligase (LplA) and Bioorthogonal Inverse Electron Demand Diels-Alder Reaction.

    Science.gov (United States)

    Baalmann, Mathis; Best, Marcel; Wombacher, Richard

    2018-01-01

    Here, we describe a two-step protocol for selective protein labeling based on enzyme-mediated peptide labeling utilizing lipoic acid ligase (LplA) and bioorthogonal chemistry. The method can be applied to purified proteins, protein in cell lysates, as well as living cells. In a first step a W37V mutant of the lipoic acid ligase (LplA W37V ) from Escherichia coli is utilized to ligate a synthetic chemical handle site-specifically to a lysine residue in a 13 amino acid peptide motif-a short sequence that can be genetically expressed as a fusion with any protein of interest. In a second step, a molecular probe can be attached to the chemical handle in a bioorthogonal Diels-Alder reaction with inverse electron demand (DA inv ). This method is a complementary approach to protein labeling using genetic code expansion and circumvents larger protein tags while maintaining label specificity, providing experimental flexibility and straightforwardness.

  7. Wheat germ oil enrichment in broiler feed with α-lipoic acid to enhance the antioxidant potential and lipid stability of meat

    Science.gov (United States)

    2013-01-01

    Background Lipid peroxidation is the cause of declining the meat quality. Natural antioxidants plays a vital role in enhancing the stability and quality of meat. The supplementation of natural antioxidants in feed decreases lipid peroxidation and improves the stability of meat. Methods The present research was conducted to determine the effect of α-lipoic acid, α-tocopherol and wheat germ oil on the status of antioxidants, quality and lipid stability of broiler meat. One day old male broilers were fed with different feeds containing antioxidants i.e. natural (wheat germ oil) and synthetic α-tocopherol and α-lipoic acid during the two experimental years. Results The feed treatments have significant variation on the body weight and feed conversion ratio (FCR) while having no influence on the feed intake. The broilers fed on wheat germ oil (natural α-tocopherol) gained maximum body weight (2451.97 g & 2466.07 g) in the experimental years 2010–11 & 2011–12, respectively. The higher total phenolic contents were found in the broilers fed on wheat germ oil plus α-lipoic acid in breast (162.73±4.8 mg Gallic acid equivalent/100 g & 162.18±4.5 mg Gallic acid equivalent/100 g) and leg (149.67±3.3 mg Gallic acid equivalent/100 g & 146.07±3.2 mg Gallic acid equivalent/100 g) meat during both experimental years. Similar trend was observed for the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power assay (FRAP). The production of malondialdehydes in the breast and leg meat increased with progressive increase in the time period. The deposition of α-tocopherol (AT) and α-lipoic acid (ALA) contents were found to be higher in the broilers fed on wheat germ oil plus α-lipoic acid in breast and leg meat during the both experimental years. Conclusion In conclusion, the combination of wheat germ oil and α-lipoic acid has more beneficial for stability and the quality of the broiler meat and more work should be needed in future for the bio

  8. Lipoic acid entrains the hepatic circadian clock and lipid metabolic proteins that have been desynchronized with advanced age

    International Nuclear Information System (INIS)

    Keith, Dove; Finlay, Liam; Butler, Judy; Gómez, Luis; Smith, Eric; Moreau, Régis; Hagen, Tory

    2014-01-01

    Highlights: • 24 month old rats were supplemented with 0.2% lipoic acid in the diet for 2 weeks. • Lipoic acid shifts phase of core circadian clock proteins. • Lipoic acid corrects age-induced desynchronized lipid metabolism rhythms. - Abstract: It is well established that lipid metabolism is controlled, in part, by circadian clocks. However, circadian clocks lose temporal precision with age and correlates with elevated incidence in dyslipidemia and metabolic syndrome in older adults. Because our lab has shown that lipoic acid (LA) improves lipid homeostasis in aged animals, we hypothesized that LA affects the circadian clock to achieve these results. We fed 24 month old male F344 rats a diet supplemented with 0.2% (w/w) LA for 2 weeks prior to sacrifice and quantified hepatic circadian clock protein levels and clock-controlled lipid metabolic enzymes. LA treatment caused a significant phase-shift in the expression patterns of the circadian clock proteins Period (Per) 2, Brain and Muscle Arnt-Like1 (BMAL1), and Reverse Erythroblastosis virus (Rev-erb) β without altering the amplitude of protein levels during the light phase of the day. LA also significantly altered the oscillatory patterns of clock-controlled proteins associated with lipid metabolism. The level of peroxisome proliferator-activated receptor (PPAR) α was significantly increased and acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) were both significantly reduced, suggesting that the LA-supplemented aged animals are in a catabolic state. We conclude that LA remediates some of the dyslipidemic processes associated with advanced age, and this mechanism may be at least partially through entrainment of circadian clocks

  9. Lipoic acid entrains the hepatic circadian clock and lipid metabolic proteins that have been desynchronized with advanced age

    Energy Technology Data Exchange (ETDEWEB)

    Keith, Dove; Finlay, Liam; Butler, Judy [Linus Pauling Institute, Oregon State University (United States); Gómez, Luis; Smith, Eric [Linus Pauling Institute, Oregon State University (United States); Biochemistry Biophysics Department, Oregon State University (United States); Moreau, Régis [Linus Pauling Institute, Oregon State University (United States); Hagen, Tory [Linus Pauling Institute, Oregon State University (United States); Biochemistry Biophysics Department, Oregon State University (United States)

    2014-07-18

    Highlights: • 24 month old rats were supplemented with 0.2% lipoic acid in the diet for 2 weeks. • Lipoic acid shifts phase of core circadian clock proteins. • Lipoic acid corrects age-induced desynchronized lipid metabolism rhythms. - Abstract: It is well established that lipid metabolism is controlled, in part, by circadian clocks. However, circadian clocks lose temporal precision with age and correlates with elevated incidence in dyslipidemia and metabolic syndrome in older adults. Because our lab has shown that lipoic acid (LA) improves lipid homeostasis in aged animals, we hypothesized that LA affects the circadian clock to achieve these results. We fed 24 month old male F344 rats a diet supplemented with 0.2% (w/w) LA for 2 weeks prior to sacrifice and quantified hepatic circadian clock protein levels and clock-controlled lipid metabolic enzymes. LA treatment caused a significant phase-shift in the expression patterns of the circadian clock proteins Period (Per) 2, Brain and Muscle Arnt-Like1 (BMAL1), and Reverse Erythroblastosis virus (Rev-erb) β without altering the amplitude of protein levels during the light phase of the day. LA also significantly altered the oscillatory patterns of clock-controlled proteins associated with lipid metabolism. The level of peroxisome proliferator-activated receptor (PPAR) α was significantly increased and acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) were both significantly reduced, suggesting that the LA-supplemented aged animals are in a catabolic state. We conclude that LA remediates some of the dyslipidemic processes associated with advanced age, and this mechanism may be at least partially through entrainment of circadian clocks.

  10. Effect of the Administration of Alpha-Lipoic Acid on Contrast Sensitivity in Patients with Type 1 and Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Anna Gębka

    2014-01-01

    Full Text Available The aim of this study was to estimate the effects of oral supplementation of alpha-lipoic acid (ALA on contrast sensitivity (CS in patients with type 1 diabetes mellitus (T1DM and type 2 diabetes mellitus (T2DM. The study included 12 patients with T1DM aged 43±12 years, 48 patients with T2DM aged 59±10 years, and 20 control subjects aged 33±8 years. Patients from each studied group, including the control group, were randomly assigned to receive 300 mg of ALA orally once daily for 3 months. CS was evaluated with the Functional Acuity Contrast Test (FACT, Stereo Optical. In the group of patients with T1DM receiving ALA for 3 months CS remained stable and improved in those with T2DM. Reduction of CS in both T1DM and T2DM patients without alpha-lipoic acid supplementation was observed. In the control group on alpha-lipoic acid supplementation, CS improvement was noticed at one spatial frequency. Changes in the CS were observed, despite stable visual acuity and eye fundus image in all studied subjects. Our study demonstrated that oral administration of alpha-lipoic acid had influence on CS in both T1DM and T2DM patients.

  11. The importance of 1,2-dithiolane structure in α-lipoic acid for the downregulation of cell surface β1-integrin expression of human bladder cancer cells.

    Science.gov (United States)

    Yamasaki, Masao; Soda, Shozen; Sakakibara, Yoichi; Suiko, Masahito; Nishiyama, Kazuo

    2014-01-01

    Here, we show that cell surface β1-integrin expression, cell adhesion to fibronectin, migration, and invasion were all significantly inhibited by α-lipoic acid. These effects were not observed when cells were treated with dihydrolipoic acid or caprylic acid. These data reveal that the 1,2-dithiolane structure plays an important role in the action of α-lipoic acid.

  12. Antioxidant effect of erdosteine and lipoic acid in ovarian ischemia-reperfusion injury.

    Science.gov (United States)

    Dokuyucu, R; Karateke, A; Gokce, H; Kurt, R K; Ozcan, O; Ozturk, S; Tas, Z A; Karateke, F; Duru, M

    2014-12-01

    To investigate the effects of erdosteine and alpha lipoic acid (ALA) in a rat model of ovarian ischaemia-reperfusion injury. Forty-eight female Wistar albino rats were separated, at random, into six groups of eight rats. The groups were classified as: sham, torsion, detorsion, detorsion+erdosteine 100mg/kg, detorsion+alpha lipoic acid (ALA) 100mg/kg, and detorsion+erdosteine+ALA. The investigators executing the biochemical and histological analyses were blinded to the randomization until the end of the study. The TOS (Total Oxidant Status) and OSI (Oxidative Stress Index) levels are higher in the Torsion and Detorsion groups when compared with the ones in the Sham group (pOSI and total histological score in the sham, torsion and detorsion groups (r=0.765, pOSI in the rats that received erdosteine and/or ALA were significantly lower compared with the sham, torsion and detorsion groups (pOSI were lower in the detorsion+erdosteine+ALA group compared with the detorsion+erdosteine and detorsion+ALA groups (pmodel; combination treatment had a greater effect than either agent alone. Treatment with erdosteine and/or ALA was found to preserve the loss of reproductive capacity normally observed after ovarian torsion. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  13. Grafting of 4-aminomethylbenzensulfonamide-lipoic acid conjugate on gold nanoparticles

    Science.gov (United States)

    Stiti, M.; Bouzit, H.; Abdaoui, M.; Winum, J. Y.

    2012-02-01

    In this paper, we describe the synthesis of goldnanoparticles bearing aminomethylbenzensulfonamide via a lipoyl moiety. The resulting stable nanoparticles with an average size of 4.0 nm have been achieved by a facile and high-yielding one phase method, by the action of 4-aminomethylbenzensulfonamide-lipoic acid bioconjugate on chloroauric acide, using dimethylsulfoxide (DMSO) as the solvent and sodium tetrahydridoborate (NaBH4) as the reducing agent. UV-vis absorption, transmission electron microscopy (TEM) and X-ray diffraction were used to analyse the morphology and the structure of the obtained nanoparticles. Preliminary study shows that these new nanoparticles are endowed with highly and specific inhibitory activity for the isoform (IX) of carbonic anhydrase over expressed in many cancers, and are therefore attractive candidate to be used both in diagnosis and in treatment of tumours.

  14. Ginger and alpha lipoic acid ameliorate age-related ultrastructural changes in rat liver.

    Science.gov (United States)

    Mahmoud, Y I; Hegazy, H G

    2016-01-01

    Because of the important role that oxidative stress is thought to play in the aging process, antioxidants could be candidates for preventing its related pathologies. We investigated the ameliorative effects of two antioxidant supplements, ginger and alpha lipoic acid (ALA), on hepatic ultrastructural alterations in old rats. Livers of young (4 months) and old (24 months) Wistar rats were studied using transmission electron microscopy. Livers of old rats showed sinusoidal collapse and congestion, endothelial thickening and defenestration, and inconsistent perisinusoidal extracellular matrix deposition. Aged hepatocytes were characterized by hypertrophy, cytoplasmic vacuolization and a significant increase in the volume densities of the nuclei, mitochondria and dense bodies. Lipofuscin accumulation and decreased microvilli in bile canaliculi and space of Disse also were observed. The adverse alterations were ameliorated significantly by both ginger and ALA supplementation; ALA was more effective than ginger. Ginger and ALA appear to be promising anti-aging agents based on their amelioration of ultrastructural alterations in livers of old rats.

  15. Lipoic acid effects on glutamate and taurine concentrations in rat hippocampus after pilocarpine-induced seizures

    Directory of Open Access Journals (Sweden)

    P S Santos

    2011-01-01

    Full Text Available Pilocarpine-induced seizures can be mediated by increases in oxidative stress and by cerebral amino acid changes. The present research suggests that antioxidant compounds may afford some level of neuroprotection against the neurotoxicity of seizures in cellular level. The objective of the present study was to evaluate the lipoic acid (LA effects in glutamate and taurine contents in rat hippocampus after pilocarpine-induced seizures. Wistar rats were treated intraperitoneally (i.p. with 0.9% saline (Control, pilocarpine (400 mg/kg, Pilocarpine, LA (10 mg/kg, LA, and the association of LA (10 mg/kg plus pilocarpine (400 mg/kg, that was injected 30 min before of administration of LA (LA plus pilocarpine. Animals were observed during 24 h. The amino acid concentrations were measured using high-performance liquid chromatograph (HPLC. In pilocarpine group, it was observed a significant increase in glutamate content (37% and a decrease in taurine level (18% in rat hippocampus, when compared to control group. Antioxidant pretreatment significantly reduced the glutamate level (28% and augmented taurine content (32% in rat hippocampus, when compared to pilocarpine group. Our findings strongly support amino acid changes in hippocampus during seizures induced by pilocarpine, and suggest that glutamate-induced brain damage plays a crucial role in pathogenic consequences of seizures, and imply that strong protective effect could be achieved using lipoic acid through the release or decrease in metabolization rate of taurine amino acid during seizures.

  16. Effect of alpha-lipoic acid on endometrial implants in an experimental rat model.

    Science.gov (United States)

    Pınar, Neslihan; Soylu Karapınar, Oya; Özcan, Oğuzhan; Özgür, Tümay; Bayraktar, Suphi

    2017-10-01

    To investigate the antioxidant and anti-inflammatory effects of alpha-lipoic acid (ALA) in the treatment of endometriosis in an experimental rat model by evaluating biochemical and histopathologic parameters. Experimental endometriosis was induced by the peritoneal implantation of autologous endometrial tissue. The rats were randomly divided into two groups with eight rats each. Group I was intraperitoneally administered ALA 100 mg/kg/day for 14 days. Group II was intraperitoneally administered saline solution at the same dosage and over the same period. Endometrial implant volume was measured in both groups both pre- and post-treatment. Tumor necrosis factor alpha (TNF-α) was measured in peritoneal fluid. Total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) were assessed in serum. The implants were histopathologically evaluated. In the ALA group, the serum TOS and OSI levels, the endometrial implant volumes, the TNF-α levels in serum and peritoneal fluid, and the histopathologic scores were significantly lower compared to the control group (P < 0.05). Alpha-lipoic acid may have a therapeutic potential in the treatment of endometriosis due to its antioxidant and anti-inflammatory effects. © 2017 Société Française de Pharmacologie et de Thérapeutique.

  17. Alpha-Lipoic acid supplementation inhibits oxidative damage, accelerating chronic wound healing in patients undergoing hyperbaric oxygen therapy

    Czech Academy of Sciences Publication Activity Database

    Alleva, R.; Nasole, E.; Di Donato, F.; Borghi, B.; Neužil, Jiří; Tomasetti, M.

    2005-01-01

    Roč. 333, č. 2 (2005), s. 404-410 ISSN 0006-291X Institutional research plan: CEZ:AV0Z50520514 Keywords : alpha-lipoic acid * chronic wound * ROS Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.000, year: 2005

  18. d-chiro-Inositol and alpha lipoic acid treatment of metabolic and menses disorders in women with PCOS.

    Science.gov (United States)

    Cianci, Antonio; Panella, Marco; Fichera, Michele; Falduzzi, Cristina; Bartolo, Manuela; Caruso, Salvatore

    2015-06-01

    To evaluate the effects of the combination of d-chiro-inositol (DCI) and alpha lipoic acid on menses and metabolic disorders in women with polycystic ovary syndrome (PCOS). Forty-six women (26 study group subjects and 20 controls) of reproductive age with PCOS according to Rotterdam criteria were enrolled in this prospective study. Fasting serum samples were collected from each woman. Homeostasis model of insulin resistance, insulin levels, lipid profile, frequency of menstrual cycles, number of ovarian peripheral cysts and BMI of both groups were investigated at baseline and after 180 days. Clinical and metabolic aspects of women on DCI and lipoic acid treatment underwent improvement (p treatment has been thought because it plays an essential role in mitochondrial specific pathways that generate energy from glucose and its potent effect as antioxidant. The association might have a strong impact on metabolic profile even with a short-term treatment. Further investigations are needed to evaluate other effects on reproductive physiology of women with PCOS.

  19. Oral benfotiamine plus alpha-lipoic acid normalises complication-causing pathways in type 1 diabetes.

    Science.gov (United States)

    Du, X; Edelstein, D; Brownlee, M

    2008-10-01

    We determined whether fixed doses of benfotiamine in combination with slow-release alpha-lipoic acid normalise markers of reactive oxygen species-induced pathways of complications in humans. Male participants with and without type 1 diabetes were studied in the General Clinical Research Centre of the Albert Einstein College of Medicine. Glycaemic status was assessed by measuring baseline values of three different indicators of hyperglycaemia. Intracellular AGE formation, hexosamine pathway activity and prostacyclin synthase activity were measured initially, and after 2 and 4 weeks of treatment. In the nine participants with type 1 diabetes, treatment had no effect on any of the three indicators used to assess hyperglycaemia. However, treatment with benfotiamine plus alpha-lipoic acid completely normalised increased AGE formation, reduced increased monocyte hexosamine-modified proteins by 40% and normalised the 70% decrease in prostacyclin synthase activity from 1,709 +/- 586 pg/ml 6-keto-prostaglandin F(1alpha) to 4,696 +/- 533 pg/ml. These results show that the previously demonstrated beneficial effects of these agents on complication-causing pathways in rodent models of diabetic complications also occur in humans with type 1 diabetes.

  20. Lipoic Acid Decreases the Viability of Breast Cancer Cells and Activity of PTP1B and SHP2.

    Science.gov (United States)

    Kuban-Jankowska, Alicja; Gorska-Ponikowska, Magdalena; Wozniak, Michal

    2017-06-01

    Protein tyrosine phosphatases PTP1B and SHP2 are potential targets for anticancer therapy, because of the essential role they play in the development of tumors. PTP1B and SHP2 are overexpressed in breast cancer cells, thus inhibition of their activity can be potentially effective in breast cancer therapy. Lipoic acid has been previously reported to inhibit the proliferation of colon, breast and thyroid cancer cells. We investigated the effect of alpha-lipoic acid (ALA) and its reduced form of dihydrolipoic acid (DHLA) on the viability of MCF-7 cancer cells and on the enzymatic activity of PTP1B and SHP2 phosphatases. ALA and DHLA decrease the activity of PTP1B and SHP2, and have inhibitory effects on the viability and proliferation of breast cancer cells. ALA and DHLA can be considered as potential agents for the adjunctive treatment of breast cancer. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  1. Development of Cholinesterase Inhibitors Using (a)-Lipoic Acid-benzyl Piperazine Hybrid Molecules

    International Nuclear Information System (INIS)

    Kim, Beomcheol; Lee, Seunghwan; Jang, Mi; Shon, Min Young; Park, Jeong Ho

    2013-01-01

    A series of hybrid molecules between (α)-lipoic acid (ALA) and benzyl piperazines were synthesized and their in vitro cholinesterase [acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE)] inhibitory activities were evaluated. Even though the parent compounds did not show any inhibitory activity against cholinesterase (ChE), all hybrid molecules showed BuChE inhibitory activity. Some hybrid compounds also displayed AChE inhibitory activity. Specifically, ALA-1-(3-methylbenzyl)piperazine (15) was shown to be an effective inhibitor of both BuChE (IC 50 = 2.3 ± 0.7 μM) and AChE (IC 50 = 30.31 ± 0.64 μM). An inhibition kinetic study using compound 15 indicated a mixed inhibition type. Its binding affinity (K i ) value to BuChE is 2.91 ± 0.15 μM

  2. Consequences of the Combined α-tocopherol, Ascorbic Acid and α-lipoic Acid on the Glutathione, Cholesterol and Fatty Acid Composition in Muscle and Liver of Diabetic Rats

    OpenAIRE

    Okkes YILMAZ; Yasemin ERSAN; Ayse Dilek OZSAHIN; Ali Ihsan OZTURK; Yusuf OZKAN

    2013-01-01

    Objective(s): Our objective was to evaluate the effects of a triple antioxidant combination [?-tocopherol (AT), ascorbic acid (AA) and ?-lipoic acid (LA); AT+AA+LA] on the cholesterol and glutathione levels, and the fatty acid composition of liver and muscle tissues in diabetic rats. Materials and Methods: Forty-three Wistar rats were randomly divided into five groups. The first group was used as a control. The second, third and fourth groups received STZ (45 mg/kg) in citrate buffer. The fou...

  3. Development of Cholinesterase Inhibitors Using (a)-Lipoic Acid-benzyl Piperazine Hybrid Molecules

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Beomcheol; Lee, Seunghwan; Jang, Mi; Shon, Min Young; Park, Jeong Ho [Hanbat National Univ., Daejeon (Korea, Republic of)

    2013-11-15

    A series of hybrid molecules between (α)-lipoic acid (ALA) and benzyl piperazines were synthesized and their in vitro cholinesterase [acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE)] inhibitory activities were evaluated. Even though the parent compounds did not show any inhibitory activity against cholinesterase (ChE), all hybrid molecules showed BuChE inhibitory activity. Some hybrid compounds also displayed AChE inhibitory activity. Specifically, ALA-1-(3-methylbenzyl)piperazine (15) was shown to be an effective inhibitor of both BuChE (IC{sub 50} = 2.3 ± 0.7 μM) and AChE (IC{sub 50} = 30.31 ± 0.64 μM). An inhibition kinetic study using compound 15 indicated a mixed inhibition type. Its binding affinity (K{sub i}) value to BuChE is 2.91 ± 0.15 μM.

  4. α-lipoic acid inhibits oxidative stress in testis and attenuates testicular toxicity in rats exposed to carbimazole during embryonic period

    Directory of Open Access Journals (Sweden)

    P. Prathima

    Full Text Available The aim of this study was to evaluate the probable protective effect of α-lipoic acid against testicular toxicity in rats exposed to carbimazole during the embryonic period. Time-mated pregnant rats were exposed to carbimazole from the embryonic days 9–21. After completion of the gestation period, all the rats were allowed to deliver pups and weaned. At postnatal day 100, F1 male pups were assessed for the selected reproductive endpoints. Gestational exposure to carbimazole decreased the reproductive organ indices, testicular daily sperm count, epididymal sperm variables viz., sperm count, viable sperm, motile sperm and HOS-tail coiled sperms. Significant decrease in the activity levels of 3β- and 17β-hydroxysteroid dehydrogenases and expression of StAR mRNA levels with a significant increase in the total cholesterol levels were observed in the testis of experimental rats over the controls. These events were also accompanied by a significant reduction in the serum testosterone levels in CBZ exposed rats, indicating reduced steroidogenesis. In addition, the deterioration of the testicular architecture and reduced fertility ability were noticed in the carbimazole exposed rats. Significant reduction in the activity levels of superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase and reduced glutathione content with a significant increase in the levels of lipid peroxidation were observed in the testis of carbimazole exposed rats over the controls. Conversely, supplementation of α-lipoic acid (70 mg/Kg bodyweight ameliorated the male reproductive health in rats exposed to carbimazole during the embryonic period as evidenced by enhanced reproductive organ weights, selected sperm variables, testicular steroidogenesis, and testicular enzymatic and non-enzymatic antioxidants. To conclude, diminished testicular antioxidant balance associated with reduced spermatogenesis and steroidogenesis might be responsible

  5. α-Lipoic acid exhibits anti-amyloidogenicity for β-amyloid fibrils in vitro

    International Nuclear Information System (INIS)

    Ono, Kenjiro; Hirohata, Mie; Yamada, Masahito

    2006-01-01

    Inhibition of the formation of β-amyloid fibrils (fAβ), as well as the destabilization of preformed fAβ in the CNS would be attractive therapeutic targets for the treatment of Alzheimer's disease (AD). Using fluorescence spectroscopic analysis with thioflavin T and electron microscopic studies, we examined the effects of α-lipoic acid (LA) and the metabolic product of LA, dihydrolipoic acid (DHLA), on the formation, extension, and destabilization of fAβ at pH 7.5 at 37 o C in vitro. LA and DHLA dose-dependently inhibited fAβ formation from amyloid β-protein, as well as their extension. Moreover, they destabilized preformed fAβs. LA and DHLA could be key molecules for the development of therapeutics for AD

  6. Two-step protein labeling by using lipoic acid ligase with norbornene substrates and subsequent inverse-electron demand Diels-Alder reaction.

    Science.gov (United States)

    Best, Marcel; Degen, Anna; Baalmann, Mathis; Schmidt, Tobias T; Wombacher, Richard

    2015-05-26

    Inverse-electron-demand Diels-Alder cycloaddition (DAinv ) between strained alkenes and tetrazines is a highly bio-orthogonal reaction that has been applied in the specific labeling of biomolecules. In this work we present a two-step labeling protocol for the site-specific labeling of proteins based on attachment of a highly stable norbornene derivative to a specific peptide sequence by using a mutant of the enzyme lipoic acid ligase A (LplA(W37V) ), followed by the covalent attachment of tetrazine-modified fluorophores to the norbornene moiety through the bio-orthogonal DAinv  . We investigated 15 different norbornene derivatives for their selective enzymatic attachment to a 13-residue lipoic acid acceptor peptide (LAP) by using a standardized HPLC protocol. Finally, we used this two-step labeling strategy to label proteins in cell lysates in a site-specific manner and performed cell-surface labeling on living cells. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Tolerability in the elderly population of high-dose alpha lipoic acid: a potential antioxidant therapy for the eye

    Directory of Open Access Journals (Sweden)

    Sarezky D

    2016-09-01

    Full Text Available Daniel Sarezky, Aaishah R Raquib, Joshua L Dunaief, Benjamin J Kim Scheie Eye Institute, Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA Purpose: Alpha lipoic acid (ALA is an antioxidant and iron-chelating supplement that has potential benefits for geographic atrophy in dry age-related macular degeneration as well as other eye diseases. The purpose of this study was to determine the tolerability of ALA in the elderly population. Patients and methods: Fifteen subjects, age ≥65 years, took sequential ALA doses of 600, 800, and 1,200 mg. Each dose was taken once daily with a meal for 5 days. After each dose was taken by the subjects for 5 days, the subjects were contacted by phone, a review of systems was performed, and they were asked if they thought they could tolerate taking that dose of ALA for an extended period of time. Results: The 600 mg dose was well tolerated. At the 800 mg dose, one subject had an intolerable flushing sensation. At the 1,200 mg dose, two subjects had intolerable upper gastrointestinal side effects and one subject had an intolerable flushing sensation. Subjects taking gastrointestinal prophylaxis medications had no upper gastrointestinal side effects. Conclusion: High-dose ALA is not completely tolerated by the elderly. These preliminary data suggest that gastrointestinal prophylaxis may improve tolerability. (ClinicalTrials.gov, NCT02613572. Keywords: age-related macular degeneration, geographic atrophy, antioxidant, gastrointestinal, dietary supplements, lipoic acid

  8. Protective Effect of Alpha Lipoic Acid on Rat Sciatic Nerve Ischemia Reperfusion Damage

    Directory of Open Access Journals (Sweden)

    Ozan Turamanlar

    2015-06-01

    Full Text Available Background: Alpha lipoic acid is a potent antioxidant that plays numerous roles in human health. This study examined the effect of ALA on rat sciatic nerve ischemia reperfusion damage. Aims: Protective effect of alpha lipoic acid (ALA on sciatic nerve following ischemia-reperfusion in rats was investigated by using light microscopy and biochemical methods. Provided that the protective effect of ALA on sciatic nerve is proven, we think the damage to the sciatic nerve that has already occurred or might occur in patients for various reasons maybe prevented or stopped by giving ALA in convenient doses. Study Design: Animal experiment. Methods: Forty-two adult male Sprague-Dawley rats (250-300 grams were used in this study. Rats were randomly divided into six groups including one control (Group 1, one sham (Group 2, two ischemia-reperfusion (Groups 3 and 4 and two treatment groups (Groups5 and 6. Doses of 60 and 100 mg/kg ALA were given (Group 5 and 6 intra peritoneally twice, 1 and 24 hours before the ischemia to each treatment group. Ischemia was carried out the abdominal aorta starting from the distal part of the renal vein for two hours followed by reperfusion for three hours. In immunohistochemical methods, fibronectin immunoreactivity was analyzed. For biochemical analyses, the tissues were taken in eppendorf microtubes and superoxide dismutase (SOD and glutathione peroxidase (GSHPx enzyme activities as well as malondialdehyde (MDA and nitricoxide (NO levels were measured. Results: Fibronectin was observed to have increased significantly in the ischemia group; on the other hand, it was observed to have decreased in parallel to the doses in the ALA groups. Biochemical studies showed that SOD and GSHPx declined with ischemia-reperfusion, but the activities of these enzymes were increased in the treatment groups in parallel with the dose. It was found that increased MDA levels with ischemia-reperfusion were decreased in parallel with ALA dose

  9. The issue of HPLC determination of endogenous lipoic acid in human plasma.

    Science.gov (United States)

    Sechovcová, Soňa; Královcová, Pavla; Kanďár, Roman; Ventura, Karel

    2018-05-01

    Lipoic acid (LA) is used extensively as a therapeutic agent for the treatment of various diseases. Many methods have been reported for the determination of LA plasma levels and its metabolites after its supplementation, but available information concerning endogenous plasma levels is still scarce. Studies which directly focused on determining the endogenous plasma levels provided highly controversial results, endogenous plasma levels of LA: 2.4 and 4.9 nmol/L respectively. However, the levels of free LA in the plasma of nonsupplemented voluntary blood donors were not detectable in all cases. The presented results of our study show that endogenous concentrations of LA are <1.85 nmol/L. Copyright © 2017 John Wiley & Sons, Ltd.

  10. Homology modeling of Homo sapiens lipoic acid synthase: Substrate docking and insights on its binding mode.

    Science.gov (United States)

    Krishnamoorthy, Ezhilarasi; Hassan, Sameer; Hanna, Luke Elizabeth; Padmalayam, Indira; Rajaram, Rama; Viswanathan, Vijay

    2017-05-07

    Lipoic acid synthase (LIAS) is an iron-sulfur cluster mitochondrial enzyme which catalyzes the final step in the de novo pathway for the biosynthesis of lipoic acid, a potent antioxidant. Recently there has been significant interest in its role in metabolic diseases and its deficiency in LIAS expression has been linked to conditions such as diabetes, atherosclerosis and neonatal-onset epilepsy, suggesting a strong inverse correlation between LIAS reduction and disease status. In this study we use a bioinformatics approach to predict its structure, which would be helpful to understanding its role. A homology model for LIAS protein was generated using X-ray crystallographic structure of Thermosynechococcus elongatus BP-1 (PDB ID: 4U0P). The predicted structure has 93% of the residues in the most favour region of Ramachandran plot. The active site of LIAS protein was mapped and docked with S-Adenosyl Methionine (SAM) using GOLD software. The LIAS-SAM complex was further refined using molecular dynamics simulation within the subsite 1 and subsite 3 of the active site. To the best of our knowledge, this is the first study to report a reliable homology model of LIAS protein. This study will facilitate a better understanding mode of action of the enzyme-substrate complex for future studies in designing drugs that can target LIAS protein. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. α-Lipoic acid antioxidant treatment limits glaucoma-related retinal ganglion cell death and dysfunction.

    Directory of Open Access Journals (Sweden)

    Denise M Inman

    Full Text Available Oxidative stress has been implicated in neurodegenerative diseases, including glaucoma. However, due to the lack of clinically relevant models and expense of long-term testing, few studies have modeled antioxidant therapy for prevention of neurodegeneration. We investigated the contribution of oxidative stress to the pathogenesis of glaucoma in the DBA/2J mouse model of glaucoma. Similar to other neurodegenerative diseases, we observed lipid peroxidation and upregulation of oxidative stress-related mRNA and protein in DBA/2J retina. To test the role of oxidative stress in disease progression, we chose to deliver the naturally occurring, antioxidant α-lipoic acid (ALA to DBA/2J mice in their diet. We used two paradigms for ALA delivery: an intervention paradigm in which DBA/2J mice at 6 months of age received ALA in order to intervene in glaucoma development, and a prevention paradigm in which DBA/2J mice were raised on a diet supplemented with ALA, with the goal of preventing glaucoma development. At 10 and 12 months of age (after 4 and 11 months of dietary ALA respectively, we measured changes in genes and proteins related to oxidative stress, retinal ganglion cell (RGC number, axon transport, and axon number and integrity. Both ALA treatment paradigms showed increased antioxidant gene and protein expression, increased protection of RGCs and improved retrograde transport compared to control. Measures of lipid peroxidation, protein nitrosylation, and DNA oxidation in retina verified decreased oxidative stress in the prevention and intervention paradigms. These data demonstrate the utility of dietary therapy for reducing oxidative stress and improving RGC survival in glaucoma.

  12. Protective Role of Alpha Lipoic Acid Against Disorders Induced by Gamma Radiation

    International Nuclear Information System (INIS)

    Abd El Azeem, Kh.N.M.

    2011-01-01

    Ionizing radiation interacts with living cells, causing a variety of biochemical changes depending on exposed and absorbed doses, duration of exposure, interval after exposure and susceptibility of tissues to ionizing radiation. So, it may increase the oxidative stress and damage of body organs. Alpha-lipoic acid (ALA-also known as thioctic acid) appears to be readily absorbed from an oral dose and converts easily to its reduced form, dihydro lipoic acid (DHLA), in many tissues of the body. ALA can neutralize free radicals in both fatty and watery regions of cells. The present study has been designed to evaluate the possible efficiency of ALA as antioxidant and radio-protector against radiation induced oxidative stress in different organs (liver, kidney and heart) in rats through estimation of the activity of markers of serum liver, kidney and heart function, in addition to the histopathological differentiation of these organs by light and electron microscope. Five equal groups were conducted for the study: control, ALA (30 mg/kg body wt), irradiated (each rat was exposed to 6 Gy as a fractionated dose of gamma (γ) radiation), irradiated plus ALA (each rat received ALA for 9 days simultaneously during exposure) and ALA plus irradiation plus ALA groups (each rat received ALA for a week pre-exposure plus 9 days during exposure). Radiation doses were fractionated dose levels of 2 Gy each 3 days to reach accumulative dose of 6 Gy. After 3 days of each exposure rats were sacrificed, except, those left for recovery test one month after last exposure. The results revealed that whole body γ-irradiation of rats induces oxidative stress in liver, kidney and heart obviously manifested by significant elevation in alanine and aspartate transaminase ( ALT and AST), alkaline phosphatase (ALP), urea, creatinine and creatine kinase (CK-MB). ALA treated-irradiated rats showed lower significantly values indicating remarkable improvement in all measured parameters and

  13. Critical appraisal of the use of alpha lipoic acid (thioctic acid in the treatment of symptomatic diabetic polyneuropathy

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    McIlduff CE

    2011-09-01

    Full Text Available Courtney E McIlduff, Seward B RutkoveDepartment of Neurology, Beth Israel Deaconess Medical Center, Boston, MA, USABackground: The most common of the neuropathies associated with diabetes mellitus, diabetic sensorimotor polyneuropathy (DSPN is a syndrome of diffuse, length-dependent, symmetric nerve dysfunction. The condition is linked with substantial morbidity, frequent healthcare utilization, and compromised quality of life due to related discomfort. Correspondingly, antidepressants, anticonvulsants, and opioids are regularly prescribed with the goal of pain control. However, the agents rarely provide complete pain relief and fail to address progression of the disorder. Whereas strict blood glucose control can slow the onset and worsening of DSPN, near-normoglycemia is not easily attainable. Evidence implicating oxidative processes in the pathogenesis of DSPN offers one potentially important therapeutic avenue. Due to its properties as a potent antioxidant, alpha lipoic acid (ALA could mitigate the development of DSPN and attenuate resultant symptoms and signs. Approved for treatment of DSPN in Germany, the agent is not more widely used due to uncertainty about its efficacy and reported adverse effects. Here we review the effectiveness and tolerability of ALA in the treatment of symptomatic DSPN.Methods: The MEDLINE, EMBASE, and Cochrane Library databases were searched for English-language literature on the topic. Randomized, blinded studies comparing parenteral and oral ALA with placebo in the treatment of peripheral neuropathy in diabetic adults were selected. Analysis included studies with a level of evidence of at least 2b.Results: The current appraisal summarizes data from 1160 participants in the ALADIN, SYDNEY, ORPIL, SYDNEY 2, and ALADIN III trials. In four of the studies, ALA provided significant improvement in manifestations of DSPN.Conclusion: Treatment with ALA 600 mg iv daily for 3 weeks represents a well-tolerated and effective

  14. Bioavailability of an R-α-Lipoic Acid/γ-Cyclodextrin Complex in Healthy Volunteers

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    Naoko Ikuta

    2016-06-01

    Full Text Available R-α-lipoic acid (R-LA is a cofactor of mitochondrial enzymes and a very strong antioxidant. R-LA is available as a functional food ingredient but is unstable against heat or acid. Stabilized R-LA was prepared through complexation with γ-cyclodextrin (CD, yielding R-LA/CD. R-LA/CD was orally administered to six healthy volunteers and showed higher plasma levels with an area under the plasma concentration-time curve that was 2.5 times higher than that after oral administration of non-complexed R-LA, although the time to reach the maximum plasma concentration and half-life did not differ. Furthermore, the plasma glucose level after a single oral administration of R-LA/CD or R-LA was not affected and no side effects were observed. These results indicate that R-LA/CD could be easily absorbed in the intestine. In conclusion, γ-CD complexation is a promising technology for delivering functional but unstable ingredients like R-LA.

  15. Determination of lipoic acid in human urine by capillary zone electrophoresis.

    Science.gov (United States)

    Kubalczyk, Paweł; Głowacki, Rafał

    2017-07-01

    Fast, simple, and accurate CE method enabling determination of lipoic acid (LA) in human urine has been developed and validated. LA is a disulfide-containing natural compound absorbed from the organism's diet. Due to powerful antioxidant activity, LA has been used for prevention and treatment of various diseases and disorders, e.g. cardiovascular diseases, neurodegenerative disorders, and cancer. The proposed analytical procedure consists of liquid-liquid sample extraction, reduction of LA with tris(2-carboxyethyl)phosphine, derivatization with 1-benzyl-2-chloropyridinium bromide (BCPB) followed by field amplified sample injection stacking, capillary zone electrophoresis separation, and ultraviolet-absorbance detection of LA-BCPB derivative at 322 nm. Effective baseline electrophoretic separation was achieved within 6 min under the separation voltage of 20 kV (∼80 μA) using a standard fused-silica capillary (effective length 51.5 cm, 75 μm id) and BGE consisted of 0.05 mol/L borate buffer adjusted to pH 9. The experimentally determined limit of detection for LA in urine was 1.2 μmol/L. The calibration curve obtained for LA in urine showed linearity in the range 2.5-80 μmol/L, with R 2 0.9998. The relative standard deviation of the points of the calibration curve was lower than 10%. The analytical procedure was successfully applied to analysis of real urine samples from seven healthy volunteers who received single 100 mg dose of LA. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Neuroprotective evidence of alpha-lipoic acid and desvenlafaxine on memory deficit in a neuroendocrine model of depression.

    Science.gov (United States)

    de Sousa, Caren Nádia Soares; Meneses, Lucas Nascimento; Vasconcelos, Germana Silva; da Silva Medeiros, Ingridy; Silva, Márcia Calheiros Chaves; Mouaffak, Fayçal; Kebir, Oussama; da Silva Leite, Cláudio Manuel Gonçalves; Patrocinio, Manoel Cláudio Azevedo; Macedo, Danielle; Vasconcelos, Silvânia Maria Mendes

    2018-05-07

    Cognitive impairment is present in patients with depression. We hypothesized that alpha-lipoic acid (ALA) can reduce cognitive impairment, especially when combined to antidepressants. Female mice received vehicle or corticosterone (CORT) 20 mg/kg, s.c. for 14 days. From the 15th to 21st day, the animals were divided in groups: vehicle, CORT, CORT+desvenlafaxine (DVS) 10 or 20 mg/kg, ALA 100 or 200 mg/kg, DVS10+ALA100, DVS20+ALA100, DVS10+ALA200, or DVS20+ALA200. Tail suspension (TST), social interaction (SIT), novel object recognition (NOR), and Y-maze tests were conducted. Acetylcholinesterase activity (AChE) was measured in the prefrontal cortex (PFC), hippocampus (HC), and striatum (ST). CORT caused depressive-like behavior, impairment in SIT, and cognitive deficits. Alpha-lipoic acid and DVS, alone or combined, reversed CORT effect on TST. In the NOR, ALA200 alone, DVS10+ALA100, or DVS10+ALA200 reversed the deficits in short-term memory, while DVS20 alone or DVS20+ALA200 reversed the deficits in long-term memory. In the Y-maze test, ALA200 alone, DVS20+ALA100, or DVS20+ALA200 reversed the deficits caused by CORT in the working memory. CORT increased AChE in the PFC, HC, and ST. ALA200 alone or DVS20+ALA200 reversed this effect in the PFC, while DVS20 or DVS20+ALA100 reversed this effect in the HC. In the ST, DVS10 or 20, alone or combined, and ALA100 reversed the effects of CORT. These results suggest that DVS+ALA, by reversing CORT-induced memory and social deficits, seems to be a promising therapy for the treatment of depression and reversal of cognitive impairment observed in this disorder.

  17. Erythrocyte osmotic fragility and lipid peroxidation following chronic co-exposure of rats to chlorpyrifos and deltamethrin, and the beneficial effect of alpha-lipoic acid

    Directory of Open Access Journals (Sweden)

    Chidiebere Uchendu

    2014-01-01

    Full Text Available The present study aimed to evaluate the effect of chronic co-exposure to chlorpyrifos (CPF and deltamethrin (DLT on erythrocyte osmotic fragility, lipid peroxidation and the ameliorative effect of alpha-lipoic acid (ALA on erythrocyte fragility. Thirty-six male Wistar rats divided into six groups of six rats each were used for the study. Groups I (S/oil and II (ALA were given soya oil (2 ml/kg and ALA (60 mg/kg, respectively. Rats in group III (DLT and IV (CPF were exposed to DLT (6.25 mg/kg and CPF (4.75 mg/kg (1/20th of the previously determined LD50 of 125 mg/kg and 95 mg/kg, respectively, over a period of 48 h. Rats in group V (CPF + DLT were co-exposed to CPF (4.75 mg/kg and DLT (6.25 mg/kg, while those in group VI (ALA + CPF + DLT were pretreated with ALA (60 mg/kg and then co-exposed to CPF and DLT, 45 min later. The treatments were administered by gavage once daily for a period of 16 weeks. Blood collected at the end of the experimental period were analyzed for erythrocyte osmotic fragility and malondialdehyde (MDA concentration. The study showed that chronic co-exposure to CPF and DLT resulted in an increase in erythrocyte fragility and MDA concentration which were ameliorated by supplementation with alpha-lipoic acid. The study concluded that repeated co-exposure to CPF and DLT elevated erythrocyte fragility probably due to increased lipid peroxidation, and pretreatment with alpha-lipoic acid ameliorated these alterations.

  18. Photochemical stability of lipoic acid and its impact on skin ageing.

    Science.gov (United States)

    Matsugo, Seiichi; Bito, Toshinori; Konishi, Tetsuya

    2011-08-01

    It is well known that α-lipoic acid (LA) functions as an essential co-factor of the mitochondrial multi-enzyme complex and thus plays an important role in energy metabolism. Currently, it is attracting attention as a nutritional supplement because of its unique antioxidant properties and broad spectra of cellular functions. Skin protection from photodamage and ageing is one of the functional applications of LA. Medical and cosmetic application has been widely realized in the world. However, LA has a unique structure bearing a distorted five membered 1, 2-dithiolane ring, making it quite vulnerable to UV radiation. The present article briefly reviews skin ageing from the viewpoint of oxidative stress and sun exposure and analyses the photochemical properties of LA. It also discusses the effect of LA to cellular signalling and its adequate applications to treat skin ageing caused by oxidation. Data presented in this review suggest that LA is a powerful anti-ageing agent under the appropriate usage.

  19. Effect of α-lipoic acid combined with nerve growth factor on bone metabolism, oxidative stress and nerve conduction function after femoral fracture surgery

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    An-Jun Cao

    2017-11-01

    Full Text Available Objective: To discuss the effect of 毩 -lipoic acid combined with nerve growth factor on bone metabolism, oxidative stress and nerve conduction function after femoral fracture surgery. Methods: A total of 110 patients with femoral fracture who received surgical treatment in the hospital between January 2015 and January 2017 were collected and divided into the control group (n=55 and study group (n=55 by random number table. Control group received postoperative nerve growth factor therapy, and study group received postoperative 毩 -lipoic acid combined with nerve growth factor therapy. The differences in the contents of bone metabolism and oxidative stress indexes as well as the levels of nerve conduction function indexes were compared between the two groups before and after treatment. Results: Before treatment, the differences in the contents of bone metabolism and oxidative stress indexes as well as the levels of nerve conduction function indexes were not statistically significant between the two groups. After treatment, serum bone metabolism indexes BGP and PⅠNP contents of study group were higher than those of control group while CTX-Ⅰ and TRAP contents were lower than those of control group; serum oxidative stress indexes TAC, CAT and SOD contents of study group were higher than those of control group while MDA content was lower than that of control group; limb nerve conduction velocity SCV and MCV levels of study group were higher than those of control group. Conclusion: 毩 -lipoic acid combined with nerve growth factor therapy after femoral fracture surgery can effectively balance osteoblast/ osteoclast activity, reduce oxidative stress and improve limb nerve conduction velocity.

  20. Protective Effects of Alpha-Lipoic Acid on Oleic Acid-Induced Acute Lung Injury in Rats

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    Funda Gülcü Bulmuş

    2013-09-01

    Full Text Available Background: Oxidative stress is believed to be an important factor in the pathogenesis of acute lung injury (ALI. Aims: The aim of this study was to investigate the possible protective role of alpha-lipoic acid (α-LA on oleic acid (OA-induced ALI in rats. Study Design: Animal experiment. Methods: A total of thirty-five rats were divided into five groups in the study. Group 1 served as a control group. Rats in Group 2 (α-LA were administered α-LA intraperitoneally at a dose of 100 mg/kg body weight (BW. Rats in Group 3 (OA were administered OA intravenously at a dose of 100 mg/kg BW. In Group 4 (pre-OA-α-LA, α-LA was given 15 minutes prior to OA infusion, and in Group 5 (post-OA-α-LA, α-LA was given two hours after OA infusion. Four hours after the OA infusion, rats were decapitated. Blood samples were collected to measure serum levels of malondialdehyde (MDA and glutathione (GSH, and the levels of activity for superoxide dismutase (SOD, catalase (CAT and glutathione peroxidase (GSH-Px. Lung tissue samples were taken for histopathological examination. Results: Exposure to OA resulted in increases in serum MDA levels (p<0.001, as well as histopathological lesions in lung tissue, and decreases in CAT (p<0.05, GSH-Px (p<0.05 activities and GSH (p<0.05 levels. On the other hand, MDA levels were decreased significantly (p<0.001, while CAT (p<0.05, GSH-Px (p<0.01 activities and GSH (p<0.05 levels were increased significantly in the pre-OA-α-LA group compared with the OA group. Conclusion: α-LA was found to lessen oxidative stress and to have positive effects on antioxidants in cases of OA-induced ALI. In conclusion, α-LA appears to have protective effects against ALI and potential for the prevention of ALI.

  1. Sperm quality after swim up and density gradient centrifugation sperm preparation with supplementation of alpha lipoic acid (ALA): A preliminary study

    Science.gov (United States)

    Lestari, Silvia W.; Lestari, Sarah H.; Pujianto, Dwi A.

    2018-02-01

    Intra uterine insemination (IUI) as one of the treatment for infertility, persists low success rate. A factor that contributes to the unsuccessful of IUI is sperm preparation, performed through Swim-up (SU) and Density Gradient Centrifugation (DGC) methods. Furthermore, studies have shown that Alpha Lipoic Acid (ALA) is a potent antioxidant that could enhance the sperm motility and protect the DNA integrity of the sperm [1]. This study is aimed to re-evaluate the efficiency of the DGC and SU methods in selecting sperm before being transferred for IUI by the supplementation of ALA based on the sperm DNA integrity. Semen samples were obtained from 13 men from partners of women who are infertile (normozoospermia) and underwent IUI. Semen analysis based on the guideline of World Health Organization (WHO) 2010 was performed to measure the sperm motility and velocity, before and after sperm preparation. Then, samples were incubated with Alpha Lipoic Acid (ALA) in 0.625 mg (ALA 1), 1.25 mg (ALA 2) and 2.5 mg (ALA 3). The Sperm Chromatin Dispersion (SCD) test was performed to evaluate the sperm DNA Fragmentation Index (DFI). The percentage of motile sperm was higher in prepared sperm (post-DGC and post-SU) than in whole semen. Furthermore, the percentage of motile sperm was higher in post-DGC compared to post-SU. The level of DFI after the supplementation of ALA was decreased in prepared sperm compared to the whole semen. ALA was proved capable to select the better sperm quality with decreased sperm DNA fragmentation of prepared sperm in the all of DFI category.

  2. In Vivo Anti-inflammatory Activity of Lipoic Acid Derivatives in Mice 

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    Brunon Kwiecień

    2013-04-01

    Full Text Available Background: In mammals lipoic acid (LA and its reduced form dihydrolipoic acid (DHLA function as cofactors for multienzymatic complexes catalyzing the decarboxylation of α-ketoacids. Moreover, LA is used as a drug in a variety of diseases including inflammatory diseases. The aim of the study was to examine anti-inflammatory properties of LA metabolites.Material/methods:The present paper reports the chemical synthesis of 2,4-bismethylthio-butanoic acid (BMTBA and tetranor-dihydrolipoic acid (tetranor-DHLA. BMTBA is one of the biotransformation products of LA, while tetranor-DHLA is an analogue of DHLA. Structural identity of these compounds was confirmed by 1H NMR. These compounds were assessed for their anti-inflammatory activity in mice. For this purpose, the zymosan-induced peritonitis and the carrageenan-induced hind paw edema animal models were applied.Results/conclusions: The obtained results indicated that the early vascular permeability measured at 30 min of zymosan-induced peritonitis was significantly inhibited in groups receiving BMTBA (10, 30, 50 mg/kg. The early infiltration of neutrophils measured at 4 hours of zymosan-induced peritonitis was inhibited in the group receiving BMTBA (50 mg/kg and tetranor-DHLA (50 mg/kg. The results indicated that the increase in paw edema was significantly inhibited in the groups receiving BMTBA (50, 100 mg/kg and tetranor-DHLA (30, 50 mg/kg. In summary, the present studies clearly demonstrated that both BMTBA and tetranor-DHLA were able to act as anti-inflammatory agents. This is the first study examining in vivo the anti-inflammatory properties of LA metabolites.

  3. Advantages of the Alpha-lipoic Acid Association with Chlorpromazine in a Model of Schizophrenia Induced by Ketamine in Rats: Behavioral and Oxidative Stress evidences.

    Science.gov (United States)

    Sampaio, Luis Rafael Leite; Cysne Filho, Francisco Maurício Sales; de Almeida, Jamily Cunha; Diniz, Danilo Dos Santos; Patrocínio, Cláudio Felipe Vasconcelos; de Sousa, Caren Nádia Soares; Patrocínio, Manoel Cláudio Azevedo; Macêdo, Danielle; Vasconcelos, Silvânia Maria Mendes

    2018-03-01

    Schizophrenia is a chronic mental disorder reported to compromise about 1% of the world's population. Although its pathophysiological process is not completely elucidated, evidence showing the presence of an oxidative imbalance has been increasingly highlighted in the literature. Thus, the use of antioxidant substances may be of importance for schizophrenia treatment. The objective of this study was to evaluate the behavioral and oxidative alterations by the combination of chlorpromazine (CP) and alpha-lipoic acid (ALA), a potent antioxidant, in the ketamine (KET) model of schizophrenia in rats. Male Wistar rats (200-300 g) were treated for 10 days with saline, CP or ALA alone or in combination with CP previous to KET and the behavioral (open field, Y-maze and PPI tests) and oxidative tests were performed on the last day of treatment. The results showed that KET induced hyperlocomotion, impaired working memory and decreased PPI. CP alone or in combination with ALA prevented KET-induced behavioral effects. In addition, the administration of KET decreased GSH and increased nitrite, lipid peroxidation and myeloperoxidase activity. CP alone or combined with ALA prevented the oxidative alterations induced by KET. In conclusion, the treatment with KET in rats induced behavioral impairments accompanied by hippocampal oxidative alterations, possibly related to NMDA receptors hypofunction. Besides that, CP alone or combined with ALA prevented these effects, showing a beneficial activity as antipsychotic agents. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

  4. Novel Neurovascular Protective Agents: Effects of INV-155, INV-157, INV-159, and INV-161 versus Lipoic Acid and Captopril in a Rat Stroke Model

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    Barry J. Connell

    2012-01-01

    Full Text Available Background. Lipoic acid (LA, which has significant antioxidant properties, may also function as a potent neuroprotectant. The synthetic compounds INV-155, INV-157, INV-159, and INV-161 are physiochemical combinations of lipoic acid and captopril. We sought to determine if these compounds have neuroprotective potential following middle cerebral artery occlusion (MCAO in rats. Methods. Male Sprague-Dawley rats were injected intravenously with captopril (1–50 mg/kg 30 minutes prior to MCAO. Blood pressure, heart rate, baroreceptor reflex sensitivity, and infarct size were measured. In addition, dose response effect on infarct size and cardiovascular parameters was determined using INV-155, INV-157, INV-159, and INV-161 and compared to captopril and LA. Results. Pretreatment with captopril and LA at all doses tested was neuroprotective. The compounds INV-159 (0.5–10 mg/kg and INV-161 (1–10 mg/kg produced a significant,dose-dependent decrease in infarct size. In contrast, INV-155 and INV-157 had no effect on infarct size. Conclusions. Combined pretreatment with captopril potentiated the neuroprotective benefit observed following LA alone. Both INV-159 and INV-161 were also neuroprotective. These results suggest that patients taking combinations of captopril and LA, either as combination therapy or in the form of INV-159 or INV-161, may also benefit from significant protection against cerebral infarction.

  5. [The effect of long-chain polyunsaturated higher ω-3 fatty acids, benfotiamine and α-lipoic acid on the lipid metabolism in patients with diabetes mellitus type 2 and cardiovascular autonomic neuropathy].

    Science.gov (United States)

    Sergienko, V A; Segin, V B; Samir, A; Sergienko, A A

    2013-01-01

    Eighty-one patients with diabetes mellitus type 2 (DM) and cardiovascular autonomic neuropathy were studied. The combined treatment with ω-3 PUFA, benfotiamine, and α-lipoic acid resulted in significant positive changes in total cholesterol, triacylglycerol, LDL and HDL cholesterol levels. The efficacy of this treatment was not associated with the improved compensation of DM but was a result of the direct influence of pharmacological agents on the metabolic rate studied.

  6. Safety and efficacy of an add-on therapy with curcumin phytosome and piperine and/or lipoic acid in subjects with a diagnosis of peripheral neuropathy treated with dexibuprofen

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    Di Pierro F

    2013-07-01

    Full Text Available Francesco Di Pierro,1 Roberto Settembre2 1Scientific Department, Velleja Research, Milan, Italy; 2Neurosurgery Department, Di Venere Hospital, Bari, Italy Abstract: We conducted an 8-week, open, randomized controlled clinical trial on 141 subjects affected by neuropathic pain to investigate the role of an adjunctive therapy added to the administration of dexibuprofen (400 mg twice a day and based on a multi-ingredient formula (Lipicur, consisting of lipoic acid plus curcumin phytosome and piperine, in patients with a diagnosis of lumbar sciatica, lumbar disk herniation, and/or lumbar canal stenosis (96 subjects, or with carpal tunnel syndrome (45 subjects. A total of 135 participants completed the study. Treatment with the multi-ingredient formula (Lipicur reduced neuropathic pain by more than 66% in both conditions (subjects with lumbar sciatica and with carpal tunnel syndrome, and these reductions were statistically significant. Moreover, the treatment reduced dexibuprofen use by about 40%. An add-on therapy with only lipoic acid has not shown any significant results. On the basis of its safety and efficacy, Lipicur could be considered an effective complementary therapy to be added to conventional treatments to achieve better efficacy in reducing neuropathic pain. Keywords: curcumin, phytosome, piperine, dexibuprofen, neuropathic pain

  7. Bioprotective carnitinoids: lipoic acid, butyrate, and mitochondria-targeting to treat radiation injury: mitochondrial drugs come of age.

    Science.gov (United States)

    Steliou, Kosta; Faller, Douglas V; Pinkert, Carl A; Irwin, Michael H; Moos, Walter H

    2015-06-01

    Preclinical Research Given nuclear-power-plant incidents such as the 2011 Japanese Fukushima-Daiichi disaster, an urgent need for effective medicines to protect against and treat the harmful biological effects of radiation is evident. To address such a challenge, we describe potential strategies herein including mitochondrial and epigenetic-driven methods using lipoic and butyric acid ester conjugates of carnitine. The antioxidant and other therapeutically beneficial properties of this class of agents may protect against ionizing radiation and resultant mitochondrial dysfunction. Recent studies of the compounds described herein reveal the potential-although further research and development is required to prove the effectiveness of this approach-to provide field-ready radiation-protective drugs. © 2015 Wiley Periodicals, Inc.

  8. Effects of alpha lipoic acid, ascorbic acid-6-palmitate, and fish oil on the glutathione, malonaldehyde, and fatty acids levels in erythrocytes of streptozotocin induced diabetic male rats.

    Science.gov (United States)

    Yilmaz, Okkeş; Ozkan, Yusuf; Yildirim, Mehmet; Oztürk, A Ihsan; Erşan, Yasemin

    2002-01-01

    In this research, it has been aimed to evaluate the improvement effects of alpha lipoic acid (ALA), ascorbic acid-6-palmitate (AA6P), fish oil (FO), and their combination (COM) on some biochemical properties in erythrocytes of streptozotocin (STZ)-induced diabetic male rats. According to experimental results, glutathione (GSH) level in erythrocytes decreased in diabetes (P cholesterol level was high in diabetes and D + ALA groups (P acid raised in diabetes group (P acid in D + FO, D + ALA, and diabetes groups was lower than control (P acid reduced in D + COM and D + FO groups, but its level raised in D + AA6P and D + ALA groups (P acid (LA) elevated in ALA + D, D + AA6P, and diabetes groups, linolenic acid level in diabetes, D + AA6P, and D + FO groups was lower than control (P acid (AA) decreased in D + ALA, D+ AA6P, and diabetes groups (P acid (DHA) increased in D + AA6P and D + COM (P acid level raised in diabetes group, its level reduced in D + ALA and D + FO groups (P acid level in D + ALA and D + FO groups was higher than control (P acid degree was raised by the effects of ALA and FO. Copyright 2002 Wiley-Liss, Inc.

  9. Clinical Usefulness of Oral Supplementation with Alpha-Lipoic Acid, Curcumin Phytosome, and B-Group Vitamins in Patients with Carpal Tunnel Syndrome Undergoing Surgical Treatment

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    Giorgio Pajardi

    2014-01-01

    Full Text Available We investigated the clinical usefulness of oral supplementation with a combination product containing alpha-lipoic acid, curcumin phytosome, and B-group vitamins in 180 patients with carpal tunnel syndrome (CTS, scheduled to undergo surgical decompression of the median nerve. Patients in Group A (n=60 served as controls and did not receive any treatment either before or after surgery. Patients in Group B (n=60 received oral supplementation twice a day for 3 months both before and after surgery (totaling 6 months of supplementation. Patients in Group C (n=60 received oral supplementation twice a day for 3 months before surgery only. Patients in Group B showed significantly lower nocturnal symptoms scores compared with Group A subjects at both 40 days and 3 months after surgery (both P values <0.05. Moreover, patients in Group B had a significantly lower number of positive Phalen’s tests at 3 months compared with the other study groups (P<0.05. We conclude that oral supplementation with alpha-lipoic acid, curcumin phytosome, and B-group vitamins twice a day both before and after surgery is safe and effective in CTS patients scheduled to undergo surgical decompression of the median nerve.

  10. Lipoic acid in combination with a chelator ameliorates lead-induced peroxidative damages in rat kidney

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    Sivaprasad, R.; Nagaraj, M.; Varalakshmi, P. [Department of Medical Biochemistry, University of Madras (Taramani), Chennai 600 113 (India)

    2002-08-01

    The deleterious effect of lead has been attributed to lead-induced oxidative stress with the consequence of lipid peroxidation. The present study was designed to investigate the combined effect of DL-{alpha}-lipoic acid (LA) and meso-2,3-dimercaptosuccinic acid (DMSA) on lead-induced peroxidative damages in rat kidney. The increase in peroxidated lipids in lead-poisoned rats was accompanied by alterations in antioxidant defence systems. Lead acetate (Pb, 0.2%) was administered in drinking water for 5 weeks to induce lead toxicity. LA (25 mg/kg body weight per day i.p) and DMSA (20 mg/kg body weight per day i.p) were administered individually and also in combination during the sixth week. Nephrotoxic damage was evident from decreases in the activities of {gamma}-glutamyl transferase and N-acetyl {beta}-D-glucosaminidase, which were reversed upon combined treatment with LA and DMSA. Rats subjected to lead intoxication showed a decline in the thiol capacity of the cell, accompanied by high malondialdehyde levels along with lowered activities of catalase, superoxide dismutase, glutathione peroxidase and glutathione metabolizing enzymes (glutathione reductase, glucose-6-phosphate dehydrogenase, glutathione-S-transferase). Supplementation with LA as a sole agent showed considerable changes over oxidative stress parameters. The study has highlighted the combined effect of both drugs as being more effective in reversing oxidative damage by bringing about an improvement in the reductive status of the cell. (orig.)

  11. An open-label pilot trial of alpha-lipoic acid for weight loss in patients with schizophrenia without diabetes.

    Science.gov (United States)

    Ratliff, Joseph C; Palmese, Laura B; Reutenauer, Erin L; Tek, Cenk

    2015-01-01

    A possible mechanism of antipsychotic-induced weight gain is activation of hypothalamic monophosphate-dependent kinase (AMPK) mediated by histamine 1 receptors. Alpha-lipoic acid (ALA), a potent antioxidant, counteracts this effect and may be helpful in reducing weight for patients taking antipsychotics. The objective of this open-label study was to assess the efficacy of ALA (1,200 mg) on twelve non-diabetic schizophrenia patients over ten weeks. Participants lost significant weight during the intervention (-2.2 kg±2.5 kg). ALA was well tolerated and was particularly effective for individuals taking strongly antihistaminic antipsychotics (-2.9 kg±2.6 kg vs. -0.5 kg±1.0 kg). NCT01355952.

  12. Potential Therapeutic Effects of Lipoic Acid on Memory Deficits Related to Aging and Neurodegeneration

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    Patrícia Molz

    2017-12-01

    Full Text Available The aging process comprises a series of organic alterations, affecting multiple systems, including the nervous system. Aging has been considered the main risk factor for the advance of neurodegenerative diseases, many of which are accompanied by cognitive impairment. Aged individuals show cognitive decline, which has been associated with oxidative stress, as well as mitochondrial, and consequently energetic failure. Lipoic acid (LA, a natural compound present in food and used as a dietary supplement, has been considered a promising agent for the treatment and/or prevention of neurodegenerative disorders. In spite of a number of preclinical studies showing beneficial effects of LA in memory functioning, and pointing to its neuroprotective potential effect, to date only a few studies have examined its effects in humans. Investigations performed in animal models of memory loss associated to aging and neurodegenerative disorders have shown that LA improves memory in a variety of behavioral paradigms. Moreover, cell and molecular mechanisms underlying LA effects have also been investigated. Accordingly, LA displays antioxidant, antiapoptotic, and anti-inflammatory properties in both in vivo and in vitro studies. In addition, it has been shown that LA reverses age-associated loss of neurotransmitters and their receptors, which can underlie its effects on cognitive functions. The present review article aimed at summarizing and discussing the main studies investigating the effects of LA on cognition as well as its cell and molecular effects, in order to improve the understanding of the therapeutic potential of LA on memory loss during aging and in patients suffering from neurodegenerative disorders, supporting the development of clinical trials with LA.

  13. Alpha-Lipoic acid counteracts the promoted oxidative DNA damage in the liver of septic rats

    International Nuclear Information System (INIS)

    Abd-Allah, Adel R.A.

    2006-01-01

    Viral, parasitic infections and chemical carcinogens are among the etiological factors of liver cancer. It seems important to study the initiating and promoting agents to evaluate the etiology and prevention of such life threatening disease. Intestine-derived bacteria product, lipopolysaccharide (LPS), is mainly detoxified by the liver. It has shown to induce a state of oxidative DNA damage is not fully investigated. Increased oxidative DNA damage and rate of cell proliferation may initiate or even promote cancer. In the present work, the capability of LPS to induce 8-hydroxydeoxyguanosine (8-HDG), a specific DNA adduct for oxidative DNA damage, in rat livers is tested. Furthermore, a possible protective effect of alpha lipoic acid (ALA) is also assessed. Investigated parameters are liver contents of glutathione (GSH), lipid peroxides (MDA), nitric oxide (NO) and 8-HDG in the liver-extracted DNA. Serum activities of ALT, AST and GGT as liver-function markers as well as IL2 are assessed. Moreover, liver histology is examined. LPS was given doses of 1, 3, 5, 7 and 9 mg/kg once i.p. while, the rat mortality was examined 24 hours later. ALA was given in doses of 50, 100 and 200 mg/kg once i.p. 3h before LPS is found to be 5mg/kg. LPS increased the level of 8-HDG, MDA and NO in the liver. It also induced acute liver necrosis and inflammatory cell infiltration as shown in liver-histopathology and in the significant increase in the activities of ALT, AST and GGT. LPS increased the serum level of IL2 as well. The dose 200mg/kg of ALA revealed a 100% protection against LPS-induced lethality. It also, prevented the LPS-induced increase in 8-HDG in liver extracted DNA, the liver contents of MDA and NO. ALA also rescued the LPS-induced GSH depletion. It corrected the liver function as shown by the prevention of increases in the activity of ALT, AST and GGT with a remarkable improvement in the liver histology. Moreover, it prevented the increase in serum level of IL2. These

  14. Antitumor Effects of Palladium-α-Lipoic Acid Complex Formulation as an Adjunct in Radiotherapy.

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    Veena, Ravindran Kalathil; Ajith, Thekkuttuparambil Ananthanarayanan; Janardhanan, Kainoor Krishnankutty; Antonawich, Francis

    2016-01-01

    Several investigations have been initiated to enhance the antitumor effect of radiation and ameliorate its adverse effects such as reducing blood cell counts and causing DNA damage in normal cells. Compounds that enhance the antitumor activity of radiation without reducing blood cell counts or damaging DNA in normal cells can be of immense use as an adjunct in radiotherapy. We evaluated the antitumor effect of a specific set of minerals, vitamins, and amino acids (Poly-MVA) (2 mL/kg, per os), with and without radiation, against Dalton's lymphoma ascites (DLA) and Ehrlich's ascites carcinoma (EAC) cell lines that were transplanted in a solid-tumor model. Whole-body γ-radiation exposure (2 Gy) was performed using 60Co. Poly-MVA enhanced the antitumor effect of radiation when administered beforehand. Furthermore, Poly-MVA administered once daily for 2 wk, immediately after 4 Gy irradiation, protected DNA damage in peripheral blood. It also rendered protection against the radiation-induced reduction of platelet count. The unique electronic and redox properties of palladium-α-lipoic acid complex in Poly-MVA appear to be responsible for the exhibited effect. The results conclude that the antitumor-enhancing and normal cell-protective effect of Poly-MVA warrants additional studies for its potential clinical application.

  15. Bace1 activity impairs neuronal glucose metabolism: rescue by beta-hydroxybutyrate and lipoic acid

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    John A Findlay

    2015-10-01

    Full Text Available Glucose hypometabolism and impaired mitochondrial function in neurons have been suggested to play early and perhaps causative roles in Alzheimer’s disease (AD pathogenesis. Activity of the aspartic acid protease, beta-site amyloid precursor protein (APP cleaving enzyme 1 (BACE1, responsible for beta amyloid peptide generation, has recently been demonstrated to modify glucose metabolism. We therefore examined, using a human neuroblastoma (SH-SY5Y cell line, whether increased BACE1 activity is responsible for a reduction in cellular glucose metabolism. Overexpression of active BACE1, but not a protease-dead mutant BACE1, protein in SH-SY5Y cells reduced glucose oxidation and the basal oxygen consumption rate, which was associated with a compensatory increase in glycolysis. Increased BACE1 activity had no effect on the mitochondrial electron transfer process but was found to diminish substrate delivery to the mitochondria by inhibition of key mitochondrial decarboxylation reaction enzymes. This BACE1 activity-dependent deficit in glucose oxidation was alleviated by the presence of beta hydroxybutyrate or α-lipoic acid. Consequently our data indicate that raised cellular BACE1 activity drives reduced glucose oxidation in a human neuronal cell line through impairments in the activity of specific tricarboxylic acid cycle enzymes. Because this bioenergetic deficit is recoverable by neutraceutical compounds we suggest that such agents, perhaps in conjunction with BACE1 inhibitors, may be an effective therapeutic strategy in the early-stage management or treatment of AD.

  16. Effects of EPA and lipoic acid supplementation on circulating FGF21 and the fatty acid profile in overweight/obese women following a hypocaloric diet.

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    Escoté, Xavier; Félix-Soriano, Elisa; Gayoso, Lucía; Huerta, Ana Elsa; Alvarado, María Antonella; Ansorena, Diana; Astiasarán, Iciar; Martínez, J Alfredo; Moreno-Aliaga, María Jesús

    2018-05-23

    FGF21 has emerged as a key metabolism and energy homeostasis regulator. Dietary supplementation with eicosapentaenoic acid (EPA) and/or α-lipoic acid (LIP) has shown beneficial effects on obesity. In this study, we evaluated EPA and/or LIP effects on plasma FGF21 and the fatty acid (FA) profile in overweight/obese women following hypocaloric diets. At the baseline, FGF21 levels were negatively related to the AST/ALT ratio and HMW adiponectin. The weight loss did not cause any significant changes in FGF21 levels, but after the intervention FGF21 increased in EPA-supplemented groups compared to non-EPA-supplemented groups. EPA supplementation decreased the plasma n-6-PUFA content and increased n-3-PUFAs, mainly EPA and DPA, but not DHA. In the LIP-alone supplemented group a decrease in the total SFA and n-6-PUFA content was observed after the supplementation. Furthermore, EPA affected the desaturase activity, lowering Δ4D and raising Δ5/6D. These effects were not observed in the LIP-supplemented groups. Besides, the changes in FGF21 levels were associated with the changes in EPA, n-3-PUFAs, Δ5/6D, and n-6/n-3 PUFA ratio. Altogether, our study suggests that n-3-PUFAs influence FGF21 levels in obesity, although the specific mechanisms implicated remain to be elucidated.

  17. Use of α-Lipoic Acid and Benfotiamine for Correction of Disturbance of Gastric Motor-Evacuation Function in Type 1 Diabetic Patients

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    I.O. Kostitska

    2015-09-01

    Full Text Available The therapeutic effectiveness of α-lipoic acid and benfotiamine in treating symptoms of gastroparesis in type 1 diabetic patients was evaluated. Pathogenetic correlations between increased concentration of peripheral myelin protein and a decrease in the gastric motor-evacuation function were determined. The results of a three-month course of pathogenetic therapy demonstrate the effectiveness of combination therapy which is not associated with an improved compensation of carbohydrate and lipid metabolism. It is a result of the direct effect of preparations on the investigated metabolic processes and restoration of myelination of the nerve fibers.

  18. α-Lipoic acid stabilized DTX/IR780 micelles for photoacoustic/fluorescence imaging guided photothermal therapy/chemotherapy of breast cancer.

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    Li, WenTing; Peng, JinRong; Yang, Qian; Chen, LiJuan; Zhang, Lan; Chen, XiaoXin; Qian, ZhiYong

    2018-05-01

    Micellar nanoparticles have unique advantages as carriers for therapeutic or imaging agents, owing to their smaller size and better penetration of tumors. However, some agents, due to their physical or chemical properties, are difficult to load into micelles. IR780 is one of these agents, and is also a promising near-infrared dye for fluorescence imaging (FI)/photoacoustic imaging (PAI) and cancer photothermal therapy (PTT). Its hydrophobic and high crystallization structure results in limited bioavailability in vivo. It is difficult to load into micelles constructed from an amphiphilic block polymer with relatively low molecular weight. In this study, we use computer simulation and introduce another small biomolecule, α-lipoic acid, into the micelles constructed from a mPEG-PCL copolymer, to lower the energy of molecular interaction between MPEG-PCL and IR780, and expect to enhance the loading capacity of the micelles to IR780. The introduction of α-lipoic acid decreases the energy of molecular interaction between MEPG-PCL and IR780 from -46.18 kJ mol-1 to -196.52 kJ mol-1 and increases the loading capacity and stability of the mPEG-PCL micelles to IR780, which also maintains the loading capacity to DTX. We further construct DTX/IR780 co-loaded mPEG-PCL micelles for FI/PAI dual modal imaging guided PTT/chemotherapy of cancer. By FI and PAI evaluation in vitro and in vivo, we demonstrate that the DTX/IR780 co-loaded micelles can be used as FI and PAI probes. By further evaluating the therapeutic outcome of PTT/chemotherapy co-therapy of breast cancer, we demonstrate that the DTX/IR780 co-loaded mPEG-PCL micelles can serve as promising candidates for FI and PAI guided PTT/chemotherapy of breast cancer.

  19. Dietary alpha-Lipoic Acid Alters Piglet Neurodevelopment

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    Austin T Mudd

    2016-05-01

    Full Text Available Introduction: Alpha-lipoic acid (a-LA is an antioxidant shown to ameliorate age-associated impairments of brain and cardiovascular function. Human milk is known to have high antioxidant capacity, however the role of antioxidants in the developing brain is largely uncharacterized. This exploratory study aimed to examine the dose response effects of a-LA on piglet growth and neurodevelopment. Methods: Beginning at 2 d of age, 31 male pigs received one of three diets: control (CONT [0 mg a-LA/100g], low a-LA (LOW [120 mg a-LA/100g], or high a-LA (HIGH [240 mg a-LA/100g]. From 14 to 28 d of age, pigs were subjected to spatial T-maze assessment and macrostructural and microstructural neuroimaging procedures were performed at 31 d of age.Results: No differences due to diet were observed for bodyweight gain or intestinal weight and length. Spatial T-maze assessment did not reveal learning differences due to diet in proportion of correct choices or latency to choice measures. Diffusion tensor imaging revealed decreased (P = 0.01 fractional anisotropy (FA in the internal capsule of HIGH fed pigs compared with both the CONT (P < 0.01 and LOW (P = 0.03 fed pigs, which were not different from one another. Analysis of axial diffusivity (AD within the internal capsule revealed a main effect of diet (P < 0.01 in which HIGH fed piglets exhibited smaller (P < 0.01 rates of diffusion compared with CONT piglets, but HIGH fed piglets were not different (P = 0.12 than LOW fed piglets. Tract-based spatial statistics, a comparison of FA values along white matter tracts, revealed 1,650 voxels where CONT piglets exhibited higher (P < 0.05 values compared with HIGH fed piglets. Conclusion: The lack of differences in intestinal and bodyweight measures among piglets indicate a-LA supplementation does not impact overall growth, regardless of concentration. Additionally, no observed differences between CONT and LOW fed piglets in behavior and neuroimaging measures indicate a

  20. (R-(+-α-Lipoic acid protected NG108-15 cells against H2O2-induced cell death through PI3K-Akt/GSK-3β pathway and suppression of NF-κβ-cytokines

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    Kamarudin MNA

    2014-10-01

    Full Text Available Muhamad Noor Alfarizal Kamarudin, Nur Afiqah Mohd Raflee, Sharifah Salwa Syed Hussein, Jia Ye Lo, Hadi Supriady, Habsah Abdul KadirInstitute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, MalaysiaAbstract: Alpha-lipoic acid, a potent antioxidant with multifarious pharmacological benefits has been reported to be neuroprotective in several neuronal models and used to treat neurological disorders such as Alzheimer’s disease. Nonetheless, conclusive mechanisms of alpha-lipoic acid for its protective effects particularly in NG108-15 cells have never been investigated. In this study, the intricate neuroprotective molecular mechanisms by (R-(+-alpha-lipoic acid (R-LA against H2O2-induced cell death in an in vitro model of neurodegeneration were elucidated. Pretreatment with R-LA (2 hours significantly increased NG108-15 cell viability as compared to H2O2-treated cells and mitigated the induction of apoptosis as evidenced by Hoechst 33342/propidium iodide staining. R-LA (12.5–50 µM aggrandized the reduced glutathione over glutathione disulfide ratio followed by a reduction in the intracellular reactive oxygen species level and an increase in mitochondrial membrane potential following H2O2 exposure. Moreover, pretreatment with R-LA stimulated the activation of PI3K-Akt through mTORC1 and mTORC2 components (mTOR, rictor and raptor and production of antiinflammatory cytokine, IL-10 which led to the inactivation of glycogen synthase kinase-3β (GSK-3β and reduction of both Bax/Bcl2 and Bax/Bcl-xL ratios, accompanied by inhibition of the cleaved caspase-3. Additionally, this observation was preceded by the suppression of NF-κβ p65 translocation and production of proinflammatory cytokines (IL-6 and TNF-α. The current findings accentuate new mechanistic insight of R-LA against apoptogenic and brain inflammatory factors in a neuronal model. These results further advocate the therapeutic potential of R-LA for

  1. Studying anti-oxidative properties of inclusion complexes of α-lipoic acid with γ-cyclodextrin in single living fission yeast by confocal Raman microspectroscopy

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    Noothalapati, Hemanth; Ikarashi, Ryo; Iwasaki, Keita; Nishida, Tatsuro; Kaino, Tomohiro; Yoshikiyo, Keisuke; Terao, Keiji; Nakata, Daisuke; Ikuta, Naoko; Ando, Masahiro; Hamaguchi, Hiro-o.; Kawamukai, Makoto; Yamamoto, Tatsuyuki

    2018-05-01

    α-lipoic acid (ALA) is an essential cofactor for many enzyme complexes in aerobic metabolism, especially in mitochondria of eukaryotic cells where respiration takes place. It also has excellent anti-oxidative properties. The acid has two stereo-isomers, R- and S- lipoic acid (R-LA and S-LA), but only the R-LA has biological significance and is exclusively produced in our body. A mutant strain of fission yeast, Δdps1, cannot synthesize coenzyme Q10, which is essential during yeast respiration, leading to oxidative stress. Therefore, it shows growth delay in the minimal medium. We studied anti-oxidant properties of ALA in its free form and their inclusion complexes with γ-cyclodextrin using this mutant yeast model. Both free forms R- and S-LA as well as 1:1 inclusion complexes with γ-cyclodextrin recovered growth of Δdps1 depending on the concentration and form. However, it has no effect on the growth of wild type fission yeast strain at all. Raman microspectroscopy was employed to understand the anti-oxidant property at the molecular level. A sensitive Raman band at 1602 cm-1 was monitored with and without addition of ALAs. It was found that 0.5 mM and 1.0 mM concentrations of ALAs had similar effect in both free and inclusion forms. At 2.5 mM ALAs, free forms inhibited the growth while inclusion complexes helped in recovered. 5.0 mM ALA showed inhibitory effect irrespective of form. Our results suggest that the Raman band at 1602 cm-1 is a good measure of oxidative stress in fission yeast.

  2. α-Lipoic acid improves abnormal behavior by mitigation of oxidative stress, inflammation, ferroptosis, and tauopathy in P301S Tau transgenic mice

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    Yan-Hui Zhang

    2018-04-01

    Full Text Available Alzheimer's disease (AD is the most common neurodegenerative disease and is characterized by neurofibrillary tangles (NFTs composed of Tau protein. α-Lipoic acid (LA has been found to stabilize the cognitive function of AD patients, and animal study findings have confirmed its anti-amyloidogenic properties. However, the underlying mechanisms remain unclear, especially with respect to the ability of LA to control Tau pathology and neuronal damage. Here, we found that LA supplementation effectively inhibited the hyperphosphorylation of Tau at several AD-related sites, accompanied by reduced cognitive decline in P301S Tau transgenic mice. Furthermore, we found that LA not only inhibited the activity of calpain1, which has been associated with tauopathy development and neurodegeneration via modulating the activity of several kinases, but also significantly decreased the calcium content of brain tissue in LA-treated mice. Next, we screened for various modes of neural cell death in the brain tissue of LA-treated mice. We found that caspase-dependent apoptosis was potently inhibited, whereas autophagy did not show significant changes after LA supplementation. Interestingly, Tau-induced iron overload, lipid peroxidation, and inflammation, which are involved in ferroptosis, were significantly blocked by LA administration. These results provide compelling evidence that LA plays a role in inhibiting Tau hyperphosphorylation and neuronal loss, including ferroptosis, through several pathways, suggesting that LA may be a potential therapy for tauopathies. Keywords: Tau, α-Lipoic acid, Oxidative stress, Ferroptosis, Alzheimer's disease

  3. Role of alpha-lipoic acid in the management of anemia in patients with chronic renal failure undergoing hemodialysis

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    El-Nakib GA

    2013-08-01

    Full Text Available Gehad A El-Nakib,1 Tarek M Mostafa,2 Tarek M Abbas,4 Mamdouh M El-Shishtawy,3 Mokhtar M Mabrouk,2 Mohammed A Sobh41Mansoura University Hospitals, Mansoura, Egypt; 2Faculty of Pharmacy, Tanta University, Tanta, Egypt; 3Faculty of Pharmacy, Mansoura University, Mansoura, Egypt; 4Urology and Nephrology Centre, Faculty of Medicine, Mansoura University, Mansoura, EgyptIntroduction: Anemia associated with chronic kidney disease is a serious complication necessitating expenditure of huge medical efforts and resources. This study investigates the role of alpha-lipoic acid (ALA in end stage renal disease patients undergoing hemodialysis. By the virtue of its antioxidative effects, ALA is expected to act as an erythropoietin (EPO adjuvant, and also has extended beneficial effects on endothelial dysfunction.Methods: Forty-four patients undergoing hemodialysis and receiving EPO were randomized into two groups: the first group received ALA 600 mg once daily for 3 months; while the other group represented the control group. Parameters measured at baseline and at end of study were hemoglobin, EPO doses, EPO resistance index (ERI, iron store indices, malondialdehyde, oxidized low-density lipoprotein (ox-LDL, interleukin-6 (IL-6, tumor necrosis factor-α (TNF-α, and asymmetric dimethylarginine (ADMA, as well as routine laboratory follow-up.Results: EPO doses and ERI were significantly decreased in the treatment group, while they did not change in the control group. Hemoglobin, iron store indices, malondialdehyde, oxidized ox-LDL, IL-6, TNF-α, and ADMA were similar in both treatment and control groups at baseline, and did not change by the end of study period. Likewise, routine laboratory measures were not affected by the treatment.Conclusion: ALA could be used in hemodialysis patients to reduce requirements for EPO. However, larger and longer term studies are required to clarify the exact role of ALA in hemodialysis as well as in pre-hemodialysis patients

  4. Consequences of the Combined α-tocopherol, Ascorbic Acid and α-lipoic Acid on the Glutathione, Cholesterol and Fatty Acid Composition in Muscle and Liver of Diabetic Rats.

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    Yilmaz, Okkes; Ersan, Yasemin; Dilek Ozsahin, Ayse; Ihsan Ozturk, Ali; Ozkan, Yusuf

    2013-02-01

    Our objective was to evaluate the effects of a triple antioxidant combination [α-tocopherol (AT), ascorbic acid (AA) and α-lipoic acid (LA); AT+AA+LA] on the cholesterol and glutathione levels, and the fatty acid composition of liver and muscle tissues in diabetic rats. Forty-three Wistar rats were randomly divided into five groups. The first group was used as a control. The second, third and fourth groups received STZ (45 mg/kg) in citrate buffer. The fourth and fifth groups were injected with intraperitoneal (IP) 50 mg/kg DL-AT and 50 mg /kg DL-LA four times per week and received water-soluble vitamin C (50 mg/kg) in their drinking water for a period of six weeks. Liver cholesterol levels in the AT+AA+LA group were lower than the control (Pcholesterol levels in the D-1 and D+AT+AA+LA groups were higher than the control group (P≤ 0.05). The levels of oleic acid were higher in the D-1 group and lower in the D-2 group (Pacid level in the D-1 and D-2 groups were lower (P<0.05), and higher in the D+AT+AA+LA group. Our results revealed that glutathione levels and the Stearoyl CoA Desaturase enzyme products in liver tissues of diabetic and non-diabetic rats were increased by triple antioxidant mixture.

  5. Effects of alpha-lipoic acid supplementation on growth performance, antioxidant capacity and biochemical parameters for ammonia-exposed broilers.

    Science.gov (United States)

    Lu, Min; Bai, Jie; Wei, Fengxian; Xu, Bin; Sun, Quanyou; Li, Jie; Wang, Gaili; Tang, Xiangfang; Zhang, Hongfu; Yin, Qingqiang; Li, Shaoyu

    2017-08-01

    In order to estimate the effect of alpha-lipoic acid (LA) supplementation on relieving ammonia stress of broilers, 180 22-day-old male broilers were assigned to three groups, six replicates in each group and 10 birds per replicate. The three groups were: (1) a control group without ammonia stress; (2) exposure to 70 ppm atmospheric ammonia (AM); (3) exposure to 70 ppm atmospheric ammonia and administration of 300 mg/kg LA (AM + LA). The experimental period was 3 weeks. Results showed that average daily weight gain was increased and feed conversion ratio was decreased in the AM + LA group, compared with the AM group (P ammonia stress to restore broiler production performance to normal levels. © 2016 Japanese Society of Animal Science.

  6. Complementary Cholesterol-Lowering Response of a Phytosterol/α-Lipoic Acid Combination in Obese Zucker Rats.

    Science.gov (United States)

    Rideout, Todd C; Carrier, Bradley; Wen, Shin; Raslawsky, Amy; Browne, Richard W; Harding, Scott V

    2016-01-01

    To investigate the cholesterol-lowering effectiveness of a phytosterol/α-lipoic acid (PS/αLA) therapy, thirty-two male Zucker rats were randomly assigned to 1 of 4 diets for 30 days: (i) high fat diet (HF, 40% energy from fat); (ii) HF diet supplemented with 3% phytosterols; (iii) HF diet supplemented with 0.25% αLA; or (iv) HF diet supplemented with PS (3%) and αLA (0.25%, PS/αLA). Compared with the HF diet, combination PS/αLA proved more effective in reducing non-HDL cholesterol (-55%) than either the PS (-24%) or the αLA (-25%) therapies alone. PS supplementation did not affect LDL particle number, however, αLA supplementation reduced LDL particle number when supplemented alone (-47%) or in combination with PS (-54%). Compared with the HF-fed animals, evidence of increased HDL-particle number was evident in all treatment groups to a similar extent (21-22%). PS-mediated interruption of intestinal cholesterol absorption was evident by increased fecal cholesterol loss (+52%) and compensatory increase in HMG-CoA reductase mRNA (1.6 fold of HF), however, αLA supplementation did not affect fecal cholesterol loss. Hepatic mRNA and protein expression patterns suggested that αLA modulated multiple aspects of cholesterol homeostasis including reduced synthesis (HMG-CoA reductase mRNA, 0.7 fold of HF), reduced bile acid synthesis (CYP7a1 expression, 0.17 of HF), and increased cholesterol clearance (reduced PCSK9 mRNA, 0.5 fold of HF; increased LDLr protein, 2 fold of HF). Taken together, this data suggests that PS and αLA work through unique and complementary mechanisms to provide a superior and more comprehensive cholesterol lowering response than either therapy alone.

  7. Stable and selective self-assembly of α-lipoic acid on Ge(001) for biomolecule immobilization

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    Kazmierczak, M.; Flesch, J.; Mitzloff, J.; Capellini, G.; Klesse, W. M.; Skibitzki, O.; You, C.; Bettenhausen, M.; Witzigmann, B.; Piehler, J.; Schroeder, T.; Guha, S.

    2018-05-01

    We demonstrate a novel method for the stable and selective surface functionalization of germanium (Ge) embedded in silicon dioxide. The Ge(001) surface is functionalized using α-lipoic acid (ALA), which can potentially be utilized for the immobilization of a wide range of biomolecules. We present a detailed pH-dependence study to establish the effect of the incubation pH value on the adsorption layer of the ALA molecules. A threshold pH value for functionalization is identified, dividing the examined pH range into two regions. Below a pH value of 7, the formation of a disordered ALA multilayer is observed, whereas a stable well-ordered ALA mono- to bi-layer on Ge(001) is achieved at higher pH values. Furthermore, we analyze the stability of the ALA layer under ambient conditions, revealing the most stable functionalized Ge(001) surface to effectively resist oxidation for up to one week. Our established functionalization method paves the way towards the successful immobilization of biomolecules in future Ge-based biosensors.

  8. Modulatory effects of alpha-lipoic acid (ALA) administration on insulin sensitivity in obese PCOS patients.

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    Genazzani, A D; Shefer, K; Della Casa, D; Prati, A; Napolitano, A; Manzo, A; Despini, G; Simoncini, T

    2018-05-01

    To evaluate the efficacy of alpha-lipoic acid (ALA) administration on hormonal and metabolic parameters of obese PCOS patients. A group of 32 obese PCOS patients were selected after informed consent. 20 patients referred to have first grade relatives with diabetes type I or II. Hormonal and metabolic parameters as well as OGTT were evaluated before and after 12 weeks of ALA integrative administration (400 mg per os every day). ALA administration significantly decreased insulin, glucose, BMI and HOMA index. Hyperinsulinemia and insulin response to OGTT decreased both as maximal response (Δmax) and as AUC. PCOS with diabetes relatives showed the decrease also of triglyceride and GOT. Interestingly in all PCOS no changes occurred on all hormonal parameters involved in reproduction such as LH, FSH, and androstenedione. ALA integrative administration at a low dosage as 400 mg daily improved the metabolic impairment of all PCOS patients especially in those PCOS with familiar diabetes who have a higher grade of risk of NAFLD and predisposition to diabetes.

  9. Tumor regression with a combination of drugs interfering with the tumor metabolism: efficacy of hydroxycitrate, lipoic acid and capsaicin.

    Science.gov (United States)

    Schwartz, Laurent; Guais, Adeline; Israël, Maurice; Junod, Bernard; Steyaert, Jean-Marc; Crespi, Elisabetta; Baronzio, Gianfranco; Abolhassani, Mohammad

    2013-04-01

    Cellular metabolic alterations are now well described as implicated in cancer and some strategies are currently developed to target these different pathways. In previous papers, we demonstrated that a combination of molecules (namely alpha-lipoic acid and hydroxycitrate, i.e. Metabloc™) targeting the cancer metabolism markedly decreased tumor cell growth in mice. In this work, we demonstrate that the addition of capsaicin further delays tumor growth in mice in a dose dependant manner. This is true for the three animal model tested: lung (LLC) cancer, bladder cancer (MBT-2) and melanoma B16F10. There was no apparent side effect of this ternary combination. The addition of a fourth drug (octreotide) is even more effective resulting in tumor regression in mice bearing LLC cancer. These four compounds are all known to target the cellular metabolism not its DNA. The efficacy, the apparent lack of toxicity, the long clinical track records of these medications in human medicine, all points toward the need for a clinical trial. The dramatic efficacy of treatment suggests that cancer may simply be a disease of dysregulated cellular metabolism.

  10. Effects of Alpha-Lipoic Acid Supplementation on Plasma Adiponectin Levels and Some Metabolic Risk Factors in Patients with Schizophrenia.

    Science.gov (United States)

    Vidović, Bojana; Milovanović, Srđan; Stefanović, Aleksandra; Kotur-Stevuljević, Jelena; Takić, Marija; Debeljak-Martačić, Jasmina; Pantović, Maja; Đorđević, Brižita

    2017-01-01

    Adiponectin is an adipocyte-derived plasma protein with insulin-sensitizing and anti-inflammatory properties and is suggested to be a biomarker of metabolic disturbances. The aim of this study was to investigate the effects of alpha-lipoic acid (ALA) on plasma adiponectin and some metabolic risk factors in patients with schizophrenia. The plasma adipokine levels (adiponectin and leptin), routine biochemical and anthropometric parameters, markers of oxidative stress, and the serum phospholipid fatty acid profile in eighteen schizophrenic patients at baseline, in the middle, and at the end of a 3-month long supplementation period with ALA (500 mg daily) were determined. A significant increase in the plasma adiponectin concentrations, as well as a decrease in fasting glucose and aspartate aminotransferase activity (AST), was found. Baseline AST activity was independently correlated with the adiponectin concentrations. Our data show that ALA can improve plasma adiponectin levels and may play a potential role in the treatment of metabolic risk factor in patients with schizophrenia. Future randomized controlled trials are needed to confirm these preliminary investigations.

  11. Effects of α-lipoic acid on endothelial function in aged diabetic and high-fat fed rats

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    Sena, C M; Nunes, E; Louro, T; Proença, T; Fernandes, R; Boarder, M R; Seiça, R M

    2007-01-01

    Background and purpose: This study was conducted to investigate the effects of α-lipoic acid (α-LA) on endothelial function in diabetic and high-fat fed animal models and elucidate the potential mechanism underlying the benefits of α-LA. Experimental approach: Plasma metabolites reflecting glucose and lipid metabolism, endothelial function, urinary albumin excretion (UAE), plasma and aortic malondialdehyde (MDA) and urinary 8-hydroxydeoxyguanosine (8-OHdG) were assessed in non-diabetic controls (Wistar rats), untreated Goto-Kakizaki (GK) diabetic and high-fat fed GK rats (fed with atherogenic diet only, treated with α-LA and treated with vehicle, for 3 months). Vascular eNOS, nitrotyrosine, carbonyl groups and superoxide anion were also assessed in the different groups. Key results: α-LA and soybean oil significantly reduced both total and non-HDL serum cholesterol and triglycerides induced by atherogenic diet. MDA, carbonyl groups, vascular superoxide and 8-OHdG levels were higher in GK and high-fat fed GK groups and fully reversed with α-LA treatment. High-fat fed GK diabetic rats showed significantly reduced endothelial function and increased UAE, effects ameliorated with α-LA. This endothelial dysfunction was associated with decreased NO production, decreased expression of eNOS and increased vascular superoxide production and nitrotyrosine expression. Conclusions and implications: α-LA restores endothelial function and significantly improves systemic and local oxidative stress in high-fat fed GK diabetic rats. Improved endothelial function due to α-LA was at least partially attributed to recoupling of eNOS and increased NO bioavailability and represents a pharmacological approach to prevent major complications associated with type 2 diabetes. PMID:17906683

  12. Lipoic acid attenuates inflammation via cAMP and protein kinase A signaling.

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    Sonemany Salinthone

    2010-09-01

    Full Text Available Abnormal regulation of the inflammatory response is an important component of diseases such as diabetes, Alzheimer's disease and multiple sclerosis (MS. Lipoic acid (LA has been shown to have antioxidant and anti-inflammatory properties and is being pursued as a therapy for these diseases. We first reported that LA stimulates cAMP production via activation of G-protein coupled receptors and adenylyl cyclases. LA also suppressed NK cell activation and cytotoxicity. In this study we present evidence supporting the hypothesis that the anti-inflammatory properties of LA are mediated by the cAMP/PKA signaling cascade. Additionally, we show that LA oral administration elevates cAMP levels in MS subjects.We determined the effects of LA on IL-6, IL-17 and IL-10 secretion using ELISAs. Treatment with 50 µg/ml and 100 µg/ml LA significantly reduced IL-6 levels by 19 and 34%, respectively, in T cell enriched PBMCs. IL-17 levels were also reduced by 35 and 50%, respectively. Though not significant, LA appeared to have a biphasic effect on IL-10 production. Thymidine incorporation studies showed LA inhibited T cell proliferation by 90%. T-cell activation was reduced by 50% as measured by IL-2 secretion. Western blot analysis showed that LA treatment increased phosphorylation of Lck, a downstream effector of protein kinase A. Pretreatment with a peptide inhibitor of PKA, PKI, blocked LA inhibition of IL-2 and IFN gamma production, indicating that PKA mediates these responses. Oral administration of 1200 mg LA to MS subjects resulted in increased cAMP levels in PBMCs four hours after ingestion. Average cAMP levels in 20 subjects were 43% higher than baseline.Oral administration of LA in vivo resulted in significant increases in cAMP concentration. The anti-inflammatory effects of LA are mediated in part by the cAMP/PKA signaling cascade. These novel findings enhance our understanding of the mechanisms of action of LA.

  13. α-lipoic acid suppresses neuronal excitability and attenuates colonic hypersensitivity to colorectal distention in diabetic rats

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    Sun Y

    2017-07-01

    Full Text Available Yan Sun,1,* Pan-Pan Yang,1,* Zhen-Yuan Song,2 Yu Feng,1 Duan-Min Hu,1 Ji Hu,1 Guang-Yin Xu,3 Hong-Hong Zhang1,3 1Department of Endocrinology, The Second Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 2Department of Endocrinology, The East District of Suzhou Municipal Hospital, Suzhou, People’s Republic of China; 3Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Institute of Neuroscience, Soochow University, Suzhou, People’s Republic of China *These authors contributed equally to this work Aim: Patients with long-standing diabetes often demonstrate intestinal dysfunction, characterized as constipation or colonic hypersensitivity. Our previous studies have demonstrated the roles of voltage-gated sodium channels NaV1.7 and NaV1.8 in dorsal root ganglion (DRG in colonic hypersensitivity of rats with diabetes. This study was designed to determine roles of antioxidant α-lipoic acid (ALA on sodium channel activities and colonic hypersensitivity of rats with diabetes. Methods: Streptozotocin was used to induce diabetes in adult female rats. Colonic sensitivity was measured by behavioral responses to colorectal distention in rats. The excitability and sodium channel currents of colon projection DRG neurons labeled with DiI were measured by whole-cell patch-clamp recordings. The expressions of NaV1.7 and NaV1.8 of colon DRGs were measured by western blot analysis. Results: ALA treatment significantly increased distention threshold in responding to colorectal distension in diabetic rats compared with normal saline treatment. ALA treatment also hyperpolarized the resting membrane potentials, depolarized action potential threshold, increased rheobase, and decreased frequency of action potentials evoked by ramp current stimulation. Furthermore, ALA treatment also reduced neuronal sodium current densities of DRG neurons innervating the colon from rats with diabetes. In addition, ALA

  14. Consequences of the Combined α-tocopherol, Ascorbic Acid and α-lipoic Acid on the Glutathione, Cholesterol and Fatty Acid Composition in Muscle and Liver of Diabetic Rats

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    YILMAZ, Okkes; ERSAN, Yasemin; Dilek OZSAHIN, Ayse; Ihsan OZTURK, Ali; OZKAN, Yusuf

    2013-01-01

    Objective(s): Our objective was to evaluate the effects of a triple antioxidant combination [α-tocopherol (AT), ascorbic acid (AA) and α-lipoic acid (LA); AT+AA+LA] on the cholesterol and glutathione levels, and the fatty acid composition of liver and muscle tissues in diabetic rats. Materials and Methods: Forty-three Wistar rats were randomly divided into five groups. The first group was used as a control. The second, third and fourth groups received STZ (45 mg/kg) in citrate buffer. The fourth and fifth groups were injected with intraperitoneal (IP) 50 mg/kg DL-AT and 50 mg /kg DL-LA four times per week and received water-soluble vitamin C (50 mg/kg) in their drinking water for a period of six weeks. Results: Liver cholesterol levels in the AT+AA+LA group were lower than the control (P<0.05). Glutathione level was lower in D-2 (P<0.05) and were higher in D+AT+AA+LA and AT+AA+LA groups than the control groups (P≤ 0.05). The muscle cholesterol levels in the D-1 and D+AT+AA+LA groups were higher than the control group (P≤ 0.05). The levels of oleic acid were higher in the D-1 group and lower in the D-2 group (P<0.001). The arachidonic acid level in the D-1 and D-2 groups were lower (P<0.05), and higher in the D+AT+AA+LA group. Conclusion: Our results revealed that glutathione levels and the Stearoyl CoA Desaturase enzyme products in liver tissues of diabetic and non-diabetic rats were increased by triple antioxidant mixture. PMID:24298385

  15. The Antioxidant Cofactor Alpha-Lipoic Acid May Control Endogenous Formaldehyde Metabolism in Mammals

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    Anastasia V. Shindyapina

    2017-12-01

    Full Text Available The healthy human body contains small amounts of metabolic formaldehyde (FA that mainly results from methanol oxidation by pectin methylesterase, which is active in a vegetable diet and in the gastrointestinal microbiome. With age, the ability to maintain a low level of FA decreases, which increases the risk of Alzheimer's disease and dementia. It has been shown that 1,2-dithiolane-3-pentanoic acid or alpha lipoic acid (ALA, a naturally occurring dithiol and antioxidant cofactor of mitochondrial α-ketoacid dehydrogenases, increases glutathione (GSH content and FA metabolism by mitochondrial aldehyde dehydrogenase 2 (ALDH2 thus manifests a therapeutic potential beyond its antioxidant property. We suggested that ALA can contribute to a decrease in the FA content of mammals by acting on ALDH2 expression. To test this assumption, we administered ALA in mice in order to examine the effect on FA metabolism and collected blood samples for the measurement of FA. Our data revealed that ALA efficiently eliminated FA in mice. Without affecting the specific activity of FA-metabolizing enzymes (ADH1, ALDH2, and ADH5, ALA increased the GSH content in the brain and up-regulated the expression of the FA-metabolizing ALDH2 gene in the brain, particularly in the hippocampus, but did not impact its expression in the liver in vivo or in rat liver isolated from the rest of the body. After ALA administration in mice and in accordance with the increased content of brain ALDH2 mRNA, we detected increased ALDH2 activity in brain homogenates. We hypothesized that the beneficial effects of ALA on patients with Alzheimer's disease may be associated with accelerated ALDH2-mediated FA detoxification and clearance.

  16. The Antioxidant Additive Approach for Alzheimer's Disease Therapy: New Ferulic (Lipoic) Acid Plus Melatonin Modified Tacrines as Cholinesterases Inhibitors, Direct Antioxidants, and Nuclear Factor (Erythroid-Derived 2)-Like 2 Activators.

    Science.gov (United States)

    Benchekroun, Mohamed; Romero, Alejandro; Egea, Javier; León, Rafael; Michalska, Patrycja; Buendía, Izaskun; Jimeno, María Luisa; Jun, Daniel; Janockova, Jana; Sepsova, Vendula; Soukup, Ondrej; Bautista-Aguilera, Oscar M; Refouvelet, Bernard; Ouari, Olivier; Marco-Contelles, José; Ismaili, Lhassane

    2016-11-10

    Novel multifunctional tacrines for Alzheimer's disease were obtained by Ugi-reaction between ferulic (or lipoic acid), a melatonin-like isocyanide, formaldehyde, and tacrine derivatives, according to the antioxidant additive approach in order to modulate the oxidative stress as therapeutic strategy. Compound 5c has been identified as a promising permeable agent showing excellent antioxidant properties, strong cholinesterase inhibitory activity, less hepatotoxicity than tacrine, and the best neuroprotective capacity, being able to significantly activate the Nrf2 transcriptional pathway.

  17. (R)-α-Lipoic acid inhibits fructose-induced myoglobin fructation and the formation of advanced glycation end products (AGEs) in vitro.

    Science.gov (United States)

    Ghelani, Hardik; Razmovski-Naumovski, Valentina; Pragada, Rajeswara Rao; Nammi, Srinivas

    2018-01-15

    Fructose-mediated protein glycation (fructation) has been linked to an increase in diabetic and cardiovascular complications due to over consumption of high-fructose containing diets in recent times. The objective of the present study is to evaluate the protective effect of (R)-α-lipoic acid (ALA) against fructose-induced myoglobin fructation and the formation of advanced glycation end products (AGEs) in vitro. The anti-glycation activity of ALA was determined using the formation of AGEs fluorescence intensity, iron released from the heme moiety of myoglobin and the level of fructosamine. The fructation-induced myoglobin oxidation was examined using the level of protein carbonyl content and thiol group estimation. The results showed that co-incubation of myoglobin (1 mg/mL), fructose (1 M) and ALA (1, 2 and 4 mM) significantly inhibited the formation of AGEs during the 30 day study period. ALA markedly decreased the levels of fructosamine, which is directly associated with the reduction of AGEs formation. Furthermore, ALA significantly reduced free iron release from myoglobin which is attributed to the protection of myoglobin from fructose-induced glycation. The results also demonstrated a significant protective effect of ALA on myoglobin oxidative damages, as seen from decreased protein carbonyl content and increased protein thiols. These findings provide new insights into the anti-glycation properties of ALA and emphasize that ALA supplementation is beneficial in the prevention of AGEs-mediated diabetic and cardiovascular complications.

  18. Cardioprotective effects of lipoic acid, quercetin and resveratrol on oxidative stress related to thyroid hormone alterations in long-term obesity.

    Science.gov (United States)

    Cheserek, Maureen Jepkorir; Wu, Guirong; Li, Longnan; Li, Lirong; Karangwa, Eric; Shi, Yonghui; Le, Guowei

    2016-07-01

    This study investigated possible mechanisms for cardioprotective effects of lipoic acid (LA), quercetin (Q) and resveratrol (R) on oxidative stress related to thyroid hormone alterations in long-term obesity. Female C57BL/6 mice were fed on high-fat diet (HFD), HFD+LA, HFD+R, HFD+Q and normal diet for 26weeks. Body weight, blood pressure, thyroid hormones, oxidative stress markers, angiotensin converting enzyme (ACE), nitric oxide synthase (NOS) and ion pump activities were measured, and expression of cardiac genes was analyzed by real-time polymerase chain reaction. HFD induced marked increase (Pstress, while plasma triidothyronine levels reduced. ACE activity increased (Pobesity thereby restoring plasma thyroid hormone levels and attenuating oxidative stress in the heart and thus may have therapeutic potential in heart diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. EPA, DHA, and Lipoic Acid Differentially Modulate the n-3 Fatty Acid Biosynthetic Pathway in Atlantic Salmon Hepatocytes.

    Science.gov (United States)

    Bou, Marta; Østbye, Tone-Kari; Berge, Gerd M; Ruyter, Bente

    2017-03-01

    The aim of the present study was to investigate how EPA, DHA, and lipoic acid (LA) influence the different metabolic steps in the n-3 fatty acid (FA) biosynthetic pathway in hepatocytes from Atlantic salmon fed four dietary levels (0, 0.5, 1.0 and 2.0%) of EPA, DHA or a 1:1 mixture of these FA. The hepatocytes were incubated with [1- 14 C] 18:3n-3 in the presence or absence of LA (0.2 mM). Increased endogenous levels of EPA and/or DHA and LA exposure both led to similar responses in cells with reduced desaturation and elongation of [1- 14 C] 18:3n-3 to 18:4n-3, 20:4n-3, and EPA, in agreement with reduced expression of the Δ6 desaturase gene involved in the first step of conversion. DHA production, on the other hand, was maintained even in groups with high endogenous levels of DHA, possibly due to a more complex regulation of this last step in the n-3 metabolic pathway. Inhibition of the Δ6 desaturase pathway led to increased direct elongation to 20:3n-3 by both DHA and LA. Possibly the route by 20:3n-3 and then Δ8 desaturation to 20:4n-3, bypassing the first Δ6 desaturase step, can partly explain the maintained or even increased levels of DHA production. LA increased DHA production in the phospholipid fraction of hepatocytes isolated from fish fed 0 and 0.5% EPA and/or DHA, indicating that LA has the potential to further increase the production of this health-beneficial FA in fish fed diets with low levels of EPA and/or DHA.

  20. Effects of Dietary L-carnosine and Alpha-lipoic Acid on Growth Performance, Blood Thyroid Hormones and Lipid Profiles in Finishing Pigs

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    Yinghui Bao

    2015-10-01

    Full Text Available The present study was conducted to determine the effects of L-carnosine (LC and/or alpha-lipoic acid (ALA supplementation on growth performance, blood thyroid hormones and lipid profiles in finishing pigs. A total of 40 (Landrace×Yorkshire pigs with an initial body weight of 57.93±3.14 kg were randomly allocated to 4 experimental diets using a 2×2 factorial arrangement with 2 LC supplemental levels (0 or 0.1% and 2 ALA supplemental levels (0 or 0.03% in basal diets. The results showed that pigs fed LC-supplemented diets increased final live weight, average daily gain, and average daily feed intake compared to those of pigs fed without LC-supplemented diets (p0.05. Additionally, LC supplementation increased serum triiodothyronine, thyroxine levels, and ALA supplementation increased serum triiodothyronine levels (p<0.05. Serum total cholesterol and triglycerides levels were significantly decreased in LC and ALA supplemented groups, respectively (p<0.05. Moreover, serum low density lipoprotein cholesterol levels were lower in the ALA-supplemented groups than those of pigs fed without ALA-supplemented diets (p<0.05. However, no significant LC×ALA interaction effect on growth performance, blood thyroid hormones and lipid profiles was found. This study suggested that dietary supplementation of LC resulted in better growth performance compared to that of ALA supplementation. L-carnosine and/or ALA supplementation positively modified blood lipid profiles, which may have the potential to prevent cardiovascular diseases.

  1. Response of streptozotocin-induced diabetes in rats under oxidative stress of intermittent radiation exposure to either antioxidant or insulin mimic treatment

    International Nuclear Information System (INIS)

    Noaman, E.; El-Tahawy, N.A.; Hedayat, I.S.; Mansour, S.Z.; Fahmy, Y.N.

    2005-01-01

    Diabetic rats were treated with 0.5% a-lipoic acid, as a diet supplement, or was administered with vanadyl sulphate in drinking water at a dose of 75 mg/kg with or without whole body gamma radiation exposure with repeated dose of 4 Gy/week for 4 weeks. Both treatments significantly improved diabetes-induced increase in glucose concentration. Treating diabetic rats with a-lipoic acid prevented the diabetes-induced increase in thiobarbituric acid reactive substances in plasma and significantly improved liver glutathione levels. On the other hand, treating diabetic rats with vanadyl sulphate not only prevented diabetes-induced changes of either of these oxidative stress markers but also normalized glucose concentration and ameliorated the increase in body weight gain. Diabetes with or without radiation exposure induced increase in liver conjugated diene levels and such elevation was improved by the treatment with either a-lipoic acid or vanadyl sulphate. Treating diabetic rats with a-lipoic acid and vanadyl sulphate partially improved liver No*VlC-ATPase activity and sorbitol and myo-inositol contents. The increase in liver sorbitol levels in diabetic rats was ameliorated by either treatment. These studies suggest that diabetes-induced oxidative stress may be partially responsible for the development of diabetic complications and the treatment with vanadyl sulphate was more advantageous than a-lipoic acid in handling these complications

  2. Does lipoic acid consumption affect the cytokine profile in multiple sclerosis patients: a double-blind, placebo-controlled, randomized clinical trial.

    Science.gov (United States)

    Khalili, Mohammad; Azimi, Amirreza; Izadi, Vajihe; Eghtesadi, Shahryar; Mirshafiey, Abbas; Sahraian, Mohamad Ali; Motevalian, Abbas; Norouzi, Abbas; Sanoobar, Meisam; Eskandari, Ghazaleh; Farhoudi, Mehdi; Amani, Firouz

    2014-01-01

    A limited amount of data exists regarding the effect of lipoic acid (LA), an oral antioxidant supplement, on cytokine profiles among multiple sclerosis (MS) patients. We aimed to assess the effect of daily consumption of LA on the cytokine profiles in MS patients. In this double-blind, placebo-controlled, randomized clinical trial, 52 relapsing-remitting MS patients with an age range of 18-50 years were recruited into 2 groups: LA consumption (1,200 mg/day) or placebo. Patients followed their prescribed supplements for 12 weeks. Fasting blood samples for cytokine profile measurement were collected at baseline and after the intervention. Anthropometric parameters were measured based on the standard guidelines. INF-γ, ICAM-1, TGF-β and IL-4 were significantly reduced in the LA group compared to the placebo group [(INF-γ: 0.82 ± 0.2 vs. 0.2 ± 0.2 pg/ml, p consumption of 1,200 mg LA per day beneficially affects several inflammatory cytokines including INF-γ, ICAM-1 TGF-β and IL-4. Further investigations are needed to verify the beneficial role of LA on other cytokine profiles among MS patients.

  3. Evaluation of laser therapy and alpha-lipoic acid for the treatment of burning mouth syndrome: a randomized clinical trial.

    Science.gov (United States)

    Barbosa, Natália Guimarães; Gonzaga, Amanda Katarinny Goes; de Sena Fernandes, Luzia Leiros; da Fonseca, Aldilane Gonçalves; Queiroz, Salomão Israel Monteiro Lourenço; Lemos, Telma Maria Araújo Moura; da Silveira, Éricka Janine Dantas; de Medeiros, Ana Miryam Costa

    2018-03-03

    The aim of this study was to evaluate the efficacy of low-level laser therapy (LLLT) and alpha-lipoic acid (ALA) in the treatment of burning mouth syndrome (BMS) and secondary oral burning (SOB) by unstimulated sialometry, symptom assessment, and measurement of salivary TNF-α levels. Forty-four patients were randomized into four treatment groups: BMS/laser (n = 10), BMS/ALA (n = 5), SOB/laser (n = 15), and SOB/ALA (n = 14). The control group consisted of eight healthy female subjects. Unstimulated salivary flow was measured before and after treatment, and the collected saliva was stored at - 20 °C for the analysis of TNF-α. Symptoms were evaluated before and after treatment using a pain visual analog scale. Most patients were women (81.8%) during menopause (72.2%). LLLT and ALA were efficient in increasing salivary flow only in BMS but provided symptom relief in both conditions. TNF-α levels did not differ between patients with BMS and SOB or between those patients and the control group. No differences were observed in posttreatment TNF-α levels in either condition. The results of this study suggest that LLLT and ALA are efficient therapies in reducing burning mouth symptoms, with LLLT being more efficient than ALA.

  4. Synthesis of Selective Butyrylcholinesterase Inhibitors Coupled between α-Lipoic Acid and Polyphenols by Using 2-(Piperazin-1-yl)ethanol Linker

    International Nuclear Information System (INIS)

    Yeun, Go Heun; Lee, Seung Hwan; LIm, Yong Bae; Lee, Hye Sook; Lee, Bong Ho; Park, Jeong Ho; Won, Mooho

    2013-01-01

    In the previous paper (Bull. Korean Chem. Soc., 2011, 32, 2997), the hybrid molecules between α-lipoic acid (ALA) and polyphenols (PPs) connected with neutral 2-(2-aminoethoxy)ethanol linker (linker-1) showed new biological activity such as butyrylcholinesterase (BuChE) inhibition. In order to increase the binding affinity of the hybrid compounds to cholinesterase (ChE), the neutral 2-(2-aminoethoxy)ethanol (linker 1) was switched to the cationic 2-(piperazin-1-yl)ethanol linker (linker 2). The IC 50 values of the linker-2 hybrid molecules for BuChE inhibition were lower than those of linker-1 hybrid molecules (except 9-2) and they also had the same great selectivity for BuChE over AChE (> 800 fold) as linker-1 hybrid molecules. ALA-acetyl caffeic acid (10-2, ALA-AcCA) was shown as an effective inhibitor of BuChE (IC 50 = 0.44 ± 0.24 μM). A kinetic study using 7-2 showed that it is the same mixed type inhibition as 7-1. Its inhibition constant (Ki) to BuChE is 4.3 ± 0.09 μM

  5. Synthesis of Selective Butyrylcholinesterase Inhibitors Coupled between α-Lipoic Acid and Polyphenols by Using 2-(Piperazin-1-yl)ethanol Linker

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    Yeun, Go Heun; Lee, Seung Hwan; LIm, Yong Bae; Lee, Hye Sook; Lee, Bong Ho; Park, Jeong Ho [Hanbat National Univ., Daejeon (Korea, Republic of); Won, Mooho [Kangwon National Univ., Chuncheon (Korea, Republic of)

    2013-04-15

    In the previous paper (Bull. Korean Chem. Soc., 2011, 32, 2997), the hybrid molecules between α-lipoic acid (ALA) and polyphenols (PPs) connected with neutral 2-(2-aminoethoxy)ethanol linker (linker-1) showed new biological activity such as butyrylcholinesterase (BuChE) inhibition. In order to increase the binding affinity of the hybrid compounds to cholinesterase (ChE), the neutral 2-(2-aminoethoxy)ethanol (linker 1) was switched to the cationic 2-(piperazin-1-yl)ethanol linker (linker 2). The IC{sub 50} values of the linker-2 hybrid molecules for BuChE inhibition were lower than those of linker-1 hybrid molecules (except 9-2) and they also had the same great selectivity for BuChE over AChE (> 800 fold) as linker-1 hybrid molecules. ALA-acetyl caffeic acid (10-2, ALA-AcCA) was shown as an effective inhibitor of BuChE (IC{sub 50} = 0.44 ± 0.24 μM). A kinetic study using 7-2 showed that it is the same mixed type inhibition as 7-1. Its inhibition constant (Ki) to BuChE is 4.3 ± 0.09 μM.

  6. Alpha-lipoic acid induces sodium iodide symporter expression in TPC-1 thyroid cancer cell line

    International Nuclear Information System (INIS)

    Choi, Hyun-Jeung; Kim, Tae Yong; Ruiz-Llorente, Sergio; Jeon, Min Ji; Han, Ji Min; Kim, Won Gu; Shong, Young Kee; Kim, Won Bae

    2012-01-01

    Introduction: Patients with metastatic thyroid cancers that do not uptake iodine need effective therapeutic option. Differentiation-inducing agents have been tried to restore functional expression of sodium iodide symporter (NIS) without success. Our objective was to assess the effect of alpha-lipoic acid (ALA), known as potential antioxidant, on expression of sodium iodide symporter in thyroid cancer cells. Methods: Human thyroid cancer-derived cell lines, TPC-1, were treated with ALA, and changes in NIS mRNA and protein expression were measured. ALA's effect on NIS gene promoter was evaluated, and functional NIS expression was assessed by iodide uptake assay. Results: Treatment with ALA increased NIS mRNA expression up to ten folds of control dose-dependently after 24 h of exposure. ALA increased NIS promoter activity, and increased iodide uptake by 1.6 fold. ALA induced expression of NIS protein, but had no significant effect on the plasma membrane trafficking. ALA increased phosphorylation of CREB and nuclear translocation of pCREB, and co-treatment of ALA and trichostatin A increased iodide uptake by three folds in TPC-1 cells. Conclusions: ALA is a potential agent to increase NIS transcription in TPC-1. It could be used as an adjunctive agent to increase efficacy of radioiodine therapy if combined with a strategy to increase NIS protein trafficking to cell membrane.

  7. α-Lipoic Acid Mitigates Arsenic-Induced Hematological Abnormalities in Adult Male Rats

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    Sonali Ghosh

    2017-05-01

    Full Text Available Background: Arsenic toxicity is a major global health problem and exposure via contaminated drinking water has been associated with hematological and other systemic disorders. The present investigation has been conducted in adult male rats to evaluate the protective ability of α-lipoic acid (ALA against such hematological disorders. Methods: Twenty-four adult male Wister rats (b.wt.130±10g were grouped and accordingly group I (control received the normal diet, group II (treated was given arsenic orally for 28 consecutive days as arsenic trioxide (3 mg/kgbw/rat/day whereas group III (supplemented received the same dose of arsenic along with ALA (25 mg/kgbw/rat/day as oral supplement. Hematological profile, plasma oxidant/antioxidant status, and erythrocyte morphology were assessed. Statistical analysis was done by one-way ANOVA using SPSS software (version 16.0. Results: Arsenic exposure caused reduction of erythrocyte (P=0.021, leucocyte (P<0.001, and hemoglobin (P=0.031 associated with echinocytic transformation as evidenced by light and scanning electron microscopic studies. The other significantly altered parameters include increased mean corpuscular volume (P=0.041 and lymphocytopenia (P<0.001 with insignificant neutropenia and eosinophilia. Altered serum oxidative balance as evidenced by decreased TAS (P<0.001 and increased TOS (P<0.001 with OSI (P<0.001 was also noted. The dietary supplementation of ALA has a beneficial effect against the observed (P<0.05 arsenic toxicities. It brings about the protection by restoring the hematological redox and inflammatory status near normal in treated rats. Arsenic-induced morphological alteration of erythrocytes was also partially attenuated by ALA supplementation. Conclusion: It is concluded that arsenicosis is associated with hematological alterations and ALA co-supplementation can partially alleviate these changes in an experimental male rat model.

  8. Anti-inflammatory effects of the selective phosphodiesterase 3 inhibitor, cilostazol, and antioxidants, enzymatically-modified isoquercitrin and α-lipoic acid, reduce dextran sulphate sodium-induced colorectal mucosal injury in mice.

    Science.gov (United States)

    Kangawa, Yumi; Yoshida, Toshinori; Abe, Hajime; Seto, Yoshiki; Miyashita, Taishi; Nakamura, Michi; Kihara, Tohru; Hayashi, Shim-Mo; Shibutani, Makoto

    2017-04-04

    Developing effective treatments and preventing inflammatory bowel disease (IBD) are urgent challenges in improving patients' health. It has been suggested that platelet activation and reactive oxidative species generation are involved in the pathogenesis of IBD. We examined the inhibitory effects of a selective phosphodiesterase-3 inhibitor, cilostazol (CZ), and two antioxidants, enzymatically modified isoquercitrin (EMIQ) and α-lipoic acid (ALA), against dextran sulphate sodium (DSS)-induced colitis. BALB/c mice were treated with 0.3% CZ, 1.5% EMIQ, and 0.2% ALA in their feed. Colitis was induced by administering 5% DSS in drinking water for 8days. The inhibitory effects of these substances were evaluated by measuring relevant clinical symptoms (faecal blood, diarrhoea, and body weight loss), colon length, plasma cytokine and chemokine levels, whole genome gene expression, and histopathology. Diarrhoea was suppressed by each treatment, while CZ prevented shortening of the colon length. All treatment groups exhibited decreased plasma levels of interleukin (IL)-6 and tumour necrosis factor (TNF)-α compared with the DSS group. Microarray analysis showed that cell adhesion, cytoskeleton regulation, cell proliferation, and apoptosis, which might be related to inflammatory cell infiltration and mucosal healing, were affected in all the groups. DSS-induced mucosal injuries such as mucosal loss, submucosal oedema, and inflammatory cell infiltration in the distal colon were prevented by CZ or antioxidant treatment. These results suggest that anti-inflammatory effects of these agents reduced DSS-induced mucosal injuries in mice and, therefore, may provide therapeutic benefits in IBD. Copyright © 2016 Elsevier GmbH. All rights reserved.

  9. Evaluation of Eudragit® Retard Polymers for the Microencapsulation of Alpha-Lipoic Acid.

    Science.gov (United States)

    Pecora, Tiziana M G; Musumeci, Teresa; Musumeci, Lucrezia; Fresta, Massimo; Pignatello, Rosario

    2016-01-01

    Microencapsulation of natural antioxidants in polymeric systems represents a possible strategy for improving the oral bioavailability of compounds that are otherwise poorly soluble. α-lipoic acid (ALA) was microencapsulated with polymethacrylate polymers (blends at various ratios of Eudragit® RS100 and RL100 resins). Microspheres were produced by solvent displacement of an ethanol cosolution of ALA and polymers; the microsuspensions were then freeze-dried, using trehalose as a cryoprotector. Microspheres were characterized in the solid state for micromeritic properties and drug loading, as well as by infrared spectroscopy, powder X-ray diffractometry and differential scanning calorimetry. The antioxidant activity of free and encapsulated ALA was assessed by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. In vitro release studies, performed in simulated gastric (pH 1.2) and intestinal fluid (pH 6.8), showed that, depending on polymer composition and drug-to-polymer ratio, ALA release can be slowed down, compared to the dissolution pattern of the free drug. Solid-state characterization confirmed the chemical stability of ALA in the microspheres, suggesting that ALA did not develop strong interactions with the polymer and was present in an amorphous or a disordered-crystalline state within the polymer network. As indicated by the DPPH assay, the microencapsulation of ALA in Eudragit® Retard matrices did not alter its antioxidant activity. ALA was effectively encapsulated in Eudragit® Retard matrices, showing a chemical stability up to 6 months at room conditions and at 40°C. Moreover, since the drug maintained its antioxidant activity in vitro, the potential application of these microparticulate systems for oral administration would deserve further studies.

  10. Alpha-lipoic acid attenuates cardiac fibrosis in Otsuka Long-Evans Tokushima Fatty rats

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    Lee Jung Eun

    2012-09-01

    Full Text Available Abstract Background Hyperglycemia leads to cardiac oxidative stress and an imbalance in glucose homeostasis. Diabetic cardiomyopathy is characterised by cardiac hypertrophy and fibrosis. However, the underlying mechanisms of diabetic cardiomyopathy are not fully understood. This study aimed to investigate the effects of alpha-lipoic acid (ALA on cardiac energy metabolism, antioxidant effect, and fibrosis in the hearts of Otsuka Long-Evans Tokushima fatty (OLETF rats. Methods Animals were separated into non-diabetic Long-Evans Tokushima Otsuka (LETO rats and diabetes-prone OLETF rats with or without ALA (200 mg/kg/day administration for 16 weeks. Diabetic cardiomyopathy was assessed by staining with Sirius Red. The effect of ALA on AMPK signalling, antioxidant enzymes, and fibrosis-related genes in the heart of OLETF rats were performed by Western blot analysis or immunohistochemistry. Results Western blot analysis showed that cardiac adenosine monophosphate-activated kinase (AMPK signalling was lower in OLETF rats than in LETO rats, and that ALA treatment increased the signalling in OLETF rats. Furthermore, the low antioxidant activity in OLETF rats was increased by ALA treatment. In addition to increased Sirius red staining of collagen deposits, transforming growth factor-β1 (TGF-β1 and connective tissue growth factor (CTGF were expressed at higher levels in OLETF rat hearts than in LETO rat hearts, and the levels of these factors were decreased by ALA. Conclusions ALA enhances AMPK signalling, antioxidant, and antifibrogenic effect. Theses findings suggest that ALA may have beneficial effects in the treatment of diabetic cardiomyopathy.

  11. Effect of palladium α-lipoic acid complex on energy in the brain mitochondria of aged rats.

    Science.gov (United States)

    Ajith, Thekkuttuparambil Ananthanarayanan; Nima, Nalin; Veena, Ravindran Kalathil; Janardhanan, Kainoor Krishnankutty; Antonawich, Francis

    2014-01-01

    According to the mitochondrial mutation theory of aging, the impairment of mitochondrial functions and decline of cellular bioenergetics are induced by highly reactive oxygen species (ROS). Supplementation with antioxidants may protect mitochondria against respiration-linked oxidative stress and reduce decay by preserving genomic and structural integrity. Several clinical studies have reported beneficial effects of α-lipoic acid (LA) administration in individuals with Alzheimer's disease, particularly improving their spatial orientation; however, no studies have been reported on the effects of palladium α-lipoic acid (Pd-LA). The current study examined the effects of the Pd-LA complex on mitochondrial energy status in the brains of aged rats. The study used male Wistar rats, some that were older than 24 mo and weighed approximately 350 ± 50 g and some that were younger than 24 mo and weighed approximately 175 ± 25 g. The research team divided the rats into 5 groups of 6 rats. The study was conducted at the Amala Cancer Research Centre in Amala Nagar, Thrissur, Kerala, India. Three groups of rats were controls: (1) young controls administered no solution, (2) aged controls administered 1 mL/kg of a 0.25% solution (PO) of sodium hydroxide (NaOH), and (3) positive aged controls treated with LA (7.6 mg/kg, PO) dissolved in an alkaline saline (0.25% NaOH, w/v). Two groups were intervention groups: (1) aged rats treated with 1.2 mg/kg of Pd-LA (PO) and (2) aged rats treated with 23.5 mg/kg of Pd-LA (PO). The research team administered the solutions once daily for 30 d. After 30 d, all animals were sacrificed. The research team evaluated serum transaminases, lactate dehydrogenase (LDH), serum urea, and creatinine. The activities of superoxide dismutase (SOD), catalase (CAT), and the levels of reduced glutathione (GSH) were determined in the blood samples. Krebs cycle dehydrogenases were evaluated in the brain mitochondria. Furthermore, the activities of the

  12. Triple-combination treatment with oral α-lipoic acid, betamethasone injection, and NB-UVB for non-segmental progressive vitiligo.

    Science.gov (United States)

    Li, Li; Li, Lu; Wu, Yan; Gao, Xing-Hua; Chen, Hong-Duo

    2016-06-01

    Vitiligo is an acquired depigmenting disease with uncertain etiopathogenesis and the treatment modalities need to be consistently updated. To evaluate a triple-combination treatment with oral α-lipoic acid (ALA), betamethasone injection, and narrowband ultraviolet B (NB-UVB) on vitiligo. Patients with non-segmental and progressive vitiligo lesions were randomly assigned to two groups. The treatment group and the control group were respectively treated with oral ALA and placebo, in combination with betamethasone injection and NB-UVB. The effectiveness and adverse events were evaluated by investigators and patients before and after treatment. Fifty non-segmental progressive vitiligo patients were enrolled in the study. The treatment period was 6 months. In treatment group, over 40% patients achieved > 50% improvement and ≥ 5 satisfaction score by 3-month therapy (M3). This percentage increased to 90% at M6. Treatment group achieved better efficacy than control group at M3, while no difference was seen at M6. The combined treatment with oral ALA, betamethasone injection, and NB-UVB was effective and safe on non-segmental progressive vitiligo. ALA could accelerate the initial response of repigmentation.

  13. Least median of squares and iteratively re-weighted least squares as robust linear regression methods for fluorimetric determination of α-lipoic acid in capsules in ideal and non-ideal cases of linearity.

    Science.gov (United States)

    Korany, Mohamed A; Gazy, Azza A; Khamis, Essam F; Ragab, Marwa A A; Kamal, Miranda F

    2018-03-26

    This study outlines two robust regression approaches, namely least median of squares (LMS) and iteratively re-weighted least squares (IRLS) to investigate their application in instrument analysis of nutraceuticals (that is, fluorescence quenching of merbromin reagent upon lipoic acid addition). These robust regression methods were used to calculate calibration data from the fluorescence quenching reaction (∆F and F-ratio) under ideal or non-ideal linearity conditions. For each condition, data were treated using three regression fittings: Ordinary Least Squares (OLS), LMS and IRLS. Assessment of linearity, limits of detection (LOD) and quantitation (LOQ), accuracy and precision were carefully studied for each condition. LMS and IRLS regression line fittings showed significant improvement in correlation coefficients and all regression parameters for both methods and both conditions. In the ideal linearity condition, the intercept and slope changed insignificantly, but a dramatic change was observed for the non-ideal condition and linearity intercept. Under both linearity conditions, LOD and LOQ values after the robust regression line fitting of data were lower than those obtained before data treatment. The results obtained after statistical treatment indicated that the linearity ranges for drug determination could be expanded to lower limits of quantitation by enhancing the regression equation parameters after data treatment. Analysis results for lipoic acid in capsules, using both fluorimetric methods, treated by parametric OLS and after treatment by robust LMS and IRLS were compared for both linearity conditions. Copyright © 2018 John Wiley & Sons, Ltd.

  14. [Antihypoxic effect of 3-hydroxypyridine and succinic acid derivatives and their nootropic action in alloxan diabetes].

    Science.gov (United States)

    Volchegorskiĭ, I A; Rassokhina, L M; Miroshnichenko, I Iu

    2011-01-01

    Relationship between the antihypoxic effect of 3-hydroxypyridine and succinic acid derivatives (emoxipine, reamberin and mexidol) and their effect on conditional learning, glycemia, and lipidemia was studied in rats with alloxan-induced diabetes. In parallel, the analogous relationship was investigated for alpha-lipoic acid that is regarded as a "gold standard" in treatment of diabetic neuropathy. It was established that single administration of emoxipine and mexidol in mice in doses equivalent to therapeutic-range doses in humans produces antihypoxic effect manifested by increased resistance to acute hypoxic hypoxia in test animals. Alpha-lipoic acid is inferior to emoxipin and mexidol in the degree of antihypoxic action. Reamberin does not exhibit this effect. The introduction of emoxipin, reamberin, mexidol, and alpha-lipoic acid in rats with alloxan diabetes during 7 or 14 days in doses equivalent to therapeutic-range doses in humans corrects conditional learning disorders in direct relationship with the antihypoxic activity of these drugs. The development of the nootropic effect of emoxipin, mexidol, and alpha-lipoic acid is related to a decrease in hyperglycemia and hyperlipidemia in rats with alloxan diabetes. The nootropic action of reamberin is accompanied by a transient hypoglycemizing effect and aggravation of dyslipidemic disorders. The antihypoxic activity of investigated drugs determines the direction and expression of their lipidemic effect, but is not correlated with the hypoglycemizing action these drugs on test animals with alloxan diabetes.

  15. A preliminary investigation of alpha-lipoic acid treatment of antipsychotic drug-induced weight gain in patients with schizophrenia.

    Science.gov (United States)

    Kim, Eosu; Park, Dong-Wha; Choi, Song-Hee; Kim, Jae-Jin; Cho, Hyun-Sang

    2008-04-01

    Weight gain and other metabolic disturbances have now become discouraging, major side effects of atypical antipsychotic drugs (AAPDs). The novel strategies required to counteract these serious consequences, however, should avoid modulating the activities of the neurotransmitter receptors involved because those receptors are the therapeutic targets of AAPDs. Adenosine monophosphate-activated protein kinase is an enzyme that plays a pivotal role in energy homeostasis. We hypothesized that alpha-lipoic acid (ALA), which is known to modulate adenosine monophosphate-activated protein kinase activity in the hypothalamus and peripheral tissues, would ameliorate AAPD-induced weight gain. We describe the case series of a 12-week ALA trial in schizophrenia patients treated with AAPDs. Two of 7 enrolled subjects were dropped from the study because of noncompliance and demand for new medication to treat depressive symptoms, respectively. The mean (SD) weight loss was 3.16 (3.20) kg (P = 0.043, last observation carried forward; median, 3.03 kg; range, 0-8.85 kg). On average, body mass index showed a significant reduction (P = 0.028) over the 12 weeks. During the same period, a statistically significant reduction was also observed in total cholesterol levels (P = 0.042), and there was a weak trend toward the reduction in insulin resistance (homeostasis model assessment of insulin resistance) (P = 0.080). Three subjects reported increased energy subjectively. The total scores on the Brief Psychiatric Rating Scale and the Montgomery-Asberg Depression Rating Scale did not vary significantly during the study. These preliminary data suggest the possibility that ALA can ameliorate the adverse metabolic effects induced by AAPDs. To confirm the benefits of ALA, more extended study is warranted.

  16. Restoration of dioxin-induced damage to fetal steroidogenesis and gonadotropin formation by maternal co-treatment with α-lipoic acid.

    Directory of Open Access Journals (Sweden)

    Takayuki Koga

    Full Text Available 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD, an endocrine disruptor, causes reproductive and developmental toxic effects in pups following maternal exposure in a number of animal models. Our previous studies have demonstrated that TCDD imprints sexual immaturity by suppressing the expression of fetal pituitary gonadotropins, the regulators of gonadal steroidogenesis. In the present study, we discovered that all TCDD-produced damage to fetal production of pituitary gonadotropins as well as testicular steroidogenesis can be repaired by co-treating pregnant rats with α-lipoic acid (LA, an obligate co-factor for intermediary metabolism including energy production. While LA also acts as an anti-oxidant, other anti-oxidants; i.e., ascorbic acid, butylated hydroxyanisole and edaravone, failed to exhibit any beneficial effects. Neither wasting syndrome nor CYP1A1 induction in the fetal brain caused through the activation of aryl hydrocarbon receptor (AhR could be attenuated by LA. These lines of evidence suggest that oxidative stress makes only a minor contribution to the TCDD-induced disorder of fetal steroidogenesis, and LA has a restorative effect by targeting on mechanism(s other than AhR activation. Following a metabolomic analysis, it was found that TCDD caused a more marked change in the hypothalamus, a pituitary regulator, than in the pituitary itself. Although the components of the tricarboxylic acid cycle and the ATP content of the fetal hypothalamus were significantly changed by TCDD, all these changes were again rectified by exogenous LA. We also provided evidence that the fetal hypothalamic content of endogenous LA is significantly reduced following maternal exposure to TCDD. Thus, the data obtained strongly suggest that TCDD reduces the expression of fetal pituitary gonadotropins to imprint sexual immaturity or disturb development by suppressing the level of LA, one of the key players serving energy production.

  17. Alpha lipoic acid attenuates high-fructose-induced pancreatic toxicity.

    Science.gov (United States)

    Topsakal, Senay; Ozmen, Ozlem; Cankara, Fatma Nihan; Yesilot, Sukriye; Bayram, Dilek; Genç Özdamar, Nilüfer; Kayan, Sümeyra

    2016-01-01

    Chronic consumption of high-fructose corn syrup (HFCS) causes several problems such as insulin resistance. The goal of the study was to investigate pancreatic damage induced by chronic HFCS consumption and the protective effects of alpha lipoic acid (ALA) on pancreatic cells. Wistar Albino, 4-month-old, female rats weighing 250-300 g were randomly distributed into three groups, each containing eight rats. The study included an HFCS group, an HFCS + ALA-administered group and a control group (CON). The prepared 30% solution of HFCS (F30) (24% fructose, 28% dextrose) was added to the drinking water for 10 weeks. ALA treatment was begun 4 weeks after the first HFCS administration (100 mg/kg/oral, last 6 weeks). Rats were anaesthetised and euthanised by cervical dislocation 24 h after the last ALA administration. Blood samples for biochemical tests (amylase, lipase, malondialdehyde (MDA) and catalase (CAT)) and tissue samples for histopathological and immunohistochemical examinations (caspase-3, insulin and glucagon) were collected. Comparing the control and HFCS groups, serum glucose (150.92 ± 39.77 and 236.50 ± 18.28, respectively, p < 0.05), amylase (2165.00 ± 150.76 and 3027.66 ± 729.19, respectively, p < 0.01), lipase (5.58 ± 2.22 and 11.51 ± 2.74, respectively, p < 0.01) and pancreatic tissue MDA (0.0167 ± 0.004 and 0.0193 ± 0.006, respectively, p < 0.05) levels were increased, whereas tissue CAT (0.0924 ± 0.029 and 0.0359 ± 0.023, respectively, p < 0.05) activity decreased in the HFCS group significantly. Histopathological examination revealed degenerative and necrotic changes in Langerhans islet cells and slight inflammatory cell infiltration in pancreatic tissue in the HFCS group. Immunohistochemically there was a significant decrease in insulin (2.85 ± 0.37 and 0.87 ± 0.64, respectively, p < 0.001) and glucagon (2.71 ± 0.48 and 1.00 ± 0.75, respectively, p < 0.001) secreting cell scores, whereas a

  18. Bio-active nanoemulsions enriched with gold nanoparticle, marigold extracts and lipoic acid: In vitro investigations.

    Science.gov (United States)

    Guler, Emine; Barlas, F Baris; Yavuz, Murat; Demir, Bilal; Gumus, Z Pinar; Baspinar, Yucel; Coskunol, Hakan; Timur, Suna

    2014-09-01

    A novel and efficient approach for the preparation of enriched herbal formulations was described and their potential applications including wound healing and antioxidant activity (cell based and cell free) were investigated via in vitro cell culture studies. Nigella sativa oil was enriched with Calendula officinalis extract and lipoic acid capped gold nanoparticles (AuNP-LA) using nanoemulsion systems. The combination of these bio-active compounds was used to design oil in water (O/W) and water in oil (W/O) emulsions. The resulted emulsions were characterized by particle size measurements. The phenolic content of each nanoemulsion was examined by using both colorimetric assay and chromatographic analyses. Two different methods containing cell free chemical assay (1-diphenyl-2-picrylhydrazyl method) and cell based antioxidant activity test were used to evaluate the antioxidant capacities. In order to investigate the bio-activities of the herbal formulations, in vitro cell culture experiments, including cytotoxicity, scratch assay, antioxidant activity and cell proliferation were carried out using Vero cell line as a model cell line. Furthermore, to monitor localization of the nanoemulsions after application of the cell culture, the cell images were monitored via fluorescence microscope after FITC labeling. All data confirmed that the enriched N. sativa formulations exhibited better antioxidant and wound healing activity than N. sativa emulsion without any enrichment. In conclusion, the incorporation of AuNP-LA and C. officinalis extract into the N. sativa emulsions significantly increased the bio-activities. The present work may support further studies about using the other bio-active agents for the enrichment of herbal preparations to strengthen their activities. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. the Early Effects of Gamma radiation on the diurnal changes of Some Biochemical Parameters and the Role of α-lipoic acid as an Antioxidant in Male Albino rats

    International Nuclear Information System (INIS)

    Abdel-Fattah, K.I.; Yacoub, S.F.; Abdel-Aziz, N.

    2013-01-01

    In mammals most of the physiological and behavioral systems such as sleep-wake cycle, cardiovascular activity, endocrine system, blood pressure, body temperature and hepatic metabolism are regulated by the circadian clock. The aim of the present work was to investigate the disturbances induced after gamma irradiation on the metabolic diurnal rhythm and the role of α-alpha lipoic acid (ALA) in preventing/or decreasing these disorders in rat. Male Swiss albino rats were divided into 4 groups, one of which served as a normal control group, the second group was exposed to a single whole body gamma radiation dose of 6Gy, the third group was treated by gavage with ALA 100 mg/kg/day for 20 days and the fourth one was orally administered with ALA 100 mg/kg/day for 20 days before whole body gamma radiation at a dose of 6Gy. Rats were irradiated at 10 am and sacrificed at 11 am, 12 pm, 1 pm and 2 pm and then the biochemical analyses were performed. The results showed a significant increase in the level of lipid peroxidation products (MDA) at all time intervals. A significant increase was recorded also in the amount of free radicals at 11 am and 2 pm, and pyruvic acid level at 12 pm and 2 pm. A significant reduction of glutathione level (GSH) was recorded at 12 pm, 1 pm and 2 pm in the liver of the irradiated rats. Furthermore, a significant increase was registered in blood glucose level and blood aminotransferase activities (AST, ALT) in irradiated rats. Administration of ALA has significantly attenuated the radiation induced oxidative damage. It could be concluded that the biochemical changes induced by whole body gamma irradiation of rats are dependent on the circadian cycle. Further investigations are necessary to understand these complicated relations.

  20. Lipoic Acid and Progesterone Alone or in Combination Ameliorate Retinal Degeneration in an Experimental Model of Hereditary Retinal Degeneration

    Directory of Open Access Journals (Sweden)

    Dolores T. Ramírez-Lamelas

    2018-05-01

    Full Text Available Retinitis pigmentosa (RP is a group of inherited retinopathies characterized by photoreceptors death. Our group has shown the positive progesterone (P4 actions on cell death progression in an experimental model of RP. In an effort to enhance the beneficial effects of P4, the aim of this study was to combine P4 treatment with an antioxidant [lipoic acid (LA] in the rd1 mice. rd1 and control mice were treated with 100 mg/kg body weight of P4, LA, or a combination of both on postnatal day 7 (PN7, 9, and 11, and were sacrificed at PN11. The administration of LA and/or P4 diminishes cell death in rd1 retinas. The effect obtained after the combined administration of LA and P4 is higher than the one obtained with LA or P4 alone. The three treatments decreased GFAP staining, however, in the far peripheral retina, and the two treatments that offered better results were LA and LA plus P4. LA or LA plus P4 increased retinal glutathione (GSH concentration in the rd1 mice. Although LA and P4 are able to protect photoreceptors from death in rd1 mice retinas, a better effectiveness is achieved when administering LA and P4 at the same time.

  1. Lipoic acid and redox status in barley plants subjected to salinity and elevated CO{sub 2}

    Energy Technology Data Exchange (ETDEWEB)

    Perez-Lopez, U.; Robredo, A.; Mena-Petite, A.; Munoz-Rueda, A. (Univ. del Pais Vasco/EHU, Dept. de Biologia Vegetal y Ecologia, Bilbao (Spain)); Lacuesta, M. (Univ. del Pais Vasco/EHU, Dept. de Biologia Vegetal y Ecologia, Vitoria-Gasteiz (Spain)); Sgherri, C.; Navari-Izzo, F. (Univ. di Pisa, Dipartimento di Chimica e Biotecnologie Agrarie, Pisa (Italy))

    2010-02-15

    Future environmental conditions will include elevated concentrations of salt in the soil and an elevated concentration of CO{sub 2}in the atmosphere. Because these environmental changes will likely affect reactive oxygen species (ROS) formation and cellular antioxidant metabolism in opposite ways, we analyzed changes in cellular H{sub 2}O{sub 2} and non-enzymatic antioxidant metabolite [lipoic acid (LA), ascorbate (ASA), glutathione (GSH)] content induced by salt stress (0, 80, 160 or 240 mM NaCl) under ambient (350 mumol mol-1) or elevated (700 mumol mol-1) CO{sub 2}concentrations in two barley cultivars (Hordeum vulgare L.) that differ in sensitivity to salinity (cv. Alpha is more sensitive than cv. Iranis). Under non-salinized conditions, elevated CO{sub 2}increased LA content, while ASA and GSH content decreased. Under salinized conditions and ambient CO{sub 2}, ASA increased, while GSH and LA decreased. At 240 mM NaCl, H{sub 2}O{sub 2} increased in Alpha and decreased in Iranis. When salt stress was imposed at elevated CO{sub 2}, less oxidative stress and lower increases in ASA were detected, while LA was constitutively higher. The decrease in oxidative stress could have been because of less ROS formation or to a higher constitutive LA level, which might have improved regulation of ASA and GSH reductions. Iranis had a greater capacity to synthesize ASA de novo and had higher constitutive LA content than did Alpha. Therefore, we conclude that elevated CO{sub 2}protects barley cultivars against oxidative damage. However, the magnitude of the positive effect is cultivar specific. (author)

  2. Protective Efficacy of Alpha-lipoic Acid against AflatoxinB1-induced Oxidative Damage in the Liver

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    Y. Li

    2014-06-01

    Full Text Available Alpha-lipoic acid (α-LA is not only involved in energy metabolism, but is also a powerful antioxidant that can protect against hepatic oxidative stress induced by some drugs, toxins, or under various physiological and pathophysiological conditions. Here, we investigated the effect of α-LA against liver oxidative damage in broilers exposed to aflatoxin B1 (AFB1. Birds were randomly divided into four groups and assigned different diets: basal diet, 300 mg/kg α-LA supplementation in basal diet, diet containing 74 μg/kg AFB1, and 300 mg/kg α-LA supplementation in diet containing 74 μg/kg AFB1, for 3 weeks. The results revealed that the addition of 300 mg/kg α-LA protected against the liver function damage of broilers induced by chronic low dose of AFB1 as estimated by a significant (p<0.05 change in levels of plasma total protein, albumin, alkaline phosphatase and the activities of liver glutamic-oxalacetic transaminase and glutamic-pyruvic transaminase. The histopathological analysis also showed that liver tissues were injured in the AFB1 diet, but this effect was alleviated by the addition of 300 mg/kg α-LA. Additionally, AFB1 induced a profound elevation of oxidative stress in birds, as indicated by an increase in malondialdehyde level, a decrease in glutathione peroxidase activity and a depletion of the glutathione content in the liver. All of these negative effects were inhibited by treatment with α-LA. Our results suggest that the inhibition of AFB1-induced excess production of lipid peroxides and the maintenance of intracellular antioxidant status may play important roles in the protective effects of α-LA against AFB1-induced oxidative damage in the liver.

  3. Colonic and Hepatic Modulation by Lipoic Acid and/or N-Acetylcysteine Supplementation in Mild Ulcerative Colitis Induced by Dextran Sodium Sulfate in Rats

    Science.gov (United States)

    Moura, Fabiana Andréa; de Andrade, Kívia Queiroz; de Araújo, Orlando Roberto Pimentel; Santos, Juliana Célia de Farias

    2016-01-01

    Lipoic acid (LA) and N-acetylcysteine (NAC) are antioxidant and anti-inflammatory agents that have not yet been tested on mild ulcerative colitis (UC). This study aims to evaluate the action of LA and/or NAC, on oxidative stress and inflammation markers in colonic and hepatic rat tissues with mild UC, induced by dextran sodium sulfate (DSS) (2% w/v). LA and/or NAC (100 mg·kg·day−1, each) were given, once a day, in the diet, in a pretreatment phase (7 days) and during UC induction (5 days). Colitis induction was confirmed by histological and biochemical analyses (high performance liquid chromatography, spectrophotometry, and Multiplex®). A redox imbalance occurred before an immunological disruption in the colon. NAC led to a decrease in hydrogen peroxide (H2O2), malondialdehyde (MDA) levels, and myeloperoxidase activity. In the liver, DSS did not cause damage but treatments with both antioxidants were potentially harmful, with LA increasing MDA and LA + NAC increasing H2O2, tumor necrosis factor alpha, interferon gamma, and transaminases. In summary, NAC exhibited the highest colonic antioxidant and anti-inflammatory activity, while LA + NAC caused hepatic damage. PMID:27957238

  4. Biophysical Properties of Irradiated Erythrocytes and Role of Antioxidants

    International Nuclear Information System (INIS)

    Eman Mohammed Elbakrawy, E.M.

    2010-01-01

    Irradiation of blood and blood components with gamma-irradiation is recommended for the inactivation of T-lymphocytes and prevention of transfusion-associated graft versus host diseases. The aim of the present work is to ensure that the currently applied irradiation dose 25 Gy is a safe dose based on the study of the electrical behavior, rheological properties, membrane solubilization, membrane hemolysis and scanning electron microscope of stored erythrocytes. In addition it aims to study the possibility of increasing the irradiation doses to 50 and 100 Gy. Moreover Alpha lipoic acid (a potent natural antioxidant) was added to the stored erythrocytes before irradiation for radioprotection. Irradiation of erythrocytes with 25 Gy did not show significant changes for the calculated dielectric parameters. However, increasing the irradiation doses resulted in significant decrease in the calculated dielectric parameters reflecting the damaging effects of radiation on the membrane structure. The obtained results showed that α lipoic acid can play an important role in minimizing the radiation-induced damage to the erythrocytes and conserve their electrical properties. There were non-significant changes in viscosity after exposure to 25 Gy, while a significant increase at 50 Gy and a significant decrease at 100 Gy were observed. The study found that α lipoic acid (ALA) resulted in non-significant change in viscosity after exposure to 50 Gy and 100 Gy. A significant increase in the yield stress was observed after exposure to 25 and 50 Gy while at 100 Gy, the yield stress showed a remarkable decrease. Addition of .-lipoic acid before irradiation resulted in non-significant changes in the yield stress at doses 25, 50, 100 Gy.The obtained results of the average membrane solubilization (D 50 ) and the average membrane hemolysis (H 50 ) showed non-significant change at 25 Gy; while an observable decrease was observed at 50 Gy and 100 Gy. The addition of lipoic acid did not

  5. Myoinositol combined with alpha-lipoic acid may improve the clinical and endocrine features of polycystic ovary syndrome through an insulin-independent action.

    Science.gov (United States)

    De Cicco, Simona; Immediata, Valentina; Romualdi, Daniela; Policola, Caterina; Tropea, Anna; Di Florio, Christian; Tagliaferri, Valeria; Scarinci, Elisa; Della Casa, Silvia; Lanzone, Antonio; Apa, Rosanna

    2017-09-01

    The aim of our study was to investigate the effects of a combined treatment with alpha-lipoic acid (ALA) and myoinositol (MYO) on clinical, endocrine and metabolic features of women affected by polycystic ovary syndrome (PCOS). In this pilot cohort study, forty women with PCOS were enrolled and clinical, hormonal and metabolic parameters were evaluated before and after a six-months combined treatment with ALA and MYO daily. Studied patients experienced a significant increase in the number of cycles in six months (p < 0.01). The free androgen index (FAI), the mean androstenedione and DHEAS levels significantly decreased after treatment (p < 0.05). Mean SHBG levels significantly raised (p < 0.01). A significant improvement in mean Ferriman-Gallwey (F-G) score (p < 0.01) and a significant reduction of BMI (p < 0.01) were also observed. A significant reduction of AMH levels, ovarian volume and total antral follicular count were observed in our studied women (p< 0.05). No significant changes occurred in gluco-insulinaemic and lipid parameters after treatment. The combined treatment of ALA and MYO is able to restore the menstrual pattern and to improve the hormonal milieu of PCOS women, even in the absence of apparent changes in insulin metabolism.

  6. Behavioral and neurochemical effects of alpha lipoic acid associated with omega-3 in tardive dyskinesia induced by chronic haloperidol in rats.

    Science.gov (United States)

    de Araújo, Dayane Pessoa; Camboim, Thaisa Gracielle Martins; Silva, Ana Patrícia Magalhães; Silva, Caio da Fonseca; de Sousa, Rebeca Canuto; Barbosa, Mabson Delâno Alves; Oliveira, Lucidio Clebeson; Cavalcanti, José Rodolfo Lopes de Paiva; Lucena, Eudes Euler de Souza; Guzen, Fausto Pierdoná

    2017-07-01

    Tardive dyskinesia (TD) is characterized by involuntary movements of the lower portion of the face being related to typical antipsychotic therapy. TD is associated with the oxidative imbalance in the basal ganglia. Lipoic acid (LA) and omega-3 (ω-3) are antioxidants acting as enzyme cofactors, regenerating antioxidant enzymes. This study aimed to investigate behavioral and neurochemical effects of supplementation with LA (100 mg/kg) and ω-3 (1 g/kg) in the treatment of TD induced by chronic use of haloperidol (HAL) (1 mg/kg) in rats. Wistar male rats were used, weighing between 180-200 g. The animals were treated chronically (31 days) with LA alone or associated with HAL or ω-3. Motor behavior was assessed by open-field test, the catalepsy test, and evaluation of orofacial dyskinesia. Oxidative stress was accessed by determination of lipid peroxidation and concentration of nitrite. LA and ω-3 alone or associated caused an improvement in motor performance by increasing locomotor activity in the open-field test and decreased the permanence time on the bar in the catalepsy test and decreased the orofacial dyskinesia. LA and ω-3 showed antioxidant effects, decreasing lipid peroxidation and nitrite levels. Thus, the use of LA associated with ω-3 reduced the extrapyramidal effects produced by chronic use of HAL.

  7. Cardiac fibrosis and dysfunction in experimental diabetic cardiomyopathy are ameliorated by alpha-lipoic acid

    Directory of Open Access Journals (Sweden)

    Li Chun-jun

    2012-06-01

    Full Text Available Abstract Background Alpha-lipoic acid (ALA, a naturally occurring compound, exerts powerful protective effects in various cardiovascular disease models. However, its role in protecting against diabetic cardiomyopathy (DCM has not been elucidated. In this study, we have investigated the effects of ALA on cardiac dysfunction, mitochondrial oxidative stress (MOS, extracellular matrix (ECM remodeling and interrelated signaling pathways in a diabetic rat model. Methods Diabetes was induced in rats by I.V. injection of streptozotocin (STZ at 45 mg/kg. The animals were randomly divided into 4 groups: normal groups with or without ALA treatment, and diabetes groups with or without ALA treatment. All studies were carried out 11 weeks after induction of diabetes. Cardiac catheterization was performed to evaluate cardiac function. Mitochondrial oxidative biochemical parameters were measured by spectophotometeric assays. Extracellular matrix content (total collagen, type I and III collagen was assessed by staining with Sirius Red. Gelatinolytic activity of Pro- and active matrix metalloproteinase-2 (MMP-2 levels were analyzed by a zymogram. Cardiac fibroblasts differentiation to myofibroblasts was evaluated by Western blot measuring smooth muscle actin (α-SMA and transforming growth factor–β (TGF-β. Key components of underlying signaling pathways including the phosphorylation of c-Jun N-terminal kinase (JNK, p38 MAPK and ERK were also assayed by Western blot. Results DCM was successfully induced by the injection of STZ as evidenced by abnormal heart mass and cardiac function, as well as the imbalance of ECM homeostasis. After administration of ALA, left ventricular dysfunction greatly improved; interstitial fibrosis also notably ameliorated indicated by decreased collagen deposition, ECM synthesis as well as enhanced ECM degradation. To further assess the underlying mechanism of improved DCM by ALA, redox status and cardiac remodeling associated

  8. Various levels and forms of dietary α-lipoic acid in broiler chickens: Impact on blood biochemistry, stress response, liver enzymes, and antibody titers.

    Science.gov (United States)

    Kim, D W; Mushtaq, M M H; Parvin, R; Kang, H K; Kim, J H; Na, J C; Hwangbo, J; Kim, J D; Yang, C B; Park, B J; Choi, H C

    2015-02-01

    The present experiment was conducted to evaluate the impact of various levels and forms of α-lipoic acid (ALA) on blood biochemistry, immune and stress response, and antibody titers in broiler chickens. The four levels (7.5, 15, 75, and 150 ppm) and 2 sources (powder, P-ALA and encapsulated, E-ALA) of ALA along with negative (C-) and positive control (C+; contains antibiotics) diets consisted of 10 dietary treatments, and these treatments were allocated to 1,200 1-d-old chicks and were replicated 12 times with 10 birds per replicate. Among the blood biochemistry parameters, creatinine levels were almost 3 times lower in E-ALA-supplemented diets compared to the C- diet (0.09 vs. 0.25 mg/dL; PBirds did not respond to infectious bronchitis virus (IBV) vaccination at any observed stage (P>0.05). The concentration of cortisol was reduced in chickens fed ALA-supplemented diets as compared to the C- diet (Pbiochemistry profiles and immune responses and reduced stress in broiler chickens. The encapsulated form of ALA was more effective than the powder form. © 2015 Poultry Science Association Inc.

  9. Alpha lipoic acid (ALA) modulates expression of apoptosis associated proteins in hippocampus of rats exposed during postnatal period to sodium arsenite (NaAsO2).

    Science.gov (United States)

    Dixit, Shilpi; Dhar, Pushpa; Mehra, Raj D

    2015-01-01

    The present study focused on the role of exogenous alpha lipoic acid (ALA) in amelioration of inorganic arsenic ( iAs ) induced effects on apoptosis and apoptosis associated proteins in developing rat hippocampus. NaAsO 2 (1.5/2.0 mg/kg bw) alone or along with ALA (70 mg/kg bw) was administered to rat pups (experimental groups) by intraperitoneal (i.p.) route from postnatal day (PND) 4-15. Controls received no treatment/distilled water/ALA. On PND 16, the animals were perfusion fixed and the brains were processed for paraffin embedding (CV and TUNEL staining) and cryopreservation (immunohistochemistry). The fresh brain tissue was used for Western blotting. Significant increase was observed in TUNEL positive cells and Bax (pro-apoptotic protein) expression in hippocampal sub-regions of iAs alone treated groups, whereas Bcl-2 expression was intensified in animals receiving ALA with iAs . Densitometric analysis (Western blots) revealed optimal restoration of Bax and Bcl-2 ratio in animals receiving ALA with iAs , thereby suggesting the protective role of ALA in iAs induced developmental neurotoxicity.

  10. Possibilities of pharmacologic correction of cognitive disorders in conditions of experimental equivalent of multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Nefyodov A.A.

    2015-06-01

    Full Text Available A comparative analysis of the impact of citicoline, ±-lipoic acid, nicergoline, donepezil and colloidal solution of nano-silver (CSNS on the processes of learning and consolidation of memorable track in the test of the conditional reaction of passive avoidance (CRPA in conditions of experimental allergic encephalomyelitis (EAE was conducted. Testing of passive defensive skill was performed on days 12 and 20 after the induction of EAE. To assess the impact of drugs on the inputted information processes the investigated substances were administered intragastrically (CSNS - intraperitoneally once daily in the definite dose from the second to the day 10 after the induction of EAE (latent phase of the disease, and assessing processes of conditional skill preserving, further administration of drugs by the day 20 of the experiment (average duration of EAE was used. A positive effect of citicoline, ±-lipoic acid, nicergoline and donepezil on the input information processes and the ability to prevent accelerated extinction of acquired contingent skill in the conditions of experimental pathology was established. Drugs statistically significantly increased duration of the latent period of CRPA in comparison with a group of active control by 49%, 43%, 39% and 34%, respectively. Here with preparations were characterized by a high coefficient of antiamnesic activity, by the end of the experiment it was recorded at the level of 95% (citicoline, 81% (±-lipoic acid, 76% (nicergoline and 53% (donepezil. It is shown that the ability to prevent development of cognitive impairment in conditions of experimental equivalent of multiple sclerosis decreases in the number of citicoline (500 mg/kg > ±-lipoic acid (50 mg/kg H nicergoline (10 mg/kg > donepezil (10 mg/kg.

  11. Supplementation with α-lipoic acid, CoQ10, and vitamin E augments running performance and mitochondrial function in female mice.

    Directory of Open Access Journals (Sweden)

    Arkan Abadi

    Full Text Available Antioxidant supplements are widely consumed by the general public; however, their effects of on exercise performance are controversial. The aim of this study was to examine the effects of an antioxidant cocktail (α-lipoic acid, vitamin E and coenzyme Q10 on exercise performance, muscle function and training adaptations in mice. C57Bl/J6 mice were placed on antioxidant supplement or placebo-control diets (n = 36/group and divided into trained (8 wks treadmill running (n = 12/group and untrained groups (n = 24/group. Antioxidant supplementation had no effect on the running performance of trained mice nor did it affect training adaptations; however, untrained female mice that received antioxidants performed significantly better than placebo-control mice (p ≤ 0.05. Furthermore, antioxidant-supplemented females (untrained showed elevated respiratory capacity in freshly excised muscle fibers (quadriceps femoris (p ≤ 0.05, reduced oxidative damage to muscle proteins (p ≤ 0.05, and increased expression of mitochondrial proteins (p ≤ 0.05 compared to placebo-controls. These changes were attributed to increased expression of proliferator-activated receptor gamma coactivator 1α (PGC-1α (p ≤ 0.05 via activation of AMP-activated protein kinase (AMPK (p ≤ 0.05 by antioxidant supplementation. Overall, these results indicate that this antioxidant supplement exerts gender specific effects; augmenting performance and mitochondrial function in untrained females, but does not attenuate training adaptations.

  12. Adjunctive α-lipoic acid reduces weight gain compared with placebo at 12 weeks in schizophrenic patients treated with atypical antipsychotics: a double-blind randomized placebo-controlled study.

    Science.gov (United States)

    Kim, Nam Wook; Song, Yul-Mai; Kim, Eosu; Cho, Hyun-Sang; Cheon, Keun-Ah; Kim, Su Jin; Park, Jin Young

    2016-09-01

    α-Lipoic acid (ALA) has been reported to be effective in reducing body weight in rodents and obese patients. Our previous open trial showed that ALA may play a role in reducing weight gain in patients with schizophrenia on atypical antipsychotics. The present study evaluated the efficacy of ALA in reducing weight and BMI in patients with schizophrenia who had experienced significant weight gain since taking atypical antipsychotics. In a 12-week, double-blind randomized placebo-controlled study, 22 overweight and clinically stable patients with schizophrenia were randomly assigned to receive ALA or placebo. ALA was administered at 600-1800 mg, as tolerated. Weight, BMI, abdomen fat area measured by computed tomography, and metabolic values were determined. Adverse effects were also assessed to examine safety. Overall, 15 patients completed 12 weeks of treatment. There was significant weight loss and decreased visceral fat levels in the ALA group compared with the placebo group. There were no instances of psychopathologic aggravation or severe ALA-associated adverse effects. ALA was effective in reducing weight and abdominal obesity in patients with schizophrenia who had experienced significant weight gain since beginning an atypical antipsychotic regimen. Moreover, ALA was well tolerated throughout this study. ALA might play an important role as an adjunctive treatment in decreasing obesity in patients who take atypical antipsychotics.

  13. Sulforaphane and alpha-lipoic acid upregulate the expression of the pi class of glutathione S-transferase through c-jun and Nrf2 activation.

    Science.gov (United States)

    Lii, Chong-Kuei; Liu, Kai-Li; Cheng, Yi-Ping; Lin, Ai-Hsuan; Chen, Haw-Wen; Tsai, Chia-Wen

    2010-05-01

    The anticarcinogenic effect of dietary organosulfur compounds has been partly attributed to their modulation of the activity and expression of phase II detoxification enzymes. Our previous studies indicated that garlic allyl sulfides upregulate the expression of the pi class of glutathione S-transferase (GSTP) through the activator protein-1 pathway. Here, we examined the modulatory effect of sulforaphane (SFN) and alpha-lipoic acid (LA) or dihydrolipoic acid (DHLA) on GSTP expression in rat Clone 9 liver cells. Cells were treated with LA or DHLA (50-600 micromol/L) or SFN (0.2-5 micromol/L) for 24 h. Immunoblots and real-time PCR showed that SFN, LA, and DHLA dose dependently induced GSTP protein and mRNA expression. Compared with the induction by the garlic organosulfur compound diallyl trisulfide (DATS), the effectiveness was in the order of SFN > DATS > LA = DHLA. The increase in GSTP enzyme activity in cells treated with 5 micromol/L SFN, 50 micromol/L DATS, and 600 micromol/L LA and DHLA was 172, 75, 122, and 117%, respectively (P GPEI) was required for GSTP induction by the organosulfur compounds. Electromobility gel shift assays showed that the DNA binding of GPEI to nuclear proteins reached a maximum at 0.5-1 h after SFN, LA, and DHLA treatment. Super-shift assay revealed that the transcription factors c-jun and nuclear factor erythroid-2 related factor 2 (Nrf2) were bound to GPEI. These results suggest that SFN and LA in either its oxidized or reduced form upregulate the transcription of the GSTP gene by activating c-jun and Nrf2 binding to the enhancer element GPEI.

  14. Alpha lipoic acid (ALA modulates expression of apoptosis associated proteins in hippocampus of rats exposed during postnatal period to sodium arsenite (NaAsO2

    Directory of Open Access Journals (Sweden)

    Shilpi Dixit

    2015-01-01

    Full Text Available The present study focused on the role of exogenous alpha lipoic acid (ALA in amelioration of inorganic arsenic (iAs induced effects on apoptosis and apoptosis associated proteins in developing rat hippocampus. NaAsO2 (1.5/2.0 mg/kg bw alone or along with ALA (70 mg/kg bw was administered to rat pups (experimental groups by intraperitoneal (i.p. route from postnatal day (PND 4–15. Controls received no treatment/distilled water/ALA. On PND 16, the animals were perfusion fixed and the brains were processed for paraffin embedding (CV and TUNEL staining and cryopreservation (immunohistochemistry. The fresh brain tissue was used for Western blotting. Significant increase was observed in TUNEL positive cells and Bax (pro-apoptotic protein expression in hippocampal sub-regions of iAs alone treated groups, whereas Bcl-2 expression was intensified in animals receiving ALA with iAs. Densitometric analysis (Western blots revealed optimal restoration of Bax and Bcl-2 ratio in animals receiving ALA with iAs, thereby suggesting the protective role of ALA in iAs induced developmental neurotoxicity.

  15. Effects of alpha-lipoic acid supplementation in different stages on growth performance, antioxidant capacity and meat quality in broiler chickens.

    Science.gov (United States)

    Guo, Z Y; Li, J L; Zhang, L; Jiang, Y; Gao, F; Zhou, G H

    2014-01-01

    This experiment was conducted to investigate the effect of basal dietary supplementation with 500 mg/kg alpha-lipoic acid (LA) on growth performance, antioxidant capacity and meat quality in different stages in broiler chickens. A total of 240 Arbor Acre chickens were randomly assigned into 4 treatment groups, each treatment containing 6 replicates of 10 chickens each. Group 1 was the control group without LA supplementation; Group 2 was supplied with LA in the starter period; Group 3 was supplied with LA in the grower period; and Group 4 was supplied with LA in the whole period. The results showed that LA supplementation improved average feed intake and body weight gain in all three experimental groups, especially in Group 2. LA supplementation significantly decreased abdominal fat yield in Groups 3 and 4. LA supplementation all improved hepatic total antioxidant capacity, the level of glutathione, the activities of total superoxide dismutase, catalase (CAT) and glutathione peroxidase, in particular in Group 4. LA supplementation decreased the activity of liver xanthine oxidase (XO) in all experimental groups, and that of liver monoamine oxidase in Group 3. The activities of liver CAT and XO in Group 2 were higher than that in Group 3. LA supplementation elevated the pH24 h and decreased drip loss in breast meat in Groups 3 and 4. In conclusion, LA supplementation can improve growth performance, antioxidant properties and meat quality in broiler chicken. LA supplementation in the starter period can improve growth performance and supplementation in the grower - and in the whole period can improve carcass characteristics. There was no significant difference in meat quality of broiler chickens fed on LA-supplemented diet in different stages.

  16. Brain antioxidant effect of mirtazapine and reversal of sedation by its combination with alpha-lipoic acid in a model of depression induced by corticosterone.

    Science.gov (United States)

    Oliveira, Tatiana de Queiroz; de Sousa, Caren Nádia Soares; Vasconcelos, Germana Silva; de Sousa, Luciene Costa; de Oliveira, Anneheydi Araújo; Patrocínio, Cláudio Felipe Vasconcelos; Medeiros, Ingridy da Silva; Honório Júnior, José Eduardo Ribeiro; Maes, Michael; Macedo, Danielle; Vasconcelos, Silvânia Maria Mendes

    2017-09-01

    Depression is accompanied by activated neuro-oxidative and neuro-nitrosative pathways, while targeting these pathways has clinical efficacy in depression. This study aimed to investigate the effects of mirtazapine (MIRT) alone and combined with alpha-lipoic acid (ALA) against corticosterone (CORT) induced behavioral and oxidative alterations. Male mice received vehicle or CORT 20mg/kg during 14 days. From the 15th to 21st days they were divided in groups administered: vehicle, MIRT 3mg/kg or the combinations MIRT+ALA100 or MIRT+ALA200. On the 21st day of treatment, the animals were subjected to behavioral tests. Twenty-four hours after the last drug administration hippocampus (HC) and striatum (ST) were dissected for the determination reduced glutathione (GSH), lipid peroxidation (LP) and nitrite levels. CORT induced anxiety- and depressive-like behaviors as observed by increased immobility time in the tail suspension test and decreased sucrose consumption. MIRT or MIRT+ALA are effective in reversing anxiety- and depressive-like behaviors induced by CORT. CORT and MIRT alone prolonged sleeping time and this effect was reversed by MIRT+ALA. CORT significantly increased LP, which was reversed by MIRT or MIRT+ALA. Nitrite levels were increased in CORT-treated animals and reversed by MIRT+ALA200 (HC), MIRT or MIRT+ALA (ST). A relative small sample size and lack of a washout period between drug administration and behavioral testing. MIRT or MIRT+ALA reverse CORT-induced anxiety- and depressive-like behaviors probably via their central antioxidant effects. Augmentation of MIRT with ALA may reverse sedation, an important side effect of MIRT. Randomized controlled studies are needed to examine the clinical efficacy of this combination in human depression. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Treatment with α-Lipoic Acid over 16 Weeks in Type 2 Diabetic Patients with Symptomatic Polyneuropathy Who Responded to Initial 4-Week High-Dose Loading

    Directory of Open Access Journals (Sweden)

    Hector Garcia-Alcala

    2015-01-01

    Full Text Available Effective treatment of diabetic sensorimotor polyneuropathy remains a challenge. To assess the efficacy and safety of α-lipoic acid (ALA over 20 weeks, we conducted a multicenter randomized withdrawal open-label study, in which 45 patients with type 2 diabetes and symptomatic polyneuropathy were initially treated with ALA (600 mg tid for 4 weeks (phase 1. Subsequently, responders were randomized to receive ALA (600 mg qd; n=16 or to ALA withdrawal (n=17 for 16 weeks (phase 2. During phase 1, the Total Symptom Score (TSS decreased from 8.9 ± 1.8 points to 3.46 ± 2.0 points. During phase 2, TSS improved from 3.7 ± 1.9 points to 2.5 ± 2.5 points in the ALA treated group (p<0.05 and remained unchanged in the ALA withdrawal group. The use of analgesic rescue medication was higher in the ALA withdrawal group than ALA treated group (p<0.05. In conclusion, in type 2 diabetic patients with symptomatic polyneuropathy who responded to initial 4-week high-dose (600 mg tid administration of ALA, subsequent treatment with ALA (600 mg qd over 16 weeks improved neuropathic symptoms, whereas ALA withdrawal was associated with a higher use of rescue analgesic drugs. This trial is registered with ClinicalTrials.gov Identifier: NCT02439879.

  18. Chronic treatment of (R)-α-lipoic acid reduces blood glucose and lipid levels in high-fat diet and low-dose streptozotocin-induced metabolic syndrome and type 2 diabetes in Sprague-Dawley rats.

    Science.gov (United States)

    Ghelani, Hardik; Razmovski-Naumovski, Valentina; Nammi, Srinivas

    2017-06-01

    (R)- α -lipoic acid ( ALA ), an essential cofactor in mitochondrial respiration and a potential antioxidant, possesses a wide array of metabolic benefits including anti-obesity, glucose lowering, insulin-sensitizing, and lipid-lowering effects. In this study, the curative effects of ALA (100 mg/kg) on a spectrum of conditions related to metabolic syndrome and type 2 diabetes ( T2D ) were investigated in a high-fat diet (HFD)-fed and low-dose streptozotocin (STZ)-induced rat model of metabolic syndrome and T2D . The marked rise in the levels of glucose, triglycerides, total-cholesterol, LDL-cholesterol, and VLDL-cholesterol in the blood of HFD-fed and low-dose STZ-injected rats were significantly reduced by ALA treatment. Furthermore, ALA treatment significantly increased the serum HDL-cholesterol levels and tended to inhibit diabetes-induced weight reduction. Mathematical computational analysis revealed that ALA also significantly improved insulin sensitivity and reduced the risk of atherosclerotic lesions and coronary atherogenesis. This study provides scientific evidence to substantiate the use of ALA to mitigate the glucose and lipid abnormality in metabolic syndrome and T2D .

  19. The effects of lipoic acid and α-tocopherol supplementation on the lipid profile and insulin sensitivity of patients with type 2 diabetes mellitus: a randomized, double-blind, placebo-controlled trial.

    Science.gov (United States)

    de Oliveira, Andreia Madruga; Rondó, Patrícia Helen Carvalho; Luzia, Liania Alves; D'Abronzo, Francisco Homero; Illison, Vanessa Kristine

    2011-05-01

    Antioxidants probably play an important role in the etiology of type 2 diabetes (DM2). This study evaluated the effects of supplementation with lipoic acid (LA) and α-tocopherol on the lipid profile and insulin sensitivity of DM2 patients. A randomized, double-blind, placebo-controlled trial involving 102 DM2 patients divided into four groups to receive daily supplementation for 4 months with: 600 mg LA (n = 26); 800 mg α-tocopherol (n = 25); 800 mg α-tocopherol + 600 mg LA (n = 25); placebo (n = 26). Plasma α-tocopherol, lipid profile, glucose, insulin, and the HOMA index were determined before and after supplementation. Differences within and between groups were compared by ANOVA using Bonferroni correction. Student's t-test was used to compare means of two independent variables. The vitamin E/total cholesterol ratio improved significantly in patients supplemented with vitamin E+LA and vitamin E alone (p ≤ 0.001). There were improvements of the lipid fractions in the groups receiving LA and vitamin E alone or in combination, and on the HOMA index in the LA group, but not significant. The results suggest that LA and vitamin E supplementation alone or in combination did not affect the lipid profile or insulin sensitivity of DM2 patients. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  20. Amelioration of Behavioural, Biochemical, and Neurophysiological Deficits by Combination of Monosodium Glutamate with Resveratrol/Alpha-Lipoic Acid/Coenzyme Q10 in Rat Model of Cisplatin-Induced Peripheral Neuropathy

    Directory of Open Access Journals (Sweden)

    Naini Bhadri

    2013-01-01

    Full Text Available Cisplatin or cis-diamminedichloroplatinum (II (CDDP is a cytotoxic chemotherapeutic agent with dose-dependent peripheral neuropathy as a foremost side effect characterised by ataxia, pain, and sensory impairment. Cumulative drug therapy of CDDP is known to produce severe oxidative damage. It mainly targets and accumulates in dorsal root ganglia that in turn cause damage resulting in secondary nerve fibre axonopathy. In the present study, we investigated the neuroprotective effect of the combination of monosodium glutamate (MSG with three individual antioxidants, that is, resveratrol, alpha-lipoic acid (ALA, and coenzyme Q10 (CoQ10, in cisplatin (2 mg/kg i.p. twice weekly induced peripheral neuropathy in rats. After 8 weeks of treatment the degree of neuroprotection was determined by measuring behavioral and electrophysiological properties and sciatic nerve lipid peroxidation, as well as glutathione and catalase levels. The results suggested that pretreatment with the combination of MSG (500 mg/kg/day po with resveratrol (10 mg/kg/day i.p. or ALA (20 mg/kg/day i.p. or CoQ10 (10 mg/kg weekly thrice i.p. exhibited neuroprotective effect. The maximum neuroprotection of MSG was observed in the combination with resveratrol.

  1. Omega-3 fatty acids for breast cancer prevention and survivorship.

    Science.gov (United States)

    Fabian, Carol J; Kimler, Bruce F; Hursting, Stephen D

    2015-05-04

    Women with evidence of high intake ratios of the marine omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) relative to the omega-6 arachidonic acid have been found to have a reduced risk of breast cancer compared with those with low ratios in some but not all case-control and cohort studies. If increasing EPA and DHA relative to arachidonic acid is effective in reducing breast cancer risk, likely mechanisms include reduction in proinflammatory lipid derivatives, inhibition of nuclear factor-κB-induced cytokine production, and decreased growth factor receptor signaling as a result of alteration in membrane lipid rafts. Primary prevention trials with either risk biomarkers or cancer incidence as endpoints are underway but final results of these trials are currently unavailable. EPA and DHA supplementation is also being explored in an effort to help prevent or alleviate common problems after a breast cancer diagnosis, including cardiac and cognitive dysfunction and chemotherapy-induced peripheral neuropathy. The insulin-sensitizing and anabolic properties of EPA and DHA also suggest supplementation studies to determine whether these omega-3 fatty acids might reduce chemotherapy-associated loss of muscle mass and weight gain. We will briefly review relevant omega-3 fatty acid metabolism, and early investigations in breast cancer prevention and survivorship.

  2. Evaluation of the natural product antifoulant, zosteric acid, for preventing the attachment of quagga mussels--a preliminary study.

    Science.gov (United States)

    Ram, Jeffrey L; Purohit, Sonal; Newby, Bi-Min Zhang; Cutright, Teresa J

    2012-01-01

    The effectiveness of zosteric acid, a natural antifoulant from the marine seagrass Zostera marina, in preventing the attachment of quagga mussels, a biofouling bivalve, was investigated. Animals were exposed to water containing zosteric acid ranging from 0 to 1000 ppm, and their attachment to the container glass walls was tracked with time. 500 ppm zosteric acid was not effective at detaching animals that had already attached, but was able to prevent the attachment of most unattached animals for two days. The anti-fouling effect increased with higher concentration. Low concentrations (250 ppm and below) were not effective at preventing attachment; however, 1000 ppm zosteric acid prevented attachment of mussels for the first three days of zosteric acid exposure, and only 20% of the mussels were attached by day 4. In contrast, animals in control (no zosteric acid) solutions began to attach within one day. In conclusion, zosteric acid is an effective natural product deterrent of attachment of a biofouling bivalve.

  3. Peroxide-mediated desulfurization of phosphorothioate oligonucleotides and its prevention.

    Science.gov (United States)

    Krotz, Achim H; Mehta, Rahul C; Hardee, Gregory E

    2005-02-01

    Desulfurization at the internucleotide phosphorothioate linkage of antisense oligonucleotides (ASOs) in dermatological formulations has been investigated using strong ion exchange chromatography and mass spectroscopy. The formation of phosphate diester linkages appeared to arise from a reaction between the phosphorothioate oligonucleotide and a potent oxidizing agent. Screening of excipients used in the formulation indicated that the cause of desulfurization was related to the presence of polyethylene glycol-derived nonionic surfactants MYRJ 52 or BRIJ 58. Autoxidation of the polyethylene glycol chain is suggested as the probable origin for the observed incompatibility. The ability of various antioxidants to prevent oxidative degradation of ASO-1 in simple test systems and in oil-in-water emulsions is described. It is found that in test systems both lipophilic and hydrophilic antioxidants are effective. However, in cream formulation (oil-in-water emulsions) of ASO-1 the addition of hydrophilic antioxidants L-cysteine or DL-alpha-lipoic acid has been shown to be superior in protecting the oligonucleotide from desulfurization upon storage. Copyright 2004 Wiley-Liss, Inc.

  4. l-2-Oxothiazolidine-4-Carboxylic Acid or α-Lipoic Acid Attenuates Airway Remodeling: Involvement of Nuclear Factor-κB (NF-κB, Nuclear Factor Erythroid 2p45-Related Factor-2 (Nrf2, and Hypoxia-Inducible Factor (HIF

    Directory of Open Access Journals (Sweden)

    Heung Bum Lee

    2012-06-01

    Full Text Available Reactive oxygen species (ROS play a crucial role in the pathogenesis of acute and chronic respiratory diseases. Antioxidants have been found to ameliorate airway inflammation and hyperresponsiveness in animal models employing short-term exposure to allergen. However, little data are available on the effect of antioxidants on airway remodeling and signaling pathways in chronic asthma. In the present study, we used a long-term exposure murine model of allergic airway disease to evaluate the effects of an antioxidant, l-2-oxothiazolidine-4-carboxylic acid (OTC or α-lipoic acid (LA on airway remodeling, focusing on the ROS-related hypoxia-inducible signaling. Long-term challenge of ovalbumin (OVA increased ROS production, airway inflammation, and airway hyperresponsiveness, and developed features of airway remodeling such as excessive mucus secretion, subepithelial fibrosis, and thickening of the peribronchial smooth muscle layer. Administration of OTC or LA reduced these features of asthma, including airway remodeling, which was accompanied by suppression of transforming growth factor-β1, vascular endothelial growth factor, and T-helper 2 cytokines. In addition, OVA-induced activation of nuclear factor-κB (NF-κB, nuclear factor erythroid 2p45-related factor-2 (Nrf2, hypoxia-inducible factor (HIF-1α, and HIF-2α was reduced by OTC or LA. Our results also showed that OTC or LA down-regulated phosphoinositide 3-kinase activity and decreased phosphorylation of p38 mitogen-activated protein kinase but not extracellular signal-regulated kinase 1/2 or c-Jun N-terminal kinase. These findings demonstrate that OTC and LA can inhibit activation of NF-κB, Nrf2, and HIF, leading to attenuate allergen-induced airway remodeling.

  5. Low-cost and disposable sensors for the simultaneous determination of coenzyme Q10 and α-lipoic acid using manganese (IV) oxide-modified screen-printed graphene electrodes.

    Science.gov (United States)

    Charoenkitamorn, Kanokwan; Chaiyo, Sudkate; Chailapakul, Orawon; Siangproh, Weena

    2018-04-03

    In this work, for the first time, manganese (IV) oxide-modified screen-printed graphene electrodes (MnO 2 /SPGEs) were developed for the simultaneous electrochemical detection of coenzyme Q10 (CoQ10) and α-lipoic acid (ALA). This sensor exhibits attractive benefits such as simplicity, low production costs, and disposability. Cyclic voltammetry (CV) was used to characterize the electrochemical behavior of the analyte and investigate the capacitance and electroactive surface area of the unmodified and modified electrode surfaces. The electrochemical behavior of CoQ10 and ALA on MnO 2 /SPGEs was also discussed. Additionally, square wave anodic stripping voltammetry (SWASV) was used for the quantitative determination of CoQ10 and ALA. Under optimal conditions, the obtained signals are linear in the concentration range from 2.0 to 75.0 μg mL -1 for CoQ10 and 0.3-25.0 μg mL -1 for ALA. The low limits of detection (LODs) were found to be 0.56 μg mL -1 and 0.088 μg mL -1 for CoQ10 and ALA, respectively. Moreover, we demonstrated the utility and applicability of the MnO 2 /SPGE sensor through simultaneous measurements of CoQ10 and ALA in dietary supplements. The sensor provides high accuracy measurements, exhibiting its high potential for practical applications. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Folic acid supplement use in the prevention of neural tube defects.

    LENUS (Irish Health Repository)

    Delany, C

    2011-01-01

    In 2008, planned folic acid fortification for the prevention of Neural Tube Defects (NTD) was postponed. Concurrently, the economic recession may have affected dietary folic acid intake, placing increased emphasis on supplement use. This study examined folic acid supplement use in 2009. A cross-sectional survey of 300 ante-natal women was undertaken to assess folic acid knowledge and use. Associations between demographic, obstetric variables and folic acid knowledge and use were examined. A majority, 284\\/297 (96%), had heard of folic acid, and 178\\/297 (60%) knew that it could prevent NTD. Most, 270\\/297 (91%) had taken it during their pregnancy, but only 107\\/297 (36%) had used it periconceptionally. Being older, married, planned pregnancy and better socioeconomic status were associated with periconceptional use. Periconceptional folic acid use in 2009 was very low, little changed from economic status were associated with periconceptional use. Periconceptional folic acid use in 2009 was very low, little changed from earlier years. Continuous promotion efforts are necessary. Close monitoring of folic acid intake and NTD rates is essential, particularly in the absence of fortification.

  7. Use of topical tranexamic acid or aminocaproic acid to prevent bleeding after major surgical procedures.

    Science.gov (United States)

    Ipema, Heather J; Tanzi, Maria G

    2012-01-01

    To evaluate the literature describing topical use of tranexamic acid or aminocaproic acid for prevention of postoperative bleeding after major surgical procedures. Literature was retrieved through MEDLINE (1946-September 2011) and International Pharmaceutical Abstracts (1970-September 2011) using the terms tranexamic acid, aminocaproic acid, antifibrinolytic, topical, and surgical. In addition, reference citations from publications identified were reviewed. All identified articles in English were evaluated. Clinical trials, case reports, and meta-analyses describing topical use of tranexamic acid or aminocaproic acid to prevent postoperative bleeding were included. A total of 16 publications in the setting of major surgical procedures were included; the majority of data were for tranexamic acid. For cardiac surgery, 4 trials used solutions containing tranexamic acid (1-2.5 g in 100-250 mL of 0.9% NaCl), and 1 trial assessed a solution containing aminocaproic acid (24 g in 250 mL of 0.9% NaCl). These solutions were poured into the chest cavity before sternotomy closure. For orthopedic procedures, all of the data were for topical irrigation solutions containing tranexamic acid (500 mg-3 g in 50-100 mL of 0.9% NaCl) or for intraarticular injections of tranexamic acid (250 mg to 2 g in 20-50 mL of 0.9% sodium chloride, with or without carbazochrome sodium sulfate). Overall, use of topical tranexamic acid or aminocaproic acid reduced postoperative blood loss; however, few studies reported a significant reduction in the number of packed red blood cell transfusions or units given, intensive care unit stay, or length of hospitalization. Topical application of tranexamic acid and aminocaproic acid to decrease postsurgical bleeding after major surgical procedures is a promising strategy. Further data are needed regarding the safety of this hemostatic approach.

  8. Efek Pemberian Asam Alfa Lipoat untuk Mencegah Lesi Aterosklerosis Aorta Abdominal pada Tikus Diabetes Mellitus Tipe 2

    Directory of Open Access Journals (Sweden)

    Ismawati ismawati

    2018-01-01

    Full Text Available Efek asam lipoat terhadap komplikasi diabetes mellitus telah banyak diteliti. Efek protektif asam lipoat (ALA terhadap aterosklerosis pada diabetes mellitus masih perlu diteliti. Penelitian ini bertujuan untuk men­getahui pencegahan lesi aterosklerosis oleh asam alfa lipoat pada tikus diabetes mellitus (DM tipe 2. Se­banyak 21 ekor tikus wistar jantan yang dibagi menjadi 3 kelompok; kelompok kontrol, kelompok DM dan kelompok DM +ALA. Induksi DM tipe 2 dilakukan dengan pemberian streptozotocin (50 mg/kg diikuti oleh nikotinamide (110 mg/kg dosis tunggal intraperitoneal. Asam lipoat diberikan peroral (60 mg/kg selama 3 minggu setelah hewan coba terdiagnosis DM. Penelitian yang merupakan penelitian eksperimental den­gan desain post test only with control ini dilakukan di Laboratorium Biokimia Fakultas Kedokteran Univer­sitas Riau bulan Juni - Oktober 2016. Hasil penelitian memperlihatkan skor aterosklerosis pada kelompok DM+ALA lebih rendah dibandingkan kelompok DM dan perbedaan ini bermakna secara statistik. Asam lipoat dapat mencegah pembentukan lesi aterosklerosis pada tikus DM tipe 2.   The Effect of Alpha Lipoic Acid in Preventing Atherosclerosis Lesion on the Abdominal Aorta of Diabetes Mellitus Type 2 Rats   AbstractVarious studies have studied the clinical use of alpha-lipoic acid (ALA for treating diabetic complica­tions. The protective effect of lipoic acid in atherosclerosis induced by diabetes mellitus type 2 (DM type 2 still needs further study. This study was aimed to investigate the protective effect of ALA in atherosclerosis induced by DM type 2. Twenty one rats were divided into 3 groups: control, DM−treated and DM+ALA-treated group. Type-2 diabetes was induced by intraperitoneal injection of streptozotocin (50 mg/kg followed by nicotinamide (110 mg/kg. ALA was administered orally at a dose of 60 mg/kg body weight/day throughout the feeding period for three weeks. This study was an experimental study with post-test only

  9. Folic Acid for the Prevention of Neural Tube Defects : US Preventive Services Task Force Recommendation Statement

    NARCIS (Netherlands)

    Calonge, Ned; Petitti, Diana B.; DeWitt, Thomas G.; Dietrich, Allen J.; Gregory, Kimberly D.; Grossman, David; Isham, George; LeFevre, Michael L.; Leipzig, Rosanne M.; Marion, Lucy N.; Melnyk, Bernadette; Moyer, Virginia A.; Ockene, Judith K.; Sawaya, George F.; Schwartz, J. Sanford; Wilt, Timothy

    2009-01-01

    Description: In 1996, the U. S. Preventive Services Task Force (USPSTF) recommended that all women planning or capable of pregnancy take a multivitamin supplement containing folic acid for the prevention of neural tube defects. This recommendation is an update of the 1996 USPSTF recommendation.

  10. Tetradecylthioacetic acid prevents high fat diet induced adiposity and insulin resistance

    DEFF Research Database (Denmark)

    Madsen, Lise; Guerre-Millo, Michéle; Flindt, Esben N

    2002-01-01

    Tetradecylthioacetic acid (TTA) is a non-beta-oxidizable fatty acid analog, which potently regulates lipid homeostasis. Here we evaluate the ability of TTA to prevent diet-induced and genetically determined adiposity and insulin resistance. In Wistar rats fed a high fat diet, TTA administration...... completely prevented diet-induced insulin resistance and adiposity. In genetically obese Zucker (fa/fa) rats TTA treatment reduced the epididymal adipose tissue mass and improved insulin sensitivity. All three rodent peroxisome proliferator-activated receptor (PPAR) subtypes were activated by TTA...... that a TTA-induced increase in hepatic fatty acid oxidation and ketogenesis drains fatty acids from blood and extrahepatic tissues and that this contributes significantly to the beneficial effects of TTA on fat mass accumulation and peripheral insulin sensitivity....

  11. Advances in the management of diabetic neuropathy.

    Science.gov (United States)

    Várkonyi, Tamás; Körei, Anna; Putz, Zsuzsanna; Martos, Tímea; Keresztes, Katalin; Lengyel, Csaba; Nyiraty, Szabolcs; Stirban, Alin; Jermendy, György; Kempler, Péter

    2017-10-01

    The authors review current advances in the therapy of diabetic neuropathy. The role of glycemic control and management of cardiovascular risk factors in the prevention and treatment of neuropathic complications are discussed. As further options of pathogenetically oriented treatment, recent knowledge on benfotiamine and alpha-lipoic acid is comprehensively reviewed. Alpha-lipoic acid is a powerful antioxidant and clinical trials have proven its efficacy in ameliorating neuropathic signs and symptoms. Benfotiamine acts via the activation of transketolase and thereby inhibits alternative pathways triggered by uncontrolled glucose influx in the cells comprising polyol, hexosamine, protein-kinase-C pathways and formation of advanced glycation end products. Beyond additional forms of causal treatment, choices of symptomatic treatment will be summarized. The latter is mostly represented by the anticonvulsive agents pregabalin and gabapentin as well as duloxetine widely acknowledged as antidepressant. Finally, non-pharmacological therapeutic alternatives are summarized. The authors conclude that combination therapy should be more often suggested to our patients; especially the combination of pathogenetic and symptomatic agents.

  12. The importance of γ-linolenic acid in the prevention and treatment

    Directory of Open Access Journals (Sweden)

    Małgorzata Białek

    2015-07-01

    Full Text Available The etiology of diet-related disorders is closely associated with dietary factors. A special role is attributed to intake of fat and fatty acid profile, both quantitative and qualitative. For prevention and treatment of the abovementioned diseases a proper supply of unsaturated fatty acids plays a significant role, because of their particular importance to health. γ-Linolenic acid (GLA, with three double bonds in the carbon chain, also known as all-cis 6,9,12-octadecatrienoic acid, belongs to the n-6 family of fatty acids. It plays biologically important functions in the human body, such as being a substrate for eicosanoids synthesis, involvement in the transport and oxidation of cholesterol, and being one of the components of lipid membrane. Its inadequate dietary intake or impaired formation is the cause of many inflammatory and degenerative diseases. A rich source of this fatty acid is vegetable oils, until recently used mainly in folk medicine. Nowadays, studies conducted both in animal models and in humans suggest its health-promoting properties in the prevention and treatment of atopic dermatitis, cardiovascular diseases, diabetes, cancers and rheumatoid arthritis.

  13. Prevention of Ophthalmia Neonatorum Caused by Neisseria gonorrhoeae Using a Fatty Acid-Based Formulation

    Directory of Open Access Journals (Sweden)

    Colin P. Churchward

    2017-07-01

    Full Text Available Ophthalmia neonatorum, also called neonatal conjunctivitis, acquired during delivery can occur in the first 28 days of life. Commonly caused by the bacterial pathogen Neisseria gonorrhoeae, infection can lead to corneal scarring, perforation of the eye, and blindness. One approach that can be taken to prevent the disease is the use of an ophthalmic prophylaxis, which kills the bacteria on the surface of the eye shortly after birth. Current prophylaxes are based on antibiotic ointments. However, N. gonorrhoeae is resistant to many antibiotics and alternative treatments must be developed before the condition becomes untreatable. This study focused on developing a fatty acid-based prophylaxis. For this, 37 fatty acids or fatty acid derivatives were screened in vitro for fast antigonococcal activity. Seven candidates were identified as bactericidal at 1 mM. These seven were subjected to irritation testing using three separate methods: the bovine corneal opacity and permeability (BCOP test; the hen’s egg test—chorioallantoic membrane (HET-CAM; and the red blood cell (RBC lysis assay. The candidates were also tested in artificial tear fluid to determine whether they were effective in this environment. Four of the candidates remained effective. Among these, two lead candidates, monocaprin and myristoleic acid, displayed the best potential as active compounds in the development of a fatty acid-based prophylaxis for prevention of ophthalmia neonatorum.

  14. Pretreatment with ascorbic acid prevents lethal gastrointestinal syndrome in mice receiving a massive amount of radiation

    International Nuclear Information System (INIS)

    Yamamoto, Tetsuo; Kinoshita, Manabu; Shinomiya, Nariyoshi; Hiroi, Sadayuki; Sugasawa, Hidekazu; Majima, Takashi; Seki, Shuhji; Matsushita, Yoshitaro; Saitoh, Daizoh

    2010-01-01

    While bone marrow or stem cell transplantation can rescue bone marrow aplasia in patients accidentally exposed to a lethal radiation dose, radiation-induced irreversible gastrointestinal damage (GI syndrome) is fatal. We investigated the effects of ascorbic acid on radiation-induced GI syndrome in mice. Ascorbic acid (150 mg/kg/day) was orally administered to mice for 3 days, and then the mice underwent whole body irradiation (WBI). Bone marrow transplantation (BMT) 24 h after irradiation rescued mice receiving a WBI dose of less than 12 Gy. No mice receiving 14 Gy-WBI survived, because of radiation-induced GI syndrome, even if they received BMT. However, pretreatment with ascorbic acid significantly suppressed radiation-induced DNA damage in the crypt cells and prevented denudation of intestinal mucosa; therefore, ascorbic acid in combination with BMT rescued mice after 14 Gy-WBI. DNA microarray analysis demonstrated that irradiation up-regulated expressions of apoptosis-related genes in the small intestine, including those related to the caspase-9-mediated intrinsic pathway as well as the caspase-8-mediated extrinsic pathway, and down-regulated expressions of these genes in ascorbic acid-pretreated mice. Thus, pretreatment with ascorbic acid may effectively prevent radiation-induced GI syndrome. (author)

  15. Effects of High-Dose α-Lipoic Acid on Heart Rate Variability of Type 2 Diabetes Mellitus Patients with Cardiac Autonomic Neuropathy in Korea

    Directory of Open Access Journals (Sweden)

    Sol Jae Lee

    2017-07-01

    Full Text Available BackgroundDiabetic cardiac autonomic neuropathy (CAN is one of the important complications of diabetes. It is characterized by reduced heart rate variability (HRV.MethodsIn this randomized, double-blind, placebo-controlled, multicenter trial, 75 patients were randomly assigned to one of two groups. One group (n=41 received α-lipoic acid (ALA at an oral dose of 600 mg/day for the first 12 weeks and then 1,200 mg/day for the next 12 weeks. The other group (n=34 received placebo treatment for 24 weeks. CAN was assessed by measuring HRVs in people with diabetes.ResultsMost of the baseline measures for HRVs were similar between the ALA and placebo groups. Although there were no statistically significant HRV changes in the ALA group compared to the placebo group after 24 weeks of trial, we found a positive tendency in some of the HRV parameters of the ALA group. The standard deviations of normal-to-normal RR intervals in the standing position increased by 1.87 ms in the ALA group but decreased by −3.97 ms in the placebo group (P=0.06. The power spectrum of the low frequency (LF band in the standing position increased by 15.77 ms2 in the ALA group, whereas it declined by −15.04 ms2 in the placebo group (P=0.08. The high frequency/LF ratio in the upright position increased by 0.35 in the ALA group, whereas it declined by −0.42 in the placebo group (P=0.06. There were no differences between the two groups regarding rates of adverse events.ConclusionAlthough a slight improvement tendency was seen in HRV in the ALA group, there were no statistically significant HRV changes in the ALA group compared to the placebo group after 24 weeks of trial. However, the high oral dose of ALA was well-tolerated.

  16. Kynurenic Acid Prevents Cytoskeletal Disorganization Induced by Quinolinic Acid in Mixed Cultures of Rat Striatum.

    Science.gov (United States)

    Pierozan, Paula; Biasibetti-Brendler, Helena; Schmitz, Felipe; Ferreira, Fernanda; Pessoa-Pureur, Regina; Wyse, Angela T S

    2018-06-01

    Kynurenic acid (KYNA) is a neuroactive metabolite of tryptophan known to modulate a number of mechanisms involved in neural dysfunction. Although its activity in the brain has been widely studied, the effect of KYNA counteracting the actions of quinolinic acid (QUIN) remains unknown. The present study aims at describing the ability of 100 μM KYNA preventing cytoskeletal disruption provoked by QUIN in astrocyte/neuron/microglia mixed culture. KYNA totally preserved cytoskeletal organization, cell morphology, and redox imbalance in mixed cultures exposed to QUIN. However, KYNA partially prevented morphological alteration in isolated primary astrocytes and failed to protect the morphological alterations of neurons caused by QUIN exposure. Moreover, KYNA prevented QUIN-induced microglial activation and upregulation of ionized calcium-binding adapter molecule 1 (Iba-1) and partially preserved tumor necrosis factor-α (TNF-α) level in mixed cultures. TNF-α level was also partially preserved in astrocytes. In addition to the mechanisms dependent on redox imbalance and microglial activation, KYNA prevented downregulation of connexin-43 and the loss of functionality of gap junctions (GJs), preserving cell-cell contact, cytoskeletal organization, and cell morphology in QUIN-treated cells. Furthermore, the toxicity of QUIN targeting the cytoskeleton of mixed cultures was not prevented by the N-methyl-D-aspartate (NMDA) antagonist MK-801. We suggest that KYNA protects the integrity of the cytoskeleton of mixed cultures by complex mechanisms including modulating microglial activation preventing oxidative imbalance and misregulated GJs leading to disrupted cytoskeleton in QUIN-treated cells. This study contributed to elucidate the molecular basis of KYNA protection against QUIN toxicity.

  17. Orthomolecular medicine: the therapeutic use of dietary supplements for anti-aging

    OpenAIRE

    Janson, Michael

    2006-01-01

    Dietary supplements at high doses as part of medical therapy have been controversial, but the evidence suggests that they play a significant role in prevention and treatment of diseases as well as protection from accelerated aging that results from oxygen free-radical damage, inflammation, and glycation. This literature review examines several supplements that have documented roles in medical therapy, including vitamins C and E, coenzyme Q10, alpha-lipoic acid, chromium, L-carnitine, and quer...

  18. [Folic acid: Primary prevention of neural tube defects. Literature Review].

    Science.gov (United States)

    Llamas Centeno, M J; Miguélez Lago, C

    2016-03-01

    Neural tube defects (NTD) are the most common congenital malformations of the nervous system, they have a multifactorial etiology, are caused by exposure to chemical, physical or biological toxic agents, factors deficiency, diabetes, obesity, hyperthermia, genetic alterations and unknown causes. Some of these factors are associated with malnutrition by interfering with the folic acid metabolic pathway, the vitamin responsible for neural tube closure. Its deficit produce anomalies that can cause abortions, stillbirths or newborn serious injuries that cause disability, impaired quality of life and require expensive treatments to try to alleviate in some way the alterations produced in the embryo. Folic acid deficiency is considered the ultimate cause of the production of neural tube defects, it is clear the reduction in the incidence of Espina Bifida after administration of folic acid before conception, this leads us to want to further study the action of folic acid and its application in the primary prevention of neural tube defects. More than 40 countries have made the fortification of flour with folate, achieving encouraging data of decrease in the prevalence of neural tube defects. This paper attempts to make a literature review, which clarify the current situation and future of the prevention of neural tube defects.

  19. Polycystic ovary syndrome (PCOS) and hyperandrogenism: the role of a new natural association.

    Science.gov (United States)

    Morgante, G; Cappelli, V; Di Sabatino, A; Massaro, M G; De Leo, V

    2015-10-01

    Polycystic ovary syndrome (PCOS) affects 5-10% of women of childbearing age and manifests itself through oligomenorrhea, anovulation, hirsutism, micro-polycystic ovaries. Insulin resistance is a characteristic of PCOS patients and is more pronounced in obese patients. Insulin resistance and consequent hyperinsulinemia are related to many aspects of the syndrome such as hyperandrogenism, reproductive disorders, acne and hirsutism. In the long-term it may increase the risk of cardiovascular disease and negatively affect lipid profile and blood pressure. Changes in lifestyle and diet can partially improve these aspects. The use of insulin-sensitizing drugs such as metformin often normalises the menstrual cycle, improving hyperandrogenism and, subsequently, the response to ovulation induction therapies. New molecules have recently been marketed, that produce the same results, but without the side-effects. One of these is myo-inositol, a new insulin-sensitizing molecule which has been successfully administered to women suffering from PCOS. Associations between inositol and other compounds that can increase the therapeutic effect have been proposed. Of these, we found to be interesting the association with monacolin K, a natural statin that reduces cholesterol levels starting point of the synthesis of steroids, including androgens, and lipoic acid, known for its anti-inflammatory, antioxidant and insulin-sensitizing activity. We decided to assess the efficacy of the product. We recruited 30 women aged between 24 and 32 years suffering from PCOS with insulin resistance, HOMA index>2.5 and no other endocrine diseases. The following were assessed: Body Mass Index (BMI), characteristics of menstrual cycles, lipid profile (total cholesterol, and HDL), androgens (total testosterone and androstenedione). The patients were also assessed for the degree of hirsutism using the Ferriman-Gallwey Score>8. The subjects were divided into two groups: Group A, treated with an association

  20. Tachikawa project for prevention of posttraumatic stress disorder with polyunsaturated fatty acid (TPOP): study protocol for a randomized controlled trial.

    Science.gov (United States)

    Matsuoka, Yutaka; Nishi, Daisuke; Yonemoto, Naohiro; Hamazaki, Kei; Matsumura, Kenta; Noguchi, Hiroko; Hashimoto, Kenji; Hamazaki, Tomohito

    2013-01-05

    Preclinical and clinical studies suggest that supplementation with omega-3 fatty acids after trauma might reduce subsequent posttraumatic stress disorder (PTSD). To date, we have shown in an open trial that PTSD symptoms in critically injured patients can be reduced by taking omega-3 fatty acids, hypothesized to stimulate hippocampal neurogenesis. The primary aim of the present randomized controlled trial is to examine the efficacy of omega-3 fatty acid supplementation in the secondary prevention of PTSD following accidental injury, as compared with placebo. This paper describes the rationale and protocol of this trial. The Tachikawa Project for Prevention of Posttraumatic Stress Disorder with Polyunsaturated Fatty Acid (TPOP) is a double-blinded, parallel group, randomized controlled trial to assess whether omega-3 fatty acid supplementation can prevent PTSD symptoms among accident-injured patients consecutively admitted to an intensive care unit. We plan to recruit accident-injured patients and follow them prospectively for 12 weeks. Enrolled patients will be randomized to either the omega-3 fatty acid supplement group (1,470 mg docosahexaenoic acid and 147 mg eicosapentaenoic acid daily) or placebo group. Primary outcome is score on the Clinician-Administered PTSD Scale (CAPS). We will need to randomize 140 injured patients to have 90% power to detect a 10-point difference in mean CAPS scores with omega-3 fatty acid supplementation compared with placebo. Secondary measures are diagnosis of PTSD and major depressive disorder, depressive symptoms, physiologic response in the experiment using script-driven imagery and acoustic stimulation, serum brain-derived neurotrophic factor, health-related quality of life, resilience, and aggression. Analyses will be by intent to treat. The trial was initiated on December 13 2008, with 104 subjects randomized by November 30 2012. This study promises to be the first trial to provide a novel prevention strategy for PTSD among

  1. Folic acid supplements to prevent neural tube defects: trends in East of Ireland 1996-2002.

    LENUS (Irish Health Repository)

    Ward, M

    2004-10-01

    Promotion of folic acid to prevent neural Tube Defects (NTD) has been ongoing for ten years in Ireland, without a concomitant reduction in the total birth prevalence of NTD. The effectiveness of folic acid promotion as the sole means of primary prevention of NTD is therefore questionable. We examined trends in folic acid knowledge and peri-conceptional use from 1996-2002 with the aim of assessing the value of this approach. From 1996-2002, 300 women attending ante-natal clinics in Dublin hospitals annually were surveyed regarding their knowledge and use of folic acid. During the period the proportion who had heard of folic acid rose from 54% to 94% between 1996 and 2002 (c2 test for trend: p<0.001). Knowledge that folic acid can prevent NTD also rose from 21% to 66% (c2 test for trend: p<0.001). Although the proportion who took folic acid during pregnancy increased from 14% to 83% from 1996 to 2002 (c2 test for trend: p<0.001), peri-conceptional intake did not rise above 24% in any year. There is a high awareness of folic acid and its relation to NTD, which is not matched by peri-conceptional uptake. The main barrier to peri-conceptional uptake is the lack of pregnancy planning. To date promotional campaigns appear to have been ineffective in reducing the prevalence of NTD in Ireland. Consequently, fortification of staple foodstuffs is the only practical and reliable means of primary prevention of NTD.

  2. Alterations on monoamines concentration in rat hippocampus produced by lipoic acid Alterações na concentração de monoaminas no hipocampo de ratos produzidas pelo ácido lipóico

    Directory of Open Access Journals (Sweden)

    Ítala Mônica de Sales Santos

    2010-06-01

    Full Text Available The purposes of the present study were to verify monoamines (dopamine (DA, norepinephrine (NE, serotonin (5-HT, and their metabolites (3,4-hydroxyphenylacetic acid (DOPAC, homovanillic acid (HVA and 5-hydroxyindoleacetic acid (5-HIAA contents in rat hippocampus after lipoic acid (LA administration. Wistar rats were treated with 0.9% saline (i.p., control group and LA (10, 20 or 30 mg/kg, i.p., LA10, LA20 and LA30 groups, respectively. After the treatments all groups were observed for 24 h. The NE and DA levels were increased only in 20 mg/kg dose of LA in rat hippocampus. Serotonin content and in their metabolite 5-HIAA levels was decreased in same dose of LA. On the other hand, in DOPAC and HVA levels did not show any significant change. The alterations in hippocampal monoamines can be suggested as a possible of brain mechanism of action from this antioxidant. The outcome of the study may have therapeutic implications in the treatment of neurodegenerative diseases.O objetivo do presente estudo foi verificar a concentração das monoaminas (dopamina (DA, norepinefrina (NA, serotonina (5-HT, e seus metabólitos (ácido 3,4-hidroxifenil (DOPAC, ácido homovanílico (HVA e 5 ácido hydroxiindolacético (5-HIAA no hipocampo de ratos após administração do ácido lipóico (AL. Ratos Wistar foram tratados com solução salina 0,9% (i.p., grupo controle e AL (10, 20 ou 30 mg/kg, i.p., AL10, AL20 e AL30 grupos, respectivamente. Após os tratamentos todos os grupos foram observados durante 24 h. O conteúdo de DA no hipocampo de ratos foi aumentado apenas com AL na dose de 20 mg/kg dose. A concentração de serotonina e do seu metabólito 5-HIAA também foi diminuída com esta dose de AL. Por outro lado, os níveis de DOPAC e de HVA não mostrram nenhuma mudança significativa. As alterações na concentração das monoaminas hipocampais podem ser sugeridas como um possível mecanismo de ação cerebral deste antioxidante. O resultado do estudo pode

  3. Efficacy of Poly(D,L-Lactic Acid-co-Glycolic acid)-Poly(Ethylene Glycol)-Poly(D,L-Lactic Acid-co-Glycolic Acid) Thermogel As a Barrier to Prevent Spinal Epidural Fibrosis in a Postlaminectomy Rat Model.

    Science.gov (United States)

    Li, Xiangqian; Chen, Lin; Lin, Hong; Cao, Luping; Cheng, Ji'an; Dong, Jian; Yu, Lin; Ding, Jiandong

    2017-04-01

    Experimental animal study. The authors conducted a study to determine the efficacy and safety of the poly(D,L-lactic acid-co-glycolic acid)-poly(ethylene glycol)-poly(D,L-lactic acid-co-glycolic acid) (PLGA-PEG-PLGA) thermogel to prevent peridural fibrosis in an adult rat laminectomy model. Peridural fibrosis often occurs after spinal laminectomy. It might cause persistent back and/or leg pain postoperatively and make a reoperation more difficult and dangerous. Various materials have been used to prevent epidural fibrosis, but only limited success has been achieved. The PLGA-PEG-PLGA thermogel was synthesized by us. Total L3 laminectomies were performed on 24 rats. The PLGA-PEG-PLGA thermogel or chitosan (CHS) gel (a positive control group) was applied to the operative sites in a blinded manner. In the control group, the L3 laminectomy was performed and the defect was irrigated with the NS solution 3 times. All the rats were killed 4 weeks after the surgery. The cytotoxicity of this thermogel was evaluated in vitro and the result demonstrated that no evidence of cytotoxicity was observed. The extent of epidural fibrosis, the area of epidural fibrosis, and the density of the fibroblasts and blood vessel were evaluated histologically. There were statistical differences among the PLGA-PEG-PLGA thermogel or CHS gel group compared with the control group. Although there was no difference between the PLGA-PEG-PLGA thermogel and CHS gel, the efficiency of the PLGA-PEG-PLGA thermogel was shown to be slightly improved compared with the CHS gel. The biocompatibility of the PLGA-PEG-PLGA thermogel was proven well. The application of this thermogel effectively reduced epidural scarring and prevented the subsequent adhesion to the dura mater. No side effects were noted in the rats.

  4. [Acetylsalicylic acid in primary prevention of cardiovascular events; literature study

    NARCIS (Netherlands)

    Bredie, S.J.H.; Wollersheim, H.C.H.; Verheugt, F.W.A.; Thien, Th.

    2002-01-01

    OBJECTIVE: To evaluate literature data on the use of acetylsalicylic acid (ASA) as a primary prevention measure for cardiovascular events. DESIGN: Literature search. METHOD: Using Medline, all randomised placebo-controlled trials of ASA published between 1985 and 1 May 2001, and which used

  5. Ascorbic acid prevents vascular dysfunction induced by oral glucose load in healthy subjects.

    Science.gov (United States)

    De Marchi, Sergio; Prior, Manlio; Rigoni, Anna; Zecchetto, Sara; Rulfo, Fanny; Arosio, Enrico

    2012-01-01

    To examine the effects of oral glucose load on forearm circulatory regulation before and after ascorbic acid administration in healthy subjects. Microcirculation study with laser Doppler was performed at the hand in basal conditions, after ischemia and after acetylcholine and nitroprusside; strain gauge plethysmography was performed at basal and after ischemia. The tests were repeated in the same sequence 2 hour after oral administration of glucose (75 g). The subjects were randomised for administration of ascorbic acid (1 g bid) or placebo (sodium bicarbonate 1 g bid) for 10 days. After that, the tests were repeated before and after a new oral glucose load. Blood pressure and heart rate were monitored. Macrocirculatory flux, pressure values and heart rate were unvaried throughout the study. The glucose load caused a reduction in the hyperemic peak flow with laser Doppler and plethysmography; it reduced flux recovery time and hyperemic curve area after ischemia; acetylcholine elicited a minor increase in flux with laser Doppler. The response to nitroprusside was unvaried after glucose load as compared to basal conditions. Treatment with ascorbic acid prevented the decrease in hyperemia after glucose, detected with laser Doppler and plethysmography. Ascorbic acid prevented the decreased response to acetylcholine after glucose, the response to nitroprusside was unaffected by ascorbic acid. Results after placebo were unvaried. Oral glucose load impairs endothelium dependent dilation and hyperaemia at microcirculation, probably via oxidative stress; ascorbic acid can prevent it. Copyright © 2011 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

  6. Targeting arachidonic acid pathway by natural products for cancer prevention and therapy.

    Science.gov (United States)

    Yarla, Nagendra Sastry; Bishayee, Anupam; Sethi, Gautam; Reddanna, Pallu; Kalle, Arunasree M; Dhananjaya, Bhadrapura Lakkappa; Dowluru, Kaladhar S V G K; Chintala, Ramakrishna; Duddukuri, Govinda Rao

    2016-10-01

    Arachidonic acid (AA) pathway, a metabolic process, plays a key role in carcinogenesis. Hence, AA pathway metabolic enzymes phospholipase A 2 s (PLA 2 s), cyclooxygenases (COXs) and lipoxygenases (LOXs) and their metabolic products, such as prostaglandins and leukotrienes, have been considered novel preventive and therapeutic targets in cancer. Bioactive natural products are a good source for development of novel cancer preventive and therapeutic drugs, which have been widely used in clinical practice due to their safety profiles. AA pathway inhibitory natural products have been developed as chemopreventive and therapeutic agents against several cancers. Curcumin, resveratrol, apigenin, anthocyans, berberine, ellagic acid, eugenol, fisetin, ursolic acid, [6]-gingerol, guggulsteone, lycopene and genistein are well known cancer chemopreventive agents which act by targeting multiple pathways, including COX-2. Nordihydroguaiaretic acid and baicalein can be chemopreventive molecules against various cancers by inhibiting LOXs. Several PLA 2 s inhibitory natural products have been identified with chemopreventive and therapeutic potentials against various cancers. In this review, we critically discuss the possible utility of natural products as preventive and therapeutic agents against various oncologic diseases, including prostate, pancreatic, lung, skin, gastric, oral, blood, head and neck, colorectal, liver, cervical and breast cancers, by targeting AA pathway. Further, the current status of clinical studies evaluating AA pathway inhibitory natural products in cancer is reviewed. In addition, various emerging issues, including bioavailability, toxicity and explorability of combination therapy, for the development of AA pathway inhibitory natural products as chemopreventive and therapeutic agents against human malignancy are also discussed. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Effect of ascorbic acid on prevention of hypercholesterolemia induced atherosclerosis.

    Science.gov (United States)

    Das, S; Ray, R; Snehlata; Das, N; Srivastava, L M

    2006-04-01

    The notion that oxidation of lipids and propagation of free radicals may contribute to the pathogenesis of atherosclerosis is supported by a large body of evidence. To circumvent the damage caused by oxygen free radicals, antioxidants are needed which provide the much needed neutralization of free radical by allowing the pairing of electrons. In this study we have investigated the effect of ascorbic acid, a water soluble antioxidant on the development of hypercholesterolemia induced atherosclerosis in rabbits. Rabbits were made hypercholesterolemic and atherosclerotic by feeding 100 mg cholesterol/day. Different doses of ascorbic acid were administered to these rabbits. Low dose of ascorbic acid (0.5 mg/100 g body weight/day) did not have any significant effect on the percent of total area covered by atherosclerotic plaque. However, ascorbic acid when fed at a higher dose (15 mg/100 g body weight/day) was highly effective in reducing the atherogenecity. With this dose the percent of total surface area covered by atherosclerotic plaque was significantly less (p ascorbic acid may have great promise in the prevention of hypercholesterolemia induced atherosclerosis.

  8. Application of the novel mill tailings agglomeration technology for prevention of acid mine drainage

    International Nuclear Information System (INIS)

    Amaratunga, L.M.

    1994-01-01

    Acid generation and subsequent liberation of heavy metals results from the surface disposal of sulfide mineral bearing mill tailings. Most Canadian base metals such as Ni, Cu, Zn, and Pb, as well as uranium and precious metal milling operations are producers of reactive mill tailings containing the major sulfide gangue minerals such as pyrite, pyrrhotite and arsenopyrites. A novel disposal technology by cold-bond tailings agglomeration process (CBTA) is currently being developed at Laurentian University. This process has been adapted to prevent acid mine drainage from reactive mill tailings. A preliminary study was undertaken to evaluate the application of the concept of agglomeration of reactive mill tailings using various alkaline binders and incorporating suitable chemical additives. The binders and additives are selected for their effectiveness in the prevention or retardation of the initial chemical and biochemical oxidation reactions of sulfide mineral leading to acid generation. Following a cold-bond, cold curing tailings agglomeration process, various types and dosages of chemical binders and their additives were employed. The additives under investigation were lime, sodium lauryl sulfate, potassium phosphate dibasic, sodium chloride and sodium benzoate. Some of these chemicals are well known acid neutralizers and others are inexpensive anionic surfactants, detergents and fertilizers acting as bactericides. Most of these additives have been reported in the literature as effective chemical agents used in the prevention and control of acid mine drainage from sulfide minerals. The paper also presents a leachate study to investigate the acid generation potential from each batch of reactive tailings agglomerates containing various binders and non-toxic additives

  9. Dietary Antioxidants as Modifiers of Physiologic Adaptations to Exercise

    Science.gov (United States)

    Mankowski, Robert T.; Anton, Stephen D.; Buford, Thomas W.; Leeuwenburgh, Christiaan

    2015-01-01

    Adaptive responses to exercise training (ET) are crucial in maintaining physiological homeostasis and health span. Exercise-induced aerobic bioenergetic reactions in mitochondria and cytosol increase production of reactive oxygen species (ROSs), where excess of ROS can be scavenged by enzymatic as well as non-enzymatic antioxidants to protect against deleterious oxidative stress. Free radicals, however, have recently been recognized as crucial signaling agents that promote adaptive mechanisms to ET, such as mitochondrial biogenesis, antioxidant (AO) enzyme activity defense system upregulation, insulin sensitivity, and glucose uptake in skeletal muscle. Commonly used non-enzymatic AO supplements, such as vitamins C and E, a-lipoic acid, and polyphenols, in combination with ET, have been proposed as ways to prevent exercise-induced oxidative stress and hence improve adaptation responses to endurance training. Preclinical and clinical studies to date have shown inconsistent results indicating either positive or negative effects of endurance training combined with different blends of AO supplements (mostly vitamins C and E and a-lipoic acid) on redox status, mitochondrial biogenesis pathways, and insulin sensitivity. Preclinical reports on ET combined with resveratrol, however, have shown consistent positive effects on exercise performance, mitochondrial biogenesis, and insulin sensitivity, with clinical trials reporting mixed effects. Relevant clinical studies have been few and have used inconsistent results and methodology (types of compounds, combinations, and supplementation time). The future studies would investigate the effects of specific antioxidants and other popular supplements, such as a-lipoic acid and resveratrol, on training effects in humans. Of particular importance are older adults who may be at higher risk of age-related increased oxidative stress, an impaired AO enzyme defense system, and comorbidities such as hypertension, insulin resistance, and

  10. Lipoyl dioleoylglycerol: Synthesis and potential use of a novel lipid in tribology

    Science.gov (United States)

    Lipoyl dioleoylglycerol is a lipophilic derivative of alpha-lipoic acid, a well-known antioxidant. Lipoyl dioleoylglycerol derived from vegetable oil maintains oily characteristics, suggesting potential use as a lubricant additive. Lipoyl dioleoylglycerol exists in an oxidized form with a disulfid...

  11. Brain kinin B1 receptor is upregulated by the oxidative stress and its activation leads to stereotypic nociceptive behavior in insulin-resistant rats.

    Science.gov (United States)

    Dias, Jenny Pena; Gariépy, Helaine De Brito; Ongali, Brice; Couture, Réjean

    2015-07-01

    Kinin B1 receptor (B1R) is virtually absent under physiological condition, yet it is highly expressed in models of diabetes mellitus. This study aims at determining: (1) whether B1R is induced in the brain of insulin-resistant rat through the oxidative stress; (2) the consequence of B1R activation on stereotypic nocifensive behavior; (3) the role of downstream putative mediators in B1R-induced behavioral activity. Sprague-Dawley rats were fed with 10% D-glucose in their drinking water or tap water (controls) for 4 or 12 weeks, combined either with a standard chow diet or a diet enriched with α-lipoic acid (1 g/kg feed) for 4 weeks. The distribution and density of brain B1R binding sites were assessed by autoradiography. Behavioral activity evoked by i.c.v. injection of the B1R agonist Sar-[D-Phe(8)]-des-Arg(9)-BK (10 μg) was measured before and after i.c.v. treatments with selective antagonists (10 μg) for kinin B1 (R-715, SSR240612), tachykinin NK1 (RP-67580) and glutamate NMDA (DL-AP5) receptors or with the inhibitor of NOS (L-NNA). Results showed significant increases of B1R binding sites in various brain areas of glucose-fed rats that could be prevented by the diet containing α-lipoic acid. The B1R agonist elicited head scratching, grooming, sniffing, rearing, digging, licking, face washing, wet dog shake, teeth chattering and biting in glucose-fed rats, which were absent after treatment with α-lipoic acid or antagonists/inhibitors. Data suggest that kinin B1R is upregulated by the oxidative stress in the brain of insulin-resistant rats and its activation causes stereotypic nocifensive behavior through the release of substance P, glutamate and NO. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. n-3 Fatty acids combined with flavan-3-ols prevent steatosis and liver injury in a murine model of NAFLD.

    Science.gov (United States)

    Vauzour, David; Rodriguez-Ramiro, Ildefonso; Rushbrook, Simon; Ipharraguerre, Ignacio R; Bevan, Damon; Davies, Susan; Tejera, Noemi; Mena, Pedro; de Pascual-Teresa, Sonia; Del Rio, Daniele; Gavrilovic, Jelena; Minihane, Anne Marie

    2018-01-01

    Non-alcoholic fatty liver disease (NAFLD) affects 25% of adults and at present no licensed medication has been approved. Despite its complex patho-physiology, dietary strategies aiming at delaying or preventing NAFLD have taken a reductionist approach, examining the impact of single components. Accumulating evidence suggests that n-3 LC-PUFAs are efficacious in regulating lipogenesis and fatty acid oxidation. In addition, plant derived flavonoids are also emerging as a dietary strategy for NAFLD prevention, with efficacy attributed to their insulin sensitising and indirect antioxidant effects. Based on knowledge of their complementary molecular targets, we aimed to demonstrate that the combination of n-3 LC-PUFA (n-3) and flavan-3-ols (FLAV) prevents NAFLD. In a high-fat high-fructose (HF/HFr) fed C57Bl/6J mouse model, the independent and interactive impact of n-3 and FLAV on histologically defined NAFLD, insulin sensitivity, weight gain, intestinal and hepatic gene expression, intestinal bile acids were examined. Only the combination of FLAV and n-3 (FLAVn-3) prevented steatosis as evidenced by a strong reduction in hepatocyte ballooning. While FLAV reduced body (-28-30%), adipose tissue (-45-50%) weights and serum insulin (-22-25%) as observed following an intra-peritoneal glucose tolerance test, n-3 downregulated the expression of Srebf1 and the lipogenic genes (Acaca, Fasn). Significant impacts of interventions on intestinal bile acid metabolism, farnesoid X receptor (Fxr) signalling in the intestine and liver, and hepatic expression of fatty acid transporters (Fabp4, Vldlr, Cd36) were also evident. FLAVn-3 may be a novel intervention for NAFLD. Future research should aim to demonstrate its efficacy in the prevention and treatment of human NAFLD. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Lipoic acid increases glutathione peroxidase, Na+, K+-ATPase and acetylcholinesterase activities in rat hippocampus after pilocarpine-induced seizures? O ácido lipóico aumenta as atividades da glutationa peroxidase, da Na+, K+-ATPase e da acetilcolinesterase no hipocampo de ratos após convulsões induzidas por pilocarpina?

    Directory of Open Access Journals (Sweden)

    Geane Felix de Souza

    2010-08-01

    Full Text Available In the present study we investigated the effects of lipoic acid (LA on acetylcholinesterase (AChE, glutathione peroxidase (GPx and Na+, K+-ATPase activities in rat hippocampus during seizures. Wistar rats were treated with 0.9% saline (i.p., control group, lipoic acid (20 mg/kg, i.p., LA group, pilocarpine (400 mg/kg, i.p., P400 group, and the association of pilocarpine (400 mg/kg, i.p. plus LA (20 mg/kg, i.p., 30 min before of administration of P400 (LA plus P400 group. After the treatments all groups were observed for 1 h. In P400 group, there was a significant increase in GPx activity as well as a decrease in AChE and Na+, K+-ATPase activities after seizures. In turn, LA plus P400 abolished the appearance of seizures and reversed the decreased in AChE and Na+, K+-ATPase activities produced by seizures, when compared to the P400 seizing group. The results from the present study demonstrate that preadministration of LA abolished seizure episodes induced by pilocarpine in rat, probably by increasing AChE and Na+, K+-ATPase activities in rat hippocampus.No presente estudo nós investigamos os efeitos do ácido lipóico (AL sobre as atividades da acetilcolinesterase (AChE, da glutationa peroxidase (GPx e da Na+, K+-ATPase no hipocampo de ratos durante crises convulsivas. Ratos Wistar foram tratados com solução salina a 0,9% (i.p., grupo controle, ácido lipóico (20 mg/kg, i.p., grupo AL, pilocarpina (400 mg/kg, i.p., grupo P400, e a associação de AL (20 mg/kg, i.p. com a pilocarpina (400 mg/kg, i.p., 30 min antes da administração de pilocarpina (grupo AL + P400. Após os tratamentos todos os grupos foram observados durante 1 h. No grupo P400, houve um aumento significativo na atividade da GPx, assim como uma diminuição das atividades da AChE e Na+, K+-ATPase. Por sua vez, o pré-tratamento com AL aboliu o aparecimento de convulsões e reverteu a diminuição das atividades da AChE e da Na+, K+-ATPase causadas pelas convulsões, quando

  14. Ascorbic acid supplementation partially prevents the delayed reproductive development in juvenile male rats exposed to rosuvastatin since prepuberty.

    Science.gov (United States)

    Leite, Gabriel Adan Araújo; Figueiredo, Thamiris Moreira; Sanabria, Marciana; Dias, Ana Flávia Mota Gonçalves; Silva, Patrícia Villela E; Martins Junior, Airton da Cunha; Barbosa Junior, Fernando; Kempinas, Wilma De Grava

    2017-10-01

    Dyslipidemias are occurring earlier in the population due to the increase of obesity and bad eating habits. Rosuvastatin inhibits the enzyme HMG-CoA reductase, decreasing total cholesterol. Ascorbic acid is an important antioxidant compound for male reproductive system. This study aimed to evaluate whether ascorbic acid supplementation may prevent the reproductive damage provoked by rosuvastatin administration at prepuberty. Male pups were distributed into six experimental groups that received saline solution 0.9%, 3 or 10mg/kg/day of rosuvastatin, 150mg/day of ascorbic acid, or 150mg/day of ascorbic acid associated with 3 or 10mg/kg/day of rosuvastatin from post-natal day (PND) 23 until PND53. Rosuvastatin-treated groups showed delayed puberty installation, androgen depletion and impairment on testicular and epididymal morphology. Ascorbic acid partially prevented these reproductive damages. In conclusion, rosuvastatin exposure is a probable risk to reproductive development and ascorbic acid supplementation may be useful to prevent the reproductive impairment of rosuvastatin exposure. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Iso-α-acids, Bitter Components of Beer, Prevent Inflammation and Cognitive Decline Induced in a Mouse Model of Alzheimer's Disease*

    Science.gov (United States)

    Ano, Yasuhisa; Dohata, Atsushi; Taniguchi, Yoshimasa; Hoshi, Ayaka; Uchida, Kazuyuki; Takashima, Akihiko; Nakayama, Hiroyuki

    2017-01-01

    Alongside the rapid growth in aging populations worldwide, prevention and therapy for age-related memory decline and dementia are in great demand to maintain a long, healthy life. Here we found that iso-α-acids, hop-derived bitter compounds in beer, enhance microglial phagocytosis and suppress inflammation via activation of the peroxisome proliferator-activated receptor γ. In normal mice, oral administration of iso-α-acids led to a significant increase both in CD11b and CD206 double-positive anti-inflammatory type microglia (p iso-α-acids resulted in a 21% reduction in amyloid β in the cerebral cortex as observed by immunohistochemical analysis, a significant reduction in inflammatory cytokines such as IL-1β and chemokines including macrophage inflammatory protein-1α in the cerebral cortex (p iso-α-acid-fed mice were due to the induction of microglia to an anti-inflammatory phenotype. The present study is the first to report that amyloid β deposition and inflammation are suppressed in a mouse model of Alzheimer's disease by a single component, iso-α-acids, via the regulation of microglial activation. The suppression of neuroinflammation and improvement in cognitive function suggests that iso-α-acids contained in beer may be useful for the prevention of dementia. PMID:28087694

  16. In Barrett's esophagus patients and Barrett's cell lines, ursodeoxycholic acid increases antioxidant expression and prevents DNA damage by bile acids.

    Science.gov (United States)

    Peng, Sui; Huo, Xiaofang; Rezaei, Davood; Zhang, Qiuyang; Zhang, Xi; Yu, Chunhua; Asanuma, Kiyotaka; Cheng, Edaire; Pham, Thai H; Wang, David H; Chen, Minhu; Souza, Rhonda F; Spechler, Stuart Jon

    2014-07-15

    Hydrophobic bile acids like deoxycholic acid (DCA), which cause oxidative DNA damage and activate NF-κB in Barrett's metaplasia, might contribute to carcinogenesis in Barrett's esophagus. We have explored mechanisms whereby ursodeoxycholic acid (UDCA, a hydrophilic bile acid) protects against DCA-induced injury in vivo in patients and in vitro using nonneoplastic, telomerase-immortalized Barrett's cell lines. We took biopsies of Barrett's esophagus from 21 patients before and after esophageal perfusion with DCA (250 μM) at baseline and after 8 wk of oral UDCA treatment. DNA damage was assessed by phospho-H2AX expression, neutral CometAssay, and phospho-H2AX nuclear foci formation. Quantitative PCR was performed for antioxidants including catalase and GPX1. Nrf2, catalase, and GPX1 were knocked down with siRNAs. Reporter assays were performed using a plasmid construct containing antioxidant responsive element. In patients, baseline esophageal perfusion with DCA significantly increased phospho-H2AX and phospho-p65 in Barrett's metaplasia. Oral UDCA increased GPX1 and catalase levels in Barrett's metaplasia and prevented DCA perfusion from inducing DNA damage and NF-κB activation. In cells, DCA-induced DNA damage and NF-κB activation was prevented by 24-h pretreatment with UDCA, but not by mixing UDCA with DCA. UDCA activated Nrf2 signaling to increase GPX1 and catalase expression, and protective effects of UDCA pretreatment were blocked by siRNA knockdown of these antioxidants. UDCA increases expression of antioxidants that prevent toxic bile acids from causing DNA damage and NF-κB activation in Barrett's metaplasia. Elucidation of this molecular pathway for UDCA protection provides rationale for clinical trials on UDCA for chemoprevention in Barrett's esophagus. Copyright © 2014 the American Physiological Society.

  17. Cellular glutathione prevents cytolethality of monomethylarsonic acid

    International Nuclear Information System (INIS)

    Sakurai, Teruaki; Kojima, Chikara; Ochiai, Masayuki; Ohta, Takami; Sakurai, Masumi H.; Waalkes, Michael P.; Fujiwara, Kitao

    2004-01-01

    Inorganic arsenicals are clearly toxicants and carcinogens in humans. In mammals, including humans, inorganic arsenic often undergoes methylation, forming compounds such as monomethylarsonic acid (MMAs V ) and dimethylarsinic acid (DMAs V ). However, much less information is available on the in vitro toxic potential or mechanisms of these methylated arsenicals, especially MMAs V . We studied the molecular mechanisms of in vitro cytolethality of MMAs V using a rat liver epithelial cell line (TRL 1215). MMAs V was not cytotoxic in TRL 1215 cells even at concentrations exceeding 10 mM, but it became weakly cytotoxic and induced both necrotic and apoptotic cell death when cellular reduced glutathione (GSH) was depleted with the glutathione synthase inhibitor, L-buthionine-[S,R]-sulfoximine (BSO), or the glutathione reductase inhibitor, carmustine. Similar results were observed in the other mammalian cells, such as human skin TIG-112 cells, chimpanzee skin CRT-1609 cells, and mouse metallothionein (MT) positive and MT negative embryonic cells. Ethacrynic acid (EA), an inhibitor of glutathione S-transferase (GST) that catalyses GSH-substrate conjugation, also enhanced the cytolethality of MMAs V , but aminooxyacetic acid (AOAA), an inhibitor of β-lyase that catalyses the final breakdown of GSH-substrate conjugates, had no effect. Both the cellular GSH levels and the cellular GST activity were increased by the exposure to MMAs V in TRL 1215 cells. On the other hand, the addition of exogenous extracellular GSH enhanced the cytolethality of MMAs V , although cellular GSH levels actually prevented the cytolethality of combined MMAs V and exogenous GSH. These findings indicate that human arsenic metabolite MMAs V is not a highly toxic compound in mammalian cells, and the level of cellular GSH is critical to its eventual toxic effects

  18. MINE WASTE TECHNOLOGY PROGRAM PREVENTION OF ACID MINE DRAINAGE GENERATION FROM OPEN-PIT HIGHWALLS

    Science.gov (United States)

    This document summarizes the results of Mine Waste Technology Program Activity III, Project 26, Prevention of Acid Mine Drainage Generation from Open-Pit Highwalls. The intent of this project was to obtain performance data on the ability of four technologies to prevent the gener...

  19. Ibuprofen-conjugated hyaluronate/polygalacturonic acid hydrogel for the prevention of epidural fibrosis.

    Science.gov (United States)

    Lin, Cheng-Yi; Peng, Hsiu-Hui; Chen, Mei-Hsiu; Sun, Jui-Sheng; Chang, Chih-Ju; Liu, Tse-Ying; Chen, Ming-Hong

    2016-05-01

    The formation of fibrous tissue is part of the natural healing response following a laminectomy. Severe scar tissue adhesion, known as epidural fibrosis, is a common cause of failed back surgery syndrome. In this study, by combining the advantages of drug treatment with a physical barrier, an ibuprofen-conjugated crosslinkable polygalacturonic acid and hyaluronic acid hydrogel was developed for epidural fibrosis prevention. Conjugation was confirmed and measured by 1D(1)H NMR spectroscopy.In vitroanalysis showed that the ibuprofen-conjugated polygalacturonic acid-hyaluronic acid hydrogel showed low cytotoxicity. In addition, the conjugated ibuprofen decreased prostaglandin E2production of the lipopolysaccharide-induced RAW264.7 cells. Histological data inin vivostudies indicated that the scar tissue adhesion of laminectomized male adult rats was reduced by the application of our ibuprofen-conjugated polygalacturonic acid-hyaluronic acid hydrogel. Its use also reduced the population of giant cells and collagen deposition of scar tissue without inducing extensive cell recruitment. The results of this study therefore suggest that the local delivery of ibuprofenviaa polygalacturonic acid-hyaluronic acid-based hydrogel reduces the possibility of epidural fibrosis. © The Author(s) 2016.

  20. Effects of troxerutin on cognitive deficits and glutamate cysteine ligase subunits in the hippocampus of streptozotocin-induced type 1 diabetes mellitus rats.

    Science.gov (United States)

    Zhang, Songyun; Li, Hongyan; Zhang, Lihui; Li, Jie; Wang, Ruiying; Wang, Mian

    2017-02-15

    Increasing evidence demonstrates an association between diabetes and hippocampal neuron damage. This study aimed to determine the effects of troxerutin on cognitive deficits and glutamate cysteine ligase subunits (GCLM and GCLC) in the hippocampus of streptozotocin-induced type 1 diabetes mellitus (T1DM) rats. At 12weeks after streptozotocin injection, T1DM rats were randomly divided into 4 groups (n=15 each group) to receive no treatment (T1DM), saline (T1DM+saline), alpha-lipoic acid (T1DM+alpha-lipoic acid), and troxerutin (T1DM+troxerutin), respectively, for 6weeks. Meanwhile, 10 control animals (NC group) were assessed in parallel. Learning performance was evaluated by the Morris water maze. After treatment, hippocampi were collected for pathological examination by hematoxylin and eosin (H&E) staining. Next, hippocampal superoxide dismutase (SOD) activity, and malondialdehyde (MDA) and glutathione (GSH) levels were assessed. Finally, glutamate cysteine ligase catalytic (GCLC) and glutamate cysteine ligase modifier (GCLM) subunit mRNA and protein levels were quantified by reverse transcription polymerase chain reaction (RT-PCR) and Western blot, respectively. Compared with T1DM and T1DM+saline groups, escape latency was overtly reduced in T1DM+alpha-lipoic acid and T1DM+troxerutin groups. Significantly increased GCLM and GCLC mRNA levels, GCLC protein amounts, SOD activity, and GSH levels, and reduced MDA amounts were observed in T1DM+alpha-lipoic acid and T1DM+troxerutin groups. In T1DM and T1DM+saline groups, H&E staining showed less pyramidal cells in the hippocampus, with disorganized layers, karyopyknosis, decreased endochylema, and cavitation, effects relieved in T1DM+alpha-lipoic acid and T1DM+troxerutin groups. Troxerutin alleviates oxidative stress and promotes learning in streptozotocin-induced T1DM rats, a process involving GCLC expression. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Iso-α-acids, Bitter Components of Beer, Prevent Inflammation and Cognitive Decline Induced in a Mouse Model of Alzheimer's Disease.

    Science.gov (United States)

    Ano, Yasuhisa; Dohata, Atsushi; Taniguchi, Yoshimasa; Hoshi, Ayaka; Uchida, Kazuyuki; Takashima, Akihiko; Nakayama, Hiroyuki

    2017-03-03

    Alongside the rapid growth in aging populations worldwide, prevention and therapy for age-related memory decline and dementia are in great demand to maintain a long, healthy life. Here we found that iso-α-acids, hop-derived bitter compounds in beer, enhance microglial phagocytosis and suppress inflammation via activation of the peroxisome proliferator-activated receptor γ. In normal mice, oral administration of iso-α-acids led to a significant increase both in CD11b and CD206 double-positive anti-inflammatory type microglia ( p iso-α-acids resulted in a 21% reduction in amyloid β in the cerebral cortex as observed by immunohistochemical analysis, a significant reduction in inflammatory cytokines such as IL-1β and chemokines including macrophage inflammatory protein-1α in the cerebral cortex ( p iso-α-acid-fed mice were due to the induction of microglia to an anti-inflammatory phenotype. The present study is the first to report that amyloid β deposition and inflammation are suppressed in a mouse model of Alzheimer's disease by a single component, iso-α-acids, via the regulation of microglial activation. The suppression of neuroinflammation and improvement in cognitive function suggests that iso-α-acids contained in beer may be useful for the prevention of dementia. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  2. Membrane omega-3 Fatty Acid deficiency as a preventable risk factor for comorbid coronary heart disease in major depressive disorder.

    Science.gov (United States)

    McNamara, Robert K

    2009-01-01

    Major depression disorder (MDD) significantly increases the risk for coronary heart disease (CHD) which is a leading cause of mortality in patients with MDD. Moreover, depression is frequently observed in a subset of patients following acute coronary syndrome (ACS) and increases risk for mortality. Here evidence implicating omega-3 (n-3) fatty acid deficiency in the pathoaetiology of CHD and MDD is reviewed, and the hypothesis that n-3 fatty acid deficiency is a preventable risk factor for CHD comorbidity in MDD patients is evaluated. This hypothesis is supported by cross-national and cross-sectional epidemiological surveys finding an inverse correlation between n-3 fatty acid status and prevalence rates of both CHD and MDD, prospective studies finding that lower dietary or membrane EPA+DHA levels increase risk for both MDD and CHD, case-control studies finding that the n-3 fatty acid status of MDD patients places them at high risk for emergent CHD morbidity and mortality, meta-analyses of controlled n-3 fatty acid intervention studies finding significant advantage over placebo for reducing depression symptom severity in MDD patients, and for secondary prevention of cardiac events in CHD patients, findings that n-3 fatty acid status is inversely correlated with other documented CHD risk factors, and patients diagnosed with MDD after ACS exhibit significantly lower n-3 fatty acid status compared with nondepressed ACS patients. This body of evidence provides strong support for future studies to evaluate the effects of increasing dietary n-3 fatty acid status on CHD comorbidity and mortality in MDD patients.

  3. Effect of Salicylic Acid on Prevention of Chilling Injury of Cherry Tomato (Lycopersicun esculentum cv. Messina(

    Directory of Open Access Journals (Sweden)

    hanifeh seyed hajizadeh

    2018-02-01

    Full Text Available Introduction: Fruits and vegetables play a major role in providing vitamins and minerals that are essential in the metabolism. In addition to providing vitamins and minerals compounds, they are called secondary metabolites. Tomatoes are one of the most vegetables in diets of people around the world. Low temperature stress associated with the production of reactive oxygen species causing damage can occur before or after harvest, farm, transportation, storage and marketing. Today, a greater emphasis is placed on post-harvest storage of agricultural products to increase productivity and make better use of labor resources, worker, energy and money, rather than an increase in production. One of the most promising treatments is the use of salicylic acid for prevention of the frost damage of post-harvest fruits and vegetables with different mechanisms such as increased enzymatic and non-enzymatic antioxidant system activity. Salicylic acid is known as a signal molecule in the induction defense mechanisms in plants. SA is a well-known phenol that can prevent ACO activity that is the direct precursor of ethylene and decreases Reactive Oxygen Species (ROS with increasing enzyme antioxidant activity. Salicylic acid is a natural phenolic compound known as a plant hormone having positive effect on storage life and quality of fruits. This study aimed to investigate the effects of pre- and post-harvest application of salicylic acid on antioxidant properties and quality of tomato and its effect was evaluated on prevention of chilling injury of cherry tomatoes during cold storage. Material and Methods: This research was conducted in a greenhouse of Horticulture Department of University of Maragheh. Treatments were included before harvest at fruit set stage with the control (distilled water and 0.75 mM salicylic acid spraying and after harvest, red ripened fruits were used for treatments control and immersion in 0.75 mM salicylic acid. Then all the treated fruits

  4. Total prevention of folic acid-preventable spina bifida and anencephaly would reduce child mortality in India: Implications in achieving Target 3.2 of the Sustainable Development Goals.

    Science.gov (United States)

    Kancherla, Vijaya; Oakley, Godfrey P

    2018-03-15

    The potential to reduce child mortality by preventing folic acid-preventable spina bifida and anencephaly (FAP SBA) is inadequately appreciated. To quantify possible reduction in FAP SBA-associated child mortality in low- and middle-income countries, we conducted an analysis to demonstrate in India, a country with more than 25 million births and 1.2 million under-five deaths each year, the decrease in neonatal, infant, and under-five mortality that would occur through total prevention of FAP SBA. We estimated the percent reductions in neonatal, infant, and under-five mortality that would have occurred in India in 2015 had all of FAP SBA been prevented. We also estimated the contributions of these reductions toward India's Sustainable Development Goals on child mortality indicators. We considered the overall prevalence of spina bifida and anencephaly in India as 5 per 1,000 live births, of which 90% were preventable with effective folic acid intervention. In the year 2015, folic acid interventions would have prevented about 116,070 cases of FAP SBA and 101,565 under-five deaths associated with FAP SBA. Prevention of FAP SBA would have reduced annually, neonatal, infant, and under-five mortality by 10.2%, 8.9%, and 8.3%, respectively. These reductions would have contributed 18.5% and 17.2% to the reductions in neonatal and under-five mortality, respectively, needed by India to achieve its 2030 Sustainable Developmental Goal Target 3.2 addressing preventable child mortality. Total prevention of FAP SBA clearly has a significant potential for immediate reductions in neonatal, infant, and under-five mortality in India, and similarly other countries. © 2017 Wiley Periodicals, Inc.

  5. Once-yearly zoledronic acid in hip fracture prevention

    Science.gov (United States)

    Demontiero, Oddom; Duque, Gustavo

    2009-01-01

    Osteoporosis is an escalating global problem. Hip fractures, the most catastrophic complication of osteoporosis, continue to cause significant mortality and morbidity despite increasing availability of effective preventative agents. Among these agents, oral bisphosphonates have been the first choice for the treatment and prevention of osteoporotic fractures. However, the use of oral bisphosphonates, especially in the older population, has been limited by their side effects and method of administration thus compromising their persistent use. The resultant low adherence by patients has undermined their full potential and has been associated with an increase in the incidence of fragility fractures. Recently, annual intravenous zoledronic acid (ZOL) has been approved for osteoporosis. Randomized controlled trials have demonstrated ZOL to be safe, have good tolerability and produce significant effect on bone mass and microarchitecture. Adherence has also been shown to be better with ZOL. Furthermore two large trials firmly demonstrated significant anti-osteoporotic effect (∼59% relative risk reduction of hip fractures) and mortality benefit (28% reduction in mortality) of ZOL in older persons with recent hip fractures. In this review, we report the current evidence on the use of ZOL for the prevention of hip fractures in the elderly. We also report the pharmacological characteristics and the advantages and disadvantages of ZOL in this particular group. PMID:19503777

  6. Efficiency of sulfuric acid, mined gypsum, and two gypsum by-products in soil crusting prevention and sodic soil reclamation

    Energy Technology Data Exchange (ETDEWEB)

    Amezketa, E.; Aragues, R.; Gazol, R. [Gobierno Navarra, Pamplona (Spain). Agricultural Resources Evaluation Center

    2005-06-01

    We evaluated the efficiency of four amendments (sulfuric acid, mined-gypsum, and the by-products coal-gypsum and lacto-gypsum) in crusting prevention of two calcareous nonsodic and sodic soils and in sodic soil reclamation. Treatments for crust prevention consisted of surface-applied amendments at equivalent rates of 5 Mg pure-gypsum ha{sup -1}. Treatments for sodic soil reclamation consisted of surface-applied acid and soil-incorporated gypsums at rates of 1 pure-gypsum requirement. The efficiency of these amendments was evaluated by comparing the final infiltration rates (FIR) of the amended vs. the nonamended soils measured in disturbed-soil columns pounded with low-salinity irrigation water. Electrical conductivity (EC) and Na in the leachates of the sodic soil were measured. In the crusting prevention experiment, FIRs (mm h{sup -1) of the nonsodic soil were 21 (nonamended), 33 to 35 (gypsum materials), and 53 (sulfuric acid), whereas those for the sodic soil were 0 (nonamended), 9 (lacto-gypsum), 15 to 17 (coal- and mined-gypsum), and 21 (sulfuric acid). In the sodic-soil reclamation experiment, FIRs were 0 (nonamended), 8 to 9 (gypsum-materials), and 17 (sulfuric acid) mm h{sup -1}. All amendments were effective in crusting prevention and soil reclamation, but sulfuric acid was the most efficient due to the fastest EC and Na reductions in the leachates. The three gypsum-materials were equally effective in the reclamation process and in the nonsodic soil crusting-prevention, whereas lacto-gypsum was less efficient in the sodic-soil crusting-prevention.

  7. Quantification of simvastatin in mice plasma by near-infrared and chemometric analysis of spectral data

    Directory of Open Access Journals (Sweden)

    Fahmy UA

    2016-08-01

    Full Text Available Usama A Fahmy Department of Pharmaceutics & Industrial Pharmacy, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia Abstract: Time and cost saving is an essential requirement in pharmacokinetics and bioequivalence studies. The aim of this study is to use a simple, fast, and nondestructive near-infrared transmission spectroscopic method to quantify simvastatin (SMV concentrations in mice plasma and also to improve SMV bioavailability by using alpha-lipoic acid as a carrier. Calibration curve was built at a concentration range of 10–250 ng/mL, and HPLC method was considered as a reference method. A partial least squares regression analysis model was used for method development, which gave less root mean square error cross-validation. Comparison of SMV concentrations obtained from both instruments showed no statistically significant differences between all the data. Near-infrared spectroscopy was utilized as a rapid, simple accurate method to quantify drug–plasma concentrations without need for any extraction protocols, and the significant effect of alpha-lipoic acid as a novel carrier to enhance SMV bioavailability is also addressed. Keywords: alpha lipoic acid, bioavailability, non invasive, FTIR, pharmacokinetics

  8. Preventive and therapeutic effects of tranexamic acid on postpartum bleeding

    Directory of Open Access Journals (Sweden)

    Samaneh Solltani

    2014-12-01

    Full Text Available Postpartum hemorrhage is among the leading causes of maternal mortality throughout the world. Severe blood loss contributes to  the increased blood transfusion risk with its concerned inherent adverse events and therefore increased rate of emergency re-operative interventions such as arterial ligation or hysterectomy. It also can lead to protracted anemia, particularly in low or median income countries. Extended application of antifibrinolytic agents such as tranexamic acid has been customary for long years to stop or reduce blood loss in postpartum period. However, there are not enough reliable evidence to approve the real efficacy of these drugs. In this brief and summary review, we pointed to a few conducted studies. The PubMed was searched for keyword including postpartum hemorrhage, tranexamic acid, cesarean section, vaginal delivery, and blood loss prevention. The articles with language other than English were excluded from our review.  We concluded that more convincing information is needed to determine the precise effects of tranexamic acid, and its benefits against adverse effects.

  9. Docosahexaenoic acid prevents trans-10, cis-12 conjugated linoleic acid-induced non-alcoholic fatty liver disease in mice by altering expression of hepatic genes regulating fatty acid synthesis and oxidation

    Science.gov (United States)

    Background: Concomitant supplementation with docosahexaenoic acid (22:6 n-3; DHA) prevented t10, c12- conjugated linoleic acid (CLA)-induced non-alcoholic fatty liver disease (NAFLD) and insulin resistance. Effective dose of DHA and mechanisms involved are poorly understood. Methods: We examined abi...

  10. Omega-3 Fatty Acids in Early Prevention of Inflammatory Neurodegenerative Disease: A Focus on Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    J. Thomas

    2015-01-01

    Full Text Available Alzheimer’s disease (AD is the leading cause of dementia and the most common neurodegenerative disease in the elderly. Furthermore, AD has provided the most positive indication to support the fact that inflammation contributes to neurodegenerative disease. The exact etiology of AD is unknown, but environmental and genetic factors are thought to contribute, such as advancing age, family history, presence of chronic diseases such as cardiovascular disease (CVD and diabetes, and poor diet and lifestyle. It is hypothesised that early prevention or management of inflammation could delay the onset or reduce the symptoms of AD. Normal physiological changes to the brain with ageing include depletion of long chain omega-3 fatty acids and brains of AD patients have lower docosahexaenoic acid (DHA levels. DHA supplementation can reduce markers of inflammation. This review specifically focusses on the evidence in humans from epidemiological, dietary intervention, and supplementation studies, which supports the role of long chain omega-3 fatty acids in the prevention or delay of cognitive decline in AD in its early stages. Longer term trials with long chain omega-3 supplementation in early stage AD are warranted. We also highlight the importance of overall quality and composition of the diet to protect against AD and dementia.

  11. Clofibric and ethacrynic acids prevent experimental pyelonephritis by Escherichia coli in mice.

    Science.gov (United States)

    Balagué, Claudia E; de Ruiz, Clara Silva; Rey, Rosario; de Duffard, Ana María Evangelista; Nader-Macías, María Elena

    2004-11-01

    Interfering Escherichia coli attachment to the urinary tract, using P-fimbriation inhibitors, can prevent pyelonephritis. Clofibric and ethacrynic acids are organic compounds structurally related, but with different pharmacological uses. These agents are potentially active in the urinary tract due to its elimination in an unaltered form by the renal route. This study described a pyelonephritogenic E. coli strain, grown in the presence of sub-inhibitory concentrations of clofibric or ethacrynic acids (0.1 and 1 mM, respectively), which exhibits inhibition of P1 erythrocytes agglutination and a drastic decrease in fimbriation, using electron microscopy and quantitative analyses of superficial proteins (decrease to a 17-25% in comparison with the control). In vivo assays were performed using ascending urinary tract infection in mice. The treatment with therapeutic doses of the drugs, administered 2 days before the bacterial challenge and daily until the end of the experiment (22 days), abolished renal infection after 7-10 days of drug exposure. Within this period clofibric acid did not produce adverse effects on the renal parenchyma. However, ethacrynic acid caused pyelitis and tubular cellular desquamation. These results suggested that clofibric acid might be useful in the short-term prophylaxis of urinary tract infection.

  12. Comparative Evaluation of Different Co-Antioxidants on the Photochemical- and Functional-Stability of Epigallocatechin-3-gallate in Topical Creams Exposed to Simulated Sunlight

    Directory of Open Access Journals (Sweden)

    Santo Scalia

    2013-01-01

    Full Text Available The catechin (−-epigallocatechin-3-gallate (EGCG exhibits high antioxidant activity and it has been reported to provide protection of the skin against damage induced by solar UV radiation. However, EGCG is highly unstable under sunlight. The present study aimed to compare the effectiveness of the co-antioxidant agents vitamin E, butylated hydroxytoluene, vitamin C and a-lipoic acid for their potential to protect the catechin from photochemical degradation. Model creams (oil-in-water emulsions containing EGCG (1%, w/w alone or combined with equimolar concentrations of co-antioxidant were exposed to a solar simulator at an irradiance corresponding to natural sunlight. Photodegradation was evaluated by HPLC-UV and HPLC-ESI-MS/MS. Addition of the co-antioxidants vitamin C and a-lipoic acid to the formulation significantly reduced the light-induced decomposition of EGCG from 76.9 ± 4.6% to 20.4 ± 2.7% and 12.6 ± 1.6%, respectively. Conversely, butylated hydroxytoluene had no effect (EGCG loss, 78.1 ± 4.6% and vitamin E enhanced the EGCG photolysis to 84.5 ± 3.4%. The functional stability of the catechin in the creams exposed to the solar simulator was also evaluated by measuring the in vitro antioxidant activity. Following irradiation, the reduction of the EGCG formulation antioxidant power was lower (21.8% than the extent of degradation (76.9%, suggesting the formation of photoproducts with antioxidant properties. The influence of the examined co-antioxidants on the functional stability of the catechin under simulated sunlight paralleled that measured for the EGCG photodecomposition, a-lipoic acid exerting the greatest stabilising effect (antioxidant activity decrease, 1.4%. These results demonstrated that a-lipoic acid is an effective co-antioxidant agent for the stabilization of EGCG in dermatological products for skin photoprotection.

  13. Mis-targeting of the mitochondrial protein LIPT2 leads to apoptotic cell death.

    Directory of Open Access Journals (Sweden)

    Emanuele Bernardinelli

    Full Text Available Lipoyl(Octanoyl Transferase 2 (LIPT2 is a protein involved in the post-translational modification of key energy metabolism enzymes in humans. Defects of lipoic acid synthesis and transfer start to emerge as causes of fatal or severe early-onset disease. We show that the first 31 amino acids of the N-terminus of LIPT2 represent a mitochondrial targeting sequence and inhibition of the transit of LIPT2 to the mitochondrion results in apoptotic cell death associated with activation of the apoptotic volume decrease (AVD current in normotonic conditions, as well as over-activation of the swelling-activated chloride current (IClswell, mitochondrial membrane potential collapse, caspase-3 cleavage and nuclear DNA fragmentation. The findings presented here may help elucidate the molecular mechanisms underlying derangements of lipoic acid biosynthesis.

  14. Interactions between prebiotics, probiotics, polyunsaturated fatty acids and polyphenols: diet or supplementation for metabolic syndrome prevention?

    Science.gov (United States)

    Peluso, Ilaria; Romanelli, Luca; Palmery, Maura

    2014-05-01

    The metabolic syndrome can be prevented by the Mediterranean diet, characterized by fiber, omega-3 polyunsaturated fatty acids and polyphenols. However, the composition of the Mediterranean diet, which can be viewed as a natural multiple supplement, is poorly controlled, and its beneficial effects poorly predictable. The metabolic syndrome is associated with intestinal dysbiosis and the gut microbioma seems to be the main target and player in the interactions occurring between probiotics, prebiotics, omega 3 polyunsaturated fatty acids, and polyphenols. From the reviewed evidence, it is reasonable to manage growth and metabolism of gut microflora with specific prebiotics and polyphenols. Even though the healthy properties of functional foods and nutraceuticals still need to be fully elucidated, available data suggest that well-designed supplements, containing the better ratio of omega-3 polyunsaturated fatty acids and antioxidants, specific probiotic strains, and selected polyphenols and prebiotics, could be useful in metabolic syndrome prevention and treatment.

  15. Prevention of iron- and copper-mediated DNA damage by catecholamine and amino acid neurotransmitters, L-DOPA, and curcumin: metal binding as a general antioxidant mechanism.

    Science.gov (United States)

    García, Carla R; Angelé-Martínez, Carlos; Wilkes, Jenna A; Wang, Hsiao C; Battin, Erin E; Brumaghim, Julia L

    2012-06-07

    Concentrations of labile iron and copper are elevated in patients with neurological disorders, causing interest in metal-neurotransmitter interactions. Catecholamine (dopamine, epinephrine, and norepinephrine) and amino acid (glycine, glutamate, and 4-aminobutyrate) neurotransmitters are antioxidants also known to bind metal ions. To investigate the role of metal binding as an antioxidant mechanism for these neurotransmitters, L-dihydroxyphenylalanine (L-DOPA), and curcumin, their abilities to prevent iron- and copper-mediated DNA damage were quantified, cyclic voltammetry was used to determine the relationship between their redox potentials and DNA damage prevention, and UV-vis studies were conducted to determine iron and copper binding as well as iron oxidation rates. In contrast to amino acid neurotransmitters, catecholamine neurotransmitters, L-DOPA, and curcumin prevent significant iron-mediated DNA damage (IC(50) values of 3.2 to 18 μM) and are electrochemically active. However, glycine and glutamate are more effective at preventing copper-mediated DNA damage (IC(50) values of 35 and 12.9 μM, respectively) than L-DOPA, the only catecholamine to prevent this damage (IC(50) = 73 μM). This metal-mediated DNA damage prevention is directly related to the metal-binding behaviour of these compounds. When bound to iron or copper, the catecholamines, amino acids, and curcumin significantly shift iron oxidation potentials and stabilize Fe(3+) over Fe(2+) and Cu(2+) over Cu(+), a factor that may prevent metal redox cycling in vivo. These results highlight the disparate antioxidant activities of neurotransmitters, drugs, and supplements and highlight the importance of considering metal binding when identifying antioxidants to treat and prevent neurodegenerative disorders.

  16. Potassium citrate prevents increased osteoclastogenesis resulting from acidic conditions: Implication for the treatment of postmenopausal bone loss.

    Directory of Open Access Journals (Sweden)

    Donatella Granchi

    Full Text Available The extracellular acidic milieu in bones results in activation of osteoclasts (OC and inhibition of osteoblasts (OB causing a net loss of calcium from the skeleton and the deterioration of bone microarchitecture. Alkalinization through supplementation with potassium citrate (K citrate has been proposed to limit the osteopenia progression, even though its pharmacological activity in bone microenvironment is not well defined. We evaluated if K citrate was able to prevent the adverse effects that acidic milieu induces on bone cells. OC and OB were maintained in neutral (pH 7.4 versus acidic (pH 6.9 culture medium, and treated with different K citrate concentrations. We evaluated the OC differentiation at seven days, by counting of multinucleated cells expressing tartrate-resistant acid phosphatase, and the activity of mature OC at 14 days, by quantifying of collagen degradation. To evaluate the effects on OB, we analyzed proliferation, mineralization, and expression of bone-related genes. We found that the low pH increased OC differentiation and activity and decreased OB function. The osteoclastogenesis was also promoted by RANKL concentrations ineffective at pH 7.4. Non-cytotoxic K citrate concentrations were not sufficient to steadily neutralize the acidic medium, but a inhibited the osteoclastogenesis, the collagen degradation, and the expression of genes involved in RANKL-mediated OC differentiation, b enhanced OB proliferation and alkaline phosphatase expression, whereas it did not affect the in vitro mineralization, and c were effective also in OC cultures resistant to alendronate, i.e. the positive control of osteoclastogenesis inhibition. In conclusion, K citrate prevents the increase in OC activity induced by the acidic microenvironment, and the effect does not depend exclusively on its alkalizing capacity. These data provide the biological basis for the use of K citrate in preventing the osteopenia progression resulting from low

  17. Preventive maintenance basis: Volume 24 -- Battery -- flooded lead-acid (lead-calcium, lead antimony, plante). Final report

    International Nuclear Information System (INIS)

    Worledge, D.; Hinchcliffe, G.

    1997-12-01

    US nuclear power plants are implementing preventive maintenance (PM) tasks with little documented basis beyond fundamental vendor information to support the tasks or their intervals. The Preventive Maintenance Basis project provides utilities with the technical basis for PM tasks and task intervals associated with 40 specific components such as valves, electric motors, pumps, and HVAC equipment. This document provides a program of preventive maintenance tasks suitable for application to flooded lead-acid batteries. The PM tasks that are recommended provide a cost-effective way to intercept the causes and mechanisms that lead to degradation and failure. They can be used in conjunction with material from other sources, to develop a complete PM program or to improve an existing program. This document provides a program of preventive maintenance (PM) tasks suitable for application to flooded lead-acid batteries. The PM tasks that are recommended provide a cost-effective way to intercept the causes and mechanisms that lead to degradation and failure. They can be used, in conjunction with material from other sources, to develop a complete PM program or to improve an existing program. Users of this information will be utility managers, supervisors, system engineers, craft technicians, and training instructors responsible for developing, optimizing, or fine-tuning PM programs

  18. Ursodeoxycholic acid in patients with ulcerative colitis and primary sclerosing cholangitis for prevention of colon cancer: a meta-analysis.

    Science.gov (United States)

    Ashraf, Imran; Choudhary, Abhishek; Arif, Murtaza; Matteson, Michelle L; Hammad, Hazem T; Puli, Srinivas R; Bechtold, Matthew L

    2012-04-01

    Colon cancer risk is high in patients with ulcerative colitis (UC) and primary sclerosing cholangitis (PSC). Ursodeoxycholic acid has been shown to have some promise as a chemopreventive agent. A meta-analysis was performed to compare the efficacy of ursodeoxycholic acid in the prevention of colonic neoplasia in patients with UC and PSC. Multiple databases were searched (January 2011). Studies examining the use of ursodeoxycholic acid vs. no ursodeoxycholic acid or placebo in adult patients with UC and PSC were included. Data were extracted in standard forms by two independent reviewers. Meta-analysis for the effect of ursodeoxycholic acid was performed by calculating pooled estimates of adenoma or colon cancer formation by odds ratio (OR) with random effects model. Heterogeneity was assessed by calculating the I (2) measure of inconsistency. RevMan 5 was utilized for statistical analysis. Four studies (n = 281) met the inclusion criteria. The studies were of adequate quality. Ursodeoxycholic acid demonstrated no overall improvement in adenoma (OR 0.53; 95 % CI: 0.19-1.48, p = 0.23) or colon cancer occurrence (OR 0.50; 95 % CI: 0.18-1.43, p = 0.20) as compared to no ursodeoxycholic acid or placebo in patients with UC and PSC. Ursodeoxycholic acid use in patients with UC and PSC does not appear to decrease the risk of adenomas or colon cancer.

  19. Orthomolecular medicine: the therapeutic use of dietary supplements for anti-aging.

    Science.gov (United States)

    Janson, Michael

    2006-01-01

    Dietary supplements at high doses as part of medical therapy have been controversial, but the evidence suggests that they play a significant role in prevention and treatment of diseases as well as protection from accelerated aging that results from oxygen free-radical damage, inflammation, and glycation. This literature review examines several supplements that have documented roles in medical therapy, including vitamins C and E, coenzyme Q10, alpha-lipoic acid, chromium, L-carnitine, and quercetin. The evidence shows benefits in diabetes, cardiovascular disease, hypertension, congestive heart failure, age-related deterioration of brain function and vision, and immune function, as well as other age-related health problems.

  20. Acute intestinal injury induced by acetic acid and casein: prevention by intraluminal misoprostol

    International Nuclear Information System (INIS)

    Miller, M.J.; Zhang, x.J.; Gu, x.A.; Clark, D.A.

    1991-01-01

    Acute injury was established in anesthetized rabbits by intraluminal administration of acetic acid with and without bovine casein, into loops of distal small intestine. Damage was quantified after 45 minutes by the blood-to-lumen movement of 51 Cr-labeled ethylenediaminetetraacetic acid (EDTA) and fluorescein isothiocyanate-tagged bovine serum albumin as well as luminal fluid histamine levels. The amount of titratable acetic acid used to lower the pH of the treatment solutions to pH 4.0 was increased by the addition of calcium gluconate. Luminal acetic acid caused a 19-fold increase in 51 Cr-EDTA accumulation over saline controls; casein did not modify this effect. In saline controls, loop fluid histamine levels bordered on the limits of detection (1 ng/g) but were elevated 19-fold by acetic acid exposure and markedly increased (118-fold) by the combination of acid and casein. Intraluminal misoprostol (3 or 30 micrograms/mL), administered 30 minutes before acetic acid, significantly attenuated the increase in epithelial permeability (luminal 51 Cr-EDTA, fluorescein isothiocyanate-bovine serum albumin accumulation) and histamine release (P less than 0.05). Diphenhydramine, alone or in combination with cimetidine, and indomethacin (5 mg/kg IV) were not protective. It is concluded that exposure of the epithelium to acetic acid promotes the transepithelial movement of casein leading to enhanced mast cell activation and mucosal injury. Damage to the epithelial barrier can be prevented by misoprostol

  1. Acute intestinal injury induced by acetic acid and casein: prevention by intraluminal misoprostol

    Energy Technology Data Exchange (ETDEWEB)

    Miller, M.J.; Zhang, x.J.; Gu, x.A.; Clark, D.A. (Department of Pediatrics, Louisiana State University School of Medicine, New Orleans (USA))

    1991-07-01

    Acute injury was established in anesthetized rabbits by intraluminal administration of acetic acid with and without bovine casein, into loops of distal small intestine. Damage was quantified after 45 minutes by the blood-to-lumen movement of {sup 51}Cr-labeled ethylenediaminetetraacetic acid (EDTA) and fluorescein isothiocyanate-tagged bovine serum albumin as well as luminal fluid histamine levels. The amount of titratable acetic acid used to lower the pH of the treatment solutions to pH 4.0 was increased by the addition of calcium gluconate. Luminal acetic acid caused a 19-fold increase in {sup 51}Cr-EDTA accumulation over saline controls; casein did not modify this effect. In saline controls, loop fluid histamine levels bordered on the limits of detection (1 ng/g) but were elevated 19-fold by acetic acid exposure and markedly increased (118-fold) by the combination of acid and casein. Intraluminal misoprostol (3 or 30 micrograms/mL), administered 30 minutes before acetic acid, significantly attenuated the increase in epithelial permeability (luminal {sup 51}Cr-EDTA, fluorescein isothiocyanate-bovine serum albumin accumulation) and histamine release (P less than 0.05). Diphenhydramine, alone or in combination with cimetidine, and indomethacin (5 mg/kg IV) were not protective. It is concluded that exposure of the epithelium to acetic acid promotes the transepithelial movement of casein leading to enhanced mast cell activation and mucosal injury. Damage to the epithelial barrier can be prevented by misoprostol.

  2. Fragrance chemicals lyral and lilial decrease viability of HaCat cells' by increasing free radical production and lowering intracellular ATP level: protection by antioxidants.

    Science.gov (United States)

    Usta, Julnar; Hachem, Yassmine; El-Rifai, Omar; Bou-Moughlabey, Yolla; Echtay, Karim; Griffiths, David; Nakkash-Chmaisse, Hania; Makki, Rajaa Fakhoury

    2013-02-01

    We investigate in this study the biochemical effects on cells in culture of two commonly used fragrance chemicals: lyral and lilial. Whereas both chemicals exerted a significant effect on primary keratinocyte(s), HaCat cells, no effect was obtained with any of HepG2, Hek293, Caco2, NIH3T3, and MCF7 cells. Lyral and lilial: (a) decreased the viability of HaCat cells with a 50% cell death at 100 and 60 nM respectively; (b) decreased significantly in a dose dependant manner the intracellular ATP level following 12-h of treatment; (c) inhibited complexes I and II of electron transport chain in liver sub-mitochondrial particles; and (d) increased reactive oxygen species generation that was reversed by N-acetyl cysteine and trolox and the natural antioxidant lipoic acid, without influencing the level of free and/or oxidized glutathione. Lipoic acid protected HaCat cells against the decrease in viability induced by either compound. Dehydrogenation of lyral and lilial produce α,β-unsaturated aldehydes, that reacts with lipoic acid requiring proteins resulting in their inhibition. We propose lyral and lilial as toxic to mitochondria that have a direct effect on electron transport chain, increase ROS production, derange mitochondrial membrane potential, and decrease cellular ATP level, leading thus to cell death. Copyright © 2012 Elsevier Ltd. All rights reserved.

  3. Nebulised amphotericin B-polymethacrylic acid nanoparticle prophylaxis prevents invasive aspergillosis.

    Science.gov (United States)

    Shirkhani, Khojasteh; Teo, Ian; Armstrong-James, Darius; Shaunak, Sunil

    2015-07-01

    Aspergillus species are the major life threatening fungal pathogens in transplant patients. Germination of inhaled fungal spores initiates infection, causes severe pneumonia, and has a mortality of >50%. This is leading to the consideration of pre-exposure prophylaxis to prevent infection. We made a very low MWt amphotericin B-polymethacrylic acid nanoparticle. It was not toxic to lung epithelial cells or monocyte-derived-macrophages in-vitro, or in an in-vivo transplant immuno-suppression mouse model of life threatening invasive aspergillosis. Three days of nebuliser based prophylaxis delivered the nanoparticle effectively to lung and prevented both fungal growth and lung inflammation. Protection from disease was associated with >99% killing of the Aspergillus and a 90% reduction in lung TNF-α; the primary driver of tissue destructive immuno-pathology. This study provides in-vivo proof-of-principle that very small and cost-effective nanoparticles can be made simply, and delivered safely and effectively to lung by the aerosol route to prevent fungal infections. Aspergillus is an opportunistic pathogen, which affects immunocompromised patients. One novel way to help fight against this infection is pre-exposure prophylaxis. The authors here made PMA based anionic hydrogels carrying amphotericin B, with mucoadhesive behavior. They showed that aerosol route of the drug was very effective in protecting against the disease in an in-vivo model and should provide a stepping-stone towards clinical trials in the future. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  4. Primary prevention of neural-tube defects and some other congenital abnormalities by folic acid and multivitamins: history, missed opportunity and tasks

    Science.gov (United States)

    Bártfai, Zoltán; Bánhidy, Ferenc

    2011-01-01

    The history of intervention trials of periconception folic acid with multivitamin and folic acid supplementation in women has shown a recent breakthrough in the primary prevention of structural birth defects, namely neural-tube defects and some other congenital abnormalities. Recently, some studies have demonstrated the efficacy of this new method in reducing congenital abnormalities with specific origin; for example, in the offspring of diabetic and epileptic mothers, and in pregnancy with high fever. The benefits and drawbacks of four possible uses of periconception folate/folic acid and multivitamin supplementation are discussed: we believe there has been a missed opportunity to implement this preventive approach in medical practice. The four methods are as follows: (i) dietary intake of folate and other vitamins, (ii) periconception folic acid/multivitamin supplementation, (iii) food fortification with folic acid, and (iv) the combination of oral contraceptives with 6S-5-methytetrahydrofolate (‘folate’). PMID:25083211

  5. Prevention by lactic acid bacteria of the oxidation of human LDL.

    Science.gov (United States)

    Terahara, M; Kurama, S; Takemoto, N

    2001-08-01

    Ether extracts of lactic acid bacteria were analyzed for prevention of the oxidation of erythrocyte membrane and human low-density lipoprotein in vivo. Streptococcus thermophilus 1131 and Lactobacillus delbrueckii subsp. bulgaricus 2038, yogurt starters, were chosen as test-strains, and ether extracts of these cultures were used as samples. Both strain 1131 and strain 2038 produced radical scavengers and inhibited oxidation of erythrocyte membranes and low-density lipoproteins. The antioxidative activity of strain 2038 was higher than that of strain 1131.

  6. Role of n-3 Polyunsaturated Fatty Acids and Exercise in Breast Cancer Prevention: Identifying Common Targets

    Directory of Open Access Journals (Sweden)

    Salma A. Abdelmagid

    2016-01-01

    Full Text Available Diet and exercise are recognized as important lifestyle factors that significantly influence breast cancer risk. In particular, dietary n-3 polyunsaturated fatty acids (PUFAs have been shown to play an important role in breast cancer prevention. Growing evidence also demonstrates a role for exercise in cancer and chronic disease prevention. However, the potential synergistic effect of n-3 PUFA intake and exercise is yet to be determined. This review explores targets for breast cancer prevention that are common between n-3 PUFA intake and exercise and that may be important study outcomes for future research investigating the combined effect of n-3 PUFA intake and exercise. These lines of evidence highlight potential new avenues for research and strategies for breast cancer prevention.

  7. Acid Balance, Dietary Acid Load, and Bone Effects—A Controversial Subject

    Directory of Open Access Journals (Sweden)

    Lynda Frassetto

    2018-04-01

    Full Text Available Modern Western diets, with higher contents of animal compared to fruits and vegetable products, have a greater content of acid precursors vs. base precursors, which results in a net acid load to the body. To prevent inexorable accumulation of acid in the body and progressively increasing degrees of metabolic acidosis, the body has multiple systems to buffer and titrate acid, including bone which contains large quantities of alkaline salts of calcium. Both in vitro and in vivo studies in animals and humans suggest that bone base helps neutralize part of the dietary net acid load. This raises the question of whether decades of eating a high acid diet might contribute to the loss of bone mass in osteoporosis. If this idea is true, then additional alkali ingestion in the form of net base-producing foods or alkalinizing salts could potentially prevent this acid-related loss of bone. Presently, data exists that support both the proponents as well as the opponents of this hypothesis. Recent literature reviews have tended to support either one side or the other. Assuming that the data cited by both sides is correct, we suggest a way to reconcile the discordant findings. This overview will first discuss dietary acids and bases and the idea of changes in acid balance with increasing age, then review the evidence for and against the usefulness of alkali therapy as a treatment for osteoporosis, and finally suggest a way of reconciling these two opposing points of view.

  8. Sodium Bicarbonate-Ascorbic Acid Combination for Prevention of Contrast-Induced Nephropathy in Chronic Kidney Disease Patients Undergoing Catheterization.

    Science.gov (United States)

    Komiyama, Kota; Ashikaga, Takashi; Inagaki, Dai; Miyabe, Tomonori; Arai, Marina; Yoshida, Kiyotaka; Miyazawa, Satoshi; Nakada, Akihiro; Kawamura, Iwanari; Masuda, Shinichiro; Nagamine, Sho; Hojo, Rintaro; Aoyama, Yuya; Tsuchiyama, Takaaki; Fukamizu, Seiji; Shibui, Takashi; Sakurada, Harumizu

    2017-01-25

    Sodium bicarbonate and ascorbic acid have been proposed to prevent contrast-induced nephropathy (CIN). The present study evaluated the effect of their combined use on CIN incidence.Methods and Results:We prospectively enrolled 429 patients with chronic kidney disease (CKD: baseline estimated glomerular filtration rate <60 mL/min/1.73 m 2 ) prior to elective coronary catheterization. CIN was defined as absolute (≥0.5 mg/dL) or relative (≥25%) increase in serum creatinine within 72 h. In the saline hydration (n=218) and combined sodium bicarbonate+ascorbic acid (n=211) groups, a total of 1,500-2,500 mL 0.9% saline was given before and after the procedure. In addition, the combination group received 20 mEq sodium bicarbonate and 3 g ascorbic acid i.v. before the procedure, followed by 2 g ascorbic acid after the procedure and a further 2 g after 12 h. There were no significant differences between the basic characteristics and contrast volume in the 2 groups. CIN occurred in 19 patients (8.7%) in the saline group, and in 6 patients (2.8%) in the combined treatment group (P=0.008). Combined sodium bicarbonate and ascorbic acid could prevent CIN following catheterization in CKD patients.

  9. Antimicrobial medium- and long-chain free fatty acids prevent PrfA-dependent activation of virulence genes in Listeria monocytogenes

    DEFF Research Database (Denmark)

    Sternkopf Lillebæk, Eva Maria; Lambert Nielsen, Stine; Scheel Thomasen, Rikke

    2017-01-01

    of virulence factors required for bacterial entry, intracellular replication and cell-to-cell spread. PrfA-dependent activation of virulence genes occurs primarily in the blood and during intracellular infection. In contrast, PrfA does not play a significant role in regulation of virulence gene expression...... antimicrobial free fatty acids act to downregulate transcription of PrfA-activated virulence genes. Interestingly, the inhibitory effect is also evident in cells encoding a constitutively active variant of PrfA. Collectively, our data suggest that antimicrobial medium- and long-chain free fatty acids may act...... as signals to prevent PrfA-mediated activation of virulence genes in environments where PrfA activation is not required, such as in food and the gastrointestinal tract....

  10. DOES JASMONIC ACID PREVENT THE GERMINATION

    OpenAIRE

    ÇAVUŞOĞLU, Kürşat

    2009-01-01

    Abstract: Effect of jasmonic acid on seed germination and seedling growth of barley (Hordeum vulgare L. cv. Bülbül 89) was investigated in the present study. Jasmonic acid concentrations less than 1500 µM have not inhibited the seed germination, while 1500 and 2000 µM jasmonic acid levels caused atypical germination. The germination was completely inhibited at 3000 µM level of jasmonic acid. However, the seedling growth clearly slowed down with increasing concentrations of jasmonic acid. Furt...

  11. Inhibition of fatty acid synthase prevents preadipocyte differentiation

    International Nuclear Information System (INIS)

    Schmid, Bernhard; Rippmann, Joerg F.; Tadayyon, Moh; Hamilton, Bradford S.

    2005-01-01

    Inhibition of fatty acid synthase (FAS) reduces food intake in rodents. As adipose tissue expresses FAS, we sought to investigate the effect of reduced FAS activity on adipocyte differentiation. FAS activity was suppressed either pharmacologically or by siRNA during differentiation of 3T3-L1 cells. Cerulenin (10 μM), triclosan (50 μM), and C75 (50 μM) reduced dramatically visible lipid droplet accumulation, while incorporation of [1- 14 C]acetate into lipids was reduced by 75%, 70%, and 90%, respectively. Additionally, the substances reduced FAS, CEBPα, and PPARγ mRNA by up to 85% compared to that of control differentiated cells. Transient transfection with FAS siRNA suppressed FAS mRNA and FAS activity, and this was accompanied by reduction of CEBPα and PPARγ mRNA levels, and complete prevention of lipid accumulation. CD36, a late marker of differentiation, was also reduced. Together, these results suggest that FAS generated signals may be essential to support preadipocyte differentiation

  12. Roles of Fe-S proteins: from cofactor synthesis to iron homeostasis to protein synthesis.

    Science.gov (United States)

    Pain, Debkumar; Dancis, Andrew

    2016-06-01

    Fe-S cluster assembly is an essential process for all cells. Impairment of Fe-S cluster assembly creates diseases in diverse and surprising ways. In one scenario, the loss of function of lipoic acid synthase, an enzyme with Fe-S cluster cofactor in mitochondria, impairs activity of various lipoamide-dependent enzymes with drastic consequences for metabolism. In a second scenario, the heme biosynthetic pathway in red cell precursors is specifically targeted, and iron homeostasis is perturbed, but lipoic acid synthesis is unaffected. In a third scenario, tRNA modifications arising from action of the cysteine desulfurase and/or Fe-S cluster proteins are lost, which may lead to impaired protein synthesis. These defects can then result in cancer, neurologic dysfunction or type 2 diabetes. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. A New Therapeutic Paradigm for Breast Cancer Exploiting Low Dose Estrogen-Induced Apoptosis

    Science.gov (United States)

    2009-09-01

    acetylcysteine —passe-partout or much ado about nothing? Br. J. Clin. Pharmacol. 61, 5–15 (2006). 25. S. D. Wollin and P. J. Jones, Alpha-lipoic acid and...CYP2D6 variants, as well as CYP2D6 inhibition by prescribed co-medications such as anti- depressants , may decrease tamoxifen metabolism, and thus

  14. Hypoglycemic and beta cell protective effects of andrographolide analogue for diabetes treatment

    Directory of Open Access Journals (Sweden)

    Larrick James W

    2009-07-01

    Full Text Available Abstract Background While all anti-diabetic agents can decrease blood glucose level directly or indirectly, few are able to protect and preserve both pancreatic beta cell mass and their insulin-secreting functions. Thus, there is an urgent need to find an agent or combination of agents that can lower blood glucose and preserve pancreatic beta cells at the same time. Herein, we report a dual-functional andrographolide-lipoic acid conjugate (AL-1. The anti-diabetic and beta cell protective activities of this novel andrographolide-lipoic acid conjugate were investigated. Methods In alloxan-treated mice (a model of type 1 diabetes, drugs were administered orally once daily for 6 days post-alloxan treatment. Fasting blood glucose and serum insulin were determined. Pathologic and immunohistochemical analysis of pancreatic islets were performed. Translocation of glucose transporter subtype 4 in soleus muscle was detected by western blot. In RIN-m cells in vitro, the effect of AL-1 on H2O2-induced damage and reactive oxidative species production stimulated by high glucose and glibenclamide were measured. Inhibition of nuclear factor kappa B (NF-κB activation induced by IL-1β and IFN-γ was investigated. Results In alloxan-induced diabetic mouse model, AL-1 lowered blood glucose, increased insulin and prevented loss of beta cells and their dysfunction, stimulated glucose transport protein subtype 4 (GLUT4 membrane translocation in soleus muscles. Pretreatment of RIN-m cells with AL-1 prevented H2O2-induced cellular damage, quenched glucose and glibenclamide-stimulated reactive oxidative species production, and inhibited cytokine-stimulated NF-κB activation. Conclusion We have demonstrated that AL-1 had both hypoglycemic and beta cell protective effects which translated into antioxidant and NF-κB inhibitory activity. AL-1 is a potential new anti-diabetic agent.

  15. Preventive effects of p-coumaric acid on cardiac hypertrophy and alterations in electrocardiogram, lipids, and lipoproteins in experimentally induced myocardial infarcted rats.

    Science.gov (United States)

    Roy, Abhro Jyoti; Stanely Mainzen Prince, P

    2013-10-01

    The present study evaluated the preventive effects of p-coumaric acid on cardiac hypertrophy and alterations in electrocardiogram, lipids, and lipoproteins in experimentally induced myocardial infarcted rats. Rats were pretreated with p-coumaric acid (8 mg/kg body weight) daily for a period of 7 days and then injected with isoproterenol (100mg/kg body weight) on 8th and 9th day to induce myocardial infarction. Myocardial infarction induced by isoproterenol was indicated by increased level of cardiac sensitive marker and elevated ST-segments in the electrocardiogram. Also, the levels/concentrations of serum and heart cholesterol, triglycerides and free fatty acids were increased in myocardial infarcted rats. Isoproterenol also increased the levels of serum low density and very low density lipoprotein cholesterol and decreased the levels of high density lipoprotein cholesterol. It also enhanced the activity of liver 3-hydroxy-3 methyl glutaryl-Coenzyme-A reductase. p-Coumaric acid pretreatment revealed preventive effects on all the biochemical parameters and electrocardiogram studied in myocardial infarcted rats. The in vitro study confirmed the free radical scavenging property of p-coumaric acid. Thus, p-coumaric acid prevented cardiac hypertrophy and alterations in lipids, lipoproteins, and electrocardiogram, by virtue of its antihypertrophic, antilipidemic, and free radical scavenging effects in isoproterenol induced myocardial infarcted rats. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Association between plasma fatty acids and inflammatory markers in patients with and without insulin resistance and in secondary prevention of cardiovascular disease, a cross-sectional study.

    Science.gov (United States)

    Bersch-Ferreira, Ângela Cristine; Sampaio, Geni Rodrigues; Gehringer, Marcella Omena; Torres, Elizabeth Aparecida Ferraz da Silva; Ross-Fernandes, Maria Beatriz; da Silva, Jacqueline Tereza; Torreglosa, Camila Ragne; Kovacs, Cristiane; Alves, Renata; Magnoni, Carlos Daniel; Weber, Bernardete; Rogero, Marcelo Macedo

    2018-02-21

    Proinflammatory biomarkers levels are increased among patients with cardiovascular disease, and it is known that both the presence of insulin resistance and diet may influence those levels. However, these associations are not well studied among patients with established cardiovascular disease. Our objective is to compare inflammatory biomarker levels among cardiovascular disease secondary prevention patients with and without insulin resistance, and to evaluate if there is any association between plasma fatty acid levels and inflammatory biomarker levels among them. In this cross-sectional sub-study from the BALANCE Program Trial, we collected data from 359 patients with established cardiovascular disease. Plasma fatty acids and inflammatory biomarkers (interleukin (IL)-1β, IL-6, IL-8, IL-10, IL-12, high sensitive C-reactive protein (hs-CRP), adiponectin, and tumor necrosis factor (TNF)-alpha) were measured. Biomarkers and plasma fatty acid levels of subjects across insulin resistant and not insulin resistant groups were compared, and general linear models were used to examine the association between plasma fatty acids and inflammatory biomarkers. Subjects with insulin resistance had a higher concentration of hs-CRP (p = 0.002) and IL-6 (p = 0.002) than subjects without insulin resistance. Among subjects without insulin resistance there was a positive association between stearic fatty acid and IL-6 (p = 0.032), and a negative association between alpha-linolenic fatty acid and pro-inflammatory biomarkers (p fatty acids and arachidonic fatty acid and adiponectin (p fatty acids and pro-inflammatory biomarkers (p fatty acids and adiponectin (p fatty acids. Subjects in secondary prevention for cardiovascular disease with insulin resistance have a higher concentration of hs-CRP and IL-6 than individuals without insulin resistance, and these inflammatory biomarkers are positively associated with saturated fatty acids and negatively associated with

  17. Knowledge and periconceptional use of folic acid for the prevention of neural tube defects in ethnic communities in the United Kingdom: systematic review and meta-analysis.

    Science.gov (United States)

    Peake, Jordana N; Copp, Andrew J; Shawe, Jill

    2013-07-01

    It is widely accepted that periconceptional supplementation with folic acid can prevent a significant proportion of neural tube defects (NTDs). The present study evaluated how folic acid knowledge and periconceptional use for NTD prevention varies by ethnicity in the United Kingdom (U.K.). A literature search was conducted to identify studies that included assessment of folic acid knowledge or use in U.K. women of different ethnicities. Only research and referenced sources published after 1991, the year of the landmark Medical Research Council's Vitamin Study, were included. A meta-analysis was performed of studies that assessed preconceptional folic acid use in Caucasians and non-Caucasians. Five studies met the inclusion criteria for assessment of knowledge and/or use of folic acid supplements in U.K. women including non-Caucasians. The available evidence indicates that South Asians specifically have less knowledge and lower periconceptional use of folic acid than Caucasians; one study found that West Indian and African women also had lower folic acid uptake. A synthesis of results from three of the studies, in a meta-analysis, shows that Caucasians are almost three times more likely to take folic acid before conception than non-Caucasians. From the limited evidence available, U.K. women of non-Caucasian ethnicity appear to have less knowledge and a lower uptake of folic acid supplementation than Caucasians during the periconceptional period. Implementing targeted, innovative education campaigns together with a mandatory fortification policy, including the fortification of ethnic minority foods, will be required for maximum prevention of folic acid-preventable NTDs across different ethnic groups. Copyright © 2013 Wiley Periodicals, Inc.

  18. Ellagic Acid Prevents L-NAME-Induced Hypertension via Restoration of eNOS and p47phox Expression in Rats

    Directory of Open Access Journals (Sweden)

    Thewarid Berkban

    2015-06-01

    Full Text Available The effect of ellagic acid on oxidative stress and hypertension induced by Nω-Nitro-l-arginine methyl ester hydrochloride (L-NAME was investigated. Male Sprague-Dawley rats were administrated with L-NAME (40 mg/kg/day for five weeks. L-NAME induced high systolic blood pressure (SBP and increased heart rate (HR, hindlimb vascular resistance (HVR and oxidative stress. Concurrent treatment with ellagic acid (7.5 or 15 mg/kg prevented these alterations. Co-treatment with ellagic acid was associated with up-regulation of endothelial nitric oxide synthase (eNOS protein production and alleviation of oxidative stress as indicated by decreased superoxide production in the vascular tissue, reduced plasma malondialdehyde levels, reduced NADPH oxidase subunit p47phox expression and increased plasma nitrate/nitrite levels. Our results indicate that ellagic acid attenuates hypertension by reducing NADPH oxidase subunit p47phox expression, which prevents oxidative stress and restores NO bioavailability.

  19. Capabilities of gravitational surgery for improvement of treatment results in patients with diabetic foot syndrome

    Directory of Open Access Journals (Sweden)

    M B Akhmedov

    2018-06-01

    Full Text Available Aim. Improvement of complex treatment results in patients with diabetic foot syndrome by introducing methods of gravitational surgery and α-lipoic acid. Methods. The results of treatment were analyzed for 558 patients with diabetic foot syndrome treated in Scientific Centre of Surgery named after M.A. Topchubashov (Baku, Azerbaijan from 1988 to 2015. The age varied from 28 to 83 years. The patients included 416 men and 142 women. The control group included 90 patients who at the perioperative period underwent basic therapy including antibiotics, anticoagulants, antiaggregants, dextrans, angioprotectors, spasmolytics, corticosteroids, narcotic and non-narcotic analgesics. The study group included 468 patients, along with traditional therapy receiving efferent methods (plasmapheresis, ultraviolet blood irradiation, ozone therapy and α-lipoic acid. 282 patients of the study group received outpatient treatment and 186 - complex inpatient surgical treatment. A comparative evaluation of the results was performed separately in three groups: angiopathy, neuropathy, angioneuropathy. The results were evaluated by clinical and instrumental examinations before and after treatment (6, 12, 60 months and more. Results. In the study group a satisfactory result of treatment was registered in 85.5% of patients, in the control group - in 62.2%, unsatisfactory in 14.5 and 37.8% of patients, respectively (p=0.046. Conclusion. The use of efferent methods and α-lipoic acid provided prompt elimination of numerous pathogenetic disorders observed in diabetes mellitus, decrease of amputation frequency and improvement of complex surgical treatment results in patients with diabetic foot syndrome.

  20. Treatment modalities for burning mouth syndrome: a systematic review.

    Science.gov (United States)

    de Souza, Isadora Follak; Mármora, Belkiss Câmara; Rados, Pantelis Varvaki; Visioli, Fernanda

    2018-06-01

    In the burning mouth syndrome (BMS), patients experience a burning sensation in the oral cavity with no associated injury or clinical manifestation. The etiology of this condition is still poorly understood, and therefore, treatment is challenging. The aim of this study is to perform a systematic review of treatment possibilities described in the literature for BMS. PubMed, Embase, and SciELO databases were searched for randomized clinical trials published between 1996 and 2016. Following application of inclusion and exclusion criteria, 29 papers were analyzed and divided into five subcategories according to the type of treatment described: antidepressants, alpha-lipoic acid, phytotherapeutic agents, analgesic and anti-inflammatory agents, and non-pharmacological therapies. In each category, the results found were compared with regard to the methodology employed, sample size, assessment method, presence or absence of adverse effects, and treatment outcomes. The analysis revealed that the use of antidepressants and alpha-lipoic acid has been showing promising results; however, more studies are necessary before we can have a first-line treatment strategy for patients with BMS. To review systematically the literature about Burning Mouth Syndrome treatment may aid the clinicians to choose the treatment modality to improve patients symptoms based on the best evidence.

  1. Is intravesical instillation of hyaluronic acid and chondroitin sulfate useful in preventing recurrent bacterial cystitis? A multicenter case control analysis

    OpenAIRE

    Giorgio Gugliotta; Gloria Calagna; Giorgio Adile; Salvatore Polito; Salvatore Saitta; Patrizia Speciale; Stefano Palomba; Antonino Perino; Roberta Granese; Biagio Adile

    2015-01-01

    Objective: Urinary tract infections (UTIs) are common in the female population and, over a lifetime, about half of women have at least one episode of UTI requiring antibiotic therapy. The aim of the current study was to compare two different strategies for preventing recurrent bacterial cystitis: intravesical instillation of hyaluronic acid (HA) plus chondroitin sulfate (CS), and antibiotic prophylaxis with sulfamethoxazole plus trimethoprim. Materials and methods: This was a retrospective...

  2. Omega-3 fatty acid oxidation products prevent vascular endothelial cell activation by coplanar polychlorinated biphenyls

    International Nuclear Information System (INIS)

    Majkova, Zuzana; Layne, Joseph; Sunkara, Manjula; Morris, Andrew J.; Toborek, Michal; Hennig, Bernhard

    2011-01-01

    Coplanar polychlorinated biphenyls (PCBs) may facilitate development of atherosclerosis by stimulating pro-inflammatory pathways in the vascular endothelium. Nutrition, including fish oil-derived long-chain omega-3 fatty acids, such as docosahexaenoic acid (DHA, 22:6ω-3), can reduce inflammation and thus the risk of atherosclerosis. We tested the hypothesis that cyclopentenone metabolites produced by oxidation of DHA can protect against PCB-induced endothelial cell dysfunction. Oxidized DHA (oxDHA) was prepared by incubation of the fatty acid with the free radical generator 2,2-azo-bis(2-amidinopropane) dihydrochloride (AAPH). Cellular pretreatment with oxDHA prevented production of superoxide induced by PCB77, and subsequent activation of nuclear factor-κB (NF-κB). A 4 /J 4 -neuroprostanes (NPs) were identified and quantitated using HPLC ESI tandem mass spectrometry. Levels of these NPs were markedly increased after DHA oxidation with AAPH. The protective actions of oxDHA were reversed by treatment with sodium borohydride (NaBH 4 ), which concurrently abrogated A 4 /J 4 -NP formation. Up-regulation of monocyte chemoattractant protein-1 (MCP-1) by PCB77 was markedly reduced by oxDHA, but not by un-oxidized DHA. These protective effects were proportional to the abundance of A 4 /J 4 NPs in the oxidized DHA sample. Treatment of cells with oxidized eicosapentaenoic acid (EPA, 20:5ω-3) also reduced MCP-1 expression, but less than oxDHA. Treatment with DHA-derived cyclopentenones also increased DNA binding of NF-E2-related factor-2 (Nrf2) and downstream expression of NAD(P)H:quinone oxidoreductase (NQO1), similarly to the Nrf-2 activator sulforaphane. Furthermore, sulforaphane prevented PCB77-induced MCP-1 expression, suggesting that activation of Nrf-2 mediates the observed protection against PCB77 toxicity. Our data implicate A 4 /J 4 -NPs as mediators of omega-3 fatty acid-mediated protection against the endothelial toxicity of coplanar PCBs.

  3. Cells How does cobalamin (vitamin B12) enter and traverse ...

    Indian Academy of Sciences (India)

    Administrator

    activity of glucoamylase from Aspergillus candidus and Rhizopus ... Diabetes. Mode of action of lipoic acid in diabetes. 59. Diethylhexyl phthalate. Increase in hepatic ... Definition of physical integrity of synaptosomes and myelosomes by ...

  4. Should the dose of folic acid be adjusted for Mexican population? The pilot prevention program implemented in Nuevo Leon, Mexico.

    Science.gov (United States)

    Martinez de Villarreal, Laura E

    2017-12-11

    In 1980 Smithells et al. reported that the intake of folic acid (FA) prevents the recurrence of neural tube defects (NTDs) [1]. After this and several other studies were conducted, the intake of 400 micrograms of folic acid per day, at least three months before and three months during pregnancy for prevention of NTD, was proposed [2,3,4]. Other strategies were also developed to increase folate blood levels in woman of childbearing age such as promoting the consumption of folate rich foods and food fortification (flour and most recently rice) [5]. Nevertheless, results have not been as expected due to poor consumption of folic acid supplements [6]. As a result, in the year 2000, a novel strategy was developed in order to increase folate blood levels in Mexican women. The results of the strategy are presented, as well as, a discussion about how to personalize a program for different populations.

  5. Gallic acid prevents isoproterenol-induced cardiac hypertrophy and fibrosis through regulation of JNK2 signaling and Smad3 binding activity

    Science.gov (United States)

    Ryu, Yuhee; Jin, Li; Kee, Hae Jin; Piao, Zhe Hao; Cho, Jae Yeong; Kim, Gwi Ran; Choi, Sin Young; Lin, Ming Quan; Jeong, Myung Ho

    2016-01-01

    Gallic acid, a type of phenolic acid, has been shown to have beneficial effects in inflammation, vascular calcification, and metabolic diseases. The present study was aimed at determining the effect and regulatory mechanism of gallic acid in cardiac hypertrophy and fibrosis. Cardiac hypertrophy was induced by isoproterenol (ISP) in mice and primary neonatal cardiomyocytes. Gallic acid pretreatment attenuated concentric cardiac hypertrophy. It downregulated the expression of atrial natriuretic peptide, brain natriuretic peptide, and beta-myosin heavy chain in vivo and in vitro. Moreover, it prevented interstitial collagen deposition and expression of fibrosis-associated genes. Upregulation of collagen type I by Smad3 overexpression was observed in cardiac myoblast H9c2 cells but not in cardiac fibroblasts. Gallic acid reduced the DNA binding activity of phosphorylated Smad3 in Smad binding sites of collagen type I promoter in rat cardiac fibroblasts. Furthermore, it decreased the ISP-induced phosphorylation of c-Jun N-terminal kinase (JNK) and extracellular signal regulated kinase (ERK) protein in mice. JNK2 overexpression reduced collagen type I and Smad3 expression as well as GATA4 expression in H9c2 cells and cardiac fibroblasts. Gallic acid might be a novel therapeutic agent for the prevention of cardiac hypertrophy and fibrosis by regulating the JNK2 and Smad3 signaling pathway. PMID:27703224

  6. Postoperative adhesion prevention in gynecologic surgery with hyaluronic acid.

    Science.gov (United States)

    Carta, G; Cerrone, L; Iovenitti, P

    2004-01-01

    Despite improvements in surgical instrumentation and techniques, adhesions continue to form after most procedures. Peritoneal adhesions develop in 60-90% of women who undergo major gynecological operations. This adhesion formation causes significant postoperative morbidity such as bowel obstruction (65%), infertility (15-20%), and chronic pelvic pain (40%). To demonstrate the efficacy of a hyaluronic acid product (Hyalobarrier Gel) for the prevention of adhesions in gynecological surgery. From October 2000 to July 2002, 18 women from 26 to 41 years old (mean age 33.66) underwent myomectomy via laparotomy as their first abdominal operation. Between August 2001 and May 2003, the patients underwent a second-look laparoscopy (7 women, 38.9%, 15 sites, 42.8%) or a second-look laparotomy (11 women, 61.1%, 20 sites, 57.1%) during which all the 35 sites corresponding to the previous myomectomies were analyzed. During the second-look procedure the presence, localization and severity of adhesions were evaluated using the Operative Laparoscopy Study Group Classification (OLSG) and American Fertility Society Classification (AFSC). All patients underwent a second-look laparoscopy/laparotomy and only five of 18 (27.7%) showed pelvic adhesions in seven sites (20%) of previous myomectomies. No adhesion was found on the previous sites of myomectomies of pedunculated leiomyomas so, excluding those, adhesions were found in seven of 29 sites of myomectomies (24.1%). The present study emphasizes the need for improved treatments to prevent adhesions, as there is no doubt that adhesions represent one of the major causes of female morbidity.

  7. The Role of n-3 Polyunsaturated Fatty Acids in the Prevention and Treatment of Breast Cancer

    Directory of Open Access Journals (Sweden)

    Jiajie Liu

    2014-11-01

    Full Text Available Breast cancer (BC is the most common cancer among women worldwide. Dietary fatty acids, especially n-3 polyunsaturated fatty acids (PUFA, are believed to play a role in reducing BC risk. Evidence has shown that fish consumption or intake of long-chain n-3 PUFA, such as eicosapentaenoic acid (EPA and docosahexaenoic acid (DHA, are beneficial for inhibiting mammary carcinogenesis. The evidence regarding α-linolenic acid (ALA, however, remains equivocal. It is essential to clarify the relation between ALA and cancer since ALA is the principal source of n-3 PUFA in the Western diet and the conversion of ALA to EPA and DHA is not efficient in humans. In addition, the specific anticancer roles of individual n-3 PUFA, alone, have not yet been identified. Therefore, the present review evaluates ALA, EPA and DHA consumed individually as well as in n-3 PUFA mixtures. Also, their role in the prevention of BC and potential anticancer mechanisms of action are examined. Overall, this review suggests that each n-3 PUFA has promising anticancer effects and warrants further research.

  8. Reducing cannabinoid abuse and preventing relapse by enhancing endogenous brain levels of kynurenic acid

    Science.gov (United States)

    Justinova, Zuzana; Mascia, Paola; Wu, Hui-Qiu; Secci, Maria E.; Redhi, Godfrey H.; Panlilio, Leigh V.; Scherma, Maria; Barnes, Chanel; Parashos, Alexandra; Zara, Tamara; Fratta, Walter; Solinas, Marcello; Pistis, Marco; Bergman, Jack; Kangas, Brian D.; Ferré, Sergi; Tanda, Gianluigi; Schwarcz, Robert; Goldberg, Steven R.

    2013-01-01

    In the reward circuitry of the brain, alpha-7-nicotinic acetylcholine receptors (α7nAChRs) modulate effects of delta-9-tetrahydrocannabinol (THC), marijuana’s main psychoactive ingredient. Kynurenic acid (KYNA) is an endogenous negative allosteric modulator of α7nAChRs. Here we report that the kynurenine 3-monooxygenase (KMO) inhibitor Ro 61-8048 increases brain KYNA levels and attenuates cannabinoid-induced increases in extracellular dopamine in reward-related brain areas. In the self-administration model of drug abuse, Ro 61-8048 reduced the rewarding effects of THC and the synthetic cannabinoid WIN 55,212-2 in squirrel monkeys and rats, respectively, and it also prevented relapse to drug-seeking induced by re-exposure to cannabinoids or cannabinoid-associated cues. The effects of enhancing endogenous KYNA levels with Ro 61-8048 were prevented by positive allosteric modulators of α7nAChRs. Despite a clear need, there are currently no medications approved for treatment of marijuana dependence. Modulation of KYNA provides a novel pharmacological strategy for achieving abstinence from marijuana and preventing relapse. PMID:24121737

  9. Prevention of volatile fatty acids production and limitation of odours from winery wastewaters by denitrification.

    Science.gov (United States)

    Bories, André; Guillot, Jean-Michel; Sire, Yannick; Couderc, Marie; Lemaire, Sophie-Andréa; Kreim, Virginie; Roux, Jean-Claude

    2007-07-01

    The effect of the addition of nitrate to winery wastewaters to control the formation of VFA in order to prevent odours during storage and treatment was studied in batch bioreactors at different NO(3)/chemical oxygen demand (COD) ratios and at full scale in natural evaporation ponds (2 x 7000 m(2)) by measuring olfactory intensity. In the absence of nitrate, butyric acid (2304 mgL(-1)), acetic acid (1633 mgL(-1)), propionic acid (1558 mgL(-1)), caproic acid (499 mgL(-1)) and valeric acid (298 mgL(-1)) were produced from reconstituted winery wastewater. For a ratio of NO(3)/COD=0.4 gg(-1), caproic and valeric acids were not formed. The production of butyric and propionic acids was reduced by 93.3% and 72.5%, respectively, at a ratio of NO(3)/COD=0.8, and by 97.4% and 100% at a ratio of NO(3)/COD=1.2 gg(-1). Nitrate delayed and decreased butyric acid formation in relation to the oxidoreduction potential. Studies in ponds showed that the addition of concentrated calcium nitrate (NITCAL) to winery wastewaters (3526 m(3)) in a ratio of NO(3)/COD=0.8 inhibited VFA production, with COD elimination (94%) and total nitrate degradation, and no final nitrite accumulation. On the contrary, in ponds not treated with nitrate, malodorous VFA (from propionic to heptanoïc acids) represented up to 60% of the COD. Olfactory intensity measurements in relation to the butanol scale of VFA solutions and the ponds revealed the pervasive role of VFA in the odour of the untreated pond as well as the clear decrease in the intensity and not unpleasant odour of the winery wastewater pond enriched in nitrates. The results obtained at full scale underscored the feasibility and safety of the calcium nitrate treatment as opposed to concentrated nitric acid.

  10. Interleukin-1β inhibits insulin signaling and prevents insulin-stimulated system A amino acid transport in primary human trophoblasts.

    Science.gov (United States)

    Aye, Irving L M H; Jansson, Thomas; Powell, Theresa L

    2013-12-05

    Interleukin-1β (IL-1β) promotes insulin resistance in tissues such as liver and skeletal muscle; however the influence of IL-1β on placental insulin signaling is unknown. We recently reported increased IL-1β protein expression in placentas of obese mothers, which could contribute to insulin resistance. In this study, we tested the hypothesis that IL-1β inhibits insulin signaling and prevents insulin-stimulated amino acid transport in cultured primary human trophoblast (PHT) cells. Cultured trophoblasts isolated from term placentas were treated with physiological concentrations of IL-1β (10pg/ml) for 24h. IL-1β increased the phosphorylation of insulin receptor substrate-1 (IRS-1) at Ser307 (inhibitory) and decreased total IRS-1 protein abundance but did not affect insulin receptor β expression. Furthermore, IL-1β inhibited insulin-stimulated phosphorylation of IRS-1 (Tyr612, activation site) and Akt (Thr308) and prevented insulin-stimulated increase in PI3K/p85 and Grb2 protein expression. IL-1β alone stimulated cRaf (Ser338), MEK (Ser221) and Erk1/2 (Thr202/Tyr204) phosphorylation. The inflammatory pathways nuclear factor kappa B and c-Jun N-terminal kinase, which are involved in insulin resistance, were also activated by IL-1β treatment. Moreover, IL-1β inhibited insulin-stimulated System A, but not System L amino acid uptake, indicating functional impairment of insulin signaling. In conclusion, IL-1β inhibited the insulin signaling pathway by inhibiting IRS-1 signaling and prevented insulin-stimulated System A transport, thereby promoting insulin resistance in cultured PHT cells. These findings indicate that conditions which lead to increased systemic maternal or placental IL-1β levels may attenuate the effects of maternal insulin on placental function and consequently fetal growth. Published by Elsevier Ireland Ltd.

  11. Chlorogenic acid and caffeic acid are absorbed in humans

    NARCIS (Netherlands)

    Olthof, Margreet R.; Hollman, Peter C H; Katan, Martijn B.

    2001-01-01

    Chlorogenic acid, an ester of caffeic acid and quinic acid, is a major phenolic compound in coffee; daily intake in coffee drinkers is 0.5-1 g. Chlorogenic acid and caffeic acid are antioxidants in vitro and might therefore contribute to the prevention of cardiovascular disease. However, data on the

  12. Oral bioavailability of the ether lipid plasmalogen precursor, PPI-1011, in the rabbit: a new therapeutic strategy for Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Wood Paul L

    2011-12-01

    Full Text Available Abstract Introduction Docosahexaenoic acid (DHA and DHA-containing ethanolamine plasmalogens (PlsEtn are decreased in the brain, liver and the circulation in Alzheimer's disease. Decreased supply of plasmalogen precursors to the brain by the liver, as a result of peroxisomal deficits is a process that probably starts early in the AD disease process. To overcome this metabolic compromise, we have designed an orally bioavailable DHA-containing ether lipid precursor of plasmalogens. PPI-1011 is an alkyl-diacyl plasmalogen precursor with palmitic acid at sn-1, DHA at sn-2 and lipoic acid at sn-3. This study outlines the oral pharmacokinetics of this precursor and its conversion to PlsEtn and phosphatidylethanolamines (PtdEtn. Methods Rabbits were dosed orally with PPI-1011 in hard gelatin capsules for time-course and dose response studies. Incorporation into PlsEtn and PtdEtn was monitored by LC-MS/MS. Metabolism of released lipoic acid was monitored by GC-MS. To monitor the metabolic fate of different components of PPI-1011, we labeled the sn-1 palmitic acid, sn-2 DHA and glycerol backbone with13C and monitored their metabolic fates by LC-MS/MS. Results PPI-1011 was not detected in plasma suggesting rapid release of sn-3 lipoic acid via gut lipases. This conclusion was supported by peak levels of lipoic acid metabolites in the plasma 3 hours after dosing. While PPI-1011 did not gain access to the plasma, it increased circulating levels of DHA-containing PlsEtn and PtdEtn. Labeling experiments demonstrated that the PtdEtn increases resulted from increased availability of DHA released via remodeling at sn-2 of phospholipids derived from PPI-1011. This release of DHA peaked at 6 hrs while increases in phospholipids peaked at 12 hr. Increases in circulating PlsEtn were more complex. Labeling experiments demonstrated that increases in the target PlsEtn, 16:0/22:6, consisted of 2 pools. In one pool, the intact precursor received a sn-3

  13. Reaction Characteristics of Andrographolide and its Analogue AL-1 with GSH, as a Simple Chemical Simulation of NF-κB Inhibition

    Directory of Open Access Journals (Sweden)

    Yuqiang Wang

    2012-01-01

    Full Text Available 14-α-Lipoic acid-3,19-dihydroxyandrographolide (AL-1, 2 is an analogue of andrographolide (Andro, 1 coupled to α-lipoic acid (LA, 4. AL-1 was at least 10-fold more potent than the natural parent compound Andro in inhibiting nuclear factor (NF-κB activation in RIN-m cells. In the present study, glutathione (GSH, 3 was used as a simple chemical model molecule of NF-κB with cysteine 62. The characteristics of the reaction between AL-1 or Andro and GSH were investigated to trace some possible elucidation for the inhibitive mechanism and stronger inhibition of AL-1 to NF-κB activation. The results showed that the main reaction products of AL-1 and Andro were identical, sulfhydryl adduct and amino adduct. AL-1 reacted much faster than Andro with GSH. The product yield of AL-1 was much higher than that of Andro. It was speculated that AL-1 might inhibit NF-κB by the same mechanism as Andro. And the faster reaction rate and higher yield may account for the stronger NF-κB inhibition of AL-1 when compared with Andro.

  14. Cost-effectiveness of denosumab versus zoledronic acid for preventing skeletal-related events in the Czech Republic.

    Science.gov (United States)

    Cristino, Joaquim; Finek, Jíndřich; Jandova, Petra; Kolek, Martin; Pásztor, Bálint; Giannopoulou, Christina; Qian, Yi; Brezina, Tomas; Lothgren, Mickael

    2017-08-01

    This study assessed the cost-effectiveness of the subcutaneous RANKL inhibitor, denosumab, vs the intravenous bisphosphonate, zoledronic acid, for the prevention of skeletal-related events (SREs) in patients with prostate cancer, breast cancer, and other solid tumors (OST) in the Czech Republic. A lifetime Markov model was developed to compare the effects of denosumab and zoledronic acid on costs (including drug costs and administration, patient management, SREs, and adverse events), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios from a national payer perspective. Different discount rates, time horizons, SRE rates, distributions, and nature (asymptomatic vs all SREs), and the inclusion of treatment discontinuation were considered in scenario analyses. The robustness of the model was tested using deterministic and probabilistic sensitivity analyses. Across tumor types, denosumab was associated with fewer SREs, improved QALYs, and higher total costs over a lifetime. The incremental cost per QALY gained for denosumab vs zoledronic acid was 382,673 CZK for prostate cancer, 408,450 CZK for breast cancer, and 608,133 CZK for OST. Incremental costs per SRE avoided for the same tumor type were 54,007 CZK, 51,765 CZK, and 94,426 CZK, respectively. In scenario analyses, the results remained similar to baseline, when different discount rates and time horizons were considered. At a non-official willingness-to-pay threshold of 1.2 million CZK, the probabilities of denosumab being cost-effective vs zoledronic acid were 0.64, 0.67, and 0.49 for prostate cancer, breast cancer, and OST, respectively. The SRE rates used were obtained from clinical trials; studies suggest rates may be higher in clinical practice. Additional evidence on real-world SRE rates could further improve the accuracy of the modeling. Compared with zoledronic acid, denosumab provides a cost-effective treatment option for the prevention of SREs in patients with prostate cancer

  15. Highly Conductive and Reliable Copper-Filled Isotropically Conductive Adhesives Using Organic Acids for Oxidation Prevention

    Science.gov (United States)

    Chen, Wenjun; Deng, Dunying; Cheng, Yuanrong; Xiao, Fei

    2015-07-01

    The easy oxidation of copper is one critical obstacle to high-performance copper-filled isotropically conductive adhesives (ICAs). In this paper, a facile method to prepare highly reliable, highly conductive, and low-cost ICAs is reported. The copper fillers were treated by organic acids for oxidation prevention. Compared with ICA filled with untreated copper flakes, the ICA filled with copper flakes treated by different organic acids exhibited much lower bulk resistivity. The lowest bulk resistivity achieved was 4.5 × 10-5 Ω cm, which is comparable to that of commercially available Ag-filled ICA. After 500 h of 85°C/85% relative humidity (RH) aging, the treated ICAs showed quite stable bulk resistivity and relatively stable contact resistance. Through analyzing the results of x-ray diffraction, x-ray photoelectron spectroscopy, and thermogravimetric analysis, we found that, with the assistance of organic acids, the treated copper flakes exhibited resistance to oxidation, thus guaranteeing good performance.

  16. Techniques to correct and prevent acid mine drainage: A review

    OpenAIRE

    Pozo-Antonio, Santiago; Puente-Luna, Iván; Lagüela-López, Susana; Veiga-Ríos, María

    2014-01-01

    Acid mine drainage (AMD) from mining wastes is one of the current environmental problems in the field of mining pollution that requires most action measures. This term describes the drainage generated by natural oxidation of sulfide minerals when they are exposed to the combined action of water and atmospheric oxygen. AMD is characterized by acidic effluents with a high content of sulfate and heavy metal ions in solution, which can contaminate both groundwater and surface water. Minerals resp...

  17. Acid-base properties of a limed pyritic overburden during simulated weathering

    Energy Technology Data Exchange (ETDEWEB)

    Doolittle, J.J.; Hossner, L.R. [South Dakota State University, Brookings, SD (United States). Plant Science Dept.

    1997-11-01

    Surface-mine reclamation is often hindered by the formation of acid mine soil and acid mine drainage from FeS{sub 2} oxidation. Surface soils containing FeS{sub 2} are often treated with crushed limestone (predominately CaCO{sub 3}) to prevent aid minesoil formation. The main objective of this study was to evaluate the long-term effectiveness of liming pyritic minesoil to prevent the formation of acid minesoil and acid mine drainage. Pyritic minesoils that did not receive lime became acidic very rapidly and produced acidic leachate. Almost all of the FeS{sub 2} in this treatment oxidized during the first 200 d. The addition of lime at a rate of 25% of the theoretical acid-base account (ABA) significantly slowed FeS{sub 2} oxidation, but rapid oxidation ensued after the added lime was neutralized. Treatments receiving a liming rate of 50% ABA or greater remained neutral to alkaline throughout the study. Acid-base values and residual FeS{sub 2}-CO{sub 3} data, however, indicate that the lime was dissolving from the system faster than the FeS{sub 2} was oxidizing, and all the treatments would eventually become acidic. The results indicate that the liming of a pyritic overburden to an ABA of 125% is not a sustainable solution to preventing acid minesoil and acid mine drainage. 25 refs., 6 figs., 3 tabs.

  18. Conclusions and recommendations from the symposium, Beyond Cholesterol: Prevention and Treatment of Coronary Heart Disease with n-3 Fatty Acids.

    Science.gov (United States)

    Deckelbaum, Richard J; Leaf, Alexander; Mozaffarian, Dariush; Jacobson, Terry A; Harris, William S; Akabas, Sharon R

    2008-06-01

    After the symposium "Beyond Cholesterol: Prevention and Treatment of Coronary Heart Disease with n-3 Fatty Acids," faculty who presented at the conference submitted manuscripts relating to their conference topics, and these are presented in this supplement. The content of these manuscripts was reviewed, and 2 conference calls were convened. The objective was to summarize existing evidence, gaps in evidence, and future research needed to strengthen recommendations for specific intakes of n-3 fatty acids for different conditions relating to cardiovascular disease. The following 2 questions were the main items discussed. What are the roles of n-3 fatty acids in primary versus secondary prevention of coronary heart disease? What are the roles of n-3 fatty acids in hypertriglyceridemia, in the metabolic syndrome and type 2 diabetes, and in sudden cardiac death, cardiac arrhythmias, and vulnerable plaque? Each area was summarized by using 2 general categories: 1) current knowledge for which general consensus exists, and 2) recommendations for research and policy. Additional references for these conclusions can be found in the articles included in the supplement.

  19. Valproic acid prevents retinal degeneration in a murine model of normal tension glaucoma.

    Science.gov (United States)

    Kimura, Atsuko; Guo, Xiaoli; Noro, Takahiko; Harada, Chikako; Tanaka, Kohichi; Namekata, Kazuhiko; Harada, Takayuki

    2015-02-19

    Valproic acid (VPA) is widely used for treatment of epilepsy, mood disorders, migraines and neuropathic pain. It exerts its therapeutic benefits through modulation of multiple mechanisms including regulation of gamma-aminobutyric acid and glutamate neurotransmissions, activation of pro-survival protein kinases and inhibition of histone deacetylase. The evidence for neuroprotective properties associated with VPA is emerging. Herein, we investigated the therapeutic potential of VPA in a mouse model of normal tension glaucoma (NTG). Mice with glutamate/aspartate transporter gene deletion (GLAST KO mice) demonstrate progressive retinal ganglion cell (RGC) loss and optic nerve degeneration without elevated intraocular pressure, and exhibit glaucomatous pathology including glutamate neurotoxicity and oxidative stress in the retina. VPA (300mg/kg) or vehicle (PBS) was administered via intraperitoneal injection in GLAST KO mice daily for 2 weeks from the age of 3 weeks, which coincides with the onset of glaucomatous retinal degeneration. Following completion of the treatment period, the vehicle-treated GLAST KO mouse retina showed significant RGC death. Meanwhile, VPA treatment prevented RGC death and thinning of the inner retinal layer in GLAST KO mice. In addition, in vivo electrophysiological analyses demonstrated that visual impairment observed in vehicle-treated GLAST KO mice was ameliorated with VPA treatment, clearly establishing that VPA beneficially affects both histological and functional aspects of the glaucomatous retina. We found that VPA reduces oxidative stress induced in the GLAST KO retina and stimulates the cell survival signalling pathway associated with extracellular-signal-regulated kinases (ERK). This is the first study to report the neuroprotective effects of VPA in an animal model of NTG. Our findings raise intriguing possibilities that the widely prescribed drug VPA may be a novel candidate for treatment of glaucoma. Copyright © 2015 Elsevier

  20. Weathering behaviour of overburden-coal ash blending in relation to overburden management for acid mine drainage prevention in coal surface mine

    International Nuclear Information System (INIS)

    Gautama, R.S.; Kusuma, G.J.; Lestari, I.; Anggana, R.P.

    2010-01-01

    Potentially acid forming (PAF) materials are encapsulated with non-acid forming materials (NAF) in order to prevent acid mine drainage (AMD) in surface coal mines. NAF compaction techniques with fly and bottom ashes from coal-fired power plants are used in mines with limited amounts of NAF materials. This study investigated the weathering behaviour of blended overburden and coal combustion ash in laboratory conditions. Free draining column leach tests were conducted on different blending schemes. The weathering process was simulated by spraying the samples with de-ionized water once per day. The leachates were then analyzed using X-ray diffraction and fluorescence analyses in order to identify the mineral composition of the samples over a 14 week period. Results of the study indicated that the weathering process plays a significant role in controlling infiltration rates, and may increase the capability of capping materials to prevent infiltration into PAF materials. Fly- and bottom-ash additions improved the performance of the encapsulation materials. 3 refs., 4 tabs., 2 figs.

  1. A Prevention of Pre-eclampsia with the Use of Acetylsalicylic Acid and Low-molecular Weight Heparin - Molecular Mechanisms.

    Science.gov (United States)

    Darmochwal-Kolarz, Dorota; Kolarz, Bogdan; Korzeniewski, Michal; Kimber-Trojnar, Zaneta; Patro-Malysza, Jolanta; Mierzynski, Radzisław; Przegalinska-Kałamucka, Monika; Oleszczuk, Jan

    Pre-eclampsia appears to be the main cause for the maternal and fetal morbidity and mortality. Pregnant women with pre-eclampsia are more likely to be threatened with conditions which potentially may be lethal, such as: disseminated intravascular coagulation, cerebral hemorrhage, liver and renal failure. Pregnancy complicated with pre-eclampsia is also associated with a greater risk for iatrogenic prematurity, intrauterine growth retardation, premature abruption of placenta, and even intrauterine fetal death. In the majority of cases the reasons for arterial hypertension among pregnant women remain obscure. For the past decades, there were many abortive attempts in the use of some microelements, vitamins or specific diets, such as polyunsaturated fatty acids, for the prophylaxis of pre-eclampsia. Recently, it has been shown that a prevention of pre-eclampsia with the use of a lowmolecular- weight heparins (LMWHs) and acetylsalicylic acid (ASA) could considerably reduce the frequency of preeclampsia. In this review, we present the studies concerning the applications of LMWHs and aspirin in the prophylaxis of pre-eclampsia and some important data about the mechanisms of anti-inflammatory actions of LMWHs and ASA.

  2. [Pathomechanism of diabetic neuropathy: background of the pathogenesis-oriented therapy].

    Science.gov (United States)

    Winkler, Gábor; Kempler, Péter

    2010-06-13

    The pathomechanism of diabetic neuropathy remains still poorly understood, however, a broad spectrum of novel findings associated with therapeutic consequences emerged during the last decades. Both disturbed function of primary hemostasis and increased activity of coagulation system contribute to the reduced endoneurial blood flow. Increased superoxide anion production induced by hyperglycemia leads to decreased activity of glycerinaldehid-3-phosphate dehydrogenase and to consequential increased activity of alternative pathways, including the polyol-, hexosamine-, diacilglycerol protein kinase-C- and advanced glycation pathways. Advanced glycation endproducts increase the activity of the nuclear-factor kappa-B, as well as the production of vasoactive factors and cytokines (interleukin-1, -6, tumor necrosis factor alpha). The aim of pathogenetic oriented treatment is to slow down, stop or reverse the progression of neuropathy. Components of pathogenetic oriented treatment are glycaemic control, management of risk factors, benfotiamine and alpha-lipoic acid. On one hand, transketolase-activator benfotiamine inhibits alternative pathways induced by hyperglycemia (the polyol-, hexosamine-, diacilglycerol protein kinase-C-, and advanced glycation pathways), while, on the other hand, it increases the activity of the pentose-phosphate-shunt. The clinical effectiveness of benfotiamine has been shown in many international and Hungarian trials. Alpha-lipoic acid as a powerful antioxidant decreases oxidative stress and this way increases the activity of glycerinaldehid-3-phosphate dehydrogenase. Alpha-lipoic acid administered in infusion or oral treatment decreases both symptoms of neuropathy and neuropathic deficit. In conclusion, the case of diabetic neuropathy illustrates well, how widening of our knowledge on pathogenesis might contribute to successful therapy.

  3. Biallelic Mutations in LIPT2 Cause a Mitochondrial Lipoylation Defect Associated with Severe Neonatal Encephalopathy.

    Science.gov (United States)

    Habarou, Florence; Hamel, Yamina; Haack, Tobias B; Feichtinger, René G; Lebigot, Elise; Marquardt, Iris; Busiah, Kanetee; Laroche, Cécile; Madrange, Marine; Grisel, Coraline; Pontoizeau, Clément; Eisermann, Monika; Boutron, Audrey; Chrétien, Dominique; Chadefaux-Vekemans, Bernadette; Barouki, Robert; Bole-Feysot, Christine; Nitschke, Patrick; Goudin, Nicolas; Boddaert, Nathalie; Nemazanyy, Ivan; Delahodde, Agnès; Kölker, Stefan; Rodenburg, Richard J; Korenke, G Christoph; Meitinger, Thomas; Strom, Tim M; Prokisch, Holger; Rotig, Agnes; Ottolenghi, Chris; Mayr, Johannes A; de Lonlay, Pascale

    2017-08-03

    Lipoate serves as a cofactor for the glycine cleavage system (GCS) and four 2-oxoacid dehydrogenases functioning in energy metabolism (α-oxoglutarate dehydrogenase [α-KGDHc] and pyruvate dehydrogenase [PDHc]), or amino acid metabolism (branched-chain oxoacid dehydrogenase, 2-oxoadipate dehydrogenase). Mitochondrial lipoate synthesis involves three enzymatic steps catalyzed sequentially by lipoyl(octanoyl) transferase 2 (LIPT2), lipoic acid synthetase (LIAS), and lipoyltransferase 1 (LIPT1). Mutations in LIAS have been associated with nonketotic hyperglycinemia-like early-onset convulsions and encephalopathy combined with a defect in mitochondrial energy metabolism. LIPT1 deficiency spares GCS deficiency and has been associated with a biochemical signature of combined 2-oxoacid dehydrogenase deficiency leading to early death or Leigh-like encephalopathy. We report on the identification of biallelic LIPT2 mutations in three affected individuals from two families with severe neonatal encephalopathy. Brain MRI showed major cortical atrophy with white matter abnormalities and cysts. Plasma glycine was mildly increased. Affected individuals' fibroblasts showed reduced oxygen consumption rates, PDHc, α-KGDHc activities, leucine catabolic flux, and decreased protein lipoylation. A normalization of lipoylation was observed after expression of wild-type LIPT2, arguing for LIPT2 requirement in intramitochondrial lipoate synthesis. Lipoic acid supplementation did not improve clinical condition nor activities of PDHc, α-KGDHc, or leucine metabolism in fibroblasts and was ineffective in yeast deleted for the orthologous LIP2. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  4. Retinoic Acid Is Essential for Th1 Cell Lineage Stability and Prevents Transition to a Th17 Cell Program

    Science.gov (United States)

    Brown, Chrysothemis C.; Esterhazy, Daria; Sarde, Aurelien; London, Mariya; Pullabhatla, Venu; Osma-Garcia, Ines; al-Bader, Raya; Ortiz, Carla; Elgueta, Raul; Arno, Matthew; de Rinaldis, Emanuele; Mucida, Daniel; Lord, Graham M.; Noelle, Randolph J.

    2015-01-01

    Summary CD4+ T cells differentiate into phenotypically distinct T helper cells upon antigenic stimulation. Regulation of plasticity between these CD4+ T-cell lineages is critical for immune homeostasis and prevention of autoimmune disease. However, the factors that regulate lineage stability are largely unknown. Here we investigate a role for retinoic acid (RA) in the regulation of lineage stability using T helper 1 (Th1) cells, traditionally considered the most phenotypically stable Th subset. We found that RA, through its receptor RARα, sustains stable expression of Th1 lineage specifying genes, as well as repressing genes that instruct Th17-cell fate. RA signaling is essential for limiting Th1-cell conversion into Th17 effectors and for preventing pathogenic Th17 responses in vivo. Our study identifies RA-RARα as a key component of the regulatory network governing maintenance and plasticity of Th1-cell fate and defines an additional pathway for the development of Th17 cells. PMID:25769610

  5. Docosahexaenoic acid prevents paraquat-induced reactive oxygen species production in dopaminergic neurons via enhancement of glutathione homeostasis

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hyoung Jun; Han, Jeongsu; Jang, Yunseon; Kim, Soo Jeong; Park, Ji Hoon; Seo, Kang Sik [Department of Biochemistry, College of Medicine, Chungnam National University, Daejeon (Korea, Republic of); Jeong, Soyeon; Shin, Soyeon; Lim, Kyu [Department of Biochemistry, College of Medicine, Chungnam National University, Daejeon (Korea, Republic of); Infection Signaling Network Research Center, Chungnam National University, Daejeon (Korea, Republic of); Heo, Jun Young, E-mail: junyoung3@gmail.com [Brainscience Institute, Chungnam National University, Daejeon (Korea, Republic of); Kweon, Gi Ryang, E-mail: mitochondria@cnu.ac.kr [Department of Biochemistry, College of Medicine, Chungnam National University, Daejeon (Korea, Republic of); Infection Signaling Network Research Center, Chungnam National University, Daejeon (Korea, Republic of)

    2015-01-30

    Highlights: • DHA prevents PQ-induced dopaminergic neuronal loss via decreasing of excessive ROS. • DHA increases GR and GCLm derivate GSH pool by enhancement of Nrf2 expression. • Protective mechanism is removal of PQ-induced ROS via DHA-dependent GSH pool. • DHA may be a good preventive strategy for Parkinson’s disease (PD) therapy. - Abstract: Omega-3 polyunsaturated fatty acid levels are reduced in the substantia nigra area in Parkinson’s disease patients and animal models, implicating docosahexaenoic acid (DHA) as a potential treatment for preventing Parkinson’s disease and suggesting the need for investigations into how DHA might protect against neurotoxin-induced dopaminergic neuron loss. The herbicide paraquat (PQ) induces dopaminergic neuron loss through the excessive production of reactive oxygen species (ROS). We found that treatment of dopaminergic SN4741 cells with PQ reduced cell viability in a dose-dependent manner, but pretreatment with DHA ameliorated the toxic effect of PQ. To determine the toxic mechanism of PQ, we measured intracellular ROS content in different organelles with specific dyes. As expected, all types of ROS were increased by PQ treatment, but DHA pretreatment selectively decreased cytosolic hydrogen peroxide content. Furthermore, DHA treatment-induced increases in glutathione reductase and glutamate cysteine ligase modifier subunit (GCLm) mRNA expression were positively correlated with glutathione (GSH) content. Consistent with this increase in GCLm mRNA levels, Western blot analysis revealed that DHA pretreatment increased nuclear factor-erythroid 2 related factor 2 (Nrf2) protein levels. These findings indicate that DHA prevents PQ-induced neuronal cell loss by enhancing Nrf2-regulated GSH homeostasis.

  6. Docosahexaenoic acid prevents paraquat-induced reactive oxygen species production in dopaminergic neurons via enhancement of glutathione homeostasis

    International Nuclear Information System (INIS)

    Lee, Hyoung Jun; Han, Jeongsu; Jang, Yunseon; Kim, Soo Jeong; Park, Ji Hoon; Seo, Kang Sik; Jeong, Soyeon; Shin, Soyeon; Lim, Kyu; Heo, Jun Young; Kweon, Gi Ryang

    2015-01-01

    Highlights: • DHA prevents PQ-induced dopaminergic neuronal loss via decreasing of excessive ROS. • DHA increases GR and GCLm derivate GSH pool by enhancement of Nrf2 expression. • Protective mechanism is removal of PQ-induced ROS via DHA-dependent GSH pool. • DHA may be a good preventive strategy for Parkinson’s disease (PD) therapy. - Abstract: Omega-3 polyunsaturated fatty acid levels are reduced in the substantia nigra area in Parkinson’s disease patients and animal models, implicating docosahexaenoic acid (DHA) as a potential treatment for preventing Parkinson’s disease and suggesting the need for investigations into how DHA might protect against neurotoxin-induced dopaminergic neuron loss. The herbicide paraquat (PQ) induces dopaminergic neuron loss through the excessive production of reactive oxygen species (ROS). We found that treatment of dopaminergic SN4741 cells with PQ reduced cell viability in a dose-dependent manner, but pretreatment with DHA ameliorated the toxic effect of PQ. To determine the toxic mechanism of PQ, we measured intracellular ROS content in different organelles with specific dyes. As expected, all types of ROS were increased by PQ treatment, but DHA pretreatment selectively decreased cytosolic hydrogen peroxide content. Furthermore, DHA treatment-induced increases in glutathione reductase and glutamate cysteine ligase modifier subunit (GCLm) mRNA expression were positively correlated with glutathione (GSH) content. Consistent with this increase in GCLm mRNA levels, Western blot analysis revealed that DHA pretreatment increased nuclear factor-erythroid 2 related factor 2 (Nrf2) protein levels. These findings indicate that DHA prevents PQ-induced neuronal cell loss by enhancing Nrf2-regulated GSH homeostasis

  7. Preventive effects of omega-3 and omega-6 Fatty acids on peroxide mediated oxidative stress responses in primary human trabecular meshwork cells.

    Directory of Open Access Journals (Sweden)

    Theofilos Tourtas

    Full Text Available Pathologic processes in glaucoma include increased apoptosis, accumulation of extracellular material in the trabecular meshwork and optic nerve, condensations of the cytoskeleton and precocious cellular senescence. Oxidative stress was shown to generate these alterations in primary ocular cells. Fatty acids omega-3 and -6 are alleged to constitute a prophylaxis against these deleterious effects. Here, we tested actual preventive effects omega-3 and -6 against peroxide induced stress responses in primary human trabecular meshwork cells. Changes of mitochondrial activity, proliferation, heat shock proteins, extracellular matrix components, and inflammatory markers were evaluated. Alterations of the cytoskeleton were evaluated by phalloidin labeling. Here we report a repressive effect of omega-6 on metabolic activity and proliferation, which was not detected for omega-3. Both agents were able to prevent the anti-proliferative effect of H₂O₂, but only omega-3 prevented metabolic repression. Expression of heat shock protein 27 was unaltered by both fatty acids, whereas heat shock protein 90 was significantly induced by both. Omega-6 increased fibronectin and connective tissue growth factor synthesis, as well as the amount of secreted fibronectin. Omega-3, instead, induced plasminogen activator inhibitor 1 synthesis. H₂O₂ further increased fibronectin production in omega-6 supplemented cells, which was not the case in omega-3 treated cells. H₂O₂ stimulation of plasminogen activator inhibitor 1 and connective tissue growth factor was repressed by both fatty acids. Both fatty acids appeared to abolish H₂O₂ mediated stimulation of nuclear factor κB and IL-6, but not IL-1α and IL-8. H₂O₂ induced formation of cross-linked actin networks and stress fibers, which was reduced by preemptive application of omega-3. Omega-6, in contrast, had no protective effect on that, and even seemed to promote condensation. Based on the observed side

  8. Dietary Berries and Ellagic Acid Prevent Oxidative DNA Damage and Modulate Expression of DNA Repair Genes

    Directory of Open Access Journals (Sweden)

    Ramesh C. Gupta

    2008-03-01

    Full Text Available DNA damage is a pre-requisite for the initiation of cancer and agents that reduce this damage are useful in cancer prevention. In this study, we evaluated the ability of whole berries and berry phytochemical, ellagic acid to reduce endogenous oxidative DNA damage. Ellagic acid was selected based on > 95% inhibition of 8-oxodeoxyguosine (8-oxodG and other unidentified oxidative DNA adducts induced by 4-hydroxy-17B;-estradiol and CuCl2 in vitro. Inhibition of the latter occurred at lower concentrations (10 u(microM than that for 8-oxodG (100 u(microM. In the in vivo study, female CD-1 mice (n=6 were fed either a control diet or diet supplemented with ellagic acid (400 ppm and dehydrated berries (5% w/w with varying ellagic acid contents -- blueberry (low, strawberry (medium and red raspberry (high, for 3 weeks. Blueberry and strawberry diets showed moderate reductions in endogenous DNA adducts (25%. However, both red raspberry and ellagic acid diets showed a significant reduction of 59% (p < 0.001 and 48% (p < 0.01, respectively. Both diets also resulted in a 3-8 fold over-expression of genes involved in DNA repair such as xeroderma pigmentosum group A complementing protein (XPA, DNA excision repair protein (ERCC5 and DNA ligase III (DNL3. These results suggest that red raspberry and ellagic acid reduce endogenous oxidative DNA damage by mechanisms which may involve increase in DNA repair.

  9. Vanillin improves and prevents trinitrobenzene sulfonic acid-induced colitis in mice.

    Science.gov (United States)

    Wu, Shih-Lu; Chen, Jaw-Chyun; Li, Chia-Cheng; Lo, Hsin-Yi; Ho, Tin-Yun; Hsiang, Chien-Yun

    2009-08-01

    Inflammatory bowel disease (IBD) is chronic inflammatory and relapsing disease of the gut. It has been known that activation of nuclear factor-kappaB (NF-kappaB) and production of proinflammatory cytokines play important roles in the pathogenesis of IBD. In this study, the effect of vanillin (4-hydroxy-3-methoxybenzaldehyde), a potent nuclear factor-kappaB (NF-kappaB) inhibitor, was evaluated in mice with trinitrobenzene sulfonic acid (TNBS)-induced colitis. Oral administration of vanillin improved macroscopic and histological features of TNBS-induced colitis in a dose-dependent manner. Vanillin not only prevented TNBS-induced colitis but also ameliorated the established colitis. By in vivo NF-kappaB bioluminescence imaging, electrophoretic mobility shift assay, and Western blot, we found that vanillin suppressed in vivo NF-kappaB activities through the inhibition of p65 translocation, inhibitor of nuclear factor-kappaB(IkappaB)-alpha phosphorylation, and IkappaB kinase activation. Furthermore, vanillin reduced the expressions of proinflammatory cytokines [interleukin (IL)-1beta, IL-6, interferon-gamma, and tumor necrosis factor-alpha] and stimulated the expression of anti-inflammatory cytokine (IL-4) in colonic tissues. In conclusion, this work identified vanillin as an anti-inflammatory compound with the capacity to prevent and ameliorate TNBS-induced colitis. Due to its safety, vanillin could be a potent candidate for the treatment of IBD.

  10. Dietary intervention with green dwarf banana flour (Musa sp AAA) prevents intestinal inflammation in a trinitrobenzenesulfonic acid model of rat colitis.

    Science.gov (United States)

    Scarminio, Viviane; Fruet, Andrea C; Witaicenis, Aline; Rall, Vera L M; Di Stasi, Luiz C

    2012-03-01

    Dietary products are among the therapeutic approaches used to modify intestinal microflora and to promote protective effects during the intestinal inflammatory process. Because the banana plant is rich in resistant starch, which is used by colonic microbiota for the anaerobic production of the short-chain fatty acids that serve as a major fuel source for colonocytes: first, green dwarf banana flour produces protective effects on the intestinal inflammation acting as a prebiotic and, second, combination of this dietary supplementation with prednisolone presents synergistic effects. For this, we used the trinitrobenzenesulphonic acid (TNBS) model of rat colitis. Our results revealed that the protective effect produced by a combination of 10% green dwarf banana flour with prednisolone was more pronounced than those promoted by a single administration of prednisolone or a diet containing 10% or 20% banana flour. This beneficial effect was associated with an improvement in the colonic oxidative status because the banana flour diet prevented the glutathione depletion and inhibited myeloperoxidase activity and lipid peroxidation. In addition, the intestinal anti-inflammatory activity was associated with an inhibition of alkaline phosphatase activity, a reduction in macroscopic and microscopic scores, and an extension of the lesions. In conclusion, the dietary use of the green dwarf banana flour constitutes an important dietary supplement and complementary medicine product to prevention and treatment of human inflammatory bowel disease. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. Prevention Effect of Poly-Gamma-Glutamic Acid on Tissue Damage Induced by Gamma Irradiation as a Natural Cross-Linker

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jaehun; Sung, Nakyun; Kim, Jeongsoo; Jo, Euri; Choi, Jongil; Park, Jongheum; Lee, Juwoon [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of); Lee, Kwangwon [Eulji Univ. Hospital, Daejeon (Korea, Republic of); Kwon, Jungkee [Chonbuk National Univ., Jeonju (Korea, Republic of); Kim, Taewoon [Jeonbuk Technopark, Jeonju (Korea, Republic of)

    2012-03-15

    This study was to determine the prevention effect of poly-gamma-glutamic acid (PGA) on tissue damage induced by gamma irradiation for development of xenograft. PGA (MW 2000 kDa) extracted from permeated soy bean (natto) was used in this study as natural compound, and glutaraldehyde (GA) and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) were used as a control, chemical based cross-linking agents. GA, EDC and PGA treated porcine tendons were gamma-irradiated at the dose of 30 kGy. Prevention effects against tissue damage were measured as the result of tensile strength, hydroxyproline contents and tissue morphological analysis. Tensile of porcine tendon was remarkably decreased by gamma irradiation, but increased in PGA treated group. Morphological analysis showed that collagen structure was broken by gamma irradiation, but attenuated by PGA treatment. Base on the results, it demonstrated that gamma irradiation can induce severe alteration of porcine tendon, but PGA can effectively improve the tissue damage.

  12. Prevention Effect of Poly-Gamma-Glutamic Acid on Tissue Damage Induced by Gamma Irradiation as a Natural Cross-Linker

    International Nuclear Information System (INIS)

    Kim, Jaehun; Sung, Nakyun; Kim, Jeongsoo; Jo, Euri; Choi, Jongil; Park, Jongheum; Lee, Juwoon; Lee, Kwangwon; Kwon, Jungkee; Kim, Taewoon

    2012-01-01

    This study was to determine the prevention effect of poly-gamma-glutamic acid (PGA) on tissue damage induced by gamma irradiation for development of xenograft. PGA (MW 2000 kDa) extracted from permeated soy bean (natto) was used in this study as natural compound, and glutaraldehyde (GA) and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) were used as a control, chemical based cross-linking agents. GA, EDC and PGA treated porcine tendons were gamma-irradiated at the dose of 30 kGy. Prevention effects against tissue damage were measured as the result of tensile strength, hydroxyproline contents and tissue morphological analysis. Tensile of porcine tendon was remarkably decreased by gamma irradiation, but increased in PGA treated group. Morphological analysis showed that collagen structure was broken by gamma irradiation, but attenuated by PGA treatment. Base on the results, it demonstrated that gamma irradiation can induce severe alteration of porcine tendon, but PGA can effectively improve the tissue damage

  13. Trino IB ameliorates the oxidative stress of cryptorchidism in the rat ...

    African Journals Online (AJOL)

    The study examined the effect of Trino IB, a mixture of oleuropein and -lipoic acid, on the plasma concentration of g-glutamyl transpeptidase (GGT), malondialdehyde (MDA), sperm count and apoptotic degeneration of testicular germ cells in experimentally induced cryptorchidism in adult male rats. Oral administration of ...

  14. In Vivo Short-Term Topical Application of BAY 11-7082 Prevents the Acidic Bile–Induced mRNA and miRNA Oncogenic Phenotypes in Exposed Murine Hypopharyngeal Mucosa

    Directory of Open Access Journals (Sweden)

    Clarence T. Sasaki

    2018-04-01

    Full Text Available PURPOSE: Bile-containing gastroesophageal reflux may promote cancer at extraesophageal sites. Acidic bile can accelerate NF-κB activation and molecular events, linked to premalignant changes in murine hypopharyngeal mucosa (HM. We hypothesize that short-term in vivo topical application of NF-κB inhibitor BAY 11-7082 can prevent acidic bile–induced early preneoplastic molecular events, suggesting its potential role in disease prevention. EXPERIMENTAL DESIGN: We topically exposed HM (C57Bl/6j wild-type to a mixture of bile acids at pH 3.0 with and without BAY 11-7082 3 times/day for 7 days. We used immunofluorescence, Western blotting, immunohistochemistry, quantitative polymerase chain reaction, and polymerase chain reaction microarrays to identify NF-κB activation and its associated oncogenic mRNA and miRNA phenotypes, in murine hypopharyngeal cells in vitro and in murine HM in vivo. RESULTS: Short-term exposure of HM to acidic bile is a potent stimulus accelerating the expression of NF-κB signaling (70 out of 84 genes and oncogenic molecules. Topical application of BAY 11-7082 sufficiently blocks the effect of acidic bile. BAY 11-7082 eliminates NF-κB activation in regenerating basal cells of acidic bile–treated HM and prevents overexpression of molecules central to head and neck cancer, including bcl-2, STAT3, EGFR, TNF-α, and WNT5A. NF-κB inhibitor reverses the upregulated “oncomirs” miR-155 and miR-192 and the downregulated “tumor suppressors” miR-451a and miR-375 phenotypes in HM affected by acidic bile. CONCLUSION: There is novel evidence that acidic bile–induced NF-κB–related oncogenic mRNA and miRNA phenotypes are generated after short-term 7-day mucosal exposure and that topical mucosal application of BAY 11-7082 can prevent the acidic bile–induced molecular alterations associated with unregulated cell growth and proliferation of hypopharyngeal cells.

  15. Antimicrobial medium- and long-chain free fatty acids prevent PrfA-dependent activation of virulence genes in Listeria monocytogenes.

    Science.gov (United States)

    Sternkopf Lillebæk, Eva Maria; Lambert Nielsen, Stine; Scheel Thomasen, Rikke; Færgeman, Nils J; Kallipolitis, Birgitte H

    The foodborne pathogen Listeria monocytogenes is the causative agent of the invasive disease listeriosis. Infection by L. monocytogenes involves bacterial crossing of the intestinal barrier and intracellular replication in a variety of host cells. The PrfA protein is the master regulator of virulence factors required for bacterial entry, intracellular replication and cell-to-cell spread. PrfA-dependent activation of virulence genes occurs primarily in the blood and during intracellular infection. In contrast, PrfA does not play a significant role in regulation of virulence gene expression in the intestinal environment. In the gastrointestinal phase of infection, the bacterium encounters a variety of antimicrobial agents, including medium- and long-chain free fatty acids that are commonly found in our diet and as active components of bile. Here we show that subinhibitory concentrations of specific antimicrobial free fatty acids act to downregulate transcription of PrfA-activated virulence genes. Interestingly, the inhibitory effect is also evident in cells encoding a constitutively active variant of PrfA. Collectively, our data suggest that antimicrobial medium- and long-chain free fatty acids may act as signals to prevent PrfA-mediated activation of virulence genes in environments where PrfA activation is not required, such as in food and the gastrointestinal tract. Copyright © 2017 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  16. 10-Hydroxy-2-decenoic acid prevents ultraviolet A-induced damage and matrix metalloproteinases expression in human dermal fibroblasts.

    Science.gov (United States)

    Zheng, Jinfen; Lai, Wei; Zhu, Guoxing; Wan, Miaojian; Chen, Jian; Tai, Yan; Lu, Chun

    2013-10-01

    10-Hydroxy-2-decenoic acid (10-HDA) is a major fatty acid component of royal jelly, which has been reported to have a variety of beneficial pharmacological characteristics. However, the effects of 10-HDA on skin photoageing and its potential mechanism of action are unclear. We investigated the protective effects of 10-HDA on ultraviolet (UV) A-induced damage in human dermal fibroblasts (HDFs). We then explored the inhibitory effects of 10-HDA on UVA-induced matrix metalloproteinases (MMPs) expression and elucidated the signalling pathways controlling MMPs inhibition. Primary human dermal fibroblasts were exposed to UVA. Cell proliferation, cellular senescent state and collagen content were analysed using CCK-8, senescence-associated β-galactosidase staining and Sircol collagen assay, respectively. Fluorometric assays were performed to detect the formation of reactive oxygen species (ROS) in the cells. The mRNA levels of MMP-1, MMP-3 and type I (α1) collagen were determined by quantitative real-time PCR. Western blot was applied to detect the expression of MMP-1, MMP-3, JNK and p38 MAPK. HDFs treated with 10-HDA were significantly protected from UVA-induced cytotoxicity, ROS, cellular senescence and stimulated collagen production. Moreover, 10-HDA suppressed the UVA-induced expression of MMP-1 and MMP-3 at both the transcriptional and protein levels. Treatment with 10-HDA also reduced the UVA-induced activation of the JNK and p38 MAPK pathways. The data obtained in this study provide evidence that 10-HDA could prevent UVA-induced damage and inhibit MMP-1 and MMP-3 expressions. Therefore, 10-HDA may be a potential agent for the prevention and treatment of skin photoageing. © 2012 The Authors. Journal of the European Academy of Dermatology and Venereology © 2012 European Academy of Dermatology and Venereology.

  17. Fat food for a bad mood. Could we treat and prevent depression in Type 2 diabetes by means of omega-3 polyunsaturated fatty acids?

    DEFF Research Database (Denmark)

    Pouwer, F; Nijpels, G; Beekman, Aartjan T F

    2005-01-01

    that eicosapentaenoic acid is an effective adjunct treatment of depression in diabetes, while docosahexanoic acid is not. Moreover, consumption of omega-3 PUFA reduces the risk of cardiovascular disease and may therefore indirectly decrease depression in Type 2 diabetes, via the reduction of cardiovascular......AIMS: Evidence strongly suggests that depression is a common complication of Type 2 diabetes mellitus. However, there is considerable room to improve the effectiveness of pharmacological antidepressant agents, as in only 50-60% of the depressed subjects with diabetes does pharmacotherapy lead...... to remission of depression. The aim of the present paper was to review whether polyunsaturated fatty acids (PUFA) of the omega-3 family could be used for the prevention and treatment of depression in Type 2 diabetes. METHODS: MEDLINE database and published reference lists were used to identify studies...

  18. Effect of Nrf2 activators on release of glutathione, cysteinylglycine and homocysteine by human U373 astroglial cells

    Directory of Open Access Journals (Sweden)

    Megan L. Steele

    2013-01-01

    This study compares four known Nrf2 activators, R-α-Lipoic acid (LA, tert-butylhydroquinone (TBHQ, sulforaphane (SFN and Polygonum cuspidatum extract containing 50% resveratrol (PC-Res for their effects on astroglial release of GSH and CysGly. GSH levels increased dose-dependently in response to all four drugs. Sulforaphane produced the most potent effect, increasing GSH by up to 2.4-fold. PC-Res increased GSH up to 1.6-fold, followed by TBHQ (1.5-fold and LA (1.4-fold. GSH is processed by the ectoenzyme, γ-glutamyl transpeptidase, to form CysGly. Once again, SFN produced the most potent effect, increasing CysGly by up to 1.7-fold, compared to control cells. TBHQ and PC-Res both induced fold increases of 1.3, followed by LA with a fold increase of 1.2. The results from the present study showed that sulforaphane, followed by lipoic acid, resveratrol and Polygonum multiflorum were all identified as potent “GSH and Cys-Gly boosters”.

  19. Characterisation, degradation and regeneration of luminescent Ag29 clusters in solution

    NARCIS (Netherlands)

    van der Linden, Marte; Barendregt, Arjan; van Bunningen, Arnoldus J; Chin, Patrick T K; Thies-Weesie, Dominique; de Groot, Frank M F; Meijerink, A

    2016-01-01

    Luminescent Ag clusters are prepared with lipoic acid (LA) as the ligand. Using a combination of mass spectrometry, optical spectroscopy and analytical ultracentrifugation, the clusters are found to be highly monodisperse with mass 5.6 kDa. We assign the chemical composition [Ag29(LA)12](3-) to the

  20. Ascorbic Acid

    Science.gov (United States)

    Ascorbic acid is used to prevent and treat scurvy, a disease caused by a lack of vitamin C in ... Ascorbic acid comes in extended-release (long-acting) capsules and tablets, lozenges, syrup, chewable tablets, and liquid drops to ...

  1. Retinoic acid is essential for Th1 cell lineage stability and prevents transition to a Th17 cell program.

    Science.gov (United States)

    Brown, Chrysothemis C; Esterhazy, Daria; Sarde, Aurelien; London, Mariya; Pullabhatla, Venu; Osma-Garcia, Ines; Al-Bader, Raya; Ortiz, Carla; Elgueta, Raul; Arno, Matthew; de Rinaldis, Emanuele; Mucida, Daniel; Lord, Graham M; Noelle, Randolph J

    2015-03-17

    CD4(+) T cells differentiate into phenotypically distinct T helper cells upon antigenic stimulation. Regulation of plasticity between these CD4(+) T-cell lineages is critical for immune homeostasis and prevention of autoimmune disease. However, the factors that regulate lineage stability are largely unknown. Here we investigate a role for retinoic acid (RA) in the regulation of lineage stability using T helper 1 (Th1) cells, traditionally considered the most phenotypically stable Th subset. We found that RA, through its receptor RARα, sustains stable expression of Th1 lineage specifying genes, as well as repressing genes that instruct Th17-cell fate. RA signaling is essential for limiting Th1-cell conversion into Th17 effectors and for preventing pathogenic Th17 responses in vivo. Our study identifies RA-RARα as a key component of the regulatory network governing maintenance and plasticity of Th1-cell fate and defines an additional pathway for the development of Th17 cells. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  2. Efficacy of Supplementation with B Vitamins for Stroke Prevention: A Network Meta-Analysis of Randomized Controlled Trials.

    Science.gov (United States)

    Dong, Hongli; Pi, Fuhua; Ding, Zan; Chen, Wei; Pang, Shaojie; Dong, Wenya; Zhang, Qingying

    2015-01-01

    Supplementation with B vitamins for stroke prevention has been evaluated over the years, but which combination of B vitamins is optimal for stroke prevention is unclear. We performed a network meta-analysis to assess the impact of different combinations of B vitamins on risk of stroke. A total of 17 trials (86 393 patients) comparing 7 treatment strategies and placebo were included. A network meta-analysis combined all available direct and indirect treatment comparisons to evaluate the efficacy of B vitamin supplementation for all interventions. B vitamin supplementation was associated with reduced risk of stroke and cerebral hemorrhage. The risk of stroke was lower with folic acid plus vitamin B6 as compared with folic acid plus vitamin B12 and was lower with folic acid plus vitamin B6 plus vitamin B12 as compared with placebo or folic acid plus vitamin B12. The treatments ranked in order of efficacy for stroke, from higher to lower, were folic acid plus vitamin B6 > folic acid > folic acid plus vitamin B6 plus vitamin B12 > vitamin B6 plus vitamin B12 > niacin > vitamin B6 > placebo > folic acid plus vitamin B12. B vitamin supplementation was associated with reduced risk of stroke; different B vitamins and their combined treatments had different efficacy on stroke prevention. Folic acid plus vitamin B6 might be the optimal therapy for stroke prevention. Folic acid and vitamin B6 were both valuable for stroke prevention. The efficacy of vitamin B12 remains to be studied.

  3. Efficacy of Supplementation with B Vitamins for Stroke Prevention: A Network Meta-Analysis of Randomized Controlled Trials.

    Directory of Open Access Journals (Sweden)

    Hongli Dong

    Full Text Available Supplementation with B vitamins for stroke prevention has been evaluated over the years, but which combination of B vitamins is optimal for stroke prevention is unclear. We performed a network meta-analysis to assess the impact of different combinations of B vitamins on risk of stroke.A total of 17 trials (86 393 patients comparing 7 treatment strategies and placebo were included. A network meta-analysis combined all available direct and indirect treatment comparisons to evaluate the efficacy of B vitamin supplementation for all interventions.B vitamin supplementation was associated with reduced risk of stroke and cerebral hemorrhage. The risk of stroke was lower with folic acid plus vitamin B6 as compared with folic acid plus vitamin B12 and was lower with folic acid plus vitamin B6 plus vitamin B12 as compared with placebo or folic acid plus vitamin B12. The treatments ranked in order of efficacy for stroke, from higher to lower, were folic acid plus vitamin B6 > folic acid > folic acid plus vitamin B6 plus vitamin B12 > vitamin B6 plus vitamin B12 > niacin > vitamin B6 > placebo > folic acid plus vitamin B12.B vitamin supplementation was associated with reduced risk of stroke; different B vitamins and their combined treatments had different efficacy on stroke prevention. Folic acid plus vitamin B6 might be the optimal therapy for stroke prevention. Folic acid and vitamin B6 were both valuable for stroke prevention. The efficacy of vitamin B12 remains to be studied.

  4. Role of amino acids and vitamins in prevention of and rapid recovery from fatigue in the officers and soldiers at high altitude

    Directory of Open Access Journals (Sweden)

    Wen HUANG

    2012-01-01

    Full Text Available Objective  To explore the role of amino acids and vitamins in the prevention of and recovery from the fatigue related to military operation in the officers and soldiers at high altitude. Methods  The participants were 100 officers and soldiers, whose Modified Fatigue Rating Scale (MFIS scores were >21 points. The participants were randomly divided into three groups: capsule, placebo, and granules. Amino acids capsule (8 kinds of essential amino acids and 11 kinds of vitamins were contained, placebo, or amino acid-fructose beverage was given to respective group for 14 days continuously. The 3000-m running performance of the officers and soldiers stationed on a plateau was measured on the first and 14th days. The maximal grip strength of the right hand, fist-making times per minute, and the height reaching by the hand after three-step run-up for the same candidate were observed before and after fatigue loading (3000-m running. The blood levels of lactic acid and urea nitrogen of the candidates were measured after fatigue loading on the first and the 14th days. Results  The 3000-m running performance of officers and soldiers in the capsule and granules groups on the 14th day were better than that of the first day (PP>0.05. The difference between the capsule and the granules groups in grip strength, fist-making times per minute, and hand reaching height on the 14th day were obviously lower than that on the first day (PP>0.05. The blood levels of lactic acid and urea nitrogen in the capsule and granules groups on the 14th day were lower than that on the first day (PP>0.05. Conclusions  Amino acids and vitamins preparations can obviously improve the military performance capacity of officers and soldiers stationed on the plateau. Similarly, they can effectively prevent the lowering of jumping ability and grip strength caused by military fatigue. Therefore, amino acids and vitamins preparations play an important role in the prevention of and rapid

  5. Antimicrobial activity of transition metal acid MoO3 prevents microbial growth on material surfaces

    International Nuclear Information System (INIS)

    Zollfrank, Cordt; Gutbrod, Kai; Wechsler, Peter; Guggenbichler, Josef Peter

    2012-01-01

    Serious infectious complications of patients in healthcare settings are often transmitted by materials and devices colonised by microorganisms (nosocomial infections). Current strategies to generate material surfaces with an antimicrobial activity suffer from the consumption of the antimicrobial agent and emerging multidrug-resistant pathogens amongst others. Consequently, materials surfaces exhibiting a permanent antimicrobial activity without the risk of generating resistant microorganisms are desirable. This publication reports on the extraordinary efficient antimicrobial properties of transition metal acids such as molybdic acid (H 2 MoO 4 ), which is based on molybdenum trioxide (MoO 3 ). The modification of various materials (e.g. polymers, metals) with MoO 3 particles or sol–gel derived coatings showed that the modified materials surfaces were practically free of microorganisms six hours after contamination with infectious agents. The antimicrobial activity is based on the formation of an acidic surface deteriorating cell growth and proliferation. The application of transition metal acids as antimicrobial surface agents is an innovative approach to prevent the dissemination of microorganisms in healthcare units and public environments. Highlights: ► The presented modifications of materials surfaces with MoO 3 are non-cytotoxic and decrease biofilm growth and bacteria transmission. ► The material is insensitive towards emerging resistances of bacteria. ► Strong potential to reduce spreading of infectious agents on inanimate surfaces.

  6. Prevention of fatal arrhythmias in high-risk subjects by fish oil n-3 fatty acid intake.

    Science.gov (United States)

    Leaf, Alexander; Albert, Christine M; Josephson, Mark; Steinhaus, David; Kluger, Jeffrey; Kang, Jing X; Cox, Benjamin; Zhang, Hui; Schoenfeld, David

    2005-11-01

    The long-chain n-3 fatty acids in fish have been demonstrated to have antiarrhythmic properties in experimental models and to prevent sudden cardiac death in a randomized trial of post-myocardial infarction patients. Therefore, we hypothesized that these n-3 fatty acids might prevent potentially fatal ventricular arrhythmias in high-risk patients. Four hundred two patients with implanted cardioverter/defibrillators (ICDs) were randomly assigned to double-blind treatment with either a fish oil or an olive oil daily supplement for 12 months. The primary end point, time to first ICD event for ventricular tachycardia or fibrillation (VT or VF) confirmed by stored electrograms or death from any cause, was analyzed by intention to treat. Secondary analyses were performed for "probable" ventricular arrhythmias, "on-treatment" analyses for all subjects who had taken any of their oil supplements, and "on-treatment" analyses only of those subjects who were on treatment for at least 11 months. Compliance with double-blind treatment was similar in the 2 groups; however, the noncompliance rate was high (35% of all enrollees). In the primary analysis, assignment to treatment with the fish oil supplement showed a trend toward a prolonged time to the first ICD event (VT or VF) or of death from any cause (risk reduction of 28%; P=0.057). When therapies for probable episodes of VT or VF were included, the risk reduction became significant at 31%; P=0.033. For those who stayed on protocol for at least 11 months, the antiarrhythmic benefit of fish oil was improved for those with confirmed events (risk reduction of 38%; P=0.034). Although significance was not achieved for the primary end point, this study provides evidence that for individuals at high risk of fatal ventricular arrhythmias, regular daily ingestion of fish oil fatty acids may significantly reduce potentially fatal ventricular arrhythmias.

  7. Exploration of the preventive effect of ursolic acid on retinopathy in diabetic mice and its mechanism

    Institute of Scientific and Technical Information of China (English)

    Ai-Zhong Yu

    2016-01-01

    Objective:To study the preventive effect of ursolic acid on retinopathy in diabetic mice through adjusting insulin sensitivity, glucose transport, angiogenesis and inflammation. Methods:Male C57BL/6 mice were selected as experimental animals and randomly divided into control group (N group), model group (D group) and intervention group (D+UA group), D group and D+UA group established diabetes models through intraperitoneal injection of STZ, D+UA group received intragastric administration of ursolic acid, and then insulin sensitivity, glucose metabolism in retina as well as the expression levels of GLUTs, HIF-1α/VEGF/VEGFR2 pathway and IKKβ/IKBα/NF-κB pathway in retina tissue of three groups were detected. Results:AUC of D group was significantly lower than that of N group, and HOMA-IR, sugar content in retina tissue as well as GLUT-1, GLUT-3, HIF-1α, VEGF, VEGFR2, IKKβ, IKBα, NF-κB, TNF-α, ICAM-1, VCAM-1 and E-selectin levels were significantly higher than those of N group;AUC of D+UA group was significantly higher than that of D group, and HOMA-IR, sugar content in retina tissue as well as GLUT-1, GLUT-3, HIF-1α, VEGF, VEGFR2, IKK毬, IKBα, NF-κB, TNF-α, ICAM-1, VCAM-1 and E-selectin levels were significantly lower than those of D group. Conclusion:Ursolic acid can increase insulin sensitivity, reduce sugar content in retina tissue and inhibit angiogenesis and inflammation degree in retina tissue, and has preventive effect on retinopathy in diabetic mice.

  8. Preparation, Characterization and Efficacy Evaluation of Synthetic Biocompatible Polymers Linking Natural Antioxidants

    Directory of Open Access Journals (Sweden)

    Nevio Picci

    2012-10-01

    Full Text Available The purpose of this work was the synthesis, characterization and efficacy evaluation of new biocompatible antioxidant polymers linking trans-ferulic acid or a-lipoic acid. In particular, ferulic or lipoic acid were introduced in the preformed polymeric backbone. The new antioxidant biopolymers were characterized by Fourier transform infrared spectroscopy and gel permeation chromatography. The degree of functionalization (moles of antioxidant per gram of polymer was determined by the Gaur-Gupta method for free amino group determination and by the Folin method for the phenolic groups. Their ability to inhibit lipid peroxidation were estimated in rat liver microsomal membranes induced in vitro by tert-BOOH (tert-butyl hydroperoxide, as a source of free radicals. The DPPH (1,1-diphenyl-2-picrylhydrazyl radical-scavenging effect was also evaluated. The obtained systems, with different solubility, showed strong antioxidant and antiradical activities, suggesting potential use as packaging materials for foods, cosmetics, pharmaceuticals and personal care products. Moreover, the cytotoxicity of the synthesized polymers was also evaluated on Caco-2 cell cultures in order to verify their biocompatibility when exposed to an absorptive epithelial cell line.

  9. Prevention of Preeclampsia: Is it Still a Disappointment?

    Directory of Open Access Journals (Sweden)

    Abeer Eddib

    2009-01-01

    Full Text Available Preeclampsia is a major cause of maternal mortality worldwide, with many preventive strategies tested. In this review we intend to provide a synthesis of available studies of these strategies that have been tested, including systematic reviews. We will not be performing systematic review of the studies here. Of these strategies tested only low dose acetyl salicylic acid (ASA and calcium can be considered helpful for prevention at this time. A recent meta-analysis showed a benefit of low dose ASA for both high (RR 0.75, 95% CI 0.66 to 0.85 and moderate risk groups (RR 0.86, 95% CI 0.79 to 0.95. Therefore, low dose ASA in high risk groups may be useful, with a possible smaller benefit in moderate to low risk women. Another meta-analysis looking at calcium shows benefit for both high and low risk groups with an overall reduction in the risk of preeclampsia (RR 0.48, 95% CI 0.33 to 0.69. As a result, prenatal supplementation of calcium may be beneficial for the prevention of preeclampsia. However, vitamins C and E, zinc, fish oil, and magnesium supplementation have been discounted as potential preventive strategies. Nitric oxide, folic acid, and antithrombotics have not been well studied and there is insufficient data for reliable conclusions to be made. Areas of ongoing research that appear promising in the prevention of preeclampsia include modifiable metabolic factors, angiogenic proteins, angiotensin receptor antibodies, and syncytiotrophoblast microparticles. Strategies targeting these areas may provide opportunities for therapeutic interventions.

  10. Cross-linked hyaluronic acid in pressure ulcer prevention.

    Science.gov (United States)

    Beniamino, P; Vadalà, M; Laurino, C

    2016-07-02

    Long-term bedridden patients are at high risk of acquring pressure ulcers (PUs). In this group of patients, prevention is necessary to cut the health costs, improve quality of life and reduce the mortality. Here, we evaluated the effectiveness of a cross-linked hyaluronic acid (HA) as plastic bulking-agent filling and remodelling the deep dermis and subcutaneous space of the skin areas exposed to the risk of necrosis. Our work hypothesis has been to inflate a sub-dermal elastic cushion, filled with a natural ECM component, with the aim to induce a stronger tissue background resistant to the ulcerative process. All the patients had an increased risk of PUs, at the sacral, ileum or heel skin. Patients were being nursed accordingly to the standard orthopaedic ward management with a pressure relieveing air mattress. The standard protocol consisted in body mobilisation every 3 hours, 24 hours a day and accurate cleaning of the skin with liquid soap and water without any towel friction and without adding any cream or lotion for the skin protection. Our filling protocol enclosed: accurate disinfection of the skin to be injected with povidone-iodine solution, followed by a local anaesthesia with 28G 13 mm needle, injecting 1.5 ml of 1% xylocaine. Then slow, deep, subcutaneous injection of cross-linked HA was performed with a 18G long needle, in order to deliver a homogeneous, soft gel layer underneath and around the whitish erythematous skin edges at risk of ulceration. Patients' tolerability of the compound and adverse events were also recorded. There were 15 patients (78-94 years old) who participated in the study. All tolerated the procedure very well and no serious side effects were declared. No skin pressure ulceration was detected in the four weeks follow-up Conclusion: We have demonstrated the safety and tolerability of a cross-linked HA subdermal injection in PUs prevention. The compound stratifies in a soft, elastic, interstitial bulk into the deep dermis, thus

  11. The bile acids, deoxycholic acid and ursodeoxycholic acid, regulate colonic epithelial wound healing.

    Science.gov (United States)

    Mroz, Magdalena S; Lajczak, Natalia K; Goggins, Bridie J; Keely, Simon; Keely, Stephen J

    2018-03-01

    The intestinal epithelium constitutes an innate barrier which, upon injury, undergoes self-repair processes known as restitution. Although bile acids are known as important regulators of epithelial function in health and disease, their effects on wound healing processes are not yet clear. Here we set out to investigate the effects of the colonic bile acids, deoxycholic acid (DCA) and ursodeoxycholic acid (UDCA), on epithelial restitution. Wound healing in T 84 cell monolayers grown on transparent, permeable supports was assessed over 48 h with or without bile acids. Cell migration was measured in Boyden chambers. mRNA and protein expression were measured by RT-PCR and Western blotting. DCA (50-150 µM) significantly inhibited wound closure in cultured epithelial monolayers and attenuated cell migration in Boyden chamber assays. DCA also induced nuclear accumulation of the farnesoid X receptor (FXR), whereas an FXR agonist, GW4064 (10 µM), inhibited wound closure. Both DCA and GW4064 attenuated the expression of CFTR Cl - channels, whereas inhibition of CFTR activity with either CFTR- inh -172 (10 µM) or GlyH-101 (25 µM) also prevented wound healing. Promoter/reporter assays revealed that FXR-induced downregulation of CFTR is mediated at the transcriptional level. In contrast, UDCA (50-150 µM) enhanced wound healing in vitro and prevented the effects of DCA. Finally, DCA inhibited and UDCA promoted mucosal healing in an in vivo mouse model. In conclusion, these studies suggest bile acids are important regulators of epithelial wound healing and are therefore good targets for development of new drugs to modulate intestinal barrier function in disease treatment. NEW & NOTEWORTHY The secondary bile acid, deoxycholic acid, inhibits colonic epithelial wound healing, an effect which appears to be mediated by activation of the nuclear bile acid receptor, FXR, with subsequent downregulation of CFTR expression and activity. In contrast, ursodeoxycholic acid promotes

  12. Out of Warburg effect: An effective cancer treatment targeting the tumor specific metabolism and dysregulated pH.

    Science.gov (United States)

    Schwartz, Laurent; Seyfried, Thomas; Alfarouk, Khalid O; Da Veiga Moreira, Jorgelindo; Fais, Stefano

    2017-04-01

    As stated by Otto Warburg nearly a century ago, cancer is a metabolic disease, a fermentation caused by malfunctioning mitochondria, resulting in increased anabolism and decreased catabolism. Treatment should, therefore, aim at restoring the energy yield. To decrease anabolism, glucose uptake should be reduced (ketogenic diet). To increase catabolism, the oxidative phosphorylation should be restored. Treatment with a combination of α-lipoic acid and hydroxycitrate has been shown to be effective in multiple animal models. This treatment, in combination with conventional chemotherapy, has yielded extremely encouraging results in glioblastoma, brain metastasis and lung cancer. Randomized trials are necessary to confirm these preliminary data. The major limitation is the fact that the combination of α-lipoic acid and hydroxycitrate can only be effective if the mitochondria are still present and/or functional. That may not be the case in the most aggressive tumors. The increased intracellular alkalosis is a strong mitogenic signal, which bypasses most inhibitory signals. Concomitant correction of this alkalosis may be a very effective treatment in case of mitochondrial failure. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Effect of processing on folic acid fortified Baladi bread and its possible effect on the prevention of colon cancer.

    Science.gov (United States)

    Omar, Rasha M; Ismail, Hanaa M; El-Lateef, Bothyna M Abd; Yousef, Mokhtar I; Gomaa, Naglaa F; Sheta, Manal

    2009-07-01

    This paper studied the possible effect of folic acid in fortified Baladi bread on the prevention of colon cancer development in rats. Wheat flour samples (82% extraction rate) and soy bean flour were analyzed to determine their folic acid contents using the High Performance Liquid Chromatography (HPLC). Unfortified and folic acid fortified Baladi breads were prepared. Samples from each step of bread preparation were analyzed for folic acid concentration. Protein, fat, ash, fibers and carbohydrates percentages were also determined. Rats were divided into five groups, four of them were injected subcutaneously with dimethylhydrazine (DMH). After 15 weeks, the rats were sacrificed for pathological examination. Results showed that the folic acid content in wheat flour (82% extraction rate) was found to be highly significantly lower than that in soybean flour. After baking, folic acid content in all breads was found to decrease significantly. The highest protein and fat contents were found in soybean flour fortified Baladi bread. The colons of rats of groups 3 (fed 5% soy flour fortified Baladi bread) and 5 (fed Baladi bread fortified with 5% soy flour+8 mg folic acid/kg wheat flour) were the mostly affected by DMH injection as premalignant changes were observed.

  14. Gallic acid prevents nonsteroidal anti-inflammatory drug-induced gastropathy in rat by blocking oxidative stress and apoptosis.

    Science.gov (United States)

    Pal, Chinmay; Bindu, Samik; Dey, Sumanta; Alam, Athar; Goyal, Manish; Iqbal, Mohd Shameel; Maity, Pallab; Adhikari, Susanta S; Bandyopadhyay, Uday

    2010-07-15

    Nonsteroidal anti-inflammatory drug (NSAID)-induced oxidative stress plays a critical role in gastric mucosal cell apoptosis and gastropathy. NSAIDs induce the generation of hydroxyl radical ((*)OH) through the release of free iron, which plays an important role in developing gastropathy. Thus, molecules having both iron-chelating and antiapoptotic properties will be beneficial in preventing NSAID-induced gastropathy. Gallic acid (GA), a polyphenolic natural product, has the capacity to chelate free iron. Here, we report that GA significantly prevents, as well as heals, NSAID-induced gastropathy. In vivo, GA blocks NSAID-mediated mitochondrial oxidative stress by preventing mitochondrial protein carbonyl formation, lipid peroxidation, and thiol depletion. In vitro, GA scavenges free radicals and blocks (*)OH-mediated oxidative damage. GA also attenuates gastric mucosal cell apoptosis in vivo as well as in vitro in cultured gastric mucosal cells as evident from the TUNEL assay. GA prevents NSAID-induced activation of caspase-9, a marker for the mitochondrial pathway of apoptosis, and restores NSAID-mediated collapse of the mitochondrial transmembrane potential and dehydrogenase activity. Thus, the inhibition of mitochondrial oxidative stress by GA is associated with the inhibition of NSAID-induced mitochondrial dysfunction and activation of apoptosis in gastric mucosal cells, which are responsible for gastric injury or gastropathy. Copyright 2010 Elsevier Inc. All rights reserved.

  15. A novel once daily microparticulate dosage form comprising lansoprazole to prevent nocturnal acid breakthrough in the case of gastro-esophageal reflux disease: preparation, pharmacokinetic and pharmacodynamic evaluation.

    Science.gov (United States)

    Alai, Milind; Lin, Wen Jen

    2013-01-01

    The objective of this study was to formulate and evaluate the lansoprazole (LPZ)-loaded microparticles to prevent nocturnal acid breakthrough in the case of gastro-esophageal reflux disease (GERD). The microparticulate delivery system was prepared by solvent evaporation method using Eudragit RS100 as a matrix polymer followed by enteric coated with Eudragit S100 and hydroxypropyl methylcellulose phthalate HP55 using spray drying method. The enteric coated microparticles were stable in gastric pH condition. In vivo pharmacokinetic and pharmacodynamic studies in male Wistar rats demonstrated that enteric coated microparticles sustained release of LPZ and promoted ulcer healing activity. In other words, the microparticulate dosage form provided effective drug concentration for a longer period as compared to conventional extended release dosage form, and showed sufficient anti-acid secretion activity to treat acid related disorders including the enrichment of nocturnal acid breakthrough event based on a once daily administration.

  16. Conjugated linoleic acid as a potential protective factor in prevention of breast cancer 

    Directory of Open Access Journals (Sweden)

    Agnieszka Białek

    2013-01-01

    Full Text Available Cancers are the second leading cause of deaths in Poland, among both women and men. Breast cancer is the malignancy most frequently diagnosed in women. In 2008 mammary cancer was diagnosed in up to 14 500 patients. It is also the second most common cause of cancer deaths among women in our country. Although the etiology of most cases of this disease is not known, risk factors include a variety of nutritional factors. The amount of fat consumed in the diet and the quantity and quality of fatty acids are especially crucial. Among fatty acids to which great importance in modification of cancer risk is attributed are conjugated linoleic acid. Conjugated linoleic acids (CLA are a group of positional and geometric isomers of linoleic acid, with a conjugated double bond system in the carbon chain. The main natural source of them is milk and dairy products and meat of different species of ruminants, in which cis-9, trans-11 octadecadienoic acid (rumenic acid occurs in the largest quantities, constituting over 90�0of the total pool of CLA. Another important isomer is trans-10, cis-12 octadecadienoic acid, which occurs with rumenic acid in dietary supplements, usually in the ratio 1:1. Surveys conducted show their possible health promoting effects in obesity, atherosclerosis, cardiovascular diseases, osteoporosis, diabetes, insulin resistance, inflammation, and various types of cancer, especially breast cancer. 

  17. Randomized, Prospective Comparison of Ursodeoxycholic Acid for the Prevention of Gallstones after Sleeve Gastrectomy.

    Science.gov (United States)

    Adams, Lindsay B; Chang, Craig; Pope, Janet; Kim, Yeonsoo; Liu, Pei; Yates, Amy

    2016-05-01

    Several studies have examined the role of ursodeoxycholic acid (UDCA) for the prevention of cholelithiasis (gallstones) following rapid weight loss from restrictive diets, vertical band gastroplasty, and Roux-en-Y gastric bypass. However, to date, there have been no prospective, controlled studies examining the role of UDCA for the prevention of gallstones following sleeve gastrectomy (SG). This study was conducted to identify the effectiveness of UDCA for prevention of gallstones after SG. Following SG, eligible patients were randomized to a control group who did not receive UDCA treatment or to a group who were prescribed 300 mg UDCA twice daily for 6 months. Gallbladder ultrasounds were performed preoperatively and at 6 and 12 months postoperatively. Patients with positive findings preoperatively were excluded from the study. Compliance with UDCA was assessed. Between December 2011 and April 2013, 37 patients were randomized to the UDCA treatment arm and 38 patients were randomized to no treatment. At baseline, the two groups were similar. At 6 months, the UDCA group had a statistically significant lower incidence of gallstones (p = 0.032). Analysis revealed no significant difference in gallstones between the two groups at 1 year (p = 0.553 and p = 0.962, respectively). The overall gallstone formation rate was 29.8%. The incidence of gallstones is higher than previously estimated in SG patients. UDCA significantly lowers the gallstone formation rate at 6 months postoperatively.

  18. ischemic brain injury in neonatal rats

    African Journals Online (AJOL)

    Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, ... Methods: Forty-eight rats (P7-pups) were randomly assigned to one of four groups: ... Keywords: Hypoxic–ischemic brain injury, α-Lipoic acid, Cerebral infarct area, Edema, Antioxidants, .... Of the 48 rats initially used in the current study, 5.

  19. Preventive and curative effects of dicaffeoylquinic acid on early pulmonary fibrosis in mice

    International Nuclear Information System (INIS)

    Liu Tao; Song Liangwen; Dong Junxing; Huang Shanying; Li Yang

    2005-01-01

    Objective: To explore the effect of dicaffeoylquinic acid (IBE5) on prevention and treatment of pulmonary fibrosis induced by bleomycin (BLM) in mice and its mechanism. Methods: Hydroxyproline content determination, imaging analysis, collagen I and III assay, α-smooth muscle actin (α-SMA) and matrix metalloproteinase 7 (MMP-7 ) immunohistochemistry were performed. Results: 1)Hydroxyproline content decreased in fibrotic lung tissue after administration of IBE5(P<0.05). 2)The number of pulmonary alveoli reduced, alveolus interstitium was thickened and collagen deposition and fibrosis were formed in lung tissue of BLM group. The break of pulmonary alveoli and extension of pulmonary fibrosis were decreased by use of IBE5 (P<0.05). 3)A lot of collagen I and III were synthesized in lung interstitium in BLM group and their quantity was reduced in IBE5 group (P<0.05). 4) In BLM group, α-SMA expression increased and located in myofibroblasts in fibrotic area, and MMP7 immunohistochemical signal was located in myofibroblasts also. They were decreased in IBE5 group(P<0.05). Conclusion: IBE5 plays a preventive and curative role in pulmonary fibrosis by inhibition of transformation of fibroblasts towards myofibroblasts and MMP7 expression. (authors)

  20. [Effects of sucralfate and acid-suppressive drugs on preventing ventilator- associated pneumonia of mechanically ventilated patients: a meta-analysis].

    Science.gov (United States)

    He, Hongli; Hu, Shuling; Chen, Qihong; Liu, Ling; Huang, Yingzi; Yang, Yi; Qiu, Haibo

    2014-01-01

    To evaluate the effect of sucralfate and acid-suppressive drugs on preventing ventilator-associated pneumonia (VAP) in mechanically ventilated patients. All randomized controlled trials (RCTs), which studied the effect of sucralfate and acid-suppressive drugs on the incidence of VAP in mechanically ventilated patients, were searched from PubMed, Embase and the Cochrane Library during January 1966 to March 2013 via manual and computer retrieval. All related data were extracted. Meta analysis was conducted using the statistical software RevMan 5.2 and the quality of the RCTs was strictly evaluated with the methods recommended by the Cochrane Collaboration. A total of 15 RCTs involving 1315 patients in the sucralfate group and 1568 patients in the acid-suppressive drug group were included in this study. The incidence of VAP was significantly reduced in the sucralfate group (RR = 0.81, 95%CI 0.7-0.95, P = 0.008), while no difference was found between the two groups in the incidence of stress-related gastrointestinal bleeding (RR = 0.96, 95%CI 0.59-1.58, P = 0.88). No statistical difference was found in the days on ventilator, duration of ICU stay and ICU mortality in the two groups (all P values > 0.05). In patients with mechanical ventilation, sucralfate could decrease the incidence of VAP, while has no such effect on the stress-related gastrointestinal bleeding, the days on ventilator, duration of ICU stay and ICU mortality.

  1. Ursodeoxycholic Acid in the Prevention of Gallstone Formation After Bariatric Surgery: an Updated Systematic Review and Meta-analysis.

    Science.gov (United States)

    Magouliotis, Dimitrios E; Tasiopoulou, Vasiliki S; Svokos, Alexis A; Svokos, Konstantina A; Chatedaki, Christina; Sioka, Eleni; Zacharoulis, Dimitris

    2017-11-01

    We aim to review the available literature on obese patients treated with ursodeoxycholic acid (UDCA) in order to prevent gallstone formation after bariatric surgery. A systematic literature search was performed in PubMed, Cochrane library, and Scopus databases, in accordance with the PRISMA guidelines. Eight studies met the inclusion criteria incorporating 1355 patients. Random-effects meta-analysis showed a lower incidence of gallstone formation in patients taking UDCA. Subgroup analysis reported fewer cases of gallstone disease in the UDCA group in relation to different bariatric procedures, doses of administered UDCA, and time from bariatric surgery. Adverse events were similar in both groups. Fewer patients required cholecystectomy in UDCA group. No deaths were reported. The administration of UDCA after bariatric surgery seems to prevent gallstone formation.

  2. Parenteral safflower oil emulsion (Liposyn 10%): safety and effectiveness in treating or preventing essential fatty acid deficiency in surgical patients.

    Science.gov (United States)

    Bivins, B A; Rapp, R P; Record, K; Meng, H C; Griffen, W O

    1980-01-01

    The safety and effectiveness of a 10% safflower oil emulsion in treating or preventing essential fatty acid deficiency was tested in a prospective study of 15 surgical patients requiring total parenteral nutrition for two to four weeks. Three dosage regimens were evaluated including: Group I: 4% of calories as linoleate daily (five patients), Group II: 4% of calories as linoleate every other day (two patients), and Group III: 8% of calories every other day (eight patients). Patients were monitored for laboratory changes from baseline specifically in those areas where previous fat emulsions have caused serious deviations. No significant changes were noted in hematologic parameters, coagulation studies, cholesterol and triglyceride serum levels. Although there were sporadic mild deviations in liver function changes in several patients, no clinically significant adverse effects could be directly attributed to infusion of the fat emulsion. Three patients had baseline triene/tetraene ratios of 0.4 or greater, indicative of essential fatty/acid deficiency, and these ratios dropped to less than 0.4 within eight days of beginning therapy with the parenteral fat emulsion. The remaining 12 patients maintained a normal triene/tetraene ratio of less than 0.4 throughout the 28 day study period. All three dosage regimens were considered effective for treatment and prevention of essential fatty acid deficiency. Images Fig. 1. Fig. 2. Fig. 3. PMID:6767452

  3. Effect of amino acids and amino acid derivatives on crystallization of hemoglobin and ribonuclease A

    International Nuclear Information System (INIS)

    Ito, Len; Kobayashi, Toyoaki; Shiraki, Kentaro; Yamaguchi, Hiroshi

    2008-01-01

    The effect of the addition of amino acids and amino acid derivatives on the crystallization of hemoglobin and ribonuclease A has been evaluated. The results showed that certain types of additives expand the concentration conditions in which crystals are formed. Determination of the appropriate conditions for protein crystallization remains a highly empirical process. Preventing protein aggregation is necessary for the formation of single crystals under aggregation-prone solution conditions. Because many amino acids and amino acid derivatives offer a unique combination of solubility and stabilizing properties, they open new avenues into the field of protein aggregation research. The use of amino acids and amino acid derivatives can potentially influence processes such as heat treatment and refolding reactions. The effect of the addition of several amino acids, such as lysine, and several amino acid derivatives, such as glycine ethyl ester and glycine amide, on the crystallization of equine hemoglobin and bovine pancreatic ribonuclease A has been examined. The addition of these amino acids and amino acid derivatives expanded the range of precipitant concentration in which crystals formed without aggregation. The addition of such additives appears to promote the crystallization of proteins

  4. Effect of amino acids and amino acid derivatives on crystallization of hemoglobin and ribonuclease A

    Energy Technology Data Exchange (ETDEWEB)

    Ito, Len, E-mail: len@ksc.kwansei.ac.jp; Kobayashi, Toyoaki [School of Science and Technology, Kwansei Gakuin University, 2-1 Gakuen, Sanda, Hyogo 669-1337 (Japan); Shiraki, Kentaro [Institute of Applied Physics, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8573 (Japan); Yamaguchi, Hiroshi [School of Science and Technology, Kwansei Gakuin University, 2-1 Gakuen, Sanda, Hyogo 669-1337 (Japan)

    2008-05-01

    The effect of the addition of amino acids and amino acid derivatives on the crystallization of hemoglobin and ribonuclease A has been evaluated. The results showed that certain types of additives expand the concentration conditions in which crystals are formed. Determination of the appropriate conditions for protein crystallization remains a highly empirical process. Preventing protein aggregation is necessary for the formation of single crystals under aggregation-prone solution conditions. Because many amino acids and amino acid derivatives offer a unique combination of solubility and stabilizing properties, they open new avenues into the field of protein aggregation research. The use of amino acids and amino acid derivatives can potentially influence processes such as heat treatment and refolding reactions. The effect of the addition of several amino acids, such as lysine, and several amino acid derivatives, such as glycine ethyl ester and glycine amide, on the crystallization of equine hemoglobin and bovine pancreatic ribonuclease A has been examined. The addition of these amino acids and amino acid derivatives expanded the range of precipitant concentration in which crystals formed without aggregation. The addition of such additives appears to promote the crystallization of proteins.

  5. Preventing neural tube defects in Europe: a missed opportunity.

    Science.gov (United States)

    Busby, Araceli; Abramsky, Lenore; Dolk, Helen; Armstrong, Ben; Addor, Marie-Claude; Anneren, Goran; Armstrong, Nicola; Baguette, Andre; Barisic, Ingeborg; Berghold, Andrea; Bianca, Sebastiano; Braz, Paula; Calzolari, Elisa; Christiansen, Marianne; Cocchi, Guido; Daltveit, Anne Kjersti; De Walle, Hermien; Edwards, Grace; Gatt, Miriam; Gener, Blanca; Gillerot, Yves; Gjergja, Romana; Goujard, Janine; Haeusler, Martin; Latos-Bielenska, Anna; McDonnell, Robert; Neville, Amanda; Olars, Birgitta; Portillo, Isabel; Ritvanen, Annukka; Robert-Gnansia, Elizabeth; Rösch, Christine; Scarano, Gioacchino; Steinbicker, Volker

    2005-01-01

    Each year, more than 4500 pregnancies in the European Union are affected by neural tube defects (NTD). Unambiguous evidence of the effectiveness of periconceptional folic acid in preventing the majority of neural tube defects has been available since 1991. We report on trends in the total prevalence of neural tube defects up to 2002, in the context of a survey in 18 European countries of periconceptional folic acid supplementation (PFAS) policies and their implementation. EUROCAT is a network of population-based registries in Europe collaborating in the epidemiological surveillance of congenital anomalies. Representatives from 18 participating countries provided information about policy, health education campaigns and surveys of PFAS uptake. The yearly total prevalence of neural tube defects including livebirths, stillbirths and terminations of pregnancy was calculated from 1980 to 2002 for 34 registries, with UK and Ireland estimated separately from the rest of Europe. A meta-analysis of changes in NTD total prevalence between 1989-1991 and 2000-2002 according to PFAS policy was undertaken for 24 registries. By 2005, 13 countries had a government recommendation that women planning a pregnancy should take 0.4mg folic acid supplement daily, accompanied in 7 countries by government-led health education initiatives. In the UK and Ireland, countries with PFAS policy, there was a 30% decline in NTD total prevalence (95% CI 16-42%) but it was difficult to distinguish this from the pre-existing strong decline. In other European countries with PFAS policy, there was virtually no decline in NTD total prevalence whether a policy was in place by 1999 (2%, 95% CI 28% reduction to 32% increase) or not (8%, 95% CI 26% reduction to 16% increase). The potential for preventing NTDs by periconceptional folic acid supplementation is still far from being fulfilled in Europe. Only a public health policy including folic acid fortification of staple foods is likely to result in large

  6. Introducing a new disinfectant for U.S. aquaculture - peracetic acid

    Science.gov (United States)

    Peracetic acid (PAA) is a promising disinfectant for biosecurity in the US aquaculture industry to prevent disease outbreaks from fish pathogens. PAA is a stabilized mixture of acetic acid, hydrogen peroxide and water that breaks down quickly to water and vinegar. It is being increasingly used to ...

  7. Uptake in the pancreatic islets of nicotimamide, nicotinic acid and tryptophan and their ability to prevent streptozotocin diabetes in mice

    Energy Technology Data Exchange (ETDEWEB)

    Tjaelve, H; Wilander, E [Uppsala Univ. (Sweden)

    1976-01-01

    The uptake of the nicotinamide adenine dinucleotide (NAD)-precursors nicotinamide, nicotinic acid and tryptophan in the pancreatic islets of mice was studied by use of autoradio-graphical methods. The ability of these substances to prevent streptozotocin diabetes was studied in the same species. It was found that only nicotinamide was strongly accumulated in the pancreatic islets and nicotinamide was also the only NAD-precursor which protected against the streptozotocin diabetes. Apparently there is a relationship between the ability of the NAD-precursors to be taken up in the pancreatic islets and their ability to prevent streptozotocin diabetes.

  8. A randomized, multi-center, clinical trial to assess the efficacy and safety of alginate carboxymethylcellulose hyaluronic acid compared to carboxymethylcellulose hyaluronic acid to prevent postoperative intrauterine adhesion.

    Science.gov (United States)

    Kim, Tak; Ahn, Ki Hoon; Choi, Doo Seok; Hwang, Kyung Joo; Lee, Byoung Ick; Jung, Min Hyung; Kim, Jae Weon; Kim, Jong Hyuk; Cha, Sun Hee; Lee, Ki Hwan; Lee, Kyu Sup; Oh, Sung Tack; Cho, Chi Heum; Rhee, Jeong Ho

    2012-01-01

    To estimate the efficacy of alginate carboxymethylcellulose hyaluronic acid (ACH) gel to prevent intrauterine adhesions after hysteroscopic surgery in comparison with carboxymethylcellulose hyaluronic acid (CH) gel, which is known as an effective adhesion inhibitor. Randomized, multicenter, single-blind, clinical trial (Canadian Task Force classification I). Tertiary university hospital. One hundred eighty-seven patients with a surgically treatable intrauterine lesion (myomas, polyps, septa, intrauterine adhesion, dysfunctional uterine bleeding). Patients were randomized to 2 groups: hysteroscopic surgery plus intrauterine application of ACH or CH. The rate of adhesion formation and the adhesion severity score with type and extent were calculated 4 weeks after surgery. The ACH group had results that were comparable to the CH group in terms of the development of intrauterine adhesions at 4 weeks follow-up. The adhesion severities were not different between the 2 groups. In a subgroup without baseline intrauterine adhesion, the ACH group showed a lower intrauterine adhesion rate than the CH group (p = .016). ACH had a comparable efficacy to CH in terms of the adhesion rate and severity. In the case of no baseline intrauterine adhesion, intrauterine application of ACH after hysteroscopic surgery had a lower rate of intrauterine adhesion than application of CH. Copyright © 2012 AAGL. Published by Elsevier Inc. All rights reserved.

  9. Nutritional approach to preeclampsia prevention.

    Science.gov (United States)

    Achamrah, Najate; Ditisheim, Agnès

    2018-05-01

    Although not fully understood, the physiopathology of preeclampsia is thought to involve an abnormal placentation, diffuse endothelial cell dysfunction and increased systemic inflammation. As micronutrients play a key role in placental endothelial function, oxidative stress and expression of angiogenic factors, periconceptional micronutrient supplementation has been proposed to reduce the risk of preeclampsia. However, recent studies reported conflicting results. Calcium intake (>1 g/day) may reduce the risk of preeclampsia in women with low-calcium diet. Data from recently updated Cochrane reviews did not support routine supplementation of vitamins C, E or D for either the prevention or treatment of preeclampsia. Evidences are also poor to support zinc or folic acid supplementation for preeclampsia prevention. Dark chocolate, flavonoid-rich food, and long-chain polyunsaturated fatty acids might also be candidates for prevention of preeclampsia. Through antioxidant, anti-inflammatory or vasoactive proprieties, micronutrients are good candidates for preeclampsia prevention. Calcium supplementation is recommended to prevent preeclampsia in women with low-calcium intake. Despite positive clinical and in-vitro data, strong evidence to support periconceptional supplementation of other micronutrients for preeclampsia risk-reduction is still lacking. Further studies are also needed to evaluate the benefit of nutritional supplementation such as chocolate and long-chain polyunsaturated fatty acids.

  10. Acyl coenzyme A thioesterase 7 regulates neuronal fatty acid metabolism to prevent neurotoxicity.

    Science.gov (United States)

    Ellis, Jessica M; Wong, G William; Wolfgang, Michael J

    2013-05-01

    Numerous neurological diseases are associated with dysregulated lipid metabolism; however, the basic metabolic control of fatty acid metabolism in neurons remains enigmatic. Here we have shown that neurons have abundant expression and activity of the long-chain cytoplasmic acyl coenzyme A (acyl-CoA) thioesterase 7 (ACOT7) to regulate lipid retention and metabolism. Unbiased and targeted metabolomic analysis of fasted mice with a conditional knockout of ACOT7 in the nervous system, Acot7(N-/-), revealed increased fatty acid flux into multiple long-chain acyl-CoA-dependent pathways. The alterations in brain fatty acid metabolism were concomitant with a loss of lean mass, hypermetabolism, hepatic steatosis, dyslipidemia, and behavioral hyperexcitability in Acot7(N-/-) mice. These failures in adaptive energy metabolism are common in neurodegenerative diseases. In agreement, Acot7(N-/-) mice exhibit neurological dysfunction and neurodegeneration. These data show that ACOT7 counterregulates fatty acid metabolism in neurons and protects against neurotoxicity.

  11. Acidizing reservoirs while chelating iron with sulfosalicylic acid

    Energy Technology Data Exchange (ETDEWEB)

    McLaughlin, W A; Berkshire, D C

    1980-09-30

    A well treating process is described in which an aqueous solution of a strong acid capable of dissolving solids in a manner increasing the permeability of a subterranean earth formation is injected into a subterranean reservoir that contains an asphaltenic oil. At least the first injected portion of the aqueous acid and a solution or homogeneous dispersion of at least enough 5-sulfosalicylic acid to chelate with and prevent the formation of iron-asphaltene solids are included with substantially all of the ferric ions that become dissolved within the strong acid solution that enters the earth formation. 10 claims.

  12. A novel cost-effectiveness model of prescription eicosapentaenoic acid extrapolated to secondary prevention of cardiovascular diseases in the United States.

    Science.gov (United States)

    Philip, Sephy; Chowdhury, Sumita; Nelson, John R; Benjamin Everett, P; Hulme-Lowe, Carolyn K; Schmier, Jordana K

    2016-10-01

    Given the substantial economic and health burden of cardiovascular disease and the residual cardiovascular risk that remains despite statin therapy, adjunctive therapies are needed. The purpose of this model was to estimate the cost-effectiveness of high-purity prescription eicosapentaenoic acid (EPA) omega-3 fatty acid intervention in secondary prevention of cardiovascular diseases in statin-treated patient populations extrapolated to the US. The deterministic model utilized inputs for cardiovascular events, costs, and utilities from published sources. Expert opinion was used when assumptions were required. The model takes the perspective of a US commercial, third-party payer with costs presented in 2014 US dollars. The model extends to 5 years and applies a 3% discount rate to costs and benefits. Sensitivity analyses were conducted to explore the influence of various input parameters on costs and outcomes. Using base case parameters, EPA-plus-statin therapy compared with statin monotherapy resulted in cost savings (total 5-year costs $29,393 vs $30,587 per person, respectively) and improved utilities (average 3.627 vs 3.575, respectively). The results were not sensitive to multiple variations in model inputs and consistently identified EPA-plus-statin therapy to be the economically dominant strategy, with both lower costs and better patient utilities over the modeled 5-year period. The model is only an approximation of reality and does not capture all complexities of a real-world scenario without further inputs from ongoing trials. The model may under-estimate the cost-effectiveness of EPA-plus-statin therapy because it allows only a single event per patient. This novel model suggests that combining EPA with statin therapy for secondary prevention of cardiovascular disease in the US may be a cost-saving and more compelling intervention than statin monotherapy.

  13. Tumour–stromal interactions in acid-mediated invasion: A mathematical model

    KAUST Repository

    Martin, Natasha K.

    2010-12-01

    It is well established that the tumour microenvironment can both promote and suppress tumour growth and invasion, however, most mathematical models of invasion view the normal tissue as inhibiting tumour progression via immune modulation or spatial constraint. In particular, the production of acid by tumour cells and the subsequent creation of a low extracellular pH environment has been explored in several \\'acid-mediated tumour invasion\\' models where the acidic environment facilitates normal cell death and permits tumour invasion. In this paper, we extend the acid-invasion model developed by Gatenby and Gawlinski (1996) to include both the competitive and cooperative interactions between tumour and normal cells, by incorporating the influence of extracellular matrix and protease production at the tumour-stroma interface. Our model predicts an optimal level of tumour acidity which produces both cell death and matrix degradation. Additionally, very aggressive tumours prevent protease production and matrix degradation by excessive normal cell destruction, leading to an acellular (but matrix filled) gap between the tumour and normal tissue, a feature seen in encapsulated tumours. These results suggest, counterintuitively, that increasing tumour acidity may, in some cases, prevent tumour invasion.

  14. Tranexamic Acid versus Placebo to Prevent Blood Transfusion during Radical Cystectomy for Bladder Cancer (TACT): Study Protocol for a Randomized Controlled Trial.

    Science.gov (United States)

    Breau, Rodney H; Lavallée, Luke T; Cnossen, Sonya; Witiuk, Kelsey; Cagiannos, Ilias; Momoli, Franco; Bryson, Gregory; Kanji, Salmaan; Morash, Christopher; Turgeon, Alexis; Zarychanski, Ryan; Mallick, Ranjeeta; Knoll, Greg; Fergusson, Dean A

    2018-05-02

    Radical cystectomy for bladder cancer is associated with a high risk of needing red blood cell transfusion. Tranexamic acid reduces blood loss during cardiac and orthopedic surgery, but no study has yet evaluated tranexamic acid use during cystectomy. A randomized, double-blind (surgeon-, anesthesiologist-, patient-, data-monitor-blinded), placebo-controlled trial of tranexamic acid during cystectomy was initiated in June 2013. Prior to incision, the intervention arm participants receive a 10 mg/kg loading dose of intravenously administered tranexamic acid, followed by a 5 mg/kg/h maintenance infusion. In the control arm, the patient receives an identical volume of normal saline that is indistinguishable from the intervention. The primary outcome is any blood transfusion from the start of surgery up to 30 days post operative. There are no strict criteria to mandate the transfusion of blood products. The decision to transfuse is entirely at the discretion of the treating physicians who are blinded to patient allocation. Physicians are allowed to utilize all resources to make transfusion decisions, including serum hemoglobin concentration and vital signs. To date, 147 patients of a planned 354 have been randomized to the study. This protocol reviews pertinent data relating to blood transfusion during radical cystectomy, highlighting the need to identify methods for reducing blood loss and preventing transfusion in patients receiving radical cystectomy. It explains the clinical rationale for using tranexamic acid to reduce blood loss during cystectomy, and outlines the study methods of our ongoing randomized controlled trial. Canadian Institute for Health Research (CIHR) Protocol: MOP-342559; ClinicalTrials.gov, ID: NCT01869413. Registered on 5 June 2013.

  15. Major involvement of Na(+) -dependent multivitamin transporter (SLC5A6/SMVT) in uptake of biotin and pantothenic acid by human brain capillary endothelial cells.

    Science.gov (United States)

    Uchida, Yasuo; Ito, Katsuaki; Ohtsuki, Sumio; Kubo, Yoshiyuki; Suzuki, Takashi; Terasaki, Tetsuya

    2015-07-01

    The purpose of this study was to clarify the expression of Na(+) -dependent multivitamin transporter (SLC5A6/SMVT) and its contribution to the supply of biotin and pantothenic acid to the human brain via the blood-brain barrier. DNA microarray and immunohistochemical analyses confirmed that SLC5A6 is expressed in microvessels of human brain. The absolute expression levels of SLC5A6 protein in isolated human and monkey brain microvessels were 1.19 and 0.597 fmol/μg protein, respectively, as determined by a quantitative targeted absolute proteomics technique. Using an antibody-free method established by Kubo et al. (2015), we found that SLC5A6 was preferentially localized at the luminal membrane of brain capillary endothelium. Knock-down analysis using SLC5A6 siRNA showed that SLC5A6 accounts for 88.7% and 98.6% of total [(3) H]biotin and [(3) H]pantothenic acid uptakes, respectively, by human cerebral microvascular endothelial cell line hCMEC/D3. SLC5A6-mediated transport in hCMEC/D3 was markedly inhibited not only by biotin and pantothenic acid, but also by prostaglandin E2, lipoic acid, docosahexaenoic acid, indomethacin, ketoprofen, diclofenac, ibuprofen, phenylbutazone, and flurbiprofen. This study is the first to confirm expression of SLC5A6 in human brain microvessels and to provide evidence that SLC5A6 is a major contributor to luminal uptake of biotin and pantothenic acid at the human blood-brain barrier. In humans, it was unclear (not concluded) about what transport system at the blood-brain barrier (BBB) is responsible for the brain uptakes of two vitamins, biotin and pantothenic acid, which are necessary for brain proper function. This study clarified for the first time that the solute carrier 5A6/Na(+) -dependent multivitamin transporter SLC5A6/SMVT is responsible for the supplies of biotin and pantothenic acid into brain across the BBB in humans. DHA, docosahexaenoic acid; NSAID, non-steroidal anti-inflammatory drug; PGE2, prostaglandin E2. © 2015

  16. Natural products used for diabetes.

    Science.gov (United States)

    Shapiro, Karen; Gong, William C

    2002-01-01

    To review the efficacy and safety of natural products commonly used for diabetes. English and Spanish-language journals retrieved through a MEDLINE search of articles published between 1960 and December 2001 using these index terms: Opuntia, karela, gymnema, tecoma, alpha lipoic acid, thioctic acid, ginseng, panaxans, and diabetes. Natural products have long been used in traditional systems of medicine for diabetes. Products in common use include nopal (prickly pear cactus), fenu-greek, karela (bitter melon), gymnema, ginseng, tronadora, chromium, and alpha-lipoic acid. The popularity of these products varies among people of different ethnicities. Nopal is the most commonly used herbal hypoglycemic among persons of Mexican descent. Karela is more commonly used by persons from Asian countries. Some of these agents have gained universal appeal. For a select number of products, studies have revealed single or multiple mechanisms of action. For several of these, high soluble fiber content is a contributing factor. Based on the available evidence, several natural products in common use can lower blood glucose in patients with diabetes. Commonly used natural products often have a long history of traditional use, and pharmacists who have a stronger understanding of these products are better positioned to counsel patients on their appropriate use.

  17. Effect of Smoking and Folate Levels on the Efficacy of Folic Acid Therapy in Prevention of Stroke in Hypertensive Men.

    Science.gov (United States)

    Zhou, Ziyi; Li, Jianping; Yu, Yaren; Li, Youbao; Zhang, Yan; Liu, Lishun; Song, Yun; Zhao, Min; Wang, Yu; Tang, Genfu; He, Mingli; Xu, Xiping; Cai, Yefeng; Dong, Qiang; Yin, Delu; Huang, Xiao; Cheng, Xiaoshu; Wang, Binyan; Hou, Fan Fan; Wang, Xiaobin; Qin, Xianhui; Huo, Yong

    2018-01-01

    We aimed to examine whether the efficacy of folic acid therapy in the primary prevention of stroke is jointly affected by smoking status and baseline folate levels in a male population in a post hoc analysis of the CSPPT (China Stroke Primary Prevention Trial). Eligible participants of the CSPPT were randomly assigned to a double-blind daily treatment of a combined enalapril 10-mg and folic acid 0.8-mg tablet or an enalapril 10-mg tablet alone. In total, 8384 male participants of the CSPPT were included in the current analyses. The primary outcome was first stroke. The median treatment duration was 4.5 years. In the enalapril-alone group, the first stroke risk varied by baseline folate levels and smoking status (never versus ever). Specifically, there was an inverse association between folate levels and first stroke in never smokers ( P for linear trend=0.043). However, no such association was found in ever smokers. A test for interaction between baseline folate levels and smoking status on first stroke was significant ( P =0.045). In the total sample, folic acid therapy significantly reduced the risk of first stroke in never smokers with folate deficiency (hazard risk, 0.36; 95% confidence interval, 0.16-0.83) and in ever smokers with normal folate levels (hazard risk, 0.69; 95% confidence interval, 0.48-0.99). Baseline folate levels and smoking status can interactively affect the risk of first stroke. Our data suggest that compared with never smokers, ever smokers may require a higher dosage of folic acid to achieve a greater beneficial effect on stroke. Our findings need to be confirmed by future randomized trials. URL: https://www.clinicaltrials.gov. Unique identifier: NCT00794885. © 2017 American Heart Association, Inc.

  18. The omega-3 fatty acid, eicosapentaenoic acid (EPA, prevents the damaging effects of tumour necrosis factor (TNF-alpha during murine skeletal muscle cell differentiation

    Directory of Open Access Journals (Sweden)

    Pearson Stephen

    2008-07-01

    Full Text Available Abstract Background Eicosapentaenoic acid (EPA is a ώ-3 polyunsaturated fatty acid with anti-inflammatory and anti-cachetic properties that may have potential benefits with regards to skeletal muscle atrophy conditions where inflammation is present. It is also reported that pathologic levels of the pro-inflammatory cytokine tumour necrosis factor (TNF-α are associated with muscle wasting, exerted through inhibition of myogenic differentiation and enhanced apoptosis. These findings led us to hypothesize that EPA may have a protective effect against skeletal muscle damage induced by the actions of TNF-α. Results The deleterious effects of TNF-α on C2C12 myogenesis were completely inhibited by co-treatment with EPA. Thus, EPA prevented the TNF-mediated loss of MyHC expression and significantly increased myogenic fusion (p p p p p p Conclusion In conclusion, EPA has a protective action against the damaging effects of TNF-α on C2C12 myogenesis. These findings support further investigations of EPA as a potential therapeutic agent during skeletal muscle regeneration following injury.

  19. Phytanic acid-an overlooked bioactive fatty acid in dairy fat?

    DEFF Research Database (Denmark)

    Hellgren, Lars

    2010-01-01

    dissipation in skeletal muscles. Phytanic acid levels in serum are associated with an increased risk of developing prostate cancer, but the available data do not support a general causal link between circulating phytanic acid and prostate cancer risk. However, certain individuals, with specific single......Phytanic acid is a multibranched fatty acid with reported retinoid X receptor (RXR) and peroxisome proliferator-activated receptor-alpha (PPAR-alpha) agonist activity, which have been suggested to have preventive effects on metabolic dysfunctions. Serum level in man is strongly correlated...

  20. A Comparative Study of Effects of Omega‑3 Fatty Acids, Alpha Lipoic ...

    African Journals Online (AJOL)

    Impaired insulin secretion and insulin resistance are the basic ... Background: Diabetes Mellitus is a metabolic disorder characterized by abnormal ... Various modes of adjuvant therapy have been advocated to ... insulin sensitivity (blood glucose and HbA1c) in patients of type 2 diabetes mellitus with ... Metabolic Syndrome.

  1. Acacetin inhibits glutamate release and prevents kainic acid-induced neurotoxicity in rats.

    Directory of Open Access Journals (Sweden)

    Tzu-Yu Lin

    Full Text Available An excessive release of glutamate is considered to be a molecular mechanism associated with several neurological diseases that causes neuronal damage. Therefore, searching for compounds that reduce glutamate neurotoxicity is necessary. In this study, the possibility that the natural flavone acacetin derived from the traditional Chinese medicine Clerodendrum inerme (L. Gaertn is a neuroprotective agent was investigated. The effect of acacetin on endogenous glutamate release in rat hippocampal nerve terminals (synaptosomes was also investigated. The results indicated that acacetin inhibited depolarization-evoked glutamate release and cytosolic free Ca(2+ concentration ([Ca(2+]C in the hippocampal nerve terminals. However, acacetin did not alter synaptosomal membrane potential. Furthermore, the inhibitory effect of acacetin on evoked glutamate release was prevented by the Cav2.2 (N-type and Cav2.1 (P/Q-type channel blocker known as ω-conotoxin MVIIC. In a kainic acid (KA rat model, an animal model used for excitotoxic neurodegeneration experiments, acacetin (10 or 50 mg/kg was administrated intraperitoneally to the rats 30 min before the KA (15 mg/kg intraperitoneal injection, and subsequently induced the attenuation of KA-induced neuronal cell death and microglia activation in the CA3 region of the hippocampus. The present study demonstrates that the natural compound, acacetin, inhibits glutamate release from hippocampal synaptosomes by attenuating voltage-dependent Ca(2+ entry and effectively prevents KA-induced in vivo excitotoxicity. Collectively, these data suggest that acacetin has the therapeutic potential for treating neurological diseases associated with excitotoxicity.

  2. Peritoneal adhesion prevention with a biodegradable and injectable N,O-carboxymethyl chitosan-aldehyde hyaluronic acid hydrogel in a rat repeated-injury model

    Science.gov (United States)

    Song, Linjiang; Li, Ling; He, Tao; Wang, Ning; Yang, Suleixin; Yang, Xi; Zeng, Yan; Zhang, Wenli; Yang, Li; Wu, Qinjie; Gong, Changyang

    2016-11-01

    Postoperative peritoneal adhesion is one of the serious issues because it induces severe clinical disorders. In this study, we prepared biodegradable and injectable hydrogel composed of N,O-carboxymethyl chitosan (NOCC) and aldehyde hyaluronic acid (AHA), and assessed its anti-adhesion effect in a rigorous and severe recurrent adhesion model which is closer to clinical conditions. The flexible hydrogel, which gelated in 66 seconds at 37 °C, was cross-linked by the schiff base derived from the amino groups of NOCC and aldehyde groups in AHA. In vitro cytotoxicity test showed the hydrogel was non-toxic. In vitro and in vivo degradation examinations demonstrated the biodegradable and biocompatibility properties of the hydrogel. The hydrogel discs could prevent the invasion of fibroblasts, whereas fibroblasts encapsulated in the porous 3-dimensional hydrogels could grow and proliferate well. Furthermore, the hydrogel was applied to evaluate the anti-adhesion efficacy in a more rigorous recurrent adhesion model. Compared with normal saline group and commercial hyaluronic acid (HA) hydrogel, the NOCC-AHA hydrogel exhibited significant reduction of peritoneal adhesion. Compared to control group, the blood and abdominal lavage level of tPA was increased in NOCC-AHA hydrogel group. These findings suggested that NOCC-AHA hydrogel had a great potential to serve as an anti-adhesion candidate.

  3. Prevention of postcoronary angioplasty restenosis by omega-3 fatty acids: main results of the Esapent for Prevention of Restenosis ITalian Study (ESPRIT).

    Science.gov (United States)

    Maresta, Aleardo; Balduccelli, Marco; Varani, Elisabetta; Marzilli, Mario; Galli, Claudio; Heiman, Franca; Lavezzari, Maurizio; Stragliotto, Eduardo; De Caterina, Raffaele

    2002-06-01

    Previous trials of omega-3 fatty acids (omega-3 FA) for restenosis prevention after percutaneous transluminal coronary angioplasty (PTCA) have yielded conflicting results. We tested the hypothesis that long-term administration of omega-3 FA before PTCA may have significant effects on restenosis. We randomized 339 patients in a double-blind, placebo-controlled study of omega-3 FA (as an ethyl ester preparation given as 6 1-g capsules providing 3 g eicosapentaenoic acid and 2.1 g docosahexaenoic acid/d started 1 month before PTCA and given for 1 month thereafter, then continued at half-dose for 6 months) versus an olive oil placebo. Of these, 257 patients (125 on omega-3 FA, 132 on placebo) well matched for risk factors underwent successful balloon-only PTCA (280 total lesions) and were evaluable at 6 months with repeat angiography. Restenosis was defined at quantitative angiography as a recurrence of >50% diameter stenosis in the dilated vessel (Definition I) and as >50% loss of the short-term gain immediately after PTCA (Definition II). Restenosis rates per vessel were 29.4% and 31.6% in the omega-3 FA group, and 39.6% and 35.4% in the placebo group according to Definitions I (P =.04) and II (P = not significant), respectively. Restenosis rates per patient were 31.2% and 33.6% in the omega-3 FA group, and 40.9% and 37.1% in the placebo group according to Definitions I (P =.05) and II (P = not significant), respectively. With a long treatment before PTCA, omega-3 FA produced a small but significant decrease in the restenosis rate compared with placebo.

  4. Zoledronic Acid Injection

    Science.gov (United States)

    Zoledronic acid (Reclast) is used to prevent or treat osteoporosis (condition in which the bones become thin and weak ... of life,' end of regular menstrual periods). Zoledronic acid (Reclast) is also used to treat osteoporosis in ...

  5. A full-scale porous reactive wall for prevention of acid mine drainage

    International Nuclear Information System (INIS)

    Benner, S.G.; Blowes, D.W.; Ptacek, C.J.

    1997-01-01

    The generation and release of acidic drainage containing high concentrations of dissolved metals from decommissioned mine wastes is an environmental problem of international scale. A potential solution to many acid drainage problems is the installation of permeable reactive walls into aquifers affected by drainage water derived from mine waste materials. A permeable reactive wall installed into an aquifer impacted by low-quality mine drainage waters was installed in August 1995 at the Nickel Rim mine site near Sudbury, Ontario. The reactive mixture, containing organic matter, was designed to promote bacterially mediated sulfate reduction and subsequent metal sulfide precipitation. The reactive wall is installed to an average depth of 12 feet (3.6 m) and is 49 feet (15 m) long perpendicular to ground water flow. The wall thickness (flow path length) is 13 feet (4 m). Initial results, collected nine months after installation, indicate that sulfate reduction and metal sulfide precipitation is occurring. The reactive wall has effectively removed the capacity of the ground water to generate acidity on discharge to the surface. Calculations based on comparison to previously run laboratory column experiments indicate that the reactive wall has potential to remain effective for at least 15 years

  6. Influence of Different Antioxidants on X-Ray Induced DNA Double-Strand Breaks (DSBs Using γ-H2AX Immunofluorescence Microscopy in a Preliminary Study.

    Directory of Open Access Journals (Sweden)

    Michael Brand

    Full Text Available Radiation exposure occurs in X-ray guided interventional procedures or computed tomography (CT and γ-H2AX-foci are recognized to represent DNA double-strand breaks (DSBs as a biomarker for radiation induced damage. Antioxidants may reduce the induction of γ-H2AX-foci by binding free radicals. The aim of this study was to establish a dose-effect relationship and a time-effect relationship for the individual antioxidants on DSBs in human blood lymphocytes.Blood samples from volunteers were irradiated with 10 mGy before and after pre-incubation with different antioxidants (zinc, trolox, lipoic acid, ß-carotene, selenium, vitamin E, vitamin C, N-acetyl-L-cysteine (NAC and Q 10. Thereby, different pre-incubation times, concentrations and combinations of drugs were evaluated. For assessment of DSBs, lymphocytes were stained against the phosphorylated histone variant γ-H2AX.For zinc, trolox and lipoic acid regardless of concentration or pre-incubation time, no significant decrease of γ-H2AX-foci was found. However, ß-carotene (15%, selenium (14%, vitamin E (12%, vitamin C (25%, NAC (43% and Q 10 (18% led to a significant reduction of γ-H2AX-foci at a pre-incubation time of 1 hour. The combination of different antioxidants did not have an additive effect.Antioxidants administered prior to irradiation demonstrated the potential to reduce γ-H2AX-foci in blood lymphocytes.

  7. Abscisic acid and osmoticum prevent germination of developing alfalfa embryos, but only osmoticum maintains the synthesis of developmental proteins.

    Science.gov (United States)

    Xu, N; Coulter, K M; Derek Bewley, J

    1990-10-01

    Developing seeds of alfalfa (Medicago sativa L.) acquire the ability to germinate during the latter stages of development, the maturation drying phase. Isolated embryos placed on Murashige and Skoog medium germinate well during early and late development, but poorly during mid-development; however, when placed on water they germinate well only during the latter stage of development. Germination of isolated embryos is very slow and poor when they are incubated in the presence of surrounding seed structures (the endosperm or seed coat) taken from the mid-development stages. This inhibitory effect is also achieved by incubating embryos in 10(-5) M abscisic acid (ABA). Endogenous ABA attains a high level during mid-development, especially in the endosperm. Seeds developing in pods treated with fluridone (1-methyl-3-phenyl-5[3-(trifluoromethyl)-phenyl]-4(1H)-pyridinone) contain low levels of ABA during mid-development, and the endosperm and seed coat only weakly inhibit the germination of isolated embryos. However, intact seeds from fluridone-treated pods do not germinate viviparously, which is indicative that ABA alone is not responsible for maintaining seeds in a developing state. Application of osmoticum (e.g. 0.35 M sucrose) to isolated developing embryos prevents their germination. Also, in the developing seed in situ the osmotic potential is high. Thus internal levels of osmoticum may play a role in preventing germination of the embryo and maintaining development. Abscisic acid and osmoticum impart distinctly different metabolic responses on developing embryos, as demonstrated by their protein-synthetic capacity. Only in the presence of osmoticum do embryos synthesize proteins which are distinctly recognizable as those synthesized by developing embryos in situ, i.e. when inside the pod. Abscisic acid induces the synthesis of a few unique proteins, but these arise even in mature embryos treated with ABA. Thus while both osmoticum and ABA prevent precocious

  8. Marine OMEGA-3 fatty acids in the prevention of cardiovascular disease.

    Science.gov (United States)

    Mori, Trevor A

    2017-11-01

    Omega-6 (ω6) and omega-3 (ω3) fatty acids are two classes of dietary polyunsaturated fatty acids derived from linoleic acid (18:2ω6) and α-linolenic acid (18:3ω3), respectively. Enzymatic metabolism of linoleic and α-linolenic acids generates arachidonic acid (20:4ω6) and eicosapentaenoic acid (20:5ω3; EPA), respectively, both of which are substrates for enzymes that yield eicosanoids with multiple and varying physiological functions. Further elongation and desaturation of EPA yields the 22-carbon fatty acid docosahexaenoic acid (22:6ω3; DHA). The main dietary source of EPA and DHA for human consumption is fish, especially oily fish. There is considerable evidence that EPA and DHA are protective against cardiovascular disease (heart disease and stroke), particularly in individuals with pre-existing disease. ω3 Fatty acids benefit multiple risk factors including blood pressure, blood vessel function, heart function and blood lipids, and they have antithrombotic, anti-inflammatory and anti-oxidative actions. ω3 Fatty acids do not adversely interact with medications. Supplementation with ω3 fatty acids is recommended in individuals with elevated blood triglyceride levels and patients with coronary heart disease. A practical recommendation for the general population is to increase ω3 fatty acid intake by incorporating fish as part of a healthy diet that includes increased fruits and vegetables, and moderation of salt intake. Health authorities recommend the general population should consume at least two oily fish meals per week. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. A randomized controlled experimental study of the efficacy of platelet-rich plasma and hyaluronic acid for the prevention of adhesion formation in a rat uterine horn model.

    Science.gov (United States)

    Oz, Murat; Cetinkaya, Nilufer; Bas, Sevda; Korkmaz, Elmas; Ozgu, Emre; Terzioglu, Gokay Serdar; Buyukkagnici, Umran; Akbay, Serap; Caydere, Muzaffer; Gungor, Tayfun

    2016-09-01

    Platelet-rich plasma (PRP) has been known to possess an efficacy in tissue regeneration. The aim of this study was to determine the role of PRP on post-operative adhesion formation in an experimental rat study. Thirty Sprague-Dawley rats were randomly divided into control, hyaluronic acid, and PRP treatment groups and operated on for uterine horn adhesion modeling. Blood was collected to produce a PRP with platelet counts of 688 × 10(3)/μL, and 1 ml of either hyaluronic acid gel or PRP was administered over the standard lesions, while the control group received no medication. The evaluation of post-operative adhesions was done on the 30th post-operative day. The location, extent, type, and tenacity of adhesions as well as total adhesion scores, tissue inflammation, fibrosis and transforming growth factor-1beta (TGF-1β) expressions were evaluated. The total adhesion score was significantly lower in the PRP group (3.2 ± 1.5) compared with the hyaluronic acid (5.0 ± 1.3) and control (8.1 ± 1.7) groups. The extent of the adhesions was significantly lower in the PRP group. There was no significant difference in the type and tenacity of adhesions between the hyaluronic acid and the PRP group. The level of inflammation was significantly higher in the control group than the others, while there was no difference between the PRP and hyaluronic acid groups. TGF-1β expression was significantly lesser in the PRP group than the control and hyaluronic acid groups. PRP is more effective than hyaluronic acid treatment in preventing post-operative adhesion formation in an experimental rat uterine horn adhesion model.

  10. Burning mouth syndrome: Clinical dilemma?

    Directory of Open Access Journals (Sweden)

    Kanchan R Patil

    2008-01-01

    Full Text Available Burning Mouth Syndrome (BMS is a chronic orofacial burning pain condition usually in the absence of clinical and laboratory findings that affects many adults worldwide, yet its etiology and treatment remain poorly understood. Though it has been associated with numerous oral and systemic conditions, there has been no clear consensus on its etiology, pathogenesis and treatment. As a result, patients with inexplicable oral complaints are often referred from one health care professional to another without effective management having significant emotional impact on patients. As the dental profession expands its scope of care to oral medicine and geriatrics, BMS will be more effectively diagnosed and managed by these dental surgeons. Hence, they should be more involved in evaluation and management of these patients. The present article provides updated information on BMS including possible etiological factors and current treatment options, although data on the effectiveness of these treatment modalities remain limited. Recently researchers found that treatment with a familiar nutritional supplement- lipoic acid- is of remarkable benefit with minimal adverse effects. ALA (alpha-lipoic acid may be the effective treatment modality in management of BMS.

  11. Lactic acid bacteria from raw milk as potentially beneficial strains to prevent bovine mastitis.

    Science.gov (United States)

    Espeche, M Carolina; Pellegrino, Matías; Frola, Ignacio; Larriestra, Alejandro; Bogni, Cristina; Nader-Macías, M E Fátima

    2012-02-01

    Bovine mastitis produces a wide variety of problems in the dairy farm. The treatment of this disease is based on the use of antibiotics which are not always effective. These drugs are also responsible for the presence of residues in the milk and the increase of antibiotic-resistant strains. Probiotic products were proposed as a valid alternative to antibiotic therapies and are also useful for the prevention of infectious syndromes. With the aim of designing a probiotic product to prevent bovine mastitis, lactic acid bacteria (LAB) were isolated from foremilk samples from different dairy farms in Córdoba-Argentina. One hundred and seventeen LAB were isolated and their beneficial characteristics such as the production of inhibitory substances, surface properties and production of exopolysaccharides (EPS) were assessed. Most of them displayed low degree of hydrophobicity, autoaggregation, EPS negative phenotype and were identified as Enterococcus hirae and Pediococcus pentosaceus. Nine LAB strains inhibited three indicator bacteria. Some isolates were pre-selected and genetically identified according to the results obtained. Antibiotic resistance and virulence factors were studied for the assessment of the safety of the strains. The results obtained were compared to those reported previously from samples obtained in the North-western area of the country and some differences were found. Copyright © 2012 Elsevier Ltd. All rights reserved.

  12. Role of amino acid supplementation in the prevention of necrotizing enterocolitis in preterm neonates - a review of current evidences.

    Science.gov (United States)

    Garg, Bhawan Deep; Kabra, Nandkishor S

    2018-09-01

    Necrotizing enterocolitis (NEC) is one of the most common acute and fatal gastrointestinal emergency in very low birth weight (VLBW) preterm neonates with mortality range from 15 to 30%. NEC is likely due to multifactorial process such as oxidative injury, ischemic necrosis, and over-reactive inflammatory response to intestinal microbes. To evaluate the role of amino acid supplementation for reduction of neonatal NEC in preterm neonates. The literature search was done for various randomized control trial (RCT) by searching the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE, Web of Science, Scopus, Index Copernicus, African Index Medicus (AIM), Thomson Reuters (ESCI), Chemical Abstracts Service (CAS) and other database. This review included 15 RCTs that fulfilled inclusion criteria. The total neonates enrolled in these different RCT are 3424 (amino acid group 1711 and control 1713). Almost all participating neonates were of VLBW or extremely low birth weight (ELBW). In two trials, birth weight was between 1500-2000 grams. The intervention was started within first few days after birth and continued up to 30th day of postnatal age in most of the trials. In two trials, intervention was continued up to 120th day of postnatal age. Arginine, glutamine and N-acetyl cysteine (NAC) were used at the dose of 1.5 mol/kg/day (261 mg/kg/day), 0.3 grams/kg/day and 16-32 mg/kg/day, respectively. Role of amino acid in the prevention of neonatal NEC is not exclusively supported by the current evidence. Only three studies were able to show reduction in the incidence of NEC with amino acid supplementation (arginine, glutamine), and the remaining studies did not report any positive effect. Amino acid supplementation was not associated with significant reduction in mortality due to any causes. However, arginine supplementation was associated with significant reduction in mortality due to NEC. Two studies on glutamine were reported significant reduction in

  13. Passivation of bimetallic catalysts used in water treatment: prevention and reactivation.

    Science.gov (United States)

    Chen, Jianming; Gillham, Robert W; Gui, Lai

    2013-01-01

    With respect to degradation rates and the range in contaminants treated, bimetals such as Ni-Fe or Pd-Fe generally outperform unamended granular iron. However, the catalytic enhancement is generally short-lived, lasting from a few days to months. To take advantage of the significant benefits of bimetals, this study aims at developing an effective method for the rejuvenation of passivated bimetals and alternatively, the prevention of rapid reactivity loss of bimetals. Because the most likely cause of Ni-Fe and Pd-Fe passivation is the deposition of iron oxide films over the catalyst sites, it is hypothesized that removal of the iron oxide films will restore the lost reactivity or avoiding the deposition of iron oxide films will prevent passivation. Two organic ligands (ethylenediaminetetraacetic acid (EDTA), and [s,s]-ethylenediaminedisuccinate acid ([s,s]-EDDS)) and two acids (citric acid and sulphuric acid) were tested as possible chemical reagents for both passivation rejuvenation and prevention. Trichloroethene (TCE) and Ni-Fe were chosen as probes for chlorinated solvents and bimetals respectively. The test was carried out using small glass columns packed with Ni-Fe. TCE solution containing a single reagent at various concentrations was pumped through the Ni-Fe columns with a residence time in the Ni-Fe of about 6.6 min. TCE concentrations in the influent and effluent were measured to evaluate the performance of each chemical reagent. The results show that (i) for passivated Ni-Fe, flushing with a low concentration of acid or ligand solution without mechanical mixing can fully restore the lost reactivity; and (ii) for passivation prevention, adding a small amount of a ligand or an acid to the feed solution can successfully prevent or at least substantially reduce Ni-Fe passivation. All four chemicals tested are effective in both rejuvenation and prevention, but sulphuric acid and citric acid are considered to be the most practical reagents due to their

  14. Conjugated linolenic acids (CLnA, super CLA – natural sources and biological activity

    Directory of Open Access Journals (Sweden)

    Agnieszka Białek

    2014-11-01

    Full Text Available Polyunsaturated fatty acids (PUFA have a wide range of biological activity. Among them conjugated fatty acids are of great interest. Conjugated linoleic acids (CLA, which exert a multidirectional health-benefiting influence, and conjugated linolenic acids (CLnA, super CLA are examples of this group of fatty acids. CLnA are a group of positional and geometric isomers of octadecatrienoic acid (C18:3, which possess double bonds at positions 9, 11, 13 or 8, 10, 12 of their chain. Some vegetable oils are rich sources of CLnA, e.g. bitter melon oil (from Momordica charantia seeds and pomegranate oil (from Punica granatum seeds. The aim of this paper was to present information concerning natural sources and health-promoting activities of conjugated linolenic acids.The presented data reveal that conjugated linolenic acids may be very useful in prevention and treatment of many diseases, especially diabetes, arteriosclerosis , obesity and cancers (mammary, prostate and colon cancer. Among many potential mechanisms of their action, the fact that some CLnA are converted by oxidoreductases into CLA is very important. It seems to be very reasonable to conduct research concerning the possibility of CLnA use in prevention of many diseases.

  15. Hexanoic Acid Treatment Prevents Systemic MNSV Movement in Cucumis melo Plants by Priming Callose Deposition Correlating SA and OPDA Accumulation

    Directory of Open Access Journals (Sweden)

    Emma Fernández-Crespo

    2017-10-01

    Full Text Available Unlike fungal and bacterial diseases, no direct method is available to control viral diseases. The use of resistance-inducing compounds can be an alternative strategy for plant viruses. Here we studied the basal response of melon to Melon necrotic spot virus (MNSV and demonstrated the efficacy of hexanoic acid (Hx priming, which prevents the virus from systemically spreading. We analysed callose deposition and the hormonal profile and gene expression at the whole plant level. This allowed us to determine hormonal homeostasis in the melon roots, cotyledons, hypocotyls, stems and leaves involved in basal and hexanoic acid-induced resistance (Hx-IR to MNSV. Our data indicate important roles of salicylic acid (SA, 12-oxo-phytodienoic acid (OPDA, jasmonic-isoleucine, and ferulic acid in both responses to MNSV. The hormonal and metabolites balance, depending on the time and location associated with basal and Hx-IR, demonstrated the reprogramming of plant metabolism in MNSV-inoculated plants. The treatment with both SA and OPDA prior to virus infection significantly reduced MNSV systemic movement by inducing callose deposition. This demonstrates their relevance in Hx-IR against MNSV and a high correlation with callose deposition. Our data also provide valuable evidence to unravel priming mechanisms by natural compounds.

  16. Prevention of Cervical Cancer in Africa: A Daunting Task ...

    African Journals Online (AJOL)

    Africa has a high estimated incidence of cervical cancer, thus requiring the development of an effective prevention strategy. Cytology-based screening is beyond the capacity of many African countries, hence the need for alternatives. Visual inspection of the cervix after application of 3–5% acetic acid (VIA) is a promising ...

  17. Statins Increase Mitochondrial and Peroxisomal Fatty Acid Oxidation in the Liver and Prevent Non-Alcoholic Steatohepatitis in Mice

    Directory of Open Access Journals (Sweden)

    Han-Sol Park

    2016-04-01

    Full Text Available BackgroundNon-alcoholic fatty liver disease is the most common form of chronic liver disease in industrialized countries. Recent studies have highlighted the association between peroxisomal dysfunction and hepatic steatosis. Peroxisomes are intracellular organelles that contribute to several crucial metabolic processes, such as facilitation of mitochondrial fatty acid oxidation (FAO and removal of reactive oxygen species through catalase or plasmalogen synthesis. Statins are known to prevent hepatic steatosis and non-alcoholic steatohepatitis (NASH, but underlying mechanisms of this prevention are largely unknown.MethodsSeven-week-old C57BL/6J mice were given normal chow or a methionine- and choline-deficient diet (MCDD with or without various statins, fluvastatin, pravastatin, simvastatin, atorvastatin, and rosuvastatin (15 mg/kg/day, for 6 weeks. Histological lesions were analyzed by grading and staging systems of NASH. We also measured mitochondrial and peroxisomal FAO in the liver.ResultsStatin treatment prevented the development of MCDD-induced NASH. Both steatosis and inflammation or fibrosis grades were significantly improved by statins compared with MCDD-fed mice. Gene expression levels of peroxisomal proliferator-activated receptor α (PPARα were decreased by MCDD and recovered by statin treatment. MCDD-induced suppression of mitochondrial and peroxisomal FAO was restored by statins. Each statin's effect on increasing FAO and improving NASH was independent on its effect of decreasing cholesterol levels.ConclusionStatins prevented NASH and increased mitochondrial and peroxisomal FAO via induction of PPARα. The ability to increase hepatic FAO is likely the major determinant of NASH prevention by statins. Improvement of peroxisomal function by statins may contribute to the prevention of NASH.

  18. Drug repurposing: a systematic approach to evaluate candidate oral neuroprotective interventions for secondary progressive multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Hanna M Vesterinen

    Full Text Available To develop and implement an evidence based framework to select, from drugs already licenced, candidate oral neuroprotective drugs to be tested in secondary progressive multiple sclerosis.Systematic review of clinical studies of oral putative neuroprotective therapies in MS and four other neurodegenerative diseases with shared pathological features, followed by systematic review and meta-analyses of the in vivo experimental data for those interventions. We presented summary data to an international multi-disciplinary committee, which assessed each drug in turn using pre-specified criteria including consideration of mechanism of action.We identified a short list of fifty-two candidate interventions. After review of all clinical and pre-clinical evidence we identified ibudilast, riluzole, amiloride, pirfenidone, fluoxetine, oxcarbazepine, and the polyunsaturated fatty-acid class (Linoleic Acid, Lipoic acid; Omega-3 fatty acid, Max EPA oil as lead candidates for clinical evaluation.We demonstrate a standardised and systematic approach to candidate identification for drug rescue and repurposing trials that can be applied widely to neurodegenerative disorders.

  19. Preventing pollution from plutonium processing

    International Nuclear Information System (INIS)

    Pillay, K.K.S.

    1993-01-01

    The plutonium processing facility at Los Alamos has adopted the strategic goal of becoming a facility that processes plutonium in a way that produces only environmentally benign waste streams. Pollution prevention through source reduction and environmentally sound recycling are being pursued. General approaches to waste reductions are administrative controls, modification of process technologies, and additional waste polishing. Recycling of waste materials, such as spent acids and salts, are technical possibilities and are being pursued to accomplish additional waste reduction. Liquid waste stream polishing to remove final traces of plutonium and hazardous chemical constituents is accomplished through (a) process modifications, (b) use of alternative chemicals and sorbents for residue removal, (c) acid recycling, and (d) judicious use of a variety of waste polishing technologies. Technologies that show promise in waste minimization and pollution prevention are identified. Working toward this goal of pollution prevention is a worthwhile endeavor, not only for Los Alamos, but for the Nuclear Complex of the future

  20. Formate supplementation enhances folate-dependent nucleotide biosynthesis and prevents spina bifida in a mouse model of folic acid-resistant neural tube defects.

    Science.gov (United States)

    Sudiwala, Sonia; De Castro, Sandra C P; Leung, Kit-Yi; Brosnan, John T; Brosnan, Margaret E; Mills, Kevin; Copp, Andrew J; Greene, Nicholas D E

    2016-07-01

    The curly tail mouse provides a model for neural tube defects (spina bifida and exencephaly) that are resistant to prevention by folic acid. The major ct gene, responsible for spina bifida, corresponds to a hypomorphic allele of grainyhead-like 3 (Grhl3) but the frequency of NTDs is strongly influenced by modifiers in the genetic background. Moreover, exencephaly in the curly tail strain is not prevented by reinstatement of Grhl3 expression. In the current study we found that expression of Mthfd1L, encoding a key component of mitochondrial folate one-carbon metabolism (FOCM), is significantly reduced in ct/ct embryos compared to a partially congenic wild-type strain. This expression change is not attributable to regulation by Grhl3 or the genetic background at the Mthfd1L locus. Mitochondrial FOCM provides one-carbon units as formate for FOCM reactions in the cytosol. We found that maternal supplementation with formate prevented NTDs in curly tail embryos and also resulted in increased litter size. Analysis of the folate profile of neurulation-stage embryos showed that formate supplementation resulted in an increased proportion of formyl-THF and THF but a reduction in proportion of 5-methyl THF. In contrast, THF decreased and 5-methyl THF was relatively more abundant in the liver of supplemented dams than in controls. In embryos cultured through the period of spinal neurulation, incorporation of labelled thymidine and adenine into genomic DNA was suppressed by supplemental formate, suggesting that de novo folate-dependent biosynthesis of nucleotides (thymidylate and purines) was enhanced. We hypothesise that reduced Mthfd1L expression may contribute to susceptibility to NTDs in the curly tail strain and that formate acts as a one-carbon donor to prevent NTDs. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  1. Preventing pollution from plutonium processing

    International Nuclear Information System (INIS)

    Pillay, K.K.S.

    1995-01-01

    The plutonium processing facility at Los Alamos has adopted the strategic goal of becoming a facility that processes plutonium in a way that produces only environmentally benign waste streams. Pollution prevention through source reduction and environmentally sound recycling are being pursued. General approaches to waste reductions are administrative controls, modification of process technologies, and additional waste polishing. Recycling of waste materials, such as spent acids and salts, are technical possibilities and are being pursued to accomplish additional waste reduction. Liquid waste stream polishing to remove final traces of plutonium and hazardous chemical constituents is accomplished through process modifications, use of alternative chemicals and sorbents for residue removal, acid recycling, and judicious use of a variety of waste polishing technologies. Technologies that show promise in waste minimization and pollution prevention are identified. Working toward this goal of pollution prevention is a worthwhile endeavor , not only for Los Alamos, but for the Nuclear Complex of the future. (author) 12 refs.; 2 figs

  2. Placement of acid spoil materials

    Energy Technology Data Exchange (ETDEWEB)

    Pionke, H B; Rogowski, A S

    1982-06-01

    Potentially there are several chemical and hydrologic problems associated with placement of acid spoil materials. The rationale for a deep placement well below the soil surface, and preferably below a water table, is to prevent or minimize oxidation of pyrite to sulfuric acid and associated salts by reducing the supply of oxygen. If, however, substantial sulfuric acid or associated salts are already contained within the spoil because of present or previous mining, handling and reclamation operations (or if large supplies of indigenous salts exist, placement below a water table) may actually increase the rate of acid and salt leaching. Specific placement of acid- and salt-containing spoil should be aimed at preventing contact with percolating water or rising water tables. We recommend placement based on chemical and physical spoil properties that may affect water percolation O/sub 2/ diffusion rates in the profile. Both the deeper placement of acid spoil and coarser particle size can substantially reduce the amount of acid drainage. Placement above the water table with emphasis on percolate control may be better for high sulfate spoils, while placement below the non-fluctuating water table may be better for pyritic spoils.

  3. [Prevention of intrauterine adhesion with auto-crosslinked hyaluronic acid gel: a prospective, randomized, controlled clinical study].

    Science.gov (United States)

    Xiao, Songshu; Wan, Yajun; Zou, Fangjun; Ye, Mingzhu; Deng, Henan; Ma, Jiezhi; Wei, Yingying; Tan, Chen; Xue, Min

    2015-01-01

    To evaluate the efficacy and safety of auto-crosslinked hyaluronic acid (HA) gel for preventing intrauterine adhesion (IUA) after hysteroscopic adhesiolysis. A prospective, randomized, double blinded and controlled clinical trial (level I) was performed. According to American Fertility Society (AFS) scoring system, 120 patients (treatment group: 60 cases, control group: 60 cases) with moderate to severe IUA were enrolled. Upon completion of adhesiolysis, a Foley balloon catheter was first introduced into the uterine cavity and then 3 ml of auto-crosslinked HA gel for patients in the treatment group; patients in the control group, however, only received Foley balloon catheter. Second-look hysteroscopic examination was performed to all patients at 3 months postoperatively for evaluation of IUA. Primary endpoint was the reduction rate of IUA at 3 months after surgery. The secondary endpoints include total AFS score, score of each individual AFS category. At 3 months after surgery, auto-crosslinked HA gel resulted in significantly higher effective rate for reduction of adhesion, the effective rate were 76% (42/55) and 48% (27/56) respectively (P = 0.000 9); the total AFS score of treatment group was 2.1 ± 1.1, and significantly lower than that of control group (3.7 ± 2.5, P = 0.000 8). Application of auto-crosslinked HA gel after surgery significantly enhanced the improvement for each individual patient with regard to their adhesive type and menstrual pattern (P = 0.037 8, P = 0.000 4). The treatment group had significantly lower proportion of patients with moderate to severe adhesive stages than that of control group [13% (7/55) versus 38% (21/56), P = 0.000 6]. No adverse events and complications were observed. Auto-crosslinked HA gel coule be able to reduce IUA, decrease adhesion severity, and improve menopause postoperatively. This absorbable auto-crosslinked HA gel is proposed as a barrier for preventing IUA after intrauterine procedures.

  4. Unusual binding of ursodeoxycholic acid to ileal bile acid binding protein: role in activation of FXRα[S

    Science.gov (United States)

    Fang, Changming; Filipp, Fabian V.; Smith, Jeffrey W.

    2012-01-01

    Ursodeoxycholic acid (UDCA, ursodiol) is used to prevent damage to the liver in patients with primary biliary cirrhosis. The drug also prevents the progression of colorectal cancer and the recurrence of high-grade colonic dysplasia. However, the molecular mechanism by which UDCA elicits its beneficial effects is not entirely understood. The aim of this study was to determine whether ileal bile acid binding protein (IBABP) has a role in mediating the effects of UDCA. We find that UDCA binds to a single site on IBABP and increases the affinity for major human bile acids at a second binding site. As UDCA occupies one of the bile acid binding sites on IBABP, it reduces the cooperative binding that is often observed for the major human bile acids. Furthermore, IBABP is necessary for the full activation of farnesoid X receptor α (FXRα) by bile acids, including UDCA. These observations suggest that IBABP may have a role in mediating some of the intestinal effects of UDCA. PMID:22223860

  5. Ursodeoxycholic acid prevents ventricular conduction slowing and arrhythmia by restoring T-type calcium current in fetuses during cholestasis

    Science.gov (United States)

    Adeyemi, Oladipupo; Alvarez-Laviada, Anita; Schultz, Francisca; Ibrahim, Effendi; Trauner, Michael; Williamson, Catherine; Glukhov, Alexey V.

    2017-01-01

    Background Increased maternal serum bile acid concentrations in intrahepatic cholestasis of pregnancy (ICP) are associated with fetal cardiac arrhythmias. Ursodeoxycholic acid (UDCA) has been shown to demonstrate anti-arrhythmic properties via preventing ICP-associated cardiac conduction slowing and development of reentrant arrhythmias, although the cellular mechanism is still being elucidated. Methods High-resolution fluorescent optical mapping of electrical activity and electrocardiogram measurements were used to characterize effects of UDCA on one-day-old neonatal and adult female Langendorff-perfused rat hearts. ICP was modelled by perfusion of taurocholic acid (TC, 400μM). Whole-cell calcium currents were recorded from neonatal rat and human fetal cardiomyocytes. Results TC significantly prolonged the PR interval by 11.0±3.5% (P<0.05) and slowed ventricular conduction velocity (CV) by 38.9±5.1% (P<0.05) exclusively in neonatal and not in maternal hearts. A similar CV decline was observed with the selective T-type calcium current (ICa,T) blocker mibefradil 1μM (23.0±6.2%, P<0.05), but not with the L-type calcium current (ICa,L) blocker nifedipine 1μM (6.9±6.6%, NS). The sodium channel blocker lidocaine (30μM) reduced CV by 60.4±4.5% (P<0.05). UDCA co-treatment was protective against CV slowing induced by TC and mibefradil, but not against lidocaine. UDCA prevented the TC-induced reduction in the ICa,T density in both isolated human fetal (−10.2±1.5 versus −5.5±0.9 pA/pF, P<0.05) and neonatal rat ventricular myocytes (−22.3±1.1 versus −9.6±0.8 pA/pF, P<0.0001), whereas UDCA had limited efficacy on the ICa,L. Conclusion Our findings demonstrate that ICa,T plays a significant role in ICP-associated fetal cardiac conduction slowing and arrhythmogenesis, and is an important component of the fetus-specific anti-arrhythmic activity of UDCA. PMID:28934223

  6. Ursodeoxycholic acid prevents ventricular conduction slowing and arrhythmia by restoring T-type calcium current in fetuses during cholestasis.

    Directory of Open Access Journals (Sweden)

    Oladipupo Adeyemi

    Full Text Available Increased maternal serum bile acid concentrations in intrahepatic cholestasis of pregnancy (ICP are associated with fetal cardiac arrhythmias. Ursodeoxycholic acid (UDCA has been shown to demonstrate anti-arrhythmic properties via preventing ICP-associated cardiac conduction slowing and development of reentrant arrhythmias, although the cellular mechanism is still being elucidated.High-resolution fluorescent optical mapping of electrical activity and electrocardiogram measurements were used to characterize effects of UDCA on one-day-old neonatal and adult female Langendorff-perfused rat hearts. ICP was modelled by perfusion of taurocholic acid (TC, 400μM. Whole-cell calcium currents were recorded from neonatal rat and human fetal cardiomyocytes.TC significantly prolonged the PR interval by 11.0±3.5% (P<0.05 and slowed ventricular conduction velocity (CV by 38.9±5.1% (P<0.05 exclusively in neonatal and not in maternal hearts. A similar CV decline was observed with the selective T-type calcium current (ICa,T blocker mibefradil 1μM (23.0±6.2%, P<0.05, but not with the L-type calcium current (ICa,L blocker nifedipine 1μM (6.9±6.6%, NS. The sodium channel blocker lidocaine (30μM reduced CV by 60.4±4.5% (P<0.05. UDCA co-treatment was protective against CV slowing induced by TC and mibefradil, but not against lidocaine. UDCA prevented the TC-induced reduction in the ICa,T density in both isolated human fetal (-10.2±1.5 versus -5.5±0.9 pA/pF, P<0.05 and neonatal rat ventricular myocytes (-22.3±1.1 versus -9.6±0.8 pA/pF, P<0.0001, whereas UDCA had limited efficacy on the ICa,L.Our findings demonstrate that ICa,T plays a significant role in ICP-associated fetal cardiac conduction slowing and arrhythmogenesis, and is an important component of the fetus-specific anti-arrhythmic activity of UDCA.

  7. Inhibition of fatty acid biosynthesis prevents adipocyte lipotoxicity on human osteoblasts in vitro

    Science.gov (United States)

    Elbaz, Alexandre; Wu, Xiying; Rivas, Daniel; Gimble, Jeffrey M; Duque, Gustavo

    2010-01-01

    Abstract Although increased bone marrow fat in age-related bone loss has been associated with lower trabecular mass, the underlying mechanism responsible remains unknown. We hypothesized that marrow adipocytes exert a lipotoxic effect on osteoblast function and survival through the reversible biosynthesis of fatty acids (FA) into the bone marrow microenvironment. We have used a two-chamber system to co-culture normal human osteoblasts (NHOst) with differentiating pre-adipocytes in the absence or presence of an inhibitor of FA synthase (cerulenin) and separated by an insert that allowed unidirectional trafficking of soluble factors only and prevented direct cell–cell contact. Supernatants were assayed for the presence of FA using mass spectophotometry. After 3 weeks in co-culture, NHOst showed significantly lower levels of differentiation and function based on lower mineralization and expression of alkaline phosphatase, osterix, osteocalcin and Runx2. In addition, NHOst survival was affected by the presence of adipocytes as determined by MTS-formazan and TUNEL assays as well as higher activation of caspases 3/7. These toxic effects were inhibited by addition of cerulenin. Furthermore, culture of NHOst with either adipocyte-conditioned media alone in the absence of adipocytes themselves or with the addition of the most predominant FA (stearate or palmitate) produced similar toxic results. Finally, Runx2 nuclear binding was affected by addition of either adipocyte conditioned media or FA into the osteogenic media. We conclude that the presence of FA within the marrow milieu can contribute to the age-related changes in bone mass and can be prevented by the inhibition of FA synthase. PMID:19382912

  8. Nucleic acid-binding glycoproteins which solubilize nucleic acids in dilute acid: re-examination of the Ustilago maydis glycoproteins

    Energy Technology Data Exchange (ETDEWEB)

    Unrau, P.; Champ, D.R.; Young, J.L.; Grant, C.E.

    1980-01-01

    Holloman reported the isolation from Ustilago maydis of a glycoprotein which prevented the precipitation of nucleic acids in cold 5% trichloroacetic acid. Two glycoprotein fractions from U. maydis with this nucleic acid-solubilizing activity were isolated in our laboratory using improved purification procedures. The activity was not due to nuclease contamination. The glycoproteins are distinguished by: their ability to bind to concanavalin A-Sepharose; their differential binding to double- and single-stranded deoxyribonucleic acid, and to ribonucleic acid; their molecular weights (46,000 and 69,000); and the relative amounts present in growing versus nongrowing cells. Both fractions required sulfhydryl-reducing conditions for optimal yields, specific activity, and stability. Nucleic acid binding was cooperative, the minimum number of glycoproteins required to make a native T7 DNA molecule soluble in dilute acid being estimated at 2 and 15, respectively.

  9. Omega-3 fatty acid docosahexaenoic acid increases SorLA/LR11, a sorting protein with reduced expression in sporadic Alzheimer's disease (AD): relevance to AD prevention.

    Science.gov (United States)

    Ma, Qiu-Lan; Teter, Bruce; Ubeda, Oliver J; Morihara, Takashi; Dhoot, Dilsher; Nyby, Michael D; Tuck, Michael L; Frautschy, Sally A; Cole, Greg M

    2007-12-26

    Environmental and genetic factors, notably ApoE4, contribute to the etiology of late-onset Alzheimer's disease (LOAD). Reduced mRNA and protein for an apolipoprotein E (ApoE) receptor family member, SorLA (LR11) has been found in LOAD but not early-onset AD, suggesting that LR11 loss is not secondary to pathology. LR11 is a neuronal sorting protein that reduces amyloid precursor protein (APP) trafficking to secretases that generate beta-amyloid (Abeta). Genetic polymorphisms that reduce LR11 expression are associated with increased AD risk. However these polymorphisms account for only a fraction of cases with LR11 deficits, suggesting involvement of environmental factors. Because lipoprotein receptors are typically lipid-regulated, we postulated that LR11 is regulated by docosahexaenoic acid (DHA), an essential omega-3 fatty acid related to reduced AD risk and reduced Abeta accumulation. In this study, we report that DHA significantly increases LR11 in multiple systems, including primary rat neurons, aged non-Tg mice and an aged DHA-depleted APPsw AD mouse model. DHA also increased LR11 in a human neuronal line. In vivo elevation of LR11 was also observed with dietary fish oil in young rats with insulin resistance, a model for type II diabetes, another AD risk factor. These data argue that DHA induction of LR11 does not require DHA-depleting diets and is not age dependent. Because reduced LR11 is known to increase Abeta production and may be a significant genetic cause of LOAD, our results indicate that DHA increases in SorLA/LR11 levels may play an important role in preventing LOAD.

  10. Folic acid and pantothenic acid protection against valproic acid-induced neural tube defects in CD-1 mice

    Energy Technology Data Exchange (ETDEWEB)

    Dawson, Jennifer E [Department of Pharmacology and Toxicology and School of Environmental Studies, Queen' s University, Kingston, Ontario, K7L 3N6 (Canada); Raymond, Angela M [Department of Pharmacology and Toxicology and School of Environmental Studies, Queen' s University, Kingston, Ontario, K7L 3N6 (Canada); Winn, Louise M [Department of Pharmacology and Toxicology and School of Environmental Studies, Queen' s University, Kingston, Ontario, K7L 3N6 (Canada)

    2006-03-01

    In utero exposure to valproic acid (VPA) during pregnancy is associated with an increased risk of neural tube defects (NTDs). Although the mechanism by which VPA mediates these effects is unknown, VPA-initiated changes in embryonic protein levels have been implicated. The objectives of this study were to investigate the effect of in utero VPA exposure on embryonic protein levels of p53, NF-{kappa}B, Pim-1, c-Myb, Bax, and Bcl-2 in the CD-1 mouse. We also evaluated the protective effects of folic acid and pantothenic acid on VPA-induced NTDs and VPA-induced embryonic protein changes in this model. Pregnant CD-1 mice were administered a teratogenic dose of VPA prior to neural tube closure and embryonic protein levels were analyzed. In our study, VPA (400 mg/kg)-induced NTDs (24%) and VPA-exposed embryos with an NTD showed a 2-fold increase in p53, and 4-fold decreases in NF-{kappa}B, Pim-1, and c-Myb protein levels compared to their phenotypically normal littermates (P < 0.05). Additionally, VPA increased the ratio of embryonic Bax/Bcl-2 protein levels (P < 0.05). Pretreatment of pregnant dams with either folic acid or pantothenic acid prior to VPA significantly protected against VPA-induced NTDs (P < 0.05). Folic acid also reduced VPA-induced alterations in p53, NF-{kappa}B, Pim-1, c-Myb, and Bax/Bcl-2 protein levels, while pantothenic acid prevented VPA-induced alterations in NF-{kappa}B, Pim-1, and c-Myb. We hypothesize that folic acid and pantothenic acid protect CD-1 embryos from VPA-induced NTDs by independent, but not mutually exclusive mechanisms, both of which may be mediated by the prevention of VPA-induced alterations in proteins involved in neurulation.

  11. Uptake of biotin by Chlamydia Spp. through the use of a bacterial transporter (BioY and a host-cell transporter (SMVT.

    Directory of Open Access Journals (Sweden)

    Derek J Fisher

    Full Text Available Chlamydia spp. are obligate intracellular Gram-negative bacterial pathogens that cause disease in humans and animals. Minor variations in metabolic capacity between species have been causally linked to host and tissue tropisms. Analysis of the highly conserved genomes of Chlamydia spp. reveals divergence in the metabolism of the essential vitamin biotin with genes for either synthesis (bioF_2ADB and/or transport (bioY. Streptavidin blotting confirmed the presence of a single biotinylated protein in Chlamydia. As a first step in unraveling the need for divergent biotin acquisition strategies, we examined BioY (CTL0613 from C. trachomatis 434/Bu which is annotated as an S component of the type II energy coupling-factor transporters (ECF. Type II ECFs are typically composed of a transport specific component (S and a chromosomally unlinked energy module (AT. Intriguingly, Chlamydia lack recognizable AT modules. Using (3H-biotin and recombinant E. coli expressing CTL0613, we demonstrated that biotin was transported with high affinity (a property of Type II ECFs previously shown to require an AT module and capacity (apparent K(m of 3.35 nM and V(max of 55.1 pmol×min(-1×mg(-1. Since Chlamydia reside in a host derived membrane vacuole, termed an inclusion, we also sought a mechanism for transport of biotin from the cell cytoplasm into the inclusion vacuole. Immunofluorescence microscopy revealed that the mammalian sodium multivitamin transporter (SMVT, which transports lipoic acid, biotin, and pantothenic acid into cells, localizes to the inclusion. Since Chlamydia also are auxotrophic for lipoic and pantothenic acids, SMVT may be subverted by Chlamydia to move multiple essential compounds into the inclusion where BioY and another transporter(s would be present to facilitate transport into the bacterium. Collectively, our data validates the first BioY from a pathogenic organism and describes a two-step mechanism by which Chlamydia transport biotin

  12. Uptake of Biotin by Chlamydia Spp. through the Use of a Bacterial Transporter (BioY) and a Host-Cell Transporter (SMVT)

    Science.gov (United States)

    Fisher, Derek J.; Fernández, Reinaldo E.; Adams, Nancy E.; Maurelli, Anthony T.

    2012-01-01

    Chlamydia spp. are obligate intracellular Gram-negative bacterial pathogens that cause disease in humans and animals. Minor variations in metabolic capacity between species have been causally linked to host and tissue tropisms. Analysis of the highly conserved genomes of Chlamydia spp. reveals divergence in the metabolism of the essential vitamin biotin with genes for either synthesis (bioF_2ADB) and/or transport (bioY). Streptavidin blotting confirmed the presence of a single biotinylated protein in Chlamydia. As a first step in unraveling the need for divergent biotin acquisition strategies, we examined BioY (CTL0613) from C. trachomatis 434/Bu which is annotated as an S component of the type II energy coupling-factor transporters (ECF). Type II ECFs are typically composed of a transport specific component (S) and a chromosomally unlinked energy module (AT). Intriguingly, Chlamydia lack recognizable AT modules. Using 3H-biotin and recombinant E. coli expressing CTL0613, we demonstrated that biotin was transported with high affinity (a property of Type II ECFs previously shown to require an AT module) and capacity (apparent K(m) of 3.35 nM and V(max) of 55.1 pmol×min−1×mg−1). Since Chlamydia reside in a host derived membrane vacuole, termed an inclusion, we also sought a mechanism for transport of biotin from the cell cytoplasm into the inclusion vacuole. Immunofluorescence microscopy revealed that the mammalian sodium multivitamin transporter (SMVT), which transports lipoic acid, biotin, and pantothenic acid into cells, localizes to the inclusion. Since Chlamydia also are auxotrophic for lipoic and pantothenic acids, SMVT may be subverted by Chlamydia to move multiple essential compounds into the inclusion where BioY and another transporter(s) would be present to facilitate transport into the bacterium. Collectively, our data validates the first BioY from a pathogenic organism and describes a two-step mechanism by which Chlamydia transport biotin from the

  13. Hexanoic acid is a resistance inducer that protects tomato plants against Pseudomonas syringae by priming the jasmonic acid and salicylic acid pathways.

    Science.gov (United States)

    Scalschi, Loredana; Vicedo, Begonya; Camañes, Gemma; Fernandez-Crespo, Emma; Lapeña, Leonor; González-Bosch, Carmen; García-Agustín, Pilar

    2013-05-01

    Hexanoic acid-induced resistance (Hx-IR) is effective against several pathogens in tomato plants. Our study of the mechanisms implicated in Hx-IR against Pseudomonas syringae pv. tomato DC3000 suggests that hexanoic acid (Hx) treatment counteracts the negative effect of coronatine (COR) and jasmonyl-isoleucine (JA-Ile) on the salicylic acid (SA) pathway. In Hx-treated plants, an increase in the expression of jasmonic acid carboxyl methyltransferase (JMT) and the SA marker genes PR1 and PR5 indicates a boost in this signalling pathway at the expense of a decrease in JA-Ile. Moreover, Hx treatment potentiates 12-oxo-phytodienoic acid accumulation, which suggests that this molecule might play a role per se in Hx-IR. These results support a positive relationship between the SA and JA pathways in Hx-primed plants. Furthermore, one of the mechanisms of virulence mediated by COR is stomatal re-opening on infection with P. syringae. In this work, we observed that Hx seems to inhibit stomatal opening in planta in the presence of COR, which suggests that, on infection in tomato, this treatment suppresses effector action to prevent bacterial entry into the mesophyll. © 2012 BSPP AND BLACKWELL PUBLISHING LTD.

  14. Acid mine drainage prevention, control and treatment technology development for the Stockett/Sand Coulee area. Topical report, March 1, 1995 - March 31, 1996

    International Nuclear Information System (INIS)

    Brown, T.

    1996-01-01

    The project was initiated to assist the State of Montana to develop a methodology to ameliorate acid mine drainage problems associated with the abandoned mines located in the Stockett/Sand Coulee area near Great Falls, Montana. Extremely acidic water is continuously discharging from abandoned coal mines in the Stockett/Sand Coulee area at an estimated rate of greater than 600 acre-feet per year (about 350 to 400 gallons per minute). Due to its extreme acidity, the water is unusable and is contaminating other water supplies. Most of the local alluvial aquifers have been contaminated, and nearly 5% of the private wells that were tested in the area during the mid-1980's showed some degree of contamination. Significant government money has been spent replacing water supplies due to the magnitude of this problem. In addition, millions of dollars have been spent trying to remediate acid mine drainage occurring in this coal field. To date, the techniques used have focused on the management and containment of mine waters, rather than designing technologies that would prevent the formation of acid mine drainage

  15. The introduction of peracetic acid as a new disinfectant for U.S. aquaculture

    Science.gov (United States)

    Peracetic acid (PAA) is a promising disinfectant for biosecurity in the US aquaculture industry to prevent disease outbreaks from fish pathogens. PAA is a stabilized mixture of acetic acid, hydrogen peroxide and water that breaks down quickly to water and vinegar. It is being increasingly used to ...

  16. Preventing neural tube defects in Europe : A missed opportunity

    NARCIS (Netherlands)

    Busby, A; Armstrong, B; Dolk, H; Armstrong, N; Haeusler, M; Berghold, A; Gillerot, Y; Baguette, A; Gjerga, R; Barisic, [No Value; Christiansen, M; Goujard, J; Steinbicker, [No Value; Rosch, C; McDonnell, R; Scarano, G; Calzolari, E; Neville, A; Cocchi, G; Bianca, S; Gatt, M; De Walle, H; Braz, P; Latos-Bielenska, A; Gener, B; Portillor, [No Value; Addor, MC; Abramsky, L; Ritvanen, A; Robert-Gnansia, E; Daltveit, AK; Aneren, G; Olars, B; Edwards, G

    2005-01-01

    Each year, more than 4500 pregnancies in the European Union are affected by neural tube defects (NTD). Unambiguous evidence of the effectiveness of peri conceptional folic acid in preventing the majority of neural tube defects has been available since 1991. We report on trends in the total

  17. Prevention of formation of acid drainage from high-sulfur coal refuse by inhibition of iron- and sulfur-oxidizing microorganisms. II. Inhibition in run of mine refuse under simulated field conditions

    Energy Technology Data Exchange (ETDEWEB)

    Dugan, P.R.

    1987-01-01

    The combination of sodium lauryl sulfate and benzoic acid effectively inhibits iron- and sulfur-oxidizing bacteria in coal refuse and prevents the conversion of iron pyrite to sulfate, ferric iron, and sulfuric acid, thereby significantly reducing the formation of acidic drainage from coal refuse. The inhibitors were effective in a concentration of 1.1. mg/kg refuse, and data indicate that the SLS was in excess of the concentration required. The treatment was compatible with the use of lime for neutralization of acid present prior to inhibition of its formation.

  18. Omega-3 polyunsaturated fatty acids in the prevention of postoperative complications in colorectal cancer: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Xie H

    2016-12-01

    Full Text Available Hai Xie,1 Yan-na Chang2 1Department of Emergency, The First Hospital of Lanzhou University, 2Department of Anesthesiology, Affiliated Hospital of Gansu University of Chinese Medicine, Lanzhou, People’s Republic of China Objective: To evaluate systematically the clinical efficacy of omega-3 polyunsaturated fatty acids (PUFAs in the prevention of postoperative complications in colorectal cancer (CRC patients.Materials and methods: Published articles were identified by using search terms in online databases – PubMed, Embase, and the Cochrane Library – up to March 2016. Only randomized controlled trials investigating the efficacy of omega-3 PUFAs in CRC were selected and analyzed through a meta-analysis. Subgroup, sensitivity, and inverted funnel-plot analyses were also conducted. Results: Eleven articles with 694 CRC patients were finally included. Compared with control, omega-3 PUFA-enriched enteral or parenteral nutrition during the perioperative period reduced infectious complications (risk ratio [RR] 0.63, 95% confidence interval [CI] 0.47–0.86; P=0.004, tumor necrosis factor alpha (standard mean difference [SMD] -0.37, 95% CI -0.66 to -0.07; P=0.01, interleukin-6 (SMD -0.36, 95% CI -0.66 to -0.07; P=0.02, and hospital stay (MD -2.09, 95% CI -3.71 to -0.48; P=0.01. No significant difference was found in total complications, surgical site infection, or CD4+:CD8+ cell ratio. Conclusion: Short-term omega-3 PUFA administration was associated with reduced postoperative infectious complications, inflammatory cytokines, and hospital stay after CRC surgery. Due to heterogeneity and relatively small sample size, the optimal timing and route of administration deserve further study. Keywords: omega-3, fatty acids, fish oil, colorectal surgery, meta-analysis 

  19. Ascorbic acid prevents nonreceptor specific binding of [3H]-5-hydroxytryptamine to bovine cerebral cortex membranes

    International Nuclear Information System (INIS)

    Hamblin, M.W.; Adriaenssens, P.I.; Ariani, K.; Cawthon, R.M.; Stratford, C.A.; Tan, G.L.; Ciaranello, R.D.

    1987-01-01

    [ 3 H]-5-Hydroxytryptamine ([ 3 H]-5-HT) decomposes rapidly when exposed to air in solution at physiological pH if antioxidants are not present. The decomposition products appear to bind to two saturable sites on brain membranes (apparent Kd values = 1-2 and 100-1000 nM). This binding mimics ''specific'' ligand/receptor binding in that it is inhibited by 10 microM unlabeled 5-HT. This inhibition is not competitive, but rather is due to the prevention of [ 3 H]-5-HT breakdown by excess unlabeled 5-HT. Unlike genuine ligand/receptor binding, the binding of [ 3 H]-5-HT breakdown products is essentially irreversible and does not display a tissue distribution consistent with binding to authentic 5-HT receptors. [ 3 H]-5-HT decomposition can be eliminated by the inclusion of 0.05 to 5 mM ascorbic acid. At these concentrations ascorbic acid is not deleterious to reversible [ 3 H]-5-HT binding. When [ 3 H] 5-HT exposure to air occurs in the presence of brain membranes, the apparent antioxidant activity of brain membranes themselves affords protection against [ 3 H]-5-HT degradation equal to ascorbic acid. This protection is effective below final [ 3 H]-5-HT concentrations of 10 nM. Above 10 nM [ 3 H]-5-HT, addition of ascorbic acid or other antioxidants is necessary to avoid the occurrence of additional low affinity (apparent Kd = 15-2000 nM) binding sites that are specific but nonetheless irreversible. When care is taken to limit [ 3 H]-5-HT oxidation, the only reversible and saturable specific binding sites observed are of the 5-HT1 high affinity (Kd = 1-2 nM) type. Radioligand oxidation artifacts may be involved in previous reports of low affinity (Kd = 15-250 nM) [ 3 H]-5-HT binding sites in brain membrane preparations

  20. Citrulline and Nonessential Amino Acids Prevent Fructose-Induced Nonalcoholic Fatty Liver Disease in Rats.

    Science.gov (United States)

    Jegatheesan, Prasanthi; Beutheu, Stéphanie; Ventura, Gabrielle; Nubret, Esther; Sarfati, Gilles; Bergheim, Ina; De Bandt, Jean-Pascal

    2015-10-01

    Fructose induces nonalcoholic fatty liver disease (NAFLD). Citrulline (Cit) may exert a beneficial effect on steatosis. We compared the effects of Cit and an isonitrogenous mixture of nonessential amino acids (NEAAs) on fructose-induced NAFLD. Twenty-two male Sprague Dawley rats were randomly assigned into 4 groups (n = 4-6) to receive for 8 wk a 60% fructose diet, either alone or supplemented with Cit (1 g · kg(-1) · d(-1)), or an isonitrogenous amount of NEAAs, or the same NEAA-supplemented diet with starch and maltodextrin instead of fructose (controls). Nutritional and metabolic status, liver function, and expression of genes of hepatic lipid metabolism were determined. Compared with controls, fructose led to NAFLD with significantly higher visceral fat mass (128%), lower lean body mass (-7%), insulin resistance (135%), increased plasma triglycerides (TGs; 67%), and altered plasma amino acid concentrations with decreased Arg bioavailability (-27%). This was corrected by both NEAA and Cit supplementation. Fructose caused a 2-fold increase in the gene expression of fatty acid synthase (Fas) and 70% and 90% decreases in that of carnitine palmitoyl-transferase 1a and microsomal TG transfer protein via a nearly 10-fold higher gene expression of sterol regulatory element-binding protein-1c (Srebp1c) and carbohydrate-responsive element-binding protein (Chrebp), and a 90% lower gene expression of peroxisome proliferator-activated receptor α (Ppara). NEAA or Cit supplementation led to a Ppara gene expression similar to controls and decreased those of Srebp1c and Chrebp in the liver by 50-60%. Only Cit led to Fas gene expression and Arg bioavailability similar to controls. In our rat model, Cit and NEAAs effectively prevented fructose-induced NAFLD. On the basis of literature data and our findings, we propose that NEAAs may exert their effects specifically on the liver, whereas Cit presumably acts at both the hepatic and whole-body level, in part via improved

  1. The Extract of Aster Koraiensis Prevents Retinal Pericyte Apoptosis in Diabetic Rats and Its Active Compound, Chlorogenic Acid Inhibits AGE Formation and AGE/RAGE Interaction

    Directory of Open Access Journals (Sweden)

    Junghyun Kim

    2016-09-01

    Full Text Available Retinal capillary cell loss is a hallmark of early diabetic retinal changes. Advanced glycation end products (AGEs are believed to contribute to retinal microvascular cell loss in diabetic retinopathy. In this study, the protective effects of Aster koraiensis extract (AKE against damage to retinal vascular cells were investigated in streptozotocin (STZ-induced diabetic rats. To examine this issue further, AGE accumulation, nuclear factor-kappaB (NF-κB and inducible nitric oxide synthase (iNOS were investigated using retinal trypsin digests from streptozotocin-induced diabetic rats. In the diabetic rats, TUNEL (Terminal deoxynucleotidyl transferase mediated dUTP Nick End Labeling-positive retinal microvascular cells were markedly increased. Immunohistochemical studies revealed that AGEs were accumulated within the retinal microvascular cells, and this accumulation paralleled the activation of NF-κB and the expression of iNOS in the diabetic rats. However, AKE prevented retinal microvascular cell apoptosis through the inhibition of AGE accumulation and NF-κB activation. Moreover, to determine the active compounds of AKE, two major compounds, chlorogenic acid and 3,5-di-O-caffeoylquinic acid, were tested in an in vitro assay. Among these compounds, chlorogenic acid significantly reduced AGE formation as well as AGE/RAGE (receptor for AGEs binding activity. These results suggest that AKE, particularly chlorogenic acid, is useful in inhibiting AGE accumulation in retinal vessels and exerts a preventive effect against the injuries of diabetic retinal vascular cells.

  2. Essential fatty acid-rich diets protect against striatal oxidative damage induced by quinolinic acid in rats.

    Science.gov (United States)

    Morales-Martínez, Adriana; Sánchez-Mendoza, Alicia; Martínez-Lazcano, Juan Carlos; Pineda-Farías, Jorge Baruch; Montes, Sergio; El-Hafidi, Mohammed; Martínez-Gopar, Pablo Eliasib; Tristán-López, Luis; Pérez-Neri, Iván; Zamorano-Carrillo, Absalom; Castro, Nelly; Ríos, Camilo; Pérez-Severiano, Francisca

    2017-09-01

    Essential fatty acids have an important effect on oxidative stress-related diseases. The Huntington's disease (HD) is a hereditary neurologic disorder in which oxidative stress caused by free radicals is an important damage mechanism. The HD experimental model induced by quinolinic acid (QUIN) has been widely used to evaluate therapeutic effects of antioxidant compounds. The aim of this study was to test whether the fatty acid content in olive- or fish-oil-rich diet prevents against QUIN-related oxidative damage in rats. Rats were fed during 20 days with an olive- or a fish-oil-rich diet (15% w/w). Posterior to diet period, rats were striatally microinjected with QUIN (240 nmol/µl) or saline solution. Then, we evaluated the neurological damage, oxidative status, and gamma isoform of the peroxisome proliferator-activated receptor (PPARγ) expression. Results showed that fatty acid-rich diet, mainly by fish oil, reduced circling behavior, prevented the fall in GABA levels, increased PPARγ expression, and prevented oxidative damage in striatal tissue. In addition none of the enriched diets exerted changes neither on triglycerides or cholesterol blood levels, nor or hepatic function. This study suggests that olive- and fish-oil-rich diets exert neuroprotective effects.

  3. Well acidizing

    Energy Technology Data Exchange (ETDEWEB)

    Street, E H

    1980-01-23

    The apparatus relates in particular to a well-treating process in which an aqueous acid solution having a pH of < 2 is injected into a subterranean reservoir in a manner such that materials that contain ferric ions are present in the acid and, as the acid reacts within the reservoir and attains a pH exceeding 3, tend to be precipitated as ferric ion-containing solid materials that may plug the pores of the reservoir. Such a precipitation is prevented by dissolving in the acid solution an amount of 5-sulfosalicylic acid which is at least sufficient to sequester significant proportions of ferric ions when the pH of the acid is from 0.5 to 3 but is less than enough to cause a significant salting-out of solid materials, and an amount of citric acid which is at least sufficient to sequester significant proportions of ferric ions when the pH of the acid is from 3 to 6 but is less than enough to precipitate a significant amount of calcium citrate. The amount of the 5-sulfosalicylic acid may be from 0.01 to 0.05 moles/l and the amount of citric acid is from 0.001 to 0.009 moles/l. 11 claims.

  4. Biodegradable and thermosensitive monomethoxy poly(ethylene glycol)-poly(lactic acid) hydrogel as a barrier for prevention of post-operative abdominal adhesion.

    Science.gov (United States)

    Fu, Shao Zhi; Li, Zhi; Fan, Jun Ming; Meng, Xiao Hang; Shi, Kun; Qu, Ying; Yang, Ling Lin; Wu, Jing Bo; Fan, Juan; Luot, Feng; Qian, Zhi Yong

    2014-03-01

    Post-operative peritoneal adhesions are serious consequences of abdominal or pelvic surgery and cause severe bowel obstruction, chronic pelvic pain and infertility. In this study, a novel nano-hydrogel system based on a monomethoxy poly(ethylene glycol)-poly(lactic acid) (MPEG-PLA) di-block copolymer was studied for its ability to prevent abdominal adhesion in rats. The MPEG-PLA hydrogel at a concentration of 40% (w/v) was injected and was able to adhere to defect sites at body temperature. The ability of the hydrogel to inhibit adhesion of post-operative tissues was evaluated by utilizing a rat model of abdominal sidewall-cecum abrasion. It was possible to heal wounded tissue through regeneration of neo-peritoneal tissues ten days after surgery. Our data showed that this hydrogel system is equally as effective as current commercialized anti-adhesive products.

  5. Omega 3 fatty acid for the prevention of cognitive decline and dementia

    Directory of Open Access Journals (Sweden)

    Emma Sydenham

    2012-01-01

    Full Text Available BACKGROUND: Evidence from observational studies suggests that diets high in omega-3 long-chain polyunsaturated fatty acids (PUFA may protect people from cognitive decline and dementia. The strength of this potential protective effect has recently been tested in randomized controlled trials. OBJECTIVES: To assess the effects of omega-3 PUFA supplementation for the prevention of dementia and cognitive decline in cognitively healthy older people. METHODS: Search: We searched ALOIS - the Cochrane Dementia and Cognitive Improvement Group's Specialized Register on - 6 April 2012 using the terms: "omega 3", PUFA, "fatty acids", "fatty acid", fish, linseed, eicosapentaenoic, docosahexaenoic. Selection criteria: Randomised controlled trials of an omega-3 PUFA intervention which was provided for a minimum of six months to participants aged 60 years and over who were free from dementia or cognitive impairment at the beginning of the study. Two review authors independently assessed all trials. Data collection and analysis: The review authors sought and extracted data on incident dementia, cognitive function, safety and adherence, either from published reports or by contacting the investigators for original data. Data were extracted by two review authors. We calculated mean difference (MD or standardised mean differences (SMD and 95% confidence intervals (CI on an intention-to-treat basis, and summarized narratively information on safety and adherence. MAIN RESULTS: Information on cognitive function at the start of a study was available on 4080 participants randomised in three trials. Cognitive function data were available on 3536 participants at final follow-up. In two studies participants received gel capsules containing either omega-3 PUFA (the intervention or olive or sunflower oil (placebo for six or 24 months. In one study, participants received margarine spread for 40 months; the margarine for the intervention group contained omega-3 PUFA. Two studies

  6. Omega 3 fatty acid for the prevention of cognitive decline and dementia

    Directory of Open Access Journals (Sweden)

    Emma Sydenham

    Full Text Available BACKGROUND: Evidence from observational studies suggests that diets high in omega-3 long-chain polyunsaturated fatty acids (PUFA may protect people from cognitive decline and dementia. The strength of this potential protective effect has recently been tested in randomized controlled trials. OBJECTIVES: To assess the effects of omega-3 PUFA supplementation for the prevention of dementia and cognitive decline in cognitively healthy older people. METHODS: Search: We searched ALOIS - the Cochrane Dementia and Cognitive Improvement Group's Specialized Register on - 6 April 2012 using the terms: "omega 3", PUFA, "fatty acids", "fatty acid", fish, linseed, eicosapentaenoic, docosahexaenoic. Selection criteria: Randomised controlled trials of an omega-3 PUFA intervention which was provided for a minimum of six months to participants aged 60 years and over who were free from dementia or cognitive impairment at the beginning of the study. Two review authors independently assessed all trials. Data collection and analysis: The review authors sought and extracted data on incident dementia, cognitive function, safety and adherence, either from published reports or by contacting the investigators for original data. Data were extracted by two review authors. We calculated mean difference (MD or standardised mean differences (SMD and 95% confidence intervals (CI on an intention-to-treat basis, and summarized narratively information on safety and adherence. MAIN RESULTS: Information on cognitive function at the start of a study was available on 4080 participants randomised in three trials. Cognitive function data were available on 3536 participants at final follow-up. In two studies participants received gel capsules containing either omega-3 PUFA (the intervention or olive or sunflower oil (placebo for six or 24 months. In one study, participants received margarine spread for 40 months; the margarine for the intervention group contained omega-3 PUFA. Two studies

  7. Dietary fatty acids and cardiovascular disease: A review

    Directory of Open Access Journals (Sweden)

    Raquel Eccel Prates

    2015-09-01

    Full Text Available Fatty acids (FAs can be classified into saturated (SFA, unsaturated (poly- or monounsaturated and trans FA. Recent studies have found that both the quantity and quality of dietary FAs may influence their role in metabolic pathways. Due to their chemical composition, some FAs play a major role in the development and progression of cardiovascular disease. This is especially true for SFA and n-3 polyunsaturated fatty acids, which include marine eicosapentaenoic acid (EPA and docosahexaenoic acid (DHA. The proinflammatory effects of high SFA intake may increase the risk of atherosclerosis. On the other hand, dietary n-3 intake may reduce the risk of cardiovascular disease by decreasing atherosclerosis, inflammation, and thrombotic processes. The goal of this study was to review the current literature on the role of FA intake in the prevention and risk of cardiovascular disease.

  8. Is intravesical instillation of hyaluronic acid and chondroitin sulfate useful in preventing recurrent bacterial cystitis? A multicenter case control analysis.

    Science.gov (United States)

    Gugliotta, Giorgio; Calagna, Gloria; Adile, Giorgio; Polito, Salvatore; Saitta, Salvatore; Speciale, Patrizia; Palomba, Stefano; Perino, Antonino; Granese, Roberta; Adile, Biagio

    2015-10-01

    Urinary tract infections (UTIs) are common in the female population and, over a lifetime, about half of women have at least one episode of UTI requiring antibiotic therapy. The aim of the current study was to compare two different strategies for preventing recurrent bacterial cystitis: intravesical instillation of hyaluronic acid (HA) plus chondroitin sulfate (CS), and antibiotic prophylaxis with sulfamethoxazole plus trimethoprim. This was a retrospective review of two different cohorts of women affected by recurrent bacterial cystitis. Cases (experimental group) were women who received intravesical instillations of a sterile solution of high concentration of HA + CS in 50 mL water with calcium chloride every week during the 1(st) month and then once monthly for 4 months. The control group included women who received traditional therapy for recurrent cystitis based on daily antibiotic prophylaxis using sulfamethoxazole 200 mg plus trimethoprim 40 mg for 6 weeks. Ninety-eight and 76 patients were treated with experimental and control treatments, respectively. At 12 months after treatment, 69 and 109 UTIs were detected in the experimental and control groups, respectively. The proportion of patients free from UTIs was significantly higher in the experimental than in the control group (36.7% vs. 21.0%; p = 0.03). Experimental treatment was well tolerated and none of the patients stopped it. The intravesical instillation of HA + CS is more effective than long-term antibiotic prophylaxis for preventing recurrent bacterial cystitis. Copyright © 2015. Published by Elsevier B.V.

  9. A review of minodronic acid hydrate for the treatment of osteoporosis

    Directory of Open Access Journals (Sweden)

    Tanishima S

    2013-02-01

    Full Text Available Shinji Tanishima, Yasuo MorioDepartment of Orthopedic Surgery, Misasa Onsen Hospital, Misasa, Tottori, JapanAbstract: Minodronic acid hydrate was the first bisphosphonate developed and approved for osteoporosis treatment in Japan. With regard to inhibition of bone resorption, minodronic acid hydrate is 1000 times more effective than etidronic acid and 10–100 times more effective than alendronic acid. Clinical trials conducted to date have focused on postmenopausal female patients suffering from primary osteoporosis. In these trials, 1 mg of oral minodronic acid hydrate was administrated once daily, and a significant increase was observed in lumbar-spine and hip-joint bone density 1–2 years after administration. All markers of bone metabolism urinary collagen type 1 cross-linked N-telopeptide, urinary free deoxypyridinoline, serum bone alkaline phosphatase, and serum osteocalcin were decreased. The incidence rate of new vertebral and nonvertebral fractures was also decreased. Therefore, effectiveness in fracture prevention was confirmed. A form of minodronic acid (50 mg requiring once-monthly administration has been developed and is currently being used clinically. A comparative study between this new formulation and once-daily minodronic acid (1 mg showed no significant differences between the two formulations in terms of improvement rates in lumbar-spine and hip-joint bone density, changes in bone metabolism markers, or incidence of side effects. This indicates the noninferiority of the monthly formulation. Side effects such as osteonecrosis of the jaw or atypical femoral fractures were not reported with other bisphosphonates, although it is believed that these side effects may emerge as future studies continue to be conducted. On the basis of studies conducted to date, minodronic acid hydrate is considered effective for improving bone density and preventing fractures. We anticipate further investigations in the future

  10. The role of the Saccharomyces cerevisiae lipoate protein ligase homologue, Lip3, in lipoic acid synthesis.

    Science.gov (United States)

    Hermes, Fatemah A; Cronan, John E

    2013-10-01

    The covalent attachment of lipoate to the lipoyl domains (LDs) of the central metabolism enzymes pyruvate dehydrogenase (PDH) and oxoglutarate dehydrogenase (OGDH) is essential for their activation and thus for respiratory growth in Saccharomyces cerevisiae. A third lipoate-dependent enzyme system, the glycine cleavage system (GCV), is required for utilization of glycine as a nitrogen source. Lipoate is synthesized by extraction of its precursor, octanoyl-acyl carrier protein (ACP), from the pool of fatty acid biosynthetic intermediates. Alternatively, lipoate is salvaged from previously modified proteins or from growth medium by lipoate protein ligases (Lpls). The first Lpl to be characterized, LplA of Escherichia coli, catalyses two partial reactions: activation of the acyl chain by formation of acyl-AMP, followed by transfer of the acyl chain to lipoyl domains (LDs). There is a surprising diversity within the Lpl family of enzymes, several of which catalyse reactions other than ligation reactions. For example, the Bacillus subtilis Lpl homologue LipM is an octanoyltransferase that transfers the octanoyl moiety from octanoyl-ACP to GCV. Another B. subtilis Lpl homologue, LipL, transfers octanoate from octanoyl-GCV to other LDs in an amido-transfer reaction. Study of eukaryotic Lpls has lagged behind studies of the bacterial enzymes. We report that the Lip3 Lpl homologue of the yeast S. cerevisiae has octanoyl-CoA-protein transferase activity, and discuss implications of this activity on the physiological role of Lip3 in lipoate synthesis. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.

  11. Ursodeoxycholic and deoxycholic acids: A good and a bad bile acid for intestinal calcium absorption.

    Science.gov (United States)

    Rodríguez, Valeria; Rivoira, María; Marchionatti, Ana; Pérez, Adriana; Tolosa de Talamoni, Nori

    2013-12-01

    The aim of this study was to investigate the effect of ursodeoxycholic acid (UDCA) on intestinal Ca(2+) absorption and to find out whether the inhibition of this process caused by NaDOC could be prevented by UDCA. Chicks were employed and divided into four groups: (a) controls, (b) treated with 10mM NaDOC, (c) treated with 60 μg UDCA/100g of b.w., and (d) treated with 10mM NaDOC and 60 μg UDCA/100g of b.w. UDCA enhanced intestinal Ca(2+) absorption, which was time and dose-dependent. UDCA avoided the inhibition of intestinal Ca(2+) absorption caused by NaDOC. Both bile acids altered protein and gene expression of molecules involved in the transcellular pathway of intestinal Ca(2+) absorption, but in the opposite way. UDCA aborted the oxidative stress produced by NaDOC in the intestine. UDCA and UDCA plus NaDOC increased vitamin D receptor protein expression. In conclusion, UDCA is a beneficial bile acid for intestinal Ca(2+) absorption. Contrarily, NaDOC inhibits the intestinal cation absorption through triggering oxidative stress. The use of UDCA in patients with cholestasis would be benefited because of the protective effect on the intestinal Ca(2+) absorption, avoiding the inhibition caused by hydrophobic bile acids and neutralizing the oxidative stress. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. Salicylic acid prevents Trichoderma harzianum from entering the vascular system of roots.

    Science.gov (United States)

    Alonso-Ramírez, Ana; Poveda, Jorge; Martín, Ignacio; Hermosa, Rosa; Monte, Enrique; Nicolás, Carlos

    2014-10-01

    Trichoderma is a soil-borne fungal genus that includes species with a significant impact on agriculture and industrial processes. Some Trichoderma strains exert beneficial effects in plants through root colonization, although little is known about how this interaction takes place. To better understand this process, the root colonization of wild-type Arabidopsis and the salicylic acid (SA)-impaired mutant sid2 by a green fluorescent protein (GFP)-marked Trichoderma harzianum strain was followed under confocal microscopy. Trichoderma harzianum GFP22 was able to penetrate the vascular tissue of the sid2 mutant because of the absence of callose deposition in the cell wall of root cells. In addition, a higher colonization of sid2 roots by GFP22 compared with that in Arabidopsis wild-type roots was detected by real-time polymerase chain reaction. These results, together with differences in the expression levels of plant defence genes in the roots of both interactions, support a key role for SA in Trichoderma early root colonization stages. We observed that, without the support of SA, plants were unable to prevent the arrival of the fungus in the vascular system and its spread into aerial parts, leading to later collapse. © 2014 BSPP AND JOHN WILEY & SONS LTD.

  13. Pollution prevention in the oil and soap industry: a case study

    International Nuclear Information System (INIS)

    Abou-Elela, S.I.; Zaher, F.

    1998-01-01

    Industrial audit of a complex oil and soap factory has been carried out. The factory produces edible oils, fatty acids, soap, crude, industrial and pharmaceutical glycerin, powdered detergents, animal fodder, sodium and potassium silicates, sodium hypochlorite and hypochloric acid. The audit shows that there were a wide range of pollution prevention opportunities which could be implemented with significant financial advantages for the factory as well as reducing environmental pollution. Cost benefits for the recommended environmental improvements have been estimated. Many of the improvements had short payback periods. (author)

  14. Pollution prevention in the oil and soap industry: a case study

    Energy Technology Data Exchange (ETDEWEB)

    Abou-Elela, S.I. [National Research Center, Gizza (Egypt). Water Pollution Control Dept.; Zaher, F. [National Research Center, Gizza (Egypt). Fats and Oil Dept.

    1998-12-31

    Industrial audit of a complex oil and soap factory has been carried out. The factory produces edible oils, fatty acids, soap, crude, industrial and pharmaceutical glycerin, powdered detergents, animal fodder, sodium and potassium silicates, sodium hypochlorite and hypochloric acid. The audit shows that there were a wide range of pollution prevention opportunities which could be implemented with significant financial advantages for the factory as well as reducing environmental pollution. Cost benefits for the recommended environmental improvements have been estimated. Many of the improvements had short payback periods. (author)

  15. Potential mechanisms explaining why hydrolyzed casein-based diets outclass single amino acid-based diets in the prevention of autoimmune diabetes in diabetes-prone BB rats

    NARCIS (Netherlands)

    Visser, J. T. J.; Bos, N. A.; Harthoorn, L. F.; Stellaard, F.; Beijer-Liefers, S.; Rozing, J.; van Tol, E. A. F.

    Background It remains controversial whether avoidance of dietary diabetogenic triggers, such as cow's milk proteins, can prevent type 1 diabetes in genetically susceptible individuals. Here, different extensive casein hydrolysates (HC) and single amino acid (AA) formulations were tested for their

  16. Prevention of 5-fluorouracil-caused growth inhibition in Sordaria fimicola.

    Science.gov (United States)

    Schoen, H F; Berech, J

    1977-02-01

    Growth (dry weight accumulation) of Sordaria fimicola in standing liquid culture (sucrose-nitrate-salts-vitamins) is inhibited by the presence of 5 muM 5-fluorouracil in the medium. This inhibition is completely prevented by uracil, deoxyuridine, and 5-bromouracil, partly prevented (40 to 90% of growth observed without 5-fluorouracil) by uridine, thymidine, and 5-bromodeoxyuridine, and slightly prevented by trifluorothymine, cytosine, cytidine, deoxycytidine, and 5-methylcytosine (all at 0.5 to 1 mM). Thymidine and thymine riboside were without any apparent effect. Growth is also inhibited by 0.2 mM 6-azauracil, and this inhibition was completely prevented by uracil and uridine, partly prevented by deoxyuridine, 5-bromouracil, cytidine, and 5-methylcytosine, and slightly prevented by thymine, thymidine, 5-bromodeoxyuridine, cytosine, and deoxycytidine. The data suggest that the observed inhibition of growth by 5-fluorouracil is due to inhibition of both ribonucleic acid and deoxyribonucleic acid synthesis. The data also allow inferences concerning pyrimidine interconversions in S. fimicola; i.e., thymine can be anabolized to thymidylic acid without first being demethylated, although demethylation appears to occur also.

  17. Curative role of lactulose, L-carnitine, alpha-lipoic acid and ...

    African Journals Online (AJOL)

    levels of inflammatory markers were assessed in serum, liver and brain. Results: A ... stress, Cirrhosis, Acute liver injury. Tropical ... injury model and it has been widely studied in rats and in ... The animals received a standard pellet diet and.

  18. Surface-Tethered Iterative Carbohydrate Synthesis (STICS): A spacer study

    Science.gov (United States)

    Ganesh, N. Vijaya; Fujikawa, Kohki; Tan, Yih Horng; Nigudkar, Swati S.

    2013-01-01

    Comparative study of STICS using HPLC-assisted experimental set-up clearly demonstrated benefits of using longer spacer-anchoring systems. The use of mixed self-assembled monolayers helps to provide the required space for glycosylation reaction around the immobilized glycosyl acceptor. Both extension of the spacer length and using mixed self-assembled monolayers help to promote reaction and the beneficial effects may include moving the glycosyl acceptor further out into solution and providing additional conformational flexibility. It is possible that surface-immobilized glycosyl acceptors with a longer spacer (C8-O-C8)-lipoic acid have a higher tendency to mimic a solution-phase reaction environment than that of acceptors with shorter spacers. PMID:23822088

  19. Safflower and olive oil dietary treatments rescue aberrant embryonic arachidonic acid and nitric oxide metabolism and prevent diabetic embryopathy in rats.

    Science.gov (United States)

    Higa, R; White, V; Martínez, N; Kurtz, M; Capobianco, E; Jawerbaum, A

    2010-04-01

    Aberrant arachidonic acid and nitric oxide (NO) metabolic pathways are involved in diabetic embryopathy. Previous works have found diminished concentrations of PGE(2) and PGI(2) in embryos from diabetic rats, and that PGI(2) is capable of increasing embryonic PGE(2) concentrations through the activation of the nuclear receptor PPARdelta. PPARdelta activators are lipid molecules such as oleic and linoleic acids, present in high concentrations in olive and safflower oils, respectively. The aim of this study was to analyze the capability of dietary supplementation with either 6% olive or 6% safflower oils to regulate PGE(2), PGI(2) and NO concentrations in embryos and deciduas from control and diabetic rats during early organogenesis. Diabetes was induced by a single injection of streptozotocin (55 mg/kg) 1 week before mating. Animals were fed with the oil-supplemented diets from Days 0.5 to 10.5 of gestation. PGI(2) and PGE(2) were measured by EIA and NO through the evaluation of its stable metabolites nitrates-nitrites in 10.5 day embryos and deciduas. We found that the olive and safflower oil-supplemented treatments highly reduced resorption and malformation rates in diabetic animals, and that they were able to prevent maternal diabetes-induced alterations in embryonic and decidual PGI(2) and PGE(2) concentrations. Moreover, these dietary treatments prevented NO overproduction in embryos and deciduas from diabetic rats. These data indicate that in maternal diabetes both the embryo and the decidua benefit from the olive and safflower oil supplementation probably through mechanisms that involve the rescue of aberrant prostaglandin and NO generation and that prevent developmental damage during early organogenesis.

  20. Identification of proteins regulated by ferulic acid in a middle cerebral artery occlusion animal model-a proteomics approach.

    Science.gov (United States)

    Sung, Jin-Hee; Cho, Eun-Hae; Cho, Jae-Hyeon; Won, Chung-Kil; Kim, Myeong-Ok; Koh, Phil-Ok

    2012-11-01

    Ferulic acid plays a neuroprotective role in cerebral ischemia. The aim of this study was to identify the proteins that are differentially expressed following ferulic acid treatment during ischemic brain injury using a proteomics technique. Middle cerebral artery occlusion (MCAO) was performed to induce a focal cerebral ischemic injury in adult male rats, and ferulic acid (100 mg/kg) or vehicle was administered immediately after MCAO. Brain tissues were collected 24 hr after MCAO. The proteins in the cerebral cortex were separated using two-dimensional gel electrophoresis and were identified by mass spectrometry. We detected differentially expressed proteins between vehicle- and ferulic acid-treated animals. Adenosylhomocysteinase, isocitrate dehydrogenase [NAD(+)], mitogen-activated protein kinase kinase 1 and glyceraldehyde-3-phosphate dehydrogenase were decreased in the vehicle-treated group, and ferulic acid prevented the injury-induced decreases in these proteins. However, pyridoxal phosphate phosphatase and heat shock protein 60 were increased in the vehicle-treated group, while ferulic acid prevented the injury-induced increase in these proteins. It is accepted that these enzymes are involved in cellular metabolism and differentiation. Thus, these findings suggest evidence that ferulic acid plays a neuroprotective role against focal cerebral ischemia through the up- and down-modulation of specific enzymes.

  1. Small molecular antioxidants effectively protect from PUVA-induced oxidative stress responses underlying fibroblast senescence and photoaging.

    Science.gov (United States)

    Briganti, Stefania; Wlaschek, Meinhard; Hinrichs, Christina; Bellei, Barbara; Flori, Enrica; Treiber, Nicolai; Iben, Sebastian; Picardo, Mauro; Scharffetter-Kochanek, Karin

    2008-09-01

    Exposure of human fibroblasts to 8-methoxypsoralen plus ultraviolet-A irradiation (PUVA) results in stress-induced cellular senescence in fibroblasts. We here studied the role of the antioxidant defense system in the accumulation of reactive oxygen species (ROS) and the effect of the antioxidants alpha-tocopherol, N-acetylcysteine, and alpha-lipoic acid on PUVA-induced cellular senescence. PUVA treatment induced an immediate and increasing generation of intracellular ROS. Supplementation of PUVA-treated fibroblasts with alpha-tocopherol (alpha-Toc), N-acetylcysteine (NAC), or alpha-lipoic acid (alpha-LA) abrogated the increased ROS generation and rescued fibroblasts from the ROS-dependent changes into the cellular senescence phenotype, such as cytoplasmic enlargement, enhanced expression of senescence-associated-beta-galactosidase and matrix-metalloproteinase-1, hallmarks of photoaging and intrinsic aging. PUVA treatment disrupted the integrity of cellular membranes and impaired homeostasis and function of the cellular antioxidant system with a significant decrease in glutathione and hydrogen peroxide-detoxifying enzymes activities. Supplementation with NAC, alpha-LA, and alpha-Toc counteracted these changes. Our data provide causal evidence that (i) oxidative stress due to an imbalance in the overall cellular antioxidant capacity contributes to the induction and maintenance of the PUVA-induced fibroblast senescence and that (ii) low molecular antioxidants protect effectively against these deleterious alterations.

  2. Fermentation conditions that affect clavulanic acid production in Streptomyces clavuligerus: a systematic review

    Directory of Open Access Journals (Sweden)

    Hooi-Leng eSer

    2016-04-01

    Full Text Available The β-lactamase inhibitor, clavulanic acid is frequently used in combination with β-lactam antibiotics to treat a wide spectrum of infectious diseases. Clavulanic acid prevents drug resistance by pathogens against these β-lactam antibiotics by preventing the degradation of the β-lactam ring, thus ensuring eradication of these harmful microorganisms from the host. This systematic review provides an overview on the fermentation conditions that affect the production of clavulanic acid in the firstly described producer, Streptomyces clavuligerus. A thorough search was conducted using predefined terms in several electronic databases (PubMed, Medline, ScienceDirect, EBSCO, from database inception to June 30th 2015. Studies must involve wild-type Streptomyces clavuligerus, and full texts needed to be available. A total of 29 eligible articles were identified. Based on the literature, several factors were identified that could affect the production of clavulanic acid in S. clavuligerus. The addition of glycerol or other vegetable oils (e.g. olive oil, corn oil could potentially affect clavulanic acid production. Furthermore, some amino acids such as arginine and ornithine, could serve as potential precursors to increase clavulanic acid yield. The comparison of different fermentation systems revealed that fed-batch fermentation yields higher amounts of clavulanic acid as compared to batch fermentation, probably due to the maintenance of substrates and constant monitoring of certain entities (such as pH, oxygen availability, etc.. Overall, these findings provide vital knowledge and insight that could assist media optimization and fermentation design for clavulanic acid production in S. clavuligerus.

  3. Energy restriction does not prevent insulin resistance but does prevent liver steatosis in aging rats on a Western-style diet.

    Science.gov (United States)

    Hennebelle, Marie; Roy, Maggie; St-Pierre, Valérie; Courchesne-Loyer, Alexandre; Fortier, Mélanie; Bouzier-Sore, Anne-Karine; Gallis, Jean-Louis; Beauvieux, Marie-Christine; Cunnane, Stephen C

    2015-03-01

    The aim of this study was to evaluate the effects of long-term energy restriction (ER) on plasma, liver, and skeletal muscle metabolite profiles in aging rats fed a Western-style diet. Three groups of male Sprague-Dawley rats were studied. Group 1 consisted of 2 mo old rats fed ad libitum; group 2 were 19 mo old rats also fed ad libitum; and group 3 were 19 mo old rats subjected to 40% ER for the last 11.5 mo. To imitate a Western-style diet, all rats were given a high-sucrose, very low ω-3 polyunsaturated fatty acid (PUFA) diet. High-resolution magic angle spinning-(1)H nuclear magnetic resonance spectroscopy was used for hepatic and skeletal muscle metabolite determination, and fatty acid profiles were measured by capillary gas chromatography on plasma, liver, and skeletal muscle. ER coupled with a Western-style diet did not prevent age-induced insulin resistance or the increase in triacylglycerol content in plasma and skeletal muscle associated with aging. However, in the liver, ER did prevent steatosis and increased the percent of saturated and monounsaturated fatty acids relative to ω-6 and ω-3 PUFA. Although steatosis was reduced, the beneficial effects of ER on systemic insulin resistance and plasma and skeletal muscle metabolites observed elsewhere with a balanced diet seem to be compromised by high-sucrose and low ω-3 PUFA intake. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. A review of omega-3 ethyl esters for cardiovascular prevention and treatment of increased blood triglyceride levels

    Directory of Open Access Journals (Sweden)

    Clemens von Schacky

    2006-09-01

    Full Text Available Clemens von SchackyMedizinische Klinik and Poliklinik Innenstadt, University of Munich, Munich, GermanyAbstract: The two marine omega-3 fatty acids eicosapentaenoic acid (EPA and docosahexaenoic acid (DHA, prevalent in fish and fish oils, have been investigated as a strategy towards prophylaxis of atherosclerosis. While the results with fish and fish oils have been not as clear cut, the data generated with the purified ethyl ester forms of these two fatty acids are consistent. Although slight differences in biological activity exist between EPA and DHA, both exert a number of positive actions against atherosclerosis and its complications. EPA and DHA as ethyl esters inhibit platelet aggregability, and reduce serum triglycerides, while leaving other serum lipids essentially unaltered. Glucose metabolism has been studied extensively, and no adverse effects were seen. Pro-atherogenic cytokines are reduced, as are markers of endothelial activation. Endothelial function is improved, vascular occlusion is reduced, and the course of coronary atherosclerosis is mitigated. Heart rate is reduced, and heart rate variability is increased by EPA and DHA. An antiarrhythmic effect can be demonstrated on the supraventricular and the ventricular level. More importantly, two large studies showed reductions in clinical endpoints like sudden cardiac death or major adverse cardiac events. As a consequence, relevant cardiac societies recommend using 1 g/day of EPA and DHA for cardiovascular prevention, after a myocardial infarction and for prevention of sudden cardiac death.Keywords: sudden cardiac death, major adverse cardiac events, cardiovascular prevention, eicosapentaenoic acid, docosahexaenoic acid

  5. Acidic pH promotes intervertebral disc degeneration: Acid-sensing ion channel -3 as a potential therapeutic target.

    Science.gov (United States)

    Gilbert, Hamish T J; Hodson, Nathan; Baird, Pauline; Richardson, Stephen M; Hoyland, Judith A

    2016-11-17

    The aetiology of intervertebral disc (IVD) degeneration remains poorly understood. Painful IVD degeneration is associated with an acidic intradiscal pH but the response of NP cells to this aberrant microenvironmental factor remains to be fully characterised. The aim here was to address the hypothesis that acidic pH, similar to that found in degenerate IVDs, leads to the altered cell/functional phenotype observed during IVD degeneration, and to investigate the involvement of acid-sensing ion channel (ASIC) -3 in the response. Human NP cells were treated with a range of pH, from that of a non-degenerate (pH 7.4 and 7.1) through to mildly degenerate (pH 6.8) and severely degenerate IVD (pH 6.5 and 6.2). Increasing acidity of pH caused a decrease in cell proliferation and viability, a shift towards matrix catabolism and increased expression of proinflammatory cytokines and pain-related factors. Acidic pH resulted in an increase in ASIC-3 expression. Importantly, inhibition of ASIC-3 prevented the acidic pH induced proinflammatory and pain-related phenotype in NP cells. Acidic pH causes a catabolic and degenerate phenotype in NP cells which is inhibited by blocking ASIC-3 activity, suggesting that this may be a useful therapeutic target for treatment of IVD degeneration.

  6. Curative role of lactulose, L-carnitine, alpha-lipoic acid and ...

    African Journals Online (AJOL)

    All rights reserved. Available online at ... levels of inflammatory markers were assessed in serum, liver and brain. Results: A ... of developing overt encephalopathy. Recently, it ... and left untreated for 3 months (TAA 3 months). Group (5): rats ...

  7. Ameliorative effects of polyunsaturated fatty acids against palmitic acid-induced insulin resistance in L6 skeletal muscle cells

    Directory of Open Access Journals (Sweden)

    Sawada Keisuke

    2012-03-01

    Full Text Available Abstract Background Fatty acid-induced insulin resistance and impaired glucose uptake activity in muscle cells are fundamental events in the development of type 2 diabetes and hyperglycemia. There is an increasing demand for compounds including drugs and functional foods that can prevent myocellular insulin resistance. Methods In this study, we established a high-throughput assay to screen for compounds that can improve myocellular insulin resistance, which was based on a previously reported non-radioisotope 2-deoxyglucose (2DG uptake assay. Insulin-resistant muscle cells were prepared by treating rat L6 skeletal muscle cells with 750 μM palmitic acid for 14 h. Using the established assay, the impacts of several fatty acids on myocellular insulin resistance were determined. Results In normal L6 cells, treatment with saturated palmitic or stearic acid alone decreased 2DG uptake, whereas unsaturated fatty acids did not. Moreover, co-treatment with oleic acid canceled the palmitic acid-induced decrease in 2DG uptake activity. Using the developed assay with palmitic acid-induced insulin-resistant L6 cells, we determined the effects of other unsaturated fatty acids. We found that arachidonic, eicosapentaenoic and docosahexaenoic acids improved palmitic acid-decreased 2DG uptake at lower concentrations than the other unsaturated fatty acids, including oleic acid, as 10 μM arachidonic acid showed similar effects to 750 μM oleic acid. Conclusions We have found that polyunsaturated fatty acids, in particular arachidonic and eicosapentaenoic acids prevent palmitic acid-induced myocellular insulin resistance.

  8. Hyaluronate acid and oxidized regenerated cellulose prevent adhesion reformation after adhesiolysis in rat models

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    Zhang Y

    2016-10-01

    Full Text Available Yan Zhang, Qin Liu, Ning Yang, Xuegang Zhang Department of Gynecology, Kunshan Hospital Affiliated to Jiangsu University, Kunshan, Jiangsu, People’s Republic of China Abstract: Postsurgical adhesion formation is the most common complication in abdominal and pelvic surgery. Adhesiolysis is the most commonly applied treatment for adhesion formation but is often followed by adhesion reformation. Therefore, an efficient strategy should be adopted to solve these problems. This study aimed to explore whether hyaluronic acid and oxidized regenerated cellulose (ORC could prevent adhesion formation and reformation. Thirty female Sprague Dawley rats were randomly divided into three groups (n=10 each and subjected to different treatments during the first and second surgery. The control group was treated with isotonic sodium chloride, the ORC group was treated with ORC (1.5×1 cm, and the medical sodium hyaluronate (MSH group was treated with 1% MSH (0.5 mL. At 2 weeks after the first surgery, adhesion scores in the MSH group (1.90±0.99 and the ORC group (1.40±0.97 were significantly lower than those in the control group (3.00±0.82 (P=0.005. Similarly, 2 weeks after the second surgery, adhesion scores in the MSH group (2.00±0.82 and the ORC group (1.50±1.27 were significantly lower than those in the control group (3.50±0.53 (P=0.001. In addition, body weights in the MSH group and the ORC group did not change significantly, whereas the control group showed a consistent decrease in body weight during the experiment. Histological examination revealed that inflammatory infiltration was involved in both adhesion formation and reformation. In conclusion, hyaluronic acid and ORC were both efficient in reducing adhesion formation and reformation in the rat model. Keywords: hyaluronic acid, oxidized regenerated cellulose, adhesion formation, adhesion reformation, rat model 

  9. 10-Oxo-trans-11-octadecenoic acid generated from linoleic acid by a gut lactic acid bacterium Lactobacillus plantarum is cytoprotective against oxidative stress.

    Science.gov (United States)

    Furumoto, Hidehiro; Nanthirudjanar, Tharnath; Kume, Toshiaki; Izumi, Yasuhiko; Park, Si-Bum; Kitamura, Nahoko; Kishino, Shigenobu; Ogawa, Jun; Hirata, Takashi; Sugawara, Tatsuya

    2016-04-01

    Oxidative stress is a well-known cause of multiple diseases. The nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway plays a central role in cellular antioxidative responses. In this study, we investigated the effects of novel fatty acid metabolite derivatives of linoleic acid generated by the gut lactic acid bacteria Lactobacillus plantarum on the Nrf2-ARE pathway. 10-Oxo-trans-11-octadecenoic acid (KetoC) protected HepG2 cells from cytotoxicity induced by hydrogen peroxide. KetoC also significantly increased cellular Nrf2 protein levels, ARE-dependent transcription, and the gene expression of antioxidative enzymes such as heme oxygenase-1 (HO-1), glutamate-cysteine ligase modifier subunit (GCLM), and quinone oxidoreductase 1 (NQO1) in HepG2 cells. Additionally, a single oral dose administration of KetoC also increased antioxidative gene expression and protein levels of Nrf2 and HO-1 in mouse organs. Since other fatty acid metabolites and linoleic acid did not affect cellular antioxidative responses, the cytoprotective effect of KetoC may be because of its α,β-unsaturated carbonyl moiety. Collectively, our data suggested that KetoC activated the Nrf2-ARE pathway to enhance cellular antioxidative responses in vitro and in vivo, which further suggests that KetoC may prevent multiple diseases induced by oxidative stress. Copyright © 2016. Published by Elsevier Inc.

  10. Preventing Excessive Blood Loss During Percutaneous Nephrolithotomy by Using Tranexamic Acid: A Double Blinded Prospective Randomized Controlled Trial

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    Adnan Siddiq

    2017-12-01

    Full Text Available Objective: Percutaneous nephrolithotomy (PCNL is most frequently performed procedure for renal stones 2 cm and larger. Perioperative hemorrhage being most common complication, warrants as important predicting factor of adverse outcomes. Prevention with inexpensive and safe drug like tranexamic acid (TA would ultimately turn out to be cornerstone for establishing future guidelines. Aim of this study is to evaluate whether TA is efficacious in preventing blood loss during PCNL. Materials and Methods: Ethical review board approval taken. Sample size calculation yielded 240 patients, comprising 120 in each group. Group A receiving TA and group B receiving placebo. Age, gender, body mass index (BMI, stone size, volume and location, preoperative blood count, creatinine, urine analysis, coagulation profile and necessary radiological investigations done. Randomization through lottery method. Both patient and investigator were blinded. Hemoglobin (Hb and hematocrit (Hct levels done at 24 hours postoperatively and fall in values recorded. Results: Both groups were equal in characteristics like age, gender, BMI, stone size, volume and location (p>0.05. Operative variables like calyx punctured, position of puncture and operative time were also found to be similar in both groups. Median change in Hb in placebo group was 1.6 interquartile range (IQR 4, while in TA group was 1.3 (IQR 7.8 (p=0.001. Similarly, median change in Hct level in placebo group was 3.6 (IQR 11.8 and in TA group was 2.4 (IQR 13 (p<0.001. Sixteen patients were transfused after surgery; 12 (75% belonged to placebo group while 4 (25% belonged to TA group (p=0.038. Hospital stay was not significantly different in both groups (p=0.177 with median of 4.0 and IQR of 0 in both groups. Conclusion: TA during PCNL reduces blood loss and minimizes blood transfusion rate.

  11. Gallic acid attenuates pulmonary fibrosis in a mouse model of transverse aortic contraction-induced heart failure.

    Science.gov (United States)

    Jin, Li; Piao, Zhe Hao; Sun, Simei; Liu, Bin; Ryu, Yuhee; Choi, Sin Young; Kim, Gwi Ran; Kim, Hyung-Seok; Kee, Hae Jin; Jeong, Myung Ho

    2017-12-01

    Gallic acid, a trihydroxybenzoic acid found in tea and other plants, attenuates cardiac hypertrophy, fibrosis, and hypertension in animal models. However, the role of gallic acid in heart failure remains unknown. In this study, we show that gallic acid administration prevents heart failure-induced pulmonary fibrosis. Heart failure induced in mice, 8weeks after transverse aortic constriction (TAC) surgery, was confirmed by echocardiography. Treatment for 2weeks with gallic acid but not furosemide prevented cardiac dysfunction in mice. Gallic acid significantly inhibited TAC-induced pathological changes in the lungs, such as increased lung mass, pulmonary fibrosis, and damaged alveolar morphology. It also decreased the expression of fibrosis-related genes, including collagen types I and III, fibronectin, connective tissue growth factor (CTGF), and phosphorylated Smad3. Further, it inhibited the expression of epithelial-mesenchymal transition (EMT)-related genes, such as N-cadherin, vimentin, E-cadherin, SNAI1, and TWIST1. We suggest that gallic acid has therapeutic potential for the treatment of heart failure-induced pulmonary fibrosis. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Lipid profiling following intake of the omega 3 fatty acid DHA identifies the peroxidized metabolites F4-neuroprostanes as the best predictors of atherosclerosis prevention.

    Science.gov (United States)

    Gladine, Cécile; Newman, John W; Durand, Thierry; Pedersen, Theresa L; Galano, Jean-Marie; Demougeot, Céline; Berdeaux, Olivier; Pujos-Guillot, Estelle; Mazur, Andrzej; Comte, Blandine

    2014-01-01

    The anti-atherogenic effects of omega 3 fatty acids, namely eicosapentaenoic (EPA) and docosahexaenoic acids (DHA) are well recognized but the impact of dietary intake on bioactive lipid mediator profiles remains unclear. Such a profiling effort may offer novel targets for future studies into the mechanism of action of omega 3 fatty acids. The present study aimed to determine the impact of DHA supplementation on the profiles of polyunsaturated fatty acids (PUFA) oxygenated metabolites and to investigate their contribution to atherosclerosis prevention. A special emphasis was given to the non-enzymatic metabolites knowing the high susceptibility of DHA to free radical-mediated peroxidation and the increased oxidative stress associated with plaque formation. Atherosclerosis prone mice (LDLR(-/-)) received increasing doses of DHA (0, 0.1, 1 or 2% of energy) during 20 weeks leading to a dose-dependent reduction of atherosclerosis (R(2) = 0.97, p = 0.02), triglyceridemia (R(2) = 0.97, p = 0.01) and cholesterolemia (R(2) = 0.96, pF4-neuroprostanes, a specific class of DHA peroxidized metabolites, was strongly correlated with the hepatic DHA level. Moreover, unbiased statistical analysis including correlation analyses, hierarchical cluster and projection to latent structure discriminate analysis revealed that the hepatic level of F4-neuroprostanes was the variable most negatively correlated with the plaque extent (pF4-neuroprostanes in particular, are potential biomarkers of DHA-associated atherosclerosis prevention. While these may contribute to the anti-atherogenic effects of DHA, further in vitro investigations are needed to confirm such a contention and to decipher the molecular mechanisms of action.

  13. Training for cervical cancer prevention programs in low-resource settings: focus on visual inspection with acetic acid and cryotherapy.

    Science.gov (United States)

    Blumenthal, P D; Lauterbach, M; Sellors, J W; Sankaranarayanan, R

    2005-05-01

    The modern approach to cervical cancer prevention, characterized by use of cytology and multiple visits for diagnosis and treatment, has frequently proven challenging and unworkable in low-resource settings. Because of this, the Alliance for Cervical Cancer Prevention (ACCP) has made it a priority to investigate and assess alternative approaches, particularly the use of visual screening methods, such as visual inspection with acetic acid (VIA) and visual inspection with Lugol's iodine (VILI), for precancer and cancer detection and the use of cryotherapy as a precancer treatment method. As a result of ACCP experience in providing training to nurses and doctors in these techniques, it is now widely agreed that training should be competency based, combining both didactic and hands-on approaches, and should be done in a clinical setting that resembles the service-delivery conditions at the program site. This article reviews ACCP experiences and perceptions about the essentials of training in visual inspection and cryotherapy and presents some lessons learned with regard to training in these techniques in low-resource settings.

  14. Preventing intraperitoneal adhesions with ethyl pyruvate and hyaluronic acid/carboxymethylcellulose: a comparative study in an experimental model.

    Science.gov (United States)

    Caglayan, E Kıyak; Caglayan, K; Erdogan, N; Cinar, H; Güngör, B

    2014-10-01

    To compare the effectiveness of ethyl pyruvate (EP) with that of hyaluronic acid+carboxymethyl cellulose (Seprafilm) for the prevention of intraperitoneal adhesions. Seprafilm has been shown to be effective in many experimental and clinical studies. Thirty rats were divided into three groups at random, and uterine horn abrasion was performed by laparotomy. One group received no treatment (control group), one group received a single intraperitoneal dose of EP 50mg/kg (EP group), and a 2×1-cm patch of Seprafilm was applied in the third group (Seprafilm group). All rats were killed 14 days after surgery. Macroscopic and histopathological evaluation were performed by a surgeon and a pathologist who were blinded to group allocation. Histopathologically, inflammation, fibroblastic activity, foreign body reaction, collagen proliferation, vascular proliferation, Masson-Trichrome score, matrix metalloproteinase-2 score and vascular endothelial growth factor score were studied. Median macroscopic intraperitoneal adhesion scores for the control, EP and Seprafilm groups were 2.8, 1.2 and 1.1, respectively. Multiple comparisons between groups showed a significant difference (p0.05). After histopathological evaluation, significant differences in all parameters were found between the groups (p0.0167). In comparison with the untreated control group, EP and Seprafilm were found to reduce the formation of intraperitoneal adhesions. No significant difference was found between EP and Seprafilm. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  15. Synchrotron Based Phase Contrast Tomography of Hyper cholesteromic Rat Liver

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    Fatima A

    2017-05-01

    Full Text Available X-ray phase contrast imaging technique has been applied for the study of morphological variations in soft tissues. The effect of an antioxidant, α-lipoic acid in reducing hypercholesterolemia in rats is investigated. The experiment was conducted to measure serum lipid profile and diameter of vessels in rat liver, as liver is the most vital organ in hypolipidemic activity studies. Methods: Four groups of male Wistar rats, control (Group I, hyperlipidemic (Group II, positive control (Group III and treated Group IV were studied for serum lipid profile and liver vessels with synchrotron X-ray phase tomography. The Group I rats received chow diet, in Group II rats, administration of 20% butter rich diet induced hyperlipidemia. Group III, treated rats received hypolipidemic drug Atorvastatin and Group IV animals received a potent antioxidant DL-α-Lipoic acid. The excised liver tissue immersed in 10% formalin. X-ray phase contrast tomography was performed for comparison of diameter of liver vessels. Results: Among the four group of animals, the diameter of liver vessels was much larger in hypercholesterolemic rat (Group II. The liver vessel diameter comparison with X-ray phase contrast tomography and the lipid profile shows reduction in serum lipids and lipoproteins by ALA treatment.

  16. Efficacy of n-3 polyunsaturated fatty acids and feasibility of optimizing preventive strategies in patients at high cardiovascular risk: rationale, design and baseline characteristics of the Rischio and Prevenzione study, a large randomised trial in general practice

    Directory of Open Access Journals (Sweden)

    2010-05-01

    Full Text Available Abstract Background The optimization of preventive strategies in patients at high risk of cardiovascular events and the evaluation of bottlenecks and limitations of transferring current guidelines to the real world of clinical practice are important limiting steps to cardiovascular prevention. Treatment with n-3 polyunsaturated fatty acids improves prognosis after myocardial infarction, but evidence of this benefit is lacking in patients at high cardiovascular risk, but without a history of myocardial infarction. Methods/design Patients were eligible if their general practitioner (GP considered them at high cardiovascular risk because of a cardiovascular disease other than myocardial infarction, or multiple risk factors (at least four major risk factors in non-diabetic patients and one in diabetics. Patients were randomly allocated to treatment with n-3 polyunsaturated fatty acids (1 g daily or placebo in a double-blind study and followed up for five years by their GPs to assess the efficacy of the treatment in preventing cardiovascular mortality (including sudden death and hospitalization for cardiovascular reasons. The secondary, epidemiological, aim of the study is to assess whether it is feasible to adopt current guidelines in everyday clinical practice, with a view to optimizing all the available preventive strategies in people at high cardiovascular risk. A nation-wide network of 860 GPs admitted 12,513 patients to the study between February 2004 and March 2007. The mean age was 64 years and 62% were males. Diabetes mellitus plus one or more cardiovascular risk factors was the main inclusion criterion (47%. About 30% of patients were included because of a history of atherosclerotic cardiovascular disease, 21% for four or more risk factors, and less than 1% for other reasons. Discussion The Rischio and Prevenzione (R&P project provides a feasible model to test the efficacy of n-3 polyunsaturated fatty acid therapy in patients at high

  17. Is there A Role for Alpha-Linolenic Acid in the Fetal Programming of Health?

    Science.gov (United States)

    Leikin-Frenkel, Alicia I

    2016-03-23

    The role of ω3 alpha linolenic acid (ALA) in the maternal diet during pregnancy and lactation, and its effect on the prevention of disease and programming of health in offspring, is largely unknown. Compared to ALA, ω3 docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids have been more widely researched due to their direct implication in fetal neural development. In this literature search we found that ALA, the essential ω3 fatty acid and metabolic precursor of DHA and EPA has been, paradoxically, almost unexplored. In light of new and evolving findings, this review proposes that ALA may have an intrinsic role, beyond the role as metabolic parent of DHA and EPA, during fetal development as a regulator of gene programming for the prevention of metabolic disease and promotion of health in offspring.

  18. Nickel Inhibits Mitochondrial Fatty Acid Oxidation

    Science.gov (United States)

    Uppala, Radha; McKinney, Richard W.; Brant, Kelly A.; Fabisiak, James P.; Goetzman, Eric S.

    2015-01-01

    Nickel exposure is associated with changes in cellular energy metabolism which may contribute to its carcinogenic properties. Here, we demonstrate that nickel strongly represses mitochondrial fatty acid oxidation—the pathway by which fatty acids are catabolized for energy—in both primary human lung fibroblasts and mouse embryonic fibroblasts. At the concentrations used, nickel suppresses fatty acid oxidation without globally suppressing mitochondrial function as evidenced by increased glucose oxidation to CO2. Pre-treatment with L-carnitine, previously shown to prevent nickel-induced mitochondrial dysfunction in neuroblastoma cells, did not prevent the inhibition of fatty acid oxidation. The effect of nickel on fatty acid oxidation occurred only with prolonged exposure (>5 hr), suggesting that direct inhibition of the active sites of metabolic enzymes is not the mechanism of action. Nickel is a known hypoxia-mimetic that activates hypoxia inducible factor-1α (HIF1α). Nickel-induced inhibition of fatty acid oxidation was blunted in HIF1α knockout fibroblasts, implicating HIF1α as one contributor to the mechanism. Additionally, nickel down-regulated the protein levels of the key fatty acid oxidation enzyme very long-chain acyl-CoA dehydrogenase (VLCAD) in a dose-dependent fashion. In conclusion, inhibition of fatty acid oxidation by nickel, concurrent with increased glucose metabolism, represents a form of metabolic reprogramming that may contribute to nickel-induced carcinogenesis. PMID:26051273

  19. Ellagic Acid: A Logical Lead for Drug Development?

    Science.gov (United States)

    Shakeri, Abolfazl; Zirak, Mohammad Reza; Sahebkar, Amirhossein

    2018-01-01

    Naturally occurring polyphenols are the subject of increasing attention due to their potent antioxidant activity and their marked effects on the prevention of various oxidative stress-associated diseases such as cancer. Ellagic acid (EA) is an herbal polyphenol that is structurally a condensed dimer of gallic acid. This review aims to provide a comprehensive and updated overview on the biological activities of EA and potential therapeutic applications. EA is found in fruits and nuts, either in the combined form with hexahydroxydiphenic acid or in the bound form (ellagitannins). EA exhibits many biological properties such as antioxidant, anti-diabetic, anticancer and apoptosis-inducing activities. These biological and pharmacological properties are relevant to the treatment of several human diseases. Owing to its multiple mechanisms of action, EA represents a potential therapeutic agent against human diseases particularly cancer. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  20. Efficacy of Lactic Acid, Lactic Acid-Acetic Acid Blends, and Peracetic Acid To Reduce Salmonella on Chicken Parts under Simulated Commercial Processing Conditions.

    Science.gov (United States)

    Ramirex-Hernandez, Alejandra; Brashears, Mindy M; Sanchez-Plata, Marcos X

    2018-01-01

    The poultry processing industry has been undergoing a series of changes as it modifies processing practices to comply with new performance standards for chicken parts and comminuted poultry products. The regulatory approach encourages the use of intervention strategies to prevent and control foodborne pathogens in poultry products and thus improve food safety and protect human health. The present studies were conducted to evaluate the efficacy of antimicrobial interventions for reducing Salmonella on inoculated chicken parts under simulated commercial processing conditions. Chicken pieces were inoculated by immersion in a five-strain Salmonella cocktail at 6 log CFU/mL and then treated with organic acids and oxidizing agents on a commercial rinsing conveyor belt. The efficacy of spraying with six different treatments (sterile water, lactic acid, acetic acid, buffered lactic acid, acetic acid in combination with lactic acid, and peracetic acid) at two concentrations was evaluated on skin-on and skin-off chicken thighs at three application temperatures. Skinless chicken breasts were used to evaluate the antimicrobial efficacy of lactic acid and peracetic acid. The color stability of treated and untreated chicken parts was assessed after the acid interventions. The lactic acid and buffered lactic acid treatments produced the greatest reductions in Salmonella counts. Significant differences between the control and water treatments were identified for 5.11% lactic acid and 5.85% buffered lactic acid in both skin-on and skin-off chicken thighs. No significant effect of treatment temperature for skin-on chicken thighs was found. Lactic acid and peracetic acid were effective agents for eluting Salmonella cells attached to chicken breasts.

  1. Treatment of painful diabetic neuropathy

    Science.gov (United States)

    Petropoulos, Ioannis N.; Alam, Uazman; Malik, Rayaz A.

    2015-01-01

    Painful diabetic neuropathy (PDN) is a debilitating consequence of diabetes that may be present in as many as one in five patients with diabetes. The objective assessment of PDN is difficult, making it challenging to diagnose and assess in both clinical practice and clinical trials. No single treatment exists to prevent or reverse neuropathic changes or to provide total pain relief. Treatment of PDN is based on three major approaches: intensive glycaemic control and risk factor management, treatments based on pathogenetic mechanisms, and symptomatic pain management. Clinical guidelines recommend pain relief in PDN through the use of antidepressants such as amitriptyline and duloxetine, the γ-aminobutyric acid analogues gabapentin and pregabalin, opioids and topical agents such as capsaicin. Of these medications, duloxetine and pregabalin were approved by the US Food and Drug Administration (FDA) in 2004 and tapentadol extended release was approved in 2012 for the treatment of PDN. Proposed pathogenetic treatments include α-lipoic acid (stems reactive oxygen species formation), benfotiamine (prevents vascular damage in diabetes) and aldose-reductase inhibitors (reduces flux through the polyol pathway). There is a growing need for studies to evaluate the most potent drugs or combinations for the management of PDN to maximize pain relief and improve quality of life. A number of agents are potential candidates for future use in PDN therapy, including Nav 1.7 antagonists, N-type calcium channel blockers, NGF antibodies and angiotensin II type 2 receptor antagonists. PMID:25553239

  2. Teratology: from science to birth defects prevention.

    Science.gov (United States)

    Rasmussen, Sonja A; Erickson, J David; Reef, Susan E; Ross, Danielle S

    2009-01-01

    One of the goals of birth defects research is to better understand risk or preventive factors for birth defects so that strategies for prevention can be developed. In this article, we have selected four areas of birth defects research that have led to the development of prevention strategies. These areas include rubella virus as a cause of congenital rubella syndrome, folic acid as a preventive factor for neural tube defects, cytomegalovirus infection as a cause of birth defects and developmental disabilities, and alcohol as a cause of fetal alcohol spectrum disorders. For each of these areas, we review key clinical and research findings that led to the identification of the risk or preventive factor, milestones in the development of prevention strategies, and the progress made thus far toward prevention.

  3. Reprint of: Marine OMEGA-3 fatty acids in the prevention of cardiovascular disease.

    Science.gov (United States)

    Mori, Trevor A

    2018-04-12

    Omega-6 (ω6) and omega-3 (ω3) fatty acids are two classes of dietary polyunsaturated fatty acids derived from linoleic acid (18:2ω6) and α-linolenic acid (18:3ω3), respectively. Enzymatic metabolism of linoleic and α-linolenic acids generates arachidonic acid (20:4ω6) and eicosapentaenoic acid (20:5ω3; EPA), respectively, both of which are substrates for enzymes that yield eicosanoids with multiple and varying physiological functions. Further elongation and desaturation of EPA yields the 22-carbon fatty acid docosahexaenoic acid (22:6ω3; DHA). The main dietary source of EPA and DHA for human consumption is fish, especially oily fish. There is considerable evidence that EPA and DHA are protective against cardiovascular disease (heart disease and stroke), particularly in individuals with pre-existing disease. ω3 Fatty acids benefit multiple risk factors including blood pressure, blood vessel function, heart function and blood lipids, and they have antithrombotic, anti-inflammatory and anti-oxidative actions. ω3 Fatty acids do not adversely interact with medications. Supplementation with ω3 fatty acids is recommended in individuals with elevated blood triglyceride levels and patients with coronary heart disease. A practical recommendation for the general population is to increase ω3 fatty acid intake by incorporating fish as part of a healthy diet that includes increased fruits and vegetables, and moderation of salt intake. Health authorities recommend the general population should consume at least two oily fish meals per week. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Incorporated fish oil fatty acids prevent action potential shortening induced by circulating fish oil fatty acids

    Directory of Open Access Journals (Sweden)

    Hester M Den Ruijter

    2010-11-01

    Full Text Available Increased consumption of fatty fish, rich in omega-3 polyunsaturated fatty acids (3-PUFAs reduces the severity and number of arrhythmias. Long term 3-PUFA-intake modulates the activity of several cardiac ion channels leading to cardiac action potential shortening. Circulating 3-PUFAs in the bloodstream and incorporated 3-PUFAs in the cardiac membrane have a different mechanism to shorten the action potential. It is, however, unknown whether circulating 3-PUFAs in the bloodstream enhance or diminish the effects of incorporated 3-PUFAs. In the present study, we address this issue. Rabbits were fed a diet rich in fish oil (3 or sunflower oil (9, as control for 3 weeks. Ventricular myocytes were isolated by enzymatic dissociation and action potentials were measured using the perforated patch clamp technique in the absence and presence of acutely administered 3-PUFAs. Plasma of 3 fed rabbits contained more free eicosapentaenoic acid (EPA and isolated myocytes of 3 fed rabbits contained higher amounts of both EPA and docosahexaenoic acid (DHA in their sarcolemma compared to control. In the absence of acutely administered fatty acids, 3 myocytes had a shorter action potential with a more negative plateau than 9 myocytes. In the 9 myocytes, but not in the 3 myocytes, acute administration of a mixture of EPA+DHA shortened the action potential significantly. From these data we conclude that incorporated 3-PUFAs into the sarcolemma and acutely administered 3 fatty acids do not have a cumulative effect on action potential duration and morphology. As a consequence, patients with a high cardiac 3-PUFA status will probably not benefit from short term 3 supplementation as an antiarrhythmic therapy.

  5. The rationale for preventing cancer cachexia: targeting excessive fatty acid oxidation.

    Science.gov (United States)

    Qian, Chao-Nan

    2016-07-21

    Cachexia commonly occurs at the terminal stage of cancer and has largely unclear molecular mechanisms. A recent study published in Nature Medicine, entitled "Excessive fatty acid oxidation induces muscle atrophy in cancer cachexia," reveals that cachectic cancer cells can secrete multiple cytokines that induce excessive fatty acid oxidation, which is responsible for muscle loss in cancer cachexia. Inhibition of fatty acid oxidation using etomoxir can increase muscle mass and body weight in cancer cachexia animal models. The usage of stable cachexia animal models is also discussed in this research highlight.

  6. Biofilm-forming bacteria with varying tolerance to peracetic acid from a paper machine.

    Science.gov (United States)

    Rasimus, Stiina; Kolari, Marko; Rita, Hannu; Hoornstra, Douwe; Salkinoja-Salonen, Mirja

    2011-09-01

    Biofilms cause runnability problems in paper machines and are therefore controlled with biocides. Peracetic acid is usually effective in preventing bulky biofilms. This study investigated the microbiological status of a paper machine where low concentrations (≤ 15 ppm active ingredient) of peracetic acid had been used for several years. The paper machine contained a low amount of biofilms. Biofilm-forming bacteria from this environment were isolated and characterized by 16S rRNA gene sequencing, whole-cell fatty acid analysis, biochemical tests, and DNA fingerprinting. Seventy-five percent of the isolates were identified as members of the subclades Sphingomonas trueperi and S. aquatilis, and the others as species of the genera Burkholderia (B. cepacia complex), Methylobacterium, and Rhizobium. Although the isolation media were suitable for the common paper machine biofoulers Deinococcus, Meiothermus, and Pseudoxanthomonas, none of these were found, indicating that peracetic acid had prevented their growth. Spontaneous, irreversible loss of the ability to form biofilm was observed during subculturing of certain isolates of the subclade S. trueperi. The Sphingomonas isolates formed monoculture biofilms that tolerated peracetic acid at concentrations (10 ppm active ingredient) used for antifouling in paper machines. High pH and low conductivity of the process waters favored the peracetic acid tolerance of Sphingomonas sp. biofilms. This appears to be the first report on sphingomonads as biofilm formers in warm water using industries.

  7. Structural, Chemical and Biological Aspects of Antioxidants for Strategies Against Metal and Metalloid Exposure

    Directory of Open Access Journals (Sweden)

    Swaran J. S. Flora

    2009-01-01

    Full Text Available Oxidative stress contributes to the pathophysiology of exposure to heavy metals/metalloid. Beneficial renal effects of some medications, such as chelation therapy depend at least partially on the ability to alleviate oxidative stress. The administration of various natural or synthetic antioxidants has been shown to be of benefit in the prevention and attenuation of metal induced biochemical alterations. These include vitamins, N-acetylcysteine, α-lipoic acid, melatonin, dietary flavonoids and many others. Human studies are limited in this regard. Under certain conditions, surprisingly, the antioxidant supplements may exhibit pro-oxidant properties and even worsen metal induced toxic damage. To date, the evidence is insufficient to recommend antioxidant supplements in subject with exposure to metals. Prospective, controlled clinical trials on safety and effectiveness of different therapeutic antioxidant strategies either individually or in combination with chelating agent are indispensable. The present review focuses on structural, chemical and biological aspects of antioxidants particularly related to their chelating properties.

  8. What California sea lions exposed to domoic acid might teach us about autism: lessons for predictive and preventive medicine.

    Science.gov (United States)

    Lahvis, Garet Paul

    2017-09-01

    Autism spectrum disorder (ASD) shares many biological and behavioral similarities with the deleterious effects of domoic acid (DA) exposure. DA is produced by marine algae and most commonly by species of Pseudo-nitzschia . Humans and marine mammals can be exposed to DA when they consume whole fish or shellfish. The mammalian fetus is highly sensitive to the deleterious effects of DA exposure. Both ASD and exposures to toxic levels of DA feature repetitive behaviors, challenges with social interaction, and seizures. They can also share a commonality in brain anatomy and function, particularly the balance between excitatory and inhibitory mechanisms. The current article is relevant to predictive, preventive, and personalized medicine for three reasons. First, shellfish consumption may be a risk factor for ASD and the regulatory limit for DA should be adjusted to prevent this possibility. Human contributions to increased algal production of DA in coastal waters should be identified and reduced. Second, evaluations of sentinel species wild and free-roaming in the environment, though typically outside the purview of biomedical research, should be much more fully employed to gain insights to risk factors for human disease. To better identify and prevent disease, biomedical researchers should study wild populations. Third, studies of DA exposure highlight the possibility that glutamate additives to processed foods may also have deleterious impacts on human brain development and behavior.

  9. Resveratrol Prevents Cellular and Behavioral Sensory Alterations in the Animal Model of Autism Induced by Valproic Acid

    Directory of Open Access Journals (Sweden)

    Mellanie Fontes-Dutra

    2018-05-01

    Full Text Available Autism spectrum disorder (ASD is characterized by impairments in both social communication and interaction and repetitive or stereotyped behaviors. Although its etiology remains unknown, genetic and environmental risk factors have been associated with this disorder, including the exposure to valproic acid (VPA during pregnancy. Resveratrol (RSV is an anti-inflammatory and antioxidant molecule known to prevent social impairments in the VPA animal model of autism. This study aimed to analyze the effects of prenatal exposure to VPA, as well as possible preventive effects of RSV, on sensory behavior, the localization of GABAergic parvalbumin (PV+ neurons in sensory brain regions and the expression of proteins of excitatory and inhibitory synapses. Pregnant rats were treated daily with RSV (3.6 mg/kg from E6.5 to E18.5 and injected with VPA (600 mg/kg in the E12.5. Male pups were analyzed in Nest Seeking (NS behavior and in whisker nuisance task (WNT. At P30, the tissues were removed and analyzed by immunofluorescence and western blotting. Our data showed for the first time an altered localization of PV+-neurons in primary sensory cortex and amygdala. We also showed a reduced level of gephyrin in the primary somatosensory area (PSSA of VPA animals. The treatment with RSV prevented all the aforementioned alterations triggered by VPA. Our data shed light on the relevance of sensory component in ASD and highlights the interplay between RSV and VPA animal model as an important tool to investigate the pathophysiology of ASD.

  10. Acidity-induced watercourse defects and their prevention on the River Sanginjoki; Happamuuden aiheuttamat vesistoehaitat ja niiden torjuntakeinot Sanginjoella

    Energy Technology Data Exchange (ETDEWEB)

    Tertsunen, J.; Martinmaeki, K.; Heikkinen, K. [and others

    2012-11-15

    As the first tributary of the River Oulujoki, the River Sanginjoki is one of the most important recreational areas in the Oulu region. It is also the closest potential reproduction area for salmon and trout using the Merikoski fishway. During flood peaks, occasional low pH values reduce the recreational and ecological value of the River Sanginjoki. The origin of low pH values was located as part of the 'City and Water - Improving the recreational value and ecological restoration of River Sanginjoki -project', during the years 2008-2011. This project involved largescale monitoring of the River Sanginjoki area for pH changes, while methods for preventing and reducing low pH values were tested. Based on the project's results, guidelines were drawn up for controlling problems associated with low pH values. The report also contains general information on the River Sanginjoki and its watershed, the river's ecological state and the development of its water quality. The results demonstrated a connection between low pH values and high discharges, but the lowest pH values were measured during summer and autumn rain floods in particular. A water sample analysis with other information showed that low pH values mainly originate in soil, land use and vegetation. The origin of acid runoff mainly lies in organic acids from peatlands and moss, but local factors such as acid sulphate soils and black shales may also contribute. Due to acidic peatlands, the water of the River Sanginjoki has naturally been slightly acidic, but ditch drainage of peat- and forestland has probably increased this effect. The effect of the restoration and water protection methods used in the project varied. Some methods proved effective and can be suggested for practical use at the Sanginjoki watershed, as well as other watersheds suffering from the same problems. Development of these methods should be continued, to improve their effectiveness and durability. Although defects due to

  11. Synthesis of biodiesel from waste vegetable oil with large amounts of free fatty acids using a carbon-based solid acid catalyst

    Energy Technology Data Exchange (ETDEWEB)

    Shu, Qing; Gao, Jixian; Nawaz, Zeeshan; Liao, Yuhui; Wang, Dezheng; Wang, Jinfu [Beijing Key Laboratory of Green Chemical Reaction Engineering and Technology, Department of Chemical Engineering, Tsinghua University, Beijing 100084 (China)

    2010-08-15

    A carbon-based solid acid catalyst was prepared by the sulfonation of carbonized vegetable oil asphalt. This catalyst was employed to simultaneously catalyze esterification and transesterification to synthesis biodiesel when a waste vegetable oil with large amounts of free fatty acids (FFAs) was used as feedstock. The physical and chemical properties of this catalyst were characterized by a variety of techniques. The maximum conversion of triglyceride and FFA reached 80.5 wt.% and 94.8 wt.% after 4.5 h at 220 C, when using a 16.8 M ratio of methanol to oil and 0.2 wt.% of catalyst to oil. The high catalytic activity and stability of this catalyst was related to its high acid site density (-OH, Broensted acid sites), hydrophobicity that prevented the hydration of -OH species, hydrophilic functional groups (-SO{sub 3}H) that gave improved accessibility of methanol to the triglyceride and FFAs, and large pores that provided more acid sites for the reactants. (author)

  12. Analysis of Steam Heating of a Two-Layer TBP/N-Paraffin/Nitric Acid Mixtures

    International Nuclear Information System (INIS)

    Laurinat, J.E.; Hassan, N.M.; Rudisill, T.S.; Askew, N.M.

    1998-01-01

    This report presents an analysis of steam heating of a two-layer tri-n-butyl phosphate (TBP)/n-paraffin-nitric acid mixture.The purpose of this study is to determine if the degree of mixing provided by the steam jet or by bubbles generated by the TBP/nitric acid reaction is sufficient to prevent a runaway reaction

  13. Is there A Role for Alpha-Linolenic Acid in the Fetal Programming of Health?

    Directory of Open Access Journals (Sweden)

    Alicia I. Leikin-Frenkel

    2016-03-01

    Full Text Available The role of ω3 alpha linolenic acid (ALA in the maternal diet during pregnancy and lactation, and its effect on the prevention of disease and programming of health in offspring, is largely unknown. Compared to ALA, ω3 docosahexaenoic (DHA and eicosapentaenoic (EPA acids have been more widely researched due to their direct implication in fetal neural development. In this literature search we found that ALA, the essential ω3 fatty acid and metabolic precursor of DHA and EPA has been, paradoxically, almost unexplored. In light of new and evolving findings, this review proposes that ALA may have an intrinsic role, beyond the role as metabolic parent of DHA and EPA, during fetal development as a regulator of gene programming for the prevention of metabolic disease and promotion of health in offspring.

  14. Dietary long chain n-3 polyunsaturated fatty acids prevent impaired social behaviour and normalize brain dopamine levels in food allergic mice.

    Science.gov (United States)

    de Theije, Caroline G M; van den Elsen, Lieke W J; Willemsen, Linette E M; Milosevic, Vanja; Korte-Bouws, Gerdien A H; Lopes da Silva, Sofia; Broersen, Laus M; Korte, S Mechiel; Olivier, Berend; Garssen, Johan; Kraneveld, Aletta D

    2015-03-01

    Allergy is suggested to exacerbate impaired behaviour in children with neurodevelopmental disorders. We have previously shown that food allergy impaired social behaviour in mice. Dietary fatty acid composition may affect both the immune and nervous system. The aim of this study was to assess the effect of n-3 long chain polyunsaturated fatty acids (n-3 LCPUFA) on food allergy-induced impaired social behaviour and associated deficits in prefrontal dopamine (DA) in mice. Mice were fed either control or n-3 LCPUFA-enriched diet before and during sensitization with whey. Social behaviour, acute allergic skin response and serum immunoglobulins were assessed. Monoamine levels were measured in brain and intestine and fatty acid content in brain. N-3 LCPUFA prevented impaired social behaviour of allergic mice. Moreover, n-3 LCPUFA supplementation increased docosahexaenoic acid (DHA) incorporation into the brain and restored reduced levels of prefrontal DA and its metabolites 3,4-dihydroxyphenylacetic acid, 3-methoxytyramine and homovanillic acid in allergic mice. In addition to these brain effects, n-3 LCPUFA supplementation reduced the allergic skin response and restored decreased intestinal levels of serotonin metabolite 5-hydroxyindoleacetic acid in allergic mice. N-3 LCPUFA may have beneficial effects on food allergy-induced deficits in social behaviour, either indirectly by reducing the allergic response and restoring intestinal 5-HT signalling, or directly by DHA incorporation into neuronal membranes, affecting the DA system. Therefore, it is of interest to further investigate the relevance of food allergy-enhanced impairments in social behaviour in humans and the potential benefits of dietary n-3 LCPUFA supplementation. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Role of chemical carcinogens in epithelial and mesenchymal neoplasms with tumor initiation-promotion protocol and the effect of 13-cis retinoic acid in chemo prevention

    International Nuclear Information System (INIS)

    Bukhari, S.M.H.; Shahzad, S.Q.; Naeem, S.; Qureshi, G.R.; Naveed, I.A.

    2002-01-01

    Objective: To study the effects of chemical carcinogens on epithelial and mesenchymal tumorigenesis with tumor initiation-promotion protocol and the use of 13-cis retinoic acid as a chemo preventive agent. Design: It was an experimental study. Place and Duration of Study: The study was conducted at Postgraduate Medical Institute (PGML) Lahore for 20 weeks. Materials and Methods: Sixty albino rats were divided into six groups of ten of animals each. First group of animals (control) was not given carcinogens and 13-cis retinoic acid in second group DMBA was applied on the dorsal skin in repeated dos of 100 mu g/ml in acetone, twice a weak. In the third group DMBA was given 100 mu g/ml as single dose while TPA was given 10 mu g//ml in acetone, twice a weak after two weeks of DMBA applications. In fourth group only DMBA 100 mu g/ml in acetone was applied as a single dose. In fifth and sixth groups 13-cis retinoic acid was given topically before and after the application of DMBA and TPA. Results: First and fourth groups did not develop any tumor. In second groups 2 animals developed malignant fibrous histiocytoma, 4 squamous cell carcinoma while 1 dysphasia and 1 carcinoma in situ. Third group developed osteoma (3 animals), papilloma (3 animals, squamous cell carcinoma (01) and dysplasia (01). Conclusion: Our results showed that DMBA acts as tumor initiator while TPA as promoter. DMBA also produces tumors itself when given alone in repeated doses. The chemical carcinogens are not only a cause of epithelial carcinogenesis but also responsible for mesenchymal tumorigenesis. 13 cis retinoic acid was equally effective in both stages of tumorigenesis. It also prevents malignant conversion of chemically induced benign tumors. (author)

  16. Personnel decontamination and preventive skin care

    International Nuclear Information System (INIS)

    Henning, Klaus; Gojowczyk, Peter

    2010-01-01

    Skin contamination arises from contact with contaminated aqueous solutions and from transmission of radioactively contaminated dirt particles. As long as the surface of the skin is neither inflamed nor showing any lesions, normally only a limited part of the top layer (epidermis), i.e. the upper layers of the stratum corneum, is contaminated. The intact horny layer has a barrier function protecting against the penetration of chemicals and dirt particles. The horny layer can be damaged by water, solvents, alkaline substances, and acids. In general, it is safe to say that the horny layer acts as a natural barrier to the penetration of liquid and particulate impurities into lower layers of the skin. As long as the horny layer is intact and free from lesions, the risk of incorporation can be considered low. When decontaminating and cleansing the skin, also in daily skin cleansing, care must be taken to prevent the acid protective layer and the horny layer from being compromised. Daily cleansing and cleansing for decontamination must be carried out with a mild, weakly acidic detergent. In addition, prevention should be achieved daily by applying a non-greasy skin lotion to protect the skin. Following a systematic regular regimen in skin cleansing and preventive skin care as well as a specific approach in skin decontamination and cleansing will avoid damage to the skin and remove any contamination incurred. This approach comprises a three-pronged concept, namely skin protection, cleansing and care. (orig.)

  17. Ferulic acid promotes survival and differentiation of neural stem cells to prevent gentamicin-induced neuronal hearing loss.

    Science.gov (United States)

    Gu, Lintao; Cui, Xinhua; Wei, Wei; Yang, Jia; Li, Xuezhong

    2017-11-15

    Neural stem cells (NSCs) have exhibited promising potential in therapies against neuronal hearing loss. Ferulic acid (FA) has been widely reported to enhance neurogenic differentiation of different stem cells. We investigated the role of FA in promoting NSC transplant therapy to prevent gentamicin-induced neuronal hearing loss. NSCs were isolated from mouse cochlear tissues to establish in vitro culture, which were then treated with FA. The survival and differentiation of NSCs were evaluated. Subsequently, neurite outgrowth and excitability of the in vitro neuronal network were assessed. Gentamicin was used to induce neuronal hearing loss in mice, in the presence and absence of FA, followed by assessments of auditory brainstem response (ABR) and distortion product optoacoustic emissions (DPOAE) amplitude. FA promoted survival, neurosphere formation and differentiation of NSCs, as well as neurite outgrowth and excitability of in vitro neuronal network. Furthermore, FA restored ABR threshold shifts and DPOAE in gentamicin-induced neuronal hearing loss mouse model in vivo. Our data, for the first time, support potential therapeutic efficacy of FA in promoting survival and differentiation of NSCs to prevent gentamicin-induced neuronal hearing loss. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Long-Chain Omega-3 Fatty Acids Supplementation Accelerates Nerve Regeneration and Prevents Neuropathic Pain Behavior in Mice

    Directory of Open Access Journals (Sweden)

    Rafaela V. Silva

    2017-10-01

    Full Text Available Fish oil (FO is the main source of long chain omega-3 polyunsaturated fatty acids (ω-3 PUFAs, which display relevant analgesic and anti-inflammatory properties. Peripheral nerve injury is driven by degeneration, neuroinflammation, and neuronal plasticity which results in neuropathic pain (NP symptoms such as allodynia and hyperalgesia. We tested the preventive effect of an EPA/DHA-concentrate fish oil (CFO on NP development and regenerative features. Swiss mice received daily oral treatment with CFO 4.6 or 2.3 g/kg for 10 days after NP was induced by partial sciatic nerve ligation. Mechanical allodynia and thermal hypernociception were assessed 5 days after injury. CFO 2.3 g/kg significantly prevented mechanical and thermal sensitization, reduced TNF levels in the spinal cord, sciatic MPO activity, and ATF-3 expression on DRG cells. CFO improved Sciatic Functional Index (SFI as well as electrophysiological recordings, corroborating the increased GAP43 expression and total number of myelinated fibers observed in sciatic nerve. No locomotor activity impairment was observed in CFO treated groups. These results point to the regenerative and possibly protective properties of a combined EPA and DHA oral administration after peripheral nerve injury, as well as its anti-neuroinflammatory activity, evidencing ω-3 PUFAs promising therapeutic outcomes for NP treatment.

  19. Hyaluronic acid and oxidized regenerated cellulose prevent adhesion reformation after adhesiolysis in rat models

    Science.gov (United States)

    Zhang, Yan; Liu, Qin; Yang, Ning; Zhang, Xuegang

    2016-01-01

    Postsurgical adhesion formation is the most common complication in abdominal and pelvic surgery. Adhesiolysis is the most commonly applied treatment for adhesion formation but is often followed by adhesion reformation. Therefore, an efficient strategy should be adopted to solve these problems. This study aimed to explore whether hyaluronic acid and oxidized regenerated cellulose (ORC) could prevent adhesion formation and reformation. Thirty female Sprague Dawley rats were randomly divided into three groups (n=10 each) and subjected to different treatments during the first and second surgery. The control group was treated with isotonic sodium chloride, the ORC group was treated with ORC (1.5×1 cm), and the medical sodium hyaluronate (MSH) group was treated with 1% MSH (0.5 mL). At 2 weeks after the first surgery, adhesion scores in the MSH group (1.90±0.99) and the ORC group (1.40±0.97) were significantly lower than those in the control group (3.00±0.82) (P=0.005). Similarly, 2 weeks after the second surgery, adhesion scores in the MSH group (2.00±0.82) and the ORC group (1.50±1.27) were significantly lower than those in the control group (3.50±0.53) (P=0.001). In addition, body weights in the MSH group and the ORC group did not change significantly, whereas the control group showed a consistent decrease in body weight during the experiment. Histological examination revealed that inflammatory infiltration was involved in both adhesion formation and reformation. In conclusion, hyaluronic acid and ORC were both efficient in reducing adhesion formation and reformation in the rat model. PMID:27822014

  20. An engineered fatty acid synthase combined with a carboxylic acid reductase enables de novo production of 1-octanol in Saccharomyces cerevisiae.

    Science.gov (United States)

    Henritzi, Sandra; Fischer, Manuel; Grininger, Martin; Oreb, Mislav; Boles, Eckhard

    2018-01-01

    The ideal biofuel should not only be a regenerative fuel from renewable feedstocks, but should also be compatible with the existing fuel distribution infrastructure and with normal car engines. As the so-called drop-in biofuel, the fatty alcohol 1-octanol has been described as a valuable substitute for diesel and jet fuels and has already been produced fermentatively from sugars in small amounts with engineered bacteria via reduction of thioesterase-mediated premature release of octanoic acid from fatty acid synthase or via a reversal of the β-oxidation pathway. The previously engineered short-chain acyl-CoA producing yeast Fas1 R1834K /Fas2 fatty acid synthase variant was expressed together with carboxylic acid reductase from Mycobacterium marinum and phosphopantetheinyl transferase Sfp from Bacillus subtilis in a Saccharomyces cerevisiae Δfas1 Δfas2 Δfaa2 mutant strain. With the involvement of endogenous thioesterases, alcohol dehydrogenases, and aldehyde reductases, the synthesized octanoyl-CoA was converted to 1-octanol up to a titer of 26.0 mg L -1 in a 72-h fermentation. The additional accumulation of 90 mg L -1 octanoic acid in the medium indicated a bottleneck in 1-octanol production. When octanoic acid was supplied externally to the yeast cells, it could be efficiently converted to 1-octanol indicating that re-uptake of octanoic acid across the plasma membrane is not limiting. Additional overexpression of aldehyde reductase Ahr from Escherichia coli nearly completely prevented accumulation of octanoic acid and increased 1-octanol titers up to 49.5 mg L -1 . However, in growth tests concentrations even lower than 50.0 mg L -1 turned out to be inhibitory to yeast growth. In situ extraction in a two-phase fermentation with dodecane as second phase did not improve growth, indicating that 1-octanol acts inhibitive before secretion. Furthermore, 1-octanol production was even reduced, which results from extraction of the intermediate octanoic acid to

  1. Treatment and prevention systems for acid mine drainage and halogenated contaminants

    Science.gov (United States)

    Jin, Song [Fort Collins, CO; Fallgren, Paul H [Laramie, WY; Morris, Jeffrey M [Laramie, WY

    2012-01-31

    Embodiments include treatments for acid mine drainage generation sources (10 perhaps by injection of at least one substrate (11) and biologically constructing a protective biofilm (13) on acid mine drainage generation source materials (14). Further embodiments include treatments for degradation of contaminated water environments (17) with substrates such as returned milk and the like.

  2. Iso-α-acids, bitter components of beer, prevent obesity-induced cognitive decline.

    Science.gov (United States)

    Ayabe, Tatsuhiro; Ohya, Rena; Kondo, Keiji; Ano, Yasuhisa

    2018-03-19

    Dementia and cognitive decline have become worldwide public health problems, and it was recently reported that life-style related diseases and obesity are key risk factors in dementia. Iso-α-acids, hop-derived bitter components of beer, have been reported to have various physiological functions via activation of peroxisome proliferator-activated receptor γ. In this report, we demonstrated that daily intake of iso-α-acids suppresses inflammations in the hippocampus and improves cognitive decline induced by high fat diet (HFD). Body weight, epididymal fat weight, and plasma triglyceride levels were increased in HFD-fed mice, and significantly decreased in iso-α-acids supplemented HFD-fed mice. HFD feeding enhances the production of inflammatory cytokines and chemokines, such as TNF-α, which was significantly suppressed by iso-α-acids administration. HFD-induced neuroinflammation caused lipid peroxidation, neuronal loss, and atrophy in hippocampus, and those were not observed in iso-α-acids-treated mice. Furthermore, iso-α-acids intake significantly improved cognitive decline induced by HFD-feeding. Iso-α-acids are food derived components that suppressing both lipid accumulation and brain inflammation, thus iso-α-acids might be beneficial for the risk of dementia increased by obesity and lifestyle-related diseases.

  3. Surfactant-Enhanced Organic Acid Inactivation of Tulane Virus, a Human Norovirus Surrogate.

    Science.gov (United States)

    Lacombe, Alison; Niemira, Brendan A; Gurtler, Joshua B; Kingsley, David H; Li, Xinhui; Chen, Haiqiang

    2018-02-01

    Combination treatments of surfactants and phenolic or short-chain organic acids (SCOA) may act synergistically or additively as sanitizers to inactive foodborne viruses and prevent outbreaks. The purpose of this study was to investigate the effect of gallic acid (GA), tannic acid, p-coumaric acid, lactic acid (LA), or acetic acid (AA), in combination with sodium dodecyl sulfate (SDS), against Tulane virus (TV), a surrogate for human norovirus. An aqueous stock solution of phenolic acids or SCOA with or without SDS was prepared and diluted in a twofold dilution series to 2× the desired concentration with cell growth media (M119 plus 10% fetal bovine serum). The solution was inoculated with an equal proportion of 6 log PFU/mL TV with a treatment time of 5 min. The survival of TV was quantified using a plaque assay with LLC-MK2 cells. The minimum virucidal concentration was 0.5:0.7% (v/v) for LA-SDS at pH 3.5 (4.5-PFU/mL reduction) and 0.5:0.7% (v/v) AA-SDS at pH 4.0 (2.6-log PFU/mL reduction). GA and SDS demonstrated a minimum virucidal concentration of 12.5 mM GA-SDS at pH 7.0 (0.2:0.3% GA-SDS) with an 0.8-log PFU/mL reduction and 50 mM GA-SDS (0.8:1.4% GA-SDS at pH 7.0) increased log reduction to 1.6 log PFU/mL. The combination treatments of AA or LA with SDS at pH 7.0 did not produce significant log reduction, nor did individual treatments of tannic acid, GA, p-coumaric acid, AA, LA, or SDS. This study demonstrates that a surfactant, such as SDS, aids in the phenolic acid and SCOA toxicities against viruses. However, inactivation of TV by combination treatments is contingent upon the pH of the sanitizing solution being lower than the pK a value of the organic acid being used. This information can be used to develop sanitizing washes to disinfect food contact surfaces, thereby aiding in the prevention of foodborne outbreaks.

  4. Role of nutrients in metabolic syndrome: a 2017 update

    Directory of Open Access Journals (Sweden)

    Kern HJ

    2018-02-01

    Full Text Available Hua J Kern, Susan Hazels Mitmesser The Nature’s Bounty Co., Ronkonkoma, NY, USA Abstract: Metabolic syndrome (MetS and its associated chronic disorders including cardiovascular disease and type 2 diabetes are public health concerns in the USA and worldwide. “Good health is an investment in economic growth,” and nutrition is one of the recommended preventive measures to manage these chronic diseases. However, it is unclear whether and to what extent nutrients could be beneficial to the improvement of MetS. To help answer this question, we performed a literature review of the emerging human data on single nutrients and MetS: PubMed was searched from January 1, 2005 to June 12, 2017, using a combination of the following keywords: “nutrient” OR “vitamin” OR “mineral” OR “nutraceutical” AND “metabolic syndrome.” The summary of literature comprises macronutrients (proteins/amino acids, fatty acids, fibers, and sugar, micronutrients (antioxidant vitamins, vitamin D, folate, magnesium, and chromium, polyphenols (flavonoids, resveratrol, isoflavones, and chlorogenic acid, and other compounds (α-lipoic acid, benfotiamine, fucoxanthin, policosanol, and stanols. Bearing a holistic approach in mind, we also highlighted select lifestyle factors that may contribute to MetS (such as circadian rhythm and nutrition in early life. Observational studies have generated positive evidence supporting the beneficial role of numerous nutrients in MetS. Although the results of some clinical trials are consistent with the observational data, causality is not always clear or consistent across trials. Both nutrition and health are complex and dynamic systems with a hierarchical nature. When we design confirmatory trials to investigate nutrient(s and MetS, instead of the traditional “single-nutrient” concept, it is worth considering a holistic approach to integrate groups or classes of nutrients, lifestyle influencers (ie, diet and physical

  5. Treatment with Docosahexaenoic Acid, but Not Eicosapentaenoic Acid, Delays Ca2+-Induced Mitochondria Permeability Transition in Normal and Hypertrophied Myocardium

    OpenAIRE

    Khairallah, Ramzi J.; O'Shea, Karen M.; Brown, Bethany H.; Khanna, Nishanth; Des Rosiers, Christine; Stanley, William C.

    2010-01-01

    Intake of fish oil containing docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) prevents heart failure; however, the mechanisms are unclear. Mitochondrial permeability transition pore (MPTP) opening contributes to myocardial pathology in cardiac hypertrophy and heart failure, and treatment with DHA + EPA delays MPTP opening. Here, we assessed: 1) whether supplementation with both DHA and EPA is needed for optimal prevention of MPTP opening, and 2) whether this benefit occurs in hyper...

  6. Temporal and spatial variation in the status of acid rivers and potential prevention methods of AS soil-related leaching in peatland forestry

    Energy Technology Data Exchange (ETDEWEB)

    Saarinen, T.

    2013-06-01

    maintenance drainage in peatland forestry on runoff water quality showed a clear risk of oxidation of sulphidic materials during dry summers. This can be prevented mainly by avoiding too deep drainage. Knowledge of the hydrochemical impacts of acidic load derived from AS soils and drained peatlands is necessary for land use planning and sustainable water management of river basins affected by these soils. (orig.)

  7. Use of a lactic acid plus lactoserum intimate liquid soap for external hygiene in the prevention of bacterial vaginosis recurrence after metronidazole oral treatment.

    Science.gov (United States)

    Bahamondes, M Valeria; Portugal, Priscila Mendes; Brolazo, Eliane Melo; Simões, José Antônio; Bahamondes, Luis

    2011-01-01

    To determine the recurrence of bacterial vaginosis (BV) after the use of a lactic acid plus lactoserum liquid soap starting immediately after the treatment with oral metronidazole and the quality of life of the participants. A total of 123 women with diagnosis of BV with at least three of the following criteria: 1) homogeneous vaginal discharge without inflammation of the vagina or vulva; 2) vaginal pH ≥ 4.5; 3) positive Whiff test; and 4) "clue cells" in more than 20% of the epithelial cells in the vagina. A Nugent score ≥ 4 in the vaginal bacterioscopy was also used. After BV diagnosis, metronidazole 500 mg was administered orally bid during 7 days. Patients cured of BV were then instructed to use 7.5 to 10 mL of a lactic acid plus lactoserum liquid soap once-a-day for hygiene of the external genital region. Three subsequent control visits after starting the hygiene treatment (30, 60, and 90 days; ± 5 days) were scheduled. A questionnaire was applied in the form of visual analogue scale (VAS) in all the visits regarding: 1) level of comfort at the genital region; 2) malodorous external genitalia; 3) comfort in sexual intercourse; 4) satisfaction with intimate hygiene; and 5) self-esteem. Ninety two (74.8%) women initiated the use of a lactic acid plus lactoserum liquid soap at visit 1. At visit 2, 3, and 4 there were 84, 62 and 42 women available for evaluation, respectively. The rate of recurrence of BV was 19.0%, 24.2% and 7.1%, respectively in the three visits and vaginal candidiasis was observed in five treated women. Quality of life was evaluated in the 42 women who completed the four visits schedule and there were significant improvement in the five domains assessed. A lactic acid plus lactoserum liquid soap for external intimate hygiene may be an option for the prevention of BV recurrence after treatment and cure with oral metronidazole.

  8. Pork as a Source of Omega-3 (n-3) Fatty Acids.

    Science.gov (United States)

    Dugan, Michael E R; Vahmani, Payam; Turner, Tyler D; Mapiye, Cletos; Juárez, Manuel; Prieto, Nuria; Beaulieu, Angela D; Zijlstra, Ruurd T; Patience, John F; Aalhus, Jennifer L

    2015-12-16

    Pork is the most widely eaten meat in the world, but typical feeding practices give it a high omega-6 (n-6) to omega-3 (n-3) fatty acid ratio and make it a poor source of n-3 fatty acids. Feeding pigs n-3 fatty acids can increase their contents in pork, and in countries where label claims are permitted, claims can be met with limited feeding of n-3 fatty acid enrich feedstuffs, provided contributions of both fat and muscle are included in pork servings. Pork enriched with n-3 fatty acids is, however, not widely available. Producing and marketing n-3 fatty acid enriched pork requires regulatory approval, development costs, quality control costs, may increase production costs, and enriched pork has to be tracked to retail and sold for a premium. Mandatory labelling of the n-6/n-3 ratio and the n-3 fatty acid content of pork may help drive production of n-3 fatty acid enriched pork, and open the door to population-based disease prevention polices (i.e., food tax to provide incentives to improve production practices). A shift from the status-quo, however, will require stronger signals along the value chain indicating production of n-3 fatty acid enriched pork is an industry priority.

  9. Pork as a Source of Omega-3 (n-3) Fatty Acids

    Science.gov (United States)

    Dugan, Michael E.R.; Vahmani, Payam; Turner, Tyler D.; Mapiye, Cletos; Juárez, Manuel; Prieto, Nuria; Beaulieu, Angela D.; Zijlstra, Ruurd T.; Patience, John F.; Aalhus, Jennifer L.

    2015-01-01

    Pork is the most widely eaten meat in the world, but typical feeding practices give it a high omega-6 (n-6) to omega-3 (n-3) fatty acid ratio and make it a poor source of n-3 fatty acids. Feeding pigs n-3 fatty acids can increase their contents in pork, and in countries where label claims are permitted, claims can be met with limited feeding of n-3 fatty acid enrich feedstuffs, provided contributions of both fat and muscle are included in pork servings. Pork enriched with n-3 fatty acids is, however, not widely available. Producing and marketing n-3 fatty acid enriched pork requires regulatory approval, development costs, quality control costs, may increase production costs, and enriched pork has to be tracked to retail and sold for a premium. Mandatory labelling of the n-6/n-3 ratio and the n-3 fatty acid content of pork may help drive production of n-3 fatty acid enriched pork, and open the door to population-based disease prevention polices (i.e., food tax to provide incentives to improve production practices). A shift from the status-quo, however, will require stronger signals along the value chain indicating production of n-3 fatty acid enriched pork is an industry priority. PMID:26694475

  10. Pork as a Source of Omega-3 (n-3 Fatty Acids

    Directory of Open Access Journals (Sweden)

    Michael E.R. Dugan

    2015-12-01

    Full Text Available Pork is the most widely eaten meat in the world, but typical feeding practices give it a high omega-6 (n-6 to omega-3 (n-3 fatty acid ratio and make it a poor source of n-3 fatty acids. Feeding pigs n-3 fatty acids can increase their contents in pork, and in countries where label claims are permitted, claims can be met with limited feeding of n-3 fatty acid enrich feedstuffs, provided contributions of both fat and muscle are included in pork servings. Pork enriched with n-3 fatty acids is, however, not widely available. Producing and marketing n-3 fatty acid enriched pork requires regulatory approval, development costs, quality control costs, may increase production costs, and enriched pork has to be tracked to retail and sold for a premium. Mandatory labelling of the n-6/n-3 ratio and the n-3 fatty acid content of pork may help drive production of n-3 fatty acid enriched pork, and open the door to population-based disease prevention polices (i.e., food tax to provide incentives to improve production practices. A shift from the status-quo, however, will require stronger signals along the value chain indicating production of n-3 fatty acid enriched pork is an industry priority.

  11. Activity of caffeic acid in different fish lipid matrices: A review

    DEFF Research Database (Denmark)

    Medina, Isabel; Undeland, Ingrid; Larsson, Karin

    2012-01-01

    that the antioxidant activity depends on the physical state of the lipids and the composition of the intrinsic matrix in which they are situated. Caffeic acid significantly prevented rancidity in both unwashed and washed fish mince, the latter which was fortified with haemoglobin. In the unwashed mince, the activity......Caffeic acid, a hydroxycinnamic acid common in different vegetable sources, has been employed as a natural antioxidant for inhibiting oxidation of fish lipids present in different food matrices. The aim of this review is to discuss the mechanisms involved in the antioxidative and prooxidative...... effects of caffeic acid found in different model systems containing fish lipids. These model systems include bulk fish oils, liposomes from cod roe phospholipids, fish oil emulsions, washed cod mince, regular horse mackerel mince and a fish oil fortified fitness bar. The data reported show...

  12. 10-Oxo-trans-11-octadecenoic acid generated from linoleic acid by a gut lactic acid bacterium Lactobacillus plantarum is cytoprotective against oxidative stress

    Energy Technology Data Exchange (ETDEWEB)

    Furumoto, Hidehiro; Nanthirudjanar, Tharnath [Division of Applied Biosciences, Graduate School of Agriculture, Kyoto University, Kitashirakawa Oiwake-cho, Sakyo-ku, Kyoto 606-8502 (Japan); Kume, Toshiaki; Izumi, Yasuhiko [Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29, Simoadachi-cho, Sakyo-ku, Kyoto 606-8501 (Japan); Park, Si-Bum [Laboratory of Industrial Microbiology, Graduate School of Agriculture, Kyoto University, Kitashirakawa Oiwake-cho, Sakyo-ku, Kyoto 606-8502 (Japan); Kitamura, Nahoko; Kishino, Shigenobu; Ogawa, Jun [Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Kitashirakawa Oiwake-cho, Sakyo-ku, Kyoto 606-8502 (Japan); Hirata, Takashi [Division of Applied Biosciences, Graduate School of Agriculture, Kyoto University, Kitashirakawa Oiwake-cho, Sakyo-ku, Kyoto 606-8502 (Japan); Faculty of Rehabilitation, Shijonawategakuen University, 5-11-10, Hojo, Daitou-shi, Osaka 574-0011 (Japan); Sugawara, Tatsuya, E-mail: sugawara@kais.kyoto-u.ac.jp [Division of Applied Biosciences, Graduate School of Agriculture, Kyoto University, Kitashirakawa Oiwake-cho, Sakyo-ku, Kyoto 606-8502 (Japan)

    2016-04-01

    Oxidative stress is a well-known cause of multiple diseases. The nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway plays a central role in cellular antioxidative responses. In this study, we investigated the effects of novel fatty acid metabolite derivatives of linoleic acid generated by the gut lactic acid bacteria Lactobacillus plantarum on the Nrf2-ARE pathway. 10-Oxo-trans-11-octadecenoic acid (KetoC) protected HepG2 cells from cytotoxicity induced by hydrogen peroxide. KetoC also significantly increased cellular Nrf2 protein levels, ARE-dependent transcription, and the gene expression of antioxidative enzymes such as heme oxygenase-1 (HO-1), glutamate-cysteine ligase modifier subunit (GCLM), and NAD(P)H:quinone oxidoreductase 1 (NQO1) in HepG2 cells. Additionally, a single oral dose administration of KetoC also increased antioxidative gene expression and protein levels of Nrf2 and HO-1 in mouse organs. Since other fatty acid metabolites and linoleic acid did not affect cellular antioxidative responses, the cytoprotective effect of KetoC may be because of its α,β-unsaturated carbonyl moiety. Collectively, our data suggested that KetoC activated the Nrf2-ARE pathway to enhance cellular antioxidative responses in vitro and in vivo, which further suggests that KetoC may prevent multiple diseases induced by oxidative stress. - Highlights: • We evaluated the effect of modified fatty acids generated by Lactobacillus plantarum. • 10-Oxo-trans-11-ocatadecenoic acid (KetoC) protected cells from oxidative stress. • KetoC activated the Nrf2-ARE pathway to promote antioxidative gene expression. • KetoC promoted the expression of antioxidative enzymes in mice organs. • The cytoprotective effect of KetoC was because of α,β-unsaturated carbonyl moiety.

  13. 10-Oxo-trans-11-octadecenoic acid generated from linoleic acid by a gut lactic acid bacterium Lactobacillus plantarum is cytoprotective against oxidative stress

    International Nuclear Information System (INIS)

    Furumoto, Hidehiro; Nanthirudjanar, Tharnath; Kume, Toshiaki; Izumi, Yasuhiko; Park, Si-Bum; Kitamura, Nahoko; Kishino, Shigenobu; Ogawa, Jun; Hirata, Takashi; Sugawara, Tatsuya

    2016-01-01

    Oxidative stress is a well-known cause of multiple diseases. The nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway plays a central role in cellular antioxidative responses. In this study, we investigated the effects of novel fatty acid metabolite derivatives of linoleic acid generated by the gut lactic acid bacteria Lactobacillus plantarum on the Nrf2-ARE pathway. 10-Oxo-trans-11-octadecenoic acid (KetoC) protected HepG2 cells from cytotoxicity induced by hydrogen peroxide. KetoC also significantly increased cellular Nrf2 protein levels, ARE-dependent transcription, and the gene expression of antioxidative enzymes such as heme oxygenase-1 (HO-1), glutamate-cysteine ligase modifier subunit (GCLM), and NAD(P)H:quinone oxidoreductase 1 (NQO1) in HepG2 cells. Additionally, a single oral dose administration of KetoC also increased antioxidative gene expression and protein levels of Nrf2 and HO-1 in mouse organs. Since other fatty acid metabolites and linoleic acid did not affect cellular antioxidative responses, the cytoprotective effect of KetoC may be because of its α,β-unsaturated carbonyl moiety. Collectively, our data suggested that KetoC activated the Nrf2-ARE pathway to enhance cellular antioxidative responses in vitro and in vivo, which further suggests that KetoC may prevent multiple diseases induced by oxidative stress. - Highlights: • We evaluated the effect of modified fatty acids generated by Lactobacillus plantarum. • 10-Oxo-trans-11-ocatadecenoic acid (KetoC) protected cells from oxidative stress. • KetoC activated the Nrf2-ARE pathway to promote antioxidative gene expression. • KetoC promoted the expression of antioxidative enzymes in mice organs. • The cytoprotective effect of KetoC was because of α,β-unsaturated carbonyl moiety.

  14. Bolivian health providers' attitudes toward alternative technologies for cervical cancer prevention: a focus on visual inspection with acetic acid and cryotherapy.

    Science.gov (United States)

    Stormo, Analía Romina; Altamirano, Victor Conde; Pérez-Castells, Macarena; Espey, David; Padilla, Haydee; Panameño, Karen; Soria, Milton; Santos, Carlos; Saraiya, Mona; Luciani, Silvana

    2012-08-01

    Little is known about health providers' attitudes toward visual inspection with acetic acid (VIA) and cryotherapy in the prevention of cervical cancer, as most research in Latin America and the Caribbean (LAC) has examined attitudes of the general population. This study describes attitudes of Bolivian health professionals toward new technologies for cervical cancer prevention, focusing on VIA and cryotherapy. Between February 2011 and March 2012, we surveyed 7 nurses and 35 physicians who participated in 5-day workshops on VIA and cryotherapy conducted in Bolivia. Multiple choice and open-ended questions were used to assess participants' acceptability of these procedures and the feasibility of their implementation in the context of perceived barriers for the early detection of cervical cancer in this country. Most believed that cultural factors represent the main barrier for the early detection of cervical cancer (70%), although all stated that VIA and cryotherapy would be accepted by women, citing the advantages of VIA over cytology for this belief. Most also believed their colleagues would accept VIA and cryotherapy (71%) and that VIA should replace Pap testing (61%), reiterating the advantages of VIA for these beliefs. Those who believed the contrary expressed a general resistance to change associated with an already existing cytology program and national norms prioritizing Pap testing. Most participants had favorable attitudes toward VIA and cryotherapy; however, a sizable minority cited challenges to their adoption by colleagues and believed VIA should not replace cytology. This report can inform the development of strategies to expand the use of alternative cervical cancer screening methods in LAC and Bolivia.

  15. Amoxicillin and Clavulanic Acid

    Science.gov (United States)

    ... in a class of medications called penicillin-like antibiotics. It works by stopping the growth of bacteria. Clavulanic acid ... It works by preventing bacteria from destroying amoxicillin. Antibiotics will not work for colds, flu, or other viral infections.

  16. Curative role of lactulose, L-carnitine, alpha-lipoic acid and ...

    African Journals Online (AJOL)

    Treatment with antioxidants for 3 months significantly (p < 0.05) decreased Malondialdehyde (MDA) and nitric oxide (NO) while antioxidant enzyme activities of glutathione peroxidase (GPX) and superoxide dismutase (SOD) were significantly increased (p < 0.05) in liver and brain tissues. The expressions of serum tumor ...

  17. Supplementation of pyruvate prevents palmitate-induced impairment of glucose uptake in C2 myotubes.

    Science.gov (United States)

    Jung, Jong Gab; Choi, Sung-E; Hwang, Yoon-Jung; Lee, Sang-A; Kim, Eun Kyoung; Lee, Min-Seok; Han, Seung Jin; Kim, Hae Jin; Kim, Dae Jung; Kang, Yup; Lee, Kwan-Woo

    2011-10-15

    Elevated fatty acid levels have been thought to contribute to insulin resistance. Repression of the glucose transporter 4 (GLUT4) gene as well as impaired GLUT4 translocation may be a mediator for fatty acid-induced insulin resistance. This study was initiated to determine whether palmitate treatment repressed GLUT4 expression, whether glucose/fatty acid metabolism influenced palmitate-induced GLUT4 gene repression (PIGR), and whether attempts to prevent PIGR restored palmitate-induced impairment of glucose uptake (PIIGU) in C2 myotubes. Not only stimulators of fatty acid oxidation, such as bezafibrate, AICAR, and TOFA, but also TCA cycle substrates, such as pyruvate, leucine/glutamine, and α-ketoisocaproate/monomethyl succinate, significantly prevented PIGR. In particular, supplementing with pyruvate through methyl pyruvate resulted in nearly complete prevention of PIIGU, whereas palmitate treatment reduced the intracellular pyruvate level. These results suggest that pyruvate depletion plays a critical role in PIGR and PIIGU; thus, pyruvate supplementation may help prevent obesity-induced insulin resistance in muscle cells. Crown Copyright © 2011. Published by Elsevier Ireland Ltd. All rights reserved.

  18. Is 5-methyltetrahydrofolate an alternative to folic acid for the prevention of neural tube defects?

    Science.gov (United States)

    Obeid, Rima; Holzgreve, Wolfgang; Pietrzik, Klaus

    2013-09-01

    Women have higher requirements for folate during pregnancy. An optimal folate status must be achieved before conception and in the first trimester when the neural tube closes. Low maternal folate status is causally related to neural tube defects (NTDs). Many NTDs can be prevented by increasing maternal folate intake in the preconceptional period. Dietary folate is protective, but recommending increasing folate intake is ineffective on a population level particularly during periods of high demands. This is because the recommendations are often not followed or because the bioavailability of food folate is variable. Supplemental folate [folic acid (FA) or 5-methyltetrahydrofolate (5-methylTHF)] can effectively increase folate concentrations to the level that is considered to be protective. FA is a synthetic compound that has no biological functions unless it is reduced to dihydrofolate and tetrahydrofolate. Unmetabolized FA appears in the circulation at doses of >200 μg. Individuals show wide variations in their ability to reduce FA. Carriers of certain polymorphisms in genes related to folate metabolism or absorption can better benefit from 5-methylTHF instead of FA. 5-MethylTHF [also known as (6S)-5-methylTHF] is the predominant natural form that is readily available for transport and metabolism. In contrast to FA, 5-methylTHF has no tolerable upper intake level and does not mask vitamin B12 deficiency. Supplementation of the natural form, 5-methylTHF, is a better alternative to supplementation of FA, especially in countries not applying a fortification program. Supplemental 5-methylTHF can effectively improve folate biomarkers in young women in early pregnancy in order to prevent NTDs.

  19. [New directions in the hypotensive therapy of open-angle glaucoma (experimental and clinical research)].

    Science.gov (United States)

    Bunin, A Ia; Ermakov, V N; Filina, A A

    1993-01-01

    Clinical use of eye drops of a hybrid beta-alpha-adrenoblocker OF-4680 to reduce intraocular pressure has shown a high efficacy of the drug, not inferior to thymolol, for local hypotensive therapy of open-angle glaucoma. A combination of thymolol with taurin helped reduce the inhibiting effect of the beta-blocker on chamber humor secretion and simultaneously enhanced its discharge. The results evidence the desirability of correcting glutathion deficiency, detected in the patients with narrow-angle glaucoma, by lipoic acid.

  20. Porous reactive wall for prevention of acid mine drainage: Results of a full-scale field demonstration

    International Nuclear Information System (INIS)

    Benner, S.G.; Blowes, D.W.; Ptacek, C.J.

    1997-01-01

    A porous reactive wall was installed in August, 1995, to treat mine drainage flowing within an aquifer at the Nickel Rim mine site, near Sudbury, Ontario. The reactive mixture was designed to maximize removal of metals and acid generating capacity from the groundwater by enhancing sulfate reduction and metal sulfide precipitation. The installed structure, composed of a mixed organic substrate, is 15 meters long, 3.6 meters deep and the flow path length (wall width) is 4 meters. Results of sampling nine months after installation, indicate that sulfate reduction and metal sulfide precipitation is occurring. Comparing the chemistry of water entering the wall to treated water exiting the wall nine months after installation: SO 4 concentrations decrease by >50% (from 2400-4800 mg/L to 60-3600 mg/L), Fe concentrations decrease by >95% (from 260-1300 mg/L to 1.0-40 mg/L), pH increased from 5.8 to 7.0 and alkalinity increased from 0-60 mg/L to 700-3200 mg/L as CaCO 3 . After passing through the reactive wall, the net acid generating potential of the aquifer water was converted from acid producing to acid consuming

  1. A diagnostic and therapeutic approach to primary burning mouth syndrome.

    Science.gov (United States)

    Moghadam-Kia, Siamak; Fazel, Nasim

    Primary burning mouth syndrome (BMS) is an oral mucosal disorder that is characterized by a chronic and often debilitating intraoral burning sensation for which no localized or systemic cause can be found. BMS most commonly affects postmenopausal women. The pathophysiology of primary BMS is not well understood. Diagnosing BMS can prove to be challenging. BMS patients can also pose a therapeutic challenge to clinicians who are consulted to evaluate these patients. Most commonly used therapies include tricyclic antidepressants, α-lipoic acid, clonazepam, and cognitive-behavioral therapy. Clinical judgment, patient counseling, and monitoring of pain are important. Further research is required to assess the effectiveness of serotonin and newer serotonin-noradrenalin reuptake inhibitors. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. A comprehensive evaluation of food fortification with folic acid for the primary prevention of neural tube defects

    Directory of Open Access Journals (Sweden)

    Lam Angeline

    2004-09-01

    Full Text Available Abstract Background Periconceptional use of vitamin supplements containing folic acid reduces the risk of a neural tube defect (NTD. In November 1998, food fortification with folic acid was mandated in Canada, as a public health strategy to increase the folic acid intake of all women of childbearing age. We undertook a comprehensive population based study in Newfoundland to assess the benefits and possible adverse effects of this intervention. Methods This study was carried out in women aged 19–44 years and in seniors from November 1997 to March 1998, and from November 2000 to March 2001. The evaluation was comprised of four components: I Determination of rates of NTDs; II Dietary assessment; III Blood analysis; IV Assessment of knowledge and use of folic acid supplements. Results The annual rates of NTDs in Newfoundland varied greatly between 1976 and 1997, with a mean rate of 3.40 per 1,000 births. There was no significant change in the average rates between 1991–93 and 1994–97 (relative risk [RR] 1.01, 95% confidence interval [CI] 0.76–1.34. The rates of NTDs fell by 78% (95% CI 65%–86% after the implementation of folic acid fortification, from an average of 4.36 per 1,000 births during 1991–1997 to 0.96 per 1,000 births during 1998–2001 (RR 0.22, 95% CI 0.14–0.35. The average dietary intake of folic acid due to fortification was 70 μg/day in women aged 19–44 years and 74 μg/day in seniors. There were significant increases in serum and RBC folate levels for women and seniors after mandatory fortification. Among seniors, there were no significant changes in indices typical of vitamin B12 deficiencies, and no evidence of improved folate status masking haematological manifestations of vitamin B12 deficiency. The proportion of women aged 19–44 years taking a vitamin supplement containing folic acid increased from 17% to 28%. Conclusions Based on these findings, mandatory food fortification in Canada should continue at the

  3. Silica-supported sulfonic acids as recyclable catalyst for esterification of levulinic acid with stoichiometric amounts of alcohols

    Directory of Open Access Journals (Sweden)

    Raimondo Maggi

    2016-10-01

    Full Text Available Converting biomass into value-added chemicals holds the key to sustainable long-term carbon resource management. In this context, levulinic acid, which is easily obtained from cellulose, is valuable since it can be transformed into a variety of industrially relevant fine chemicals. Here we present a simple protocol for the selective esterification of levulinic acid using solid acid catalysts. Silica supported sulfonic acid catalysts operate under mild conditions and give good conversion and selectivity with stoichiometric amounts of alcohols. The sulfonic acid groups are tethered to the support using organic tethers. These tethers may help in preventing the deactivation of the active sites in the presence of water.

  4. Preventing AVF thrombosis: the rationale and design of the Omega-3 fatty acids (Fish Oils and Aspirin in Vascular access OUtcomes in REnal Disease (FAVOURED study

    Directory of Open Access Journals (Sweden)

    Rosman Johan

    2009-01-01

    Full Text Available Abstract Background Haemodialysis (HD is critically dependent on the availability of adequate access to the systemic circulation, ideally via a native arteriovenous fistula (AVF. The Primary failure rate of an AVF ranges between 20–54%, due to thrombosis or failure of maturation. There remains limited evidence for the use of anti-platelet agents and uncertainty as to choice of agent(s for the prevention of AVF thrombosis. We present the study protocol for a randomised, double-blind, placebo-controlled, clinical trial examining whether the use of the anti-platelet agents, aspirin and omega-3 fatty acids, either alone or in combination, will effectively reduce the risk of early thrombosis in de novo AVF. Methods/Design The study population is adult patients with stage IV or V chronic kidney disease (CKD currently on HD or where HD is planned to start within 6 months in whom a planned upper or lower arm AVF is to be the primary HD access. Using a factorial-design trial, patients will be randomised to aspirin or matching placebo, and also to omega-3 fatty acids or matching placebo, resulting in four treatment groups (aspirin placebo/omega-3 fatty acid placebo, aspirin/omega-3 fatty acid placebo, aspirin placebo/omega-3 fatty acid, aspirin/omega-3 fatty acid. Randomisation will be achieved using a dynamic balancing method over the two stratification factors of study site and upper versus lower arm AVF. The medication will be commenced pre-operatively and continued for 3 months post surgery. The primary outcome is patency of the AVF at three months after randomisation. Secondary outcome measures will include functional patency at six and twelve months, primary patency time, secondary (assisted patency time, and adverse events, particularly bleeding. Discussion This multicentre Australian and New Zealand study has been designed to determine whether the outcome of surgery to create de novo AVF can be improved by the use of aspirin and/or omega-3 fatty

  5. Preventing AVF thrombosis: the rationale and design of the Omega-3 fatty acids (Fish Oils) and Aspirin in Vascular access OUtcomes in REnal Disease (FAVOURED) study.

    Science.gov (United States)

    Irish, Ashley; Dogra, Gursharan; Mori, Trevor; Beller, Elaine; Heritier, Stephane; Hawley, Carmel; Kerr, Peter; Robertson, Amanda; Rosman, Johan; Paul-Brent, Peta-Anne; Starfield, Melissa; Polkinghorne, Kevan; Cass, Alan

    2009-01-21

    Haemodialysis (HD) is critically dependent on the availability of adequate access to the systemic circulation, ideally via a native arteriovenous fistula (AVF). The Primary failure rate of an AVF ranges between 20-54%, due to thrombosis or failure of maturation. There remains limited evidence for the use of anti-platelet agents and uncertainty as to choice of agent(s) for the prevention of AVF thrombosis. We present the study protocol for a randomised, double-blind, placebo-controlled, clinical trial examining whether the use of the anti-platelet agents, aspirin and omega-3 fatty acids, either alone or in combination, will effectively reduce the risk of early thrombosis in de novo AVF. The study population is adult patients with stage IV or V chronic kidney disease (CKD) currently on HD or where HD is planned to start within 6 months in whom a planned upper or lower arm AVF is to be the primary HD access. Using a factorial-design trial, patients will be randomised to aspirin or matching placebo, and also to omega-3 fatty acids or matching placebo, resulting in four treatment groups (aspirin placebo/omega-3 fatty acid placebo, aspirin/omega-3 fatty acid placebo, aspirin placebo/omega-3 fatty acid, aspirin/omega-3 fatty acid). Randomisation will be achieved using a dynamic balancing method over the two stratification factors of study site and upper versus lower arm AVF. The medication will be commenced pre-operatively and continued for 3 months post surgery. The primary outcome is patency of the AVF at three months after randomisation. Secondary outcome measures will include functional patency at six and twelve months, primary patency time, secondary (assisted) patency time, and adverse events, particularly bleeding. This multicentre Australian and New Zealand study has been designed to determine whether the outcome of surgery to create de novo AVF can be improved by the use of aspirin and/or omega-3 fatty acids. Recently a placebo-controlled trial has shown that

  6. Dietary Omega-3 Fatty Acids Prevented Adipocyte Hypertrophy by Downregulating DGAT-2 and FABP-4 in a Sex-Dependent Fashion.

    Science.gov (United States)

    Balogun, Kayode A; Cheema, Sukhinder K

    2016-01-01

    Obesity is characterized by an increase in fat mass primarily as a result of adipocyte hypertrophy. Diets enriched in omega (n)-3 polyunsaturated fatty acids (PUFA) are suggested to reduce obesity, however, the mechanisms are not well understood. We investigated the effect of n-3 PUFA on adipocyte hypertrophy and the key genes involved in adipocyte hypertrophy. Female C57BL/6 mice were fed semi-purified diets (20 % w/w fat) containing high n-3 PUFA before mating, during pregnancy, and until weaning. Male and female offspring were continued on high n-3 PUFA (10 % w/w), medium n-3 PUFA (4 % w/w), or low n-3 PUFA (2 % w/w) diet for 16 weeks postweaning. Adipocyte area was quantified using microscopy, and gonadal mRNA expression of acyl CoA:diacylglycerol acyltransferase-2 (DGAT-2), fatty acid binding protein-4 (FABP-4) and leptin were measured. The high n-3 PUFA group showed higher levels of total n-3 PUFA in gonadal TAG compared to the medium and low n-3 PUFA groups (P < 0.001). The high n-3 PUFA male group had a lower adipocyte area compared to the medium and low n-3 PUFA group (P < 0.001); however, no difference was observed in females. The high n-3 PUFA male group showed lower mRNA expression of FABP-4, DGAT-2 and leptin compared to the low n-3 PUFA group, with no difference in females. Plasma lipid levels were lower in the high n-3 PUFA group compared to the other groups. Our findings show for the first time that n-3 PUFA prevents adipocyte hypertrophy by downregulating FABP-4, DGAT-2 and leptin; the effects are however sex-specific.

  7. Electron beam treatment technology for exhaust gas for preventing acid rain

    International Nuclear Information System (INIS)

    Aoki, Shinji

    1990-01-01

    Recently, accompanying the increase of the use of fossil fuel, the damage due to acid rain such as withering of trees and extinction of fishes and shells has occurred worldwide, and it has become a serious problem. The sulfur oxides and nitrogen oxides contained in exhaust gas are oxidized by the action of sunbeam to become sulfuric acid and nitric acid mists, which fall in the form of rain. Acid rain is closely related to the use of the coal containing high sulfur, and it hinders the use of coal which is rich energy source. In order to simplify the processing system for boiler exhaust gas and to reduce waste water and wastes, Ebara Corp. developed the dry simultaneous desulfurizing and denitrating technology utilizing electron beam in cooperation with Japan Atomic Energy Research Institute. The flow chart of the system applied to the exhaust gas treatment in a coal-fired thermal power station is shown. The mechanism of desulfurization and denitration, and the features of this system are described. The demonstration plant was constructed in a coal-fired thermal power station in Indianapolis, Indiana, USA, and the trial operation was completed in July, 1987. The test results are reported. (K.I.)

  8. Tryptamine-Gallic Acid Hybrid Prevents Non-steroidal Anti-inflammatory Drug-induced Gastropathy

    Science.gov (United States)

    Pal, Chinmay; Bindu, Samik; Dey, Sumanta; Alam, Athar; Goyal, Manish; Iqbal, Mohd. Shameel; Sarkar, Souvik; Kumar, Rahul; Halder, Kamal Krishna; Debnath, Mita Chatterjee; Adhikari, Susanta; Bandyopadhyay, Uday

    2012-01-01

    We have investigated the gastroprotective effect of SEGA (3a), a newly synthesized tryptamine-gallic acid hybrid molecule against non-steroidal anti-inflammatory drug (NSAID)-induced gastropathy with mechanistic details. SEGA (3a) prevents indomethacin (NSAID)-induced mitochondrial oxidative stress (MOS) and dysfunctions in gastric mucosal cells, which play a pathogenic role in inducing gastropathy. SEGA (3a) offers this mitoprotective effect by scavenging of mitochondrial superoxide anion (O2˙̄) and intramitochondrial free iron released as a result of MOS. SEGA (3a) in vivo blocks indomethacin-mediated MOS, as is evident from the inhibition of indomethacin-induced mitochondrial protein carbonyl formation, lipid peroxidation, and thiol depletion. SEGA (3a) corrects indomethacin-mediated mitochondrial dysfunction in vivo by restoring defective electron transport chain function, collapse of transmembrane potential, and loss of dehydrogenase activity. SEGA (3a) not only corrects mitochondrial dysfunction but also inhibits the activation of the mitochondrial pathway of apoptosis by indomethacin. SEGA (3a) inhibits indomethacin-induced down-regulation of bcl-2 and up-regulation of bax genes in gastric mucosa. SEGA (3a) also inhibits indometacin-induced activation of caspase-9 and caspase-3 in gastric mucosa. Besides the gastroprotective effect against NSAID, SEGA (3a) also expedites the healing of already damaged gastric mucosa. Radiolabeled (99mTc-labeled SEGA (3a)) tracer studies confirm that SEGA (3a) enters into mitochondria of gastric mucosal cell in vivo, and it is quite stable in serum. Thus, SEGA (3a) bears an immense potential to be a novel gastroprotective agent against NSAID-induced gastropathy. PMID:22157011

  9. Antioxidants inhibit SAA formation and pro-inflammatory cytokine release in a human cell model of alkaptonuria.

    Science.gov (United States)

    Spreafico, Adriano; Millucci, Lia; Ghezzi, Lorenzo; Geminiani, Michela; Braconi, Daniela; Amato, Loredana; Chellini, Federico; Frediani, Bruno; Moretti, Elena; Collodel, Giulia; Bernardini, Giulia; Santucci, Annalisa

    2013-09-01

    Alkaptonuria (AKU) is an ultra-rare autosomal recessive disease that currently lacks an appropriate therapy. Recently we provided experimental evidence that AKU is a secondary serum amyloid A (SAA)-based amyloidosis. The aim of the present work was to evaluate the use of antioxidants to inhibit SAA amyloid and pro-inflammatory cytokine release in AKU. We adopted a human chondrocytic cell AKU model to evaluate the anti-amyloid capacity of a set of antioxidants that had previously been shown to counteract ochronosis in a serum AKU model. Amyloid presence was evaluated by Congo red staining. Homogentisic acid-induced SAA production and pro-inflammatory cytokine release (overexpressed in AKU patients) were evaluated by ELISA and multiplex systems, respectively. Lipid peroxidation was evaluated by means of a fluorescence-based assay. Our AKU model allowed us to prove the efficacy of ascorbic acid combined with N-acetylcysteine, taurine, phytic acid and lipoic acid in significantly inhibiting SAA production, pro-inflammatory cytokine release and membrane lipid peroxidation. All the tested antioxidant compounds were able to reduce the production of amyloid and may be the basis for establishing new therapies for AKU amyloidosis.

  10. Hydroxy decenoic acid down regulates gtfB and gtfC expression and prevents Streptococcus mutans adherence to the cell surfaces.

    Science.gov (United States)

    Yousefi, Behnam; Ghaderi, Shahrooz; Rezapoor-Lactooyi, Alireza; Amiri, Niusha; Verdi, Javad; Shoae-Hassani, Alireza

    2012-07-28

    10-Hydroxy-2-decenoic acid, an unsaturated fatty acid is the most active and unique component to the royal jelly that has antimicrobial properties. Streptococcus mutans is associated with pathogenesis of oral cavity, gingivoperiodontal diseases and bacteremia following dental manipulations. In the oral cavity, S. mutans colonize the soft tissues including tongue, palate, and buccal mucosa. When considering the role of supragingival dental plaque in caries, the proportion of acid producing bacteria (particularly S. mutans), has direct relevance to the pathogenicity of the plaque. The genes that encode glucosyltransferases (gtfs) especially gtfB and gtfC are important in S. mutans colonization and pathogenesis. This study investigated the hydroxy-decenoic acid (HDA) effects on gtfB and gtfC expression and S. mutans adherence to cells surfaces. Streptococcus mutans was treated by different concentrations of HPLC purified HDA supplied by Iran Beekeeping and Veterinary Association. Real time RT-PCR and western blot assays were conducted to evaluate gtfB and gtfC genes transcription and translation before and after HDA treatment. The bacterial attachment to the cell surfaces was evaluated microscopically. 500 μg ml-1 of HDA inhibited gtfB and gtfC mRNA transcription and its expression. The same concentration of HDA decreased 60% the adherence of S. mutans to the surface of P19 cells. Hydroxy-decenoic acid prevents gtfB and gtfC expression efficiently in the bactericide sub-concentrations and it could effectively reduce S. mutans adherence to the cell surfaces. In the future, therapeutic approaches to affecting S. mutans could be selective and it's not necessary to put down the oral flora completely.

  11. Ursodeoxycholic acid and lithocholic acid exert anti-inflammatory actions in the colon.

    Science.gov (United States)

    Ward, Joseph B J; Lajczak, Natalia K; Kelly, Orlaith B; O'Dwyer, Aoife M; Giddam, Ashwini K; Ní Gabhann, Joan; Franco, Placido; Tambuwala, Murtaza M; Jefferies, Caroline A; Keely, Simon; Roda, Aldo; Keely, Stephen J

    2017-06-01

    Ward JB, Lajczak NK, Kelly OB, O'Dwyer AM, Giddam AK, Ní Gabhann J, Franco P, Tambuwala MM, Jefferies CA, Keely S, Roda A, Keely SJ. Ursodeoxycholic acid and lithocholic acid exert anti-inflammatory actions in the colon. Am J Physiol Gastrointest Liver Physiol 312: G550-G558, 2017. First published March 30, 2017; doi:10.1152/ajpgi.00256.2016.-Inflammatory bowel diseases (IBD) comprise a group of common and debilitating chronic intestinal disorders for which currently available therapies are often unsatisfactory. The naturally occurring secondary bile acid, ursodeoxycholic acid (UDCA), has well-established anti-inflammatory and cytoprotective actions and may therefore be effective in treating IBD. We aimed to investigate regulation of colonic inflammatory responses by UDCA and to determine the potential impact of bacterial metabolism on its therapeutic actions. The anti-inflammatory efficacy of UDCA, a nonmetabolizable analog, 6α-methyl-UDCA (6-MUDCA), and its primary colonic metabolite lithocholic acid (LCA) was assessed in the murine dextran sodium sulfate (DSS) model of mucosal injury. The effects of bile acids on cytokine (TNF-α, IL-6, Il-1β, and IFN-γ) release from cultured colonic epithelial cells and mouse colonic tissue in vivo were investigated. Luminal bile acids were measured by gas chromatography-mass spectrometry. UDCA attenuated release of proinflammatory cytokines from colonic epithelial cells in vitro and was protective against the development of colonic inflammation in vivo. In contrast, although 6-MUDCA mimicked the effects of UDCA on epithelial cytokine release in vitro, it was ineffective in preventing inflammation in the DSS model. In UDCA-treated mice, LCA became the most common colonic bile acid. Finally, LCA treatment more potently inhibited epithelial cytokine release and protected against DSS-induced mucosal inflammation than did UDCA. These studies identify a new role for the primary metabolite of UDCA, LCA, in preventing colonic

  12. Nucleic acid labeling with [3H]orotic acid and nucleotide profile in rats in protein deprivation, enteral and parenteral essential amino acid administration, and 5-fluorouracil treatment

    International Nuclear Information System (INIS)

    Jakobsson, B.; el Hag, I.A.; Andersson, M.; Christensson, P.I.; Stenram, U.

    1990-01-01

    Rats were fed a 0% casein diet for 1 week, with or without enteral or parenteral administration of essential amino acids, or a 25% casein diet, in one group supplemented with 5-fluorouracil treatment. Ninety minutes before sacrifice the rats were given a tracer of [3H]orotic acid. Incorporation into the acid soluble fraction, RNA, and DNA was determined in liver, small intestine, bone marrow, and kidney. Nucleotide profile was examined in liver and intestine. Protein deficiency caused inter alia a decrease in body weight; a decrease in RNA/DNA ratio and an increase in the specific RNA labeling in liver and kidney; an altered nucleotide profile in the liver; an increase in the nucleotide/DNA and RNA/DNA ratios and a decrease in the specific labeling of the acid soluble fraction, RNA, and DNA in the bone marrow. These changes were prevented to the same extent by giving essential amino acids, either orally or intravenously. The minor changes in intestinal nucleotide profile in protein deprivation were prevented to a slightly larger extent by amino acids orally than parenterally. 5-Fluorouracil treatment gave a decrease in the RNA/DNA ratio in the liver and kidney but an increase in the nucleotide/DNA and RNA/DNA ratios in the bone marrow. Nucleotide profiles were unaltered. The amount of DNA per gram of tissue decreased in bone marrow and increased in kidney. Parenteral administration per se resulted in almost no changes

  13. Stimulation of Lactic Acid Bacteria by a Micrococcus Isolate: Evidence for Multiple Effects

    Science.gov (United States)

    Nath, K. R.; Wagner, B. J.

    1973-01-01

    Growth of, and rate of acid production by, six cultures of lactic acid bacteria were increased in the presence of Micrococcus isolate F4 or a preparation of its capsular material. Concentrations of hydrogen peroxide found in pure cultures of the lactic acid bacteria were not detectable, or were greatly reduced, in mixed culture with Micrococcus isolate F4. The capsular material was not as effective as whole cells in preventing accumulation of H2O2. Catalase stimulated growth of, and the rate of acid production by, the lactic acid bacteria, but not to the same extent as Micrococcus isolate F4 in some cultures. The existence of two mechanisms for micrococcal stimulation of the lactic acid bacteria is postulated. One mechanism involves removal of H2O2; the other has not been characterized. PMID:4199337

  14. Omega-3 fatty acids alter behavioral and oxidative stress parameters in animals subjected to fenproporex administration.

    Science.gov (United States)

    Model, Camila S; Gomes, Lara M; Scaini, Giselli; Ferreira, Gabriela K; Gonçalves, Cinara L; Rezin, Gislaine T; Steckert, Amanda V; Valvassori, Samira S; Varela, Roger B; Quevedo, João; Streck, Emilio L

    2014-03-01

    Studies have consistently reported the participation of oxidative stress in bipolar disorder (BD). Evidences indicate that omega-3 (ω3) fatty acids play several important roles in brain development and functioning. Moreover, preclinical and clinical evidence suggests roles for ω3 fatty acids in BD. Considering these evidences, the present study aimed to investigate the effects of ω3 fatty acids on locomotor behavior and oxidative stress parameters (TBARS and protein carbonyl content) in brain of rats subjected to an animal model of mania induced by fenproporex. The fenproporex treatment increased locomotor behavior in saline-treated rats under reversion and prevention model, and ω3 fatty acids prevented fenproporex-related hyperactivity. Moreover, fenproporex increased protein carbonyls in the prefrontal cortex and cerebral cortex, and the administration of ω3 fatty acids reversed this effect. Lipid peroxidation products also are increased in prefrontal cortex, striatum, hippocampus and cerebral after fenproporex administration, but ω3 fatty acids reversed this damage only in the hippocampus. On the other hand, in the prevention model, fenproporex increased carbonyl content only in the cerebral cortex, and administration of ω3 fatty acids prevented this damage. Additionally, the administration of fenproporex resulted in a marked increased of TBARS in the prefrontal cortex, hippocampus, striatum and cerebral cortex, and prevent this damage in the prefrontal cortex, hippocampus and striatum. In conclusion, we are able to demonstrate that fenproporex-induced hyperlocomotion and damage through oxidative stress were prevented by ω3 fatty acids. Thus, the ω3 fatty acids may be important adjuvant therapy of bipolar disorder.

  15. A polycarboxylic/amino functionalized hyaluronic acid derivative for the production of pH sensible hydrogels in the prevention of bacterial adhesion on biomedical surfaces.

    Science.gov (United States)

    Palumbo, Fabio Salvatore; Bavuso Volpe, Antonella; Cusimano, Maria Grazia; Pitarresi, Giovanna; Giammona, Gaetano; Schillaci, Domenico

    2015-01-15

    A graft copolymer derivative of hyaluronic acid bearing pendant amino and short polymethacrylate portions (HA-EDA-BMP-MANa) has been employed for the production of a pH sensible vancomycin releasing hydrogel and studied in vitro to test its potential anti adhesive property against Staphylococcus aureus colonization. The copolymer obtained through atom transfer radical polymerization bears chargeable (carboxyl and amino groups) portions and it could be formulated as a hydrogel at a concentration of 10%w/v. The HA-EDA-BMP-MANa hydrogels, produced at three different pH values (5, 6 and 7, respectively), were formulated with or without the addition of vancomycin (2%w/v). The vancomycin release profiles were detected and related to the starting hydrogel pH values, demonstrating that the systems were able to sustain the release of drug for more than 48 h. S. aureus adhesion tests were performed on glass culture plates and hydroxyapatite doped titanium surfaces, comparing the performances of HA-EDA-BMP-MANa hydrogel formulations (obtained with and without vancomycin) with similar formulations obtained using unmodified hyaluronic acid. The non fouling property of a selected HA-EDA-BMP-MANa hydrogel (without vancomycin) was also assayed with a BSA adsorption test. We found that the HA-EDA-BMP-MANa hydrogel even without vancomycin prevented bacterial adhesion on investigated surfaces. Copyright © 2014. Published by Elsevier B.V.

  16. Current Experience in Testing Mitochondrial Nutrients in Disorders Featuring Oxidative Stress and Mitochondrial Dysfunction: Rational Design of Chemoprevention Trials

    OpenAIRE

    Giovanni Pagano; Annarita Aiello Talamanca; Giuseppe Castello; Mario D. Cordero; Marco d'Ischia; Maria Nicola Gadaleta; Federico V. Pallardó; Sandra Petrović; Luca Tiano; Adriana Zatterale

    2014-01-01

    An extensive number of pathologies are associated with mitochondrial dysfunction (MDF) and oxidative stress (OS). Thus, mitochondrial cofactors termed “mitochondrial nutrients” (MN), such as α-lipoic acid (ALA), Coenzyme Q10 (CoQ10), and l-carnitine (CARN) (or its derivatives) have been tested in a number of clinical trials, and this review is focused on the use of MN-based clinical trials. The papers reporting on MN-based clinical trials were retrieved in MedLine up to July 2014, and evaluat...

  17. Amides of non-steroidal anti-inflammatory drugs with thiomorpholine can yield hypolipidemic agents with improved anti-inflammatory activity.

    Science.gov (United States)

    Theodosis-Nobelos, Panagiotis; Kourti, Malamati; Gavalas, Antonios; Rekka, Eleni A

    2016-02-01

    Novel amides of non steroidal anti-inflammatory drugs (NSAIDs), α-lipoic acid and indole-3-acetic acid with thiomorpholine were synthesised by a simple method and at high yields (60-92%). All the NSAID derivatives highly decreased lipidemic indices in the plasma of Triton treated hyperlipidemic rats. The most potent compound was the indomethacin derivative, which decreased total cholesterol, triglycerides and LDL cholesterol by 73%, 80% and 83%, respectively. They reduced acute inflammation equally or more than most parent acids. Hence, it could be concluded that amides of common NSAIDs with thiomorpholine acquire considerable hypolipidemic potency, while they preserve or augment their anti-inflammatory activity, thus addressing significant risk factors for atherogenesis. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. RodZ and PgsA Play Intertwined Roles in Membrane Homeostasis of Bacillus subtilis and Resistance to Weak Organic Acid Stress

    NARCIS (Netherlands)

    van Beilen, Johan; Blohmke, Christoph J.; Folkerts, Hendrik; de Boer, Richard; Zakrzewska, Anna; Kulik, Wim; Vaz, Fred M.; Brul, Stanley; Ter Beek, Alexander

    2016-01-01

    Weak organic acids like sorbic and acetic acid are widely used to prevent growth of spoilage organisms such as Bacilli. To identify genes involved in weak acid stress tolerance we screened a transposon mutant library of Bacillus subtilis for sorbic acid sensitivity. Mutants of the rodZ (ymfM) gene

  19. Animal model of acid-reflux esophagitis: pathogenic roles of acid/pepsin, prostaglandins, and amino acids.

    Science.gov (United States)

    Takeuchi, Koji; Nagahama, Kenji

    2014-01-01

    Esophagitis was induced in rats within 3 h by ligating both the pylorus and transitional region between the forestomach and glandular portion under ether anesthesia. This esophageal injury was prevented by the administration of acid suppressants and antipepsin drug and aggravated by exogenous pepsin. Damage was also aggravated by pretreatment with indomethacin and the selective COX-1 but not COX-2 inhibitor, whereas PGE2 showed a biphasic effect depending on the dose; a protection at low doses, and an aggravation at high doses, with both being mediated by EP1 receptors. Various amino acids also affected this esophagitis in different ways; L-alanine and L-glutamine had a deleterious effect, while L-arginine and glycine were highly protective, both due to yet unidentified mechanisms. It is assumed that acid/pepsin plays a major pathogenic role in this model of esophagitis; PGs derived from COX-1 are involved in mucosal defense of the esophagus; and some amino acids are protective against esophagitis. These findings also suggest a novel therapeutic approach in the treatment of esophagitis, in addition to acid suppressant therapy. The model introduced may be useful to test the protective effects of drugs on esophagitis and investigate the mucosal defense mechanism in the esophagus.

  20. Are conjugated linolenic acid isomers an alternative to conjugated linoleic acid isomers in obesity prevention?

    Science.gov (United States)

    Miranda, Jonatan; Arias, Noemi; Fernández-Quintela, Alfredo; del Puy Portillo, María

    2014-04-01

    Despite its benefits, conjugated linoleic acid (CLA) may cause side effects after long-term administration. Because of this and the controversial efficacy of CLA in humans, alternative biomolecules that may be used as functional ingredients have been studied in recent years. Thus, conjugated linolenic acid (CLNA) has been reported to be a potential anti-obesity molecule which may have additional positive effects related to obesity. According to the results reported in obesity, CLNA needs to be given at higher doses than CLA to be effective. However, because of the few studies conducted so far, it is still difficult to reach clear conclusions about the potential use of these CLNAs in obesity and its related changes (insulin resistance, dyslipidemia, or inflammation). Copyright © 2012 SEEN. Published by Elsevier Espana. All rights reserved.

  1. 3α-6α-Dihydroxy-7α-fluoro-5β-cholanoate (UPF-680), physicochemical and physiological properties of a new fluorinated bile acid that prevents 17α-ethynyl-estradiol-induced cholestasis in rats

    International Nuclear Information System (INIS)

    Clerici, Carlo; Castellani, Danilo; Asciutti, Stefania; Pellicciari, Roberto; Setchell, Kenneth D.R.; O'Connell, Nancy C.; Sadeghpour, Bahman; Camaioni, Emidio; Fiorucci, Stefano; Renga, Barbara; Nardi, Elisabetta; Sabatino, Giuseppe; Clementi, Mattia; Giuliano, Vittorio; Baldoni, Monia; Orlandi, Stefano; Mazzocchi, Alessandro; Morelli, Antonio; Morelli, Olivia

    2006-01-01

    3α-6α-Dihydroxy-7α-fluoro-5β-cholanoate (UPF-680), the 7α-fluorine analog of hyodeoxycholic acid (HDCA), was synthesized to improve bioavailability and stability of ursodeoxycholic acid (UDCA). Acute rat biliary fistula and chronic cholestasis induced by 17α-ethynyl-estradiol (17EE) models were used to study and compare the effects of UPF-680 (dose range 0.6-6.0 μmol/kg min) with UDCA on bile flow, biliary bicarbonate (HCO 3 - ), lipid output, biliary bile acid composition, hepatic enzymes and organic anion pumps. In acute infusion, UPF-680 increased bile flow in a dose-related manner, by up to 40.9%. Biliary HCO 3 - output was similarly increased. Changes were observed in phospholipid secretion only at the highest doses. Treatment with UDCA and UPF-680 reversed chronic cholestasis induced by 17EE; in this model, UDCA had no effect on bile flow in contrast to UPF-680, which significantly increased bile flow. With acute administration of UPF-680, the biliary bile acid pool became enriched with unconjugated and conjugated UPF-680 (71.7%) at the expense of endogenous cholic acid and muricholic isomers. With chronic administration of UPF-680 or UDCA, the main biliary bile acids were tauro conjugates, but modification of biliary bile acid pool was greater with UPF-680. UPF-680 increased the mRNA for cytochrome P450 7A1 (CYP7A1) and cytochrome P450 8B (CYP8B). Both UDCA and UPF-680 increased the mRNA for Na + taurocholate co-transporting polypeptide (NCTP). In conclusion, UPF-680 prevented 17EE-induced cholestasis and enriched the biliary bile acid pool with less detergent and cytotoxic bile acids. This novel fluorinated bile acid may have potential in the treatment of cholestatic liver disease

  2. Bolivian Health Providers’ Attitudes Toward Alternative Technologies for Cervical Cancer Prevention: A Focus on Visual Inspection with Acetic Acid and Cryotherapy

    Science.gov (United States)

    Stormo, Analía Romina; Altamirano, Victor Conde; Pérez-Castells, Macarena; Espey, David; Padilla, Haydee; Panameño, Karen; Soria, Milton; Santos, Carlos; Saraiya, Mona; Luciani, Silvana

    2017-01-01

    Background Little is known about health providers’ attitudes toward visual inspection with acetic acid (VIA) and cryotherapy in the prevention of cervical cancer, as most research in Latin America and the Caribbean (LAC) has examined attitudes of the general population. This study describes attitudes of Bolivian health professionals toward new technologies for cervical cancer prevention, focusing on VIA and cryotherapy. Methods Between February 2011 and March 2012, we surveyed 7 nurses and 35 physicians who participated in 5-day workshops on VIA and cryotherapy conducted in Bolivia. Multiple choice and open-ended questions were used to assess participants’ acceptability of these procedures and the feasibility of their implementation in the context of perceived barriers for the early detection of cervical cancer in this country. Results Most believed that cultural factors represent the main barrier for the early detection of cervical cancer (70%), although all stated that VIA and cryotherapy would be accepted by women, citing the advantages of VIA over cytology for this belief. Most also believed their colleagues would accept VIA and cryotherapy (71%) and that VIA should replace Pap testing (61%), reiterating the advantages of VIA for these beliefs. Those who believed the contrary expressed a general resistance to change associated with an already existing cytology program and national norms prioritizing Pap testing. Conclusions Most participants had favorable attitudes toward VIA and cryotherapy; however, a sizable minority cited challenges to their adoption by colleagues and believed VIA should not replace cytology. This report can inform the development of strategies to expand the use of alternative cervical cancer screening methods in LAC and Bolivia. PMID:22816515

  3. Surgical infection in a videolaparoscopic cholecystectomy when using peracetic acid for the sterilization of instruments.

    Science.gov (United States)

    de Melo, Edluza Maria Viana Bezerra; Leão, Cristiano de Souza; Andreto, Luciana Marques; de Mello, Maria Júlia Gonçalves

    2013-01-01

    To determine the frequency of surgical site infection in patients undergoing laparoscopic cholecystectomy with instruments sterilized by peracetic acid. We conducted a retrospective, cohort, descriptive, cross-sectional study. Peracetic acid has been used for sterilization following the protocol recommended by the manufacturer. We observed the criteria and indicators of process and structure for preventing surgical site infection pre and intraoperatively. For epidemiological surveillance, outpatient visits were scheduled for the 15th and between the 30th and 45th days after discharge. Among the 247 patients, there were two cases of surgical site infection (0.8%). One patient was readmitted to systemic antibiotic therapy and percutaneous puncture; in the other the infection was superficial and followed at the clinic. Ethical issues prevent the conduction of a prospective study because of peracetic acid have been banned for the sterilization of instruments that penetrate organs and cavities. Nevertheless, these results encourage prospective case-control studies comparing its use (historical control) with ethylene oxide sterilization.

  4. Evidence for biofilm acid neutralization by baking soda.

    Science.gov (United States)

    Zero, Domenick T

    2017-11-01

    The generating of acids from the microbial metabolism of dietary sugars and the subsequent decrease in biofilm pH below the pH at which tooth mineral begins to demineralize (critical pH) are the key elements of the dental caries process. Caries preventive strategies that rapidly neutralize biofilm acids can prevent demineralization and favor remineralization and may help prevent the development of sugar-induced dysbiosis that shifts the biofilm toward increased cariogenic potential. Although the neutralizing ability of sodium bicarbonate (baking soda) has been known for many years, its anticaries potential as an additive to fluoride dentifrice has received only limited investigation. There is evidence that baking soda rapidly can reverse the biofilm pH decrease after a sugar challenge; however, the timing of when it is used in relation to a dietary sugar exposure is critical in that the sooner its used the greater the benefit in preventing a sustained biofilm pH decrease and subsequent demineralization. Furthermore, the effectiveness of baking soda in elevating biofilm pH appears to depend on concentration. Thus, the concentration of baking soda in marketed dentifrice products, which ranges from 10% to 65%, may affect their biofilm pH neutralizing performance. People with hyposalivation particularly may benefit from using fluoride dentifrice containing baking soda because of their diminished ability to clear dietary sugars and buffer biofilm acids. Although promising, there is the need for more evidence that strategies that modify the oral ecology, such as baking soda, can alter the cariogenic (acidogenic and aciduric) properties of biofilm microorganisms. The acid neutralization of dental biofilm by using fluoride dentifrice that contains baking soda has potential for helping counteract modern high-sugar diets by rapidly neutralizing biofilm-generated acid, especially in people with hyposalivation. Copyright © 2017 American Dental Association. Published by

  5. Effects of Uric Acid on Exercise-induced Oxidative Stress

    OpenAIRE

    平井, 富弘

    2001-01-01

    We studied effects of uric acid on exercise― induced oxidative stress in humans based on a hypothesis that uric acid acts as an antioxidant to prevent from exercise―induced oxidative stress. Relation between uric acid level in plasma and increase of thiobarbituric acid reactive substance (TBARS)after the cycle ergometer exercise was examined. Thiobarbituricacid reactive substance in plasma increased after the ergometer exercise. High uric acid in plasma did not result in low increase of TBARS...

  6. Tetrahydrocannabinolic acid is a potent PPARγ agonist with neuroprotective activity.

    Science.gov (United States)

    Nadal, Xavier; Del Río, Carmen; Casano, Salvatore; Palomares, Belén; Ferreiro-Vera, Carlos; Navarrete, Carmen; Sánchez-Carnerero, Carolina; Cantarero, Irene; Bellido, Maria Luz; Meyer, Stefan; Morello, Gaetano; Appendino, Giovanni; Muñoz, Eduardo

    2017-12-01

    Phytocannabinoids are produced in Cannabis sativa L. in acidic form and are decarboxylated upon heating, processing and storage. While the biological effects of decarboxylated cannabinoids such as Δ 9 -tetrahydrocannabinol have been extensively investigated, the bioactivity of Δ 9 -tetahydrocannabinol acid (Δ 9 -THCA) is largely unknown, despite its occurrence in different Cannabis preparations. Here we have assessed possible neuroprotective actions of Δ 9 -THCA through modulation of PPARγ pathways. The effects of six phytocannabinoids on PPARγ binding and transcriptional activity were investigated. The effect of Δ 9 -THCA on mitochondrial biogenesis and PPARγ coactivator 1-α expression was investigated in Neuro-2a (N2a) cells. The neuroprotective effect was analysed in STHdh Q111/Q111 cells expressing a mutated form of the huntingtin protein and in N2a cells infected with an adenovirus carrying human huntingtin containing 94 polyQ repeats (mHtt-q94). The in vivo neuroprotective activity of Δ 9 -THCA was investigated in mice intoxicated with the mitochondrial toxin 3-nitropropionic acid (3-NPA). Cannabinoid acids bind and activate PPARγ with higher potency than their decarboxylated products. Δ 9 -THCA increased mitochondrial mass in neuroblastoma N2a cells and prevented cytotoxicity induced by serum deprivation in STHdh Q111/Q111 cells and by mutHtt-q94 in N2a cells. Δ 9 -THCA, through a PPARγ-dependent pathway, was neuroprotective in mice treated with 3-NPA, improving motor deficits and preventing striatal degeneration. In addition, Δ 9 -THCA attenuated microgliosis, astrogliosis and up-regulation of proinflammatory markers induced by 3-NPA. Δ 9 -THCA shows potent neuroprotective activity, which is worth considering for the treatment of Huntington's disease and possibly other neurodegenerative and neuroinflammatory diseases. © 2017 The British Pharmacological Society.

  7. Studies on the riboflavin, pantothenic acid, nicotinic acid and choline requirements of young Embden geese

    Science.gov (United States)

    Serafin, J.A.

    1981-01-01

    Four experiments were conducted to examine the riboflavin, pantothenic acid, nicotinic acid, and choline requirements of young Embden geese fed purified diets. Goslings fed diets deficient in either riboflavin, pantothenic acid, nicotinic acid, or choline grew poorly. Feeding a pantothenic acid-deficient diet resulted in 100% mortality. Goslings fed diets containing 530 mg/kg of choline or less developed perosis. Under the conditions of these experiments it was found that: 1) goslings require no more than 3.84 mg/kg of riboflavin and 31.2 mg/kg of nicotinic acid in the diet for rapid growth and normal development, 2) the pantothenic acid requirement of goslings is no more than 12.6 mg/kg of diet, and 3) a dietary choline level of 1530 mg/kg is adequate for both the prevention of perosis and rapid growth of goslings. The levels of vitamins found to support normal growth and development of goslings appear to be similar to requirements of other species that have been examined.

  8. Hydroxy decenoic acid down regulates gtfB and gtfC expression and prevents Streptococcus mutans adherence to the cell surfaces

    Directory of Open Access Journals (Sweden)

    Yousefi Behnam

    2012-07-01

    Full Text Available Abstract Background 10-Hydroxy-2-decenoic acid, an unsaturated fatty acid is the most active and unique component to the royal jelly that has antimicrobial properties. Streptococcus mutans is associated with pathogenesis of oral cavity, gingivoperiodontal diseases and bacteremia following dental manipulations. In the oral cavity, S. mutans colonize the soft tissues including tongue, palate, and buccal mucosa. When considering the role of supragingival dental plaque in caries, the proportion of acid producing bacteria (particularly S. mutans, has direct relevance to the pathogenicity of the plaque. The genes that encode glucosyltransferases (gtfs especially gtfB and gtfC are important in S. mutans colonization and pathogenesis. This study investigated the hydroxy-decenoic acid (HDA effects on gtfB and gtfC expression and S. mutans adherence to cells surfaces. Methods Streptococcus mutans was treated by different concentrations of HPLC purified HDA supplied by Iran Beekeeping and Veterinary Association. Real time RT-PCR and western blot assays were conducted to evaluate gtfB and gtfC genes transcription and translation before and after HDA treatment. The bacterial attachment to the cell surfaces was evaluated microscopically. Results 500 μg ml-1 of HDA inhibited gtfB and gtfC mRNA transcription and its expression. The same concentration of HDA decreased 60% the adherence of S. mutans to the surface of P19 cells. Conclusion Hydroxy-decenoic acid prevents gtfB and gtfC expression efficiently in the bactericide sub-concentrations and it could effectively reduce S. mutans adherence to the cell surfaces. In the future, therapeutic approaches to affecting S. mutans could be selective and it’s not necessary to put down the oral flora completely.

  9. Activation of Retinoid X Receptors by Phytanic Acid and Docohexaenoic Acid: Role in the Prevention and Therapy of Prostate Cancer

    National Research Council Canada - National Science Library

    Tang, Xiao-Han

    2005-01-01

    .... Meanwhile, both phytanic acid and DHA inhibited the growth of Pc-3 and LNCaP cells. Phytanic acid and retinoic acid synergistically inhibited the growth of both of these prostate cancer cell lines...

  10. The modern features of pathogenesis-induced prevention of preeclampsia

    Directory of Open Access Journals (Sweden)

    Konkov D.G.

    2016-03-01

    Full Text Available Purpose — the assessment of clinical effectiveness of preventive therapy in pregnant women with high risk of preeclampsia. Patients and methods. In the comparative study on the effectiveness of preventive therapy were participated 110 pregnant women with decidual vasculopathy and endothelial dysfunction, which had high risk of preeclampsia. We investigated the clinical efficacy for medications that containing 75 mg of acetylsalicylic acid and L-arginine. Results. The results of the study have shown that use of preventive treatment (L-arginine and acetylsalicylic acid from 12 weeks, among pregnant women with high risk of preeclampsia, led to a significant decrease of perinatal loss, reduction of clinical manifestations of preeclampsia, preterm delivery, malformations and malpresentation of the placenta, cases of asphyxia of the newborns, perinatal CNS lesions and intra-ventricular hemorrhage. Conclusions. Clinical effectiveness of preventive treatment (L-arginine and ASA among pregnant women with high risk of preeclampsia was proven. Furthermore it was recognized clinically effective use of 75 mg of ASA from 12 weeks of pregnancy. No side effects of drugs in the study were noted.

  11. Effect of dairy fat on plasma phytanic acid in healthy volunteers - a randomized controlled study

    DEFF Research Database (Denmark)

    Werner, Louise B.; Hellgren, Lars; Raff, Marianne

    2011-01-01

    BACKGROUND: Phytanic acid produced in ruminants from chlorophyll may have preventive effects on the metabolic syndrome, partly due to its reported RXR and PPAR- α agonist activity. Milk from cows fed increased levels of green plant material, contains increased phytanic acid concentrations......, but it is unknown to what extent minor increases in phytanic acid content in dairy fat leads to higher circulating levels of phytanic acid in plasma of the consumers. OBJECTIVE: To investigate if cow feeding regimes affects concentration of plasma phytanic acid and risk markers of the metabolic syndrome in human...... or high content of chlorophyll. RESULTS: There tended to be a difference in plasma phytanic acid (P = 0.0730) concentration after the dietary intervention. Plasma phytanic acid increased significantly within both groups with the highest increase in control group (24%) compared to phytanic acid group (15...

  12. Curcumin and long-chain Omega-3 polyunsaturated fatty acids for Prevention of type 2 Diabetes (COP-D): study protocol for a randomised controlled trial.

    Science.gov (United States)

    Thota, Rohith N; Acharya, Shamasunder H; Abbott, Kylie A; Garg, Manohar L

    2016-11-29

    Lifestyle interventions, including increase in physical activity and dietary counselling, have shown the ability to prevent type 2 diabetes (T2D) in high-risk state individuals, but the prevalence is still skyrocketing in Australia, in line with global prevalence. Currently, no medicines are approved by the Therapeutic Goods Administration in Australia for the management of prediabetes. Therefore, there is a need of developing a safer, biologically efficacious and cost-effective alternative for delaying the transition of individual health state from prediabetes into T2D. In the current trial we propose to evaluate the effects of curcumin and/or long-chain omega-3 polyunsaturated fatty acids on improving glycosylated haemoglobin as a primary outcome, along with secondary outcomes of glycaemic indices, lipid profile and inflammatory parameters. Eighty individuals diagnosed with prediabetes, aged between 30 and 70 years, will be randomly assigned to double placebo, curcumin alone, fish oil alone or double active groups according to a computer-generated randomisation sequence for 12 weeks. At baseline and post-intervention visits participants will be asked to provide blood samples and undergo body composition measurements. A blood sample is used for estimating glycaemic profiles, lipid profiles and inflammatory parameters (C-reactive protein, whole blood cell count, adiponectin, leptin, interleukin-6). The interim visit includes review on compliance with supplements based on capsule log and capsule count, adverse events and anthropometric measurements. In addition to these procedures, participants provide self-reported questionnaires on dietary intake (using a 3-day food record), a physical activity questionnaire and medical history. This trial aims to determine whether curcumin and/or long-chain omega-3 polyunsaturated fatty acids affect surrogate markers of glycaemic control which is relevant to delaying T2D. To date 38 participants completed the trial. No changes

  13. Short-term memory impairment after isoflurane in mice is prevented by the α5 γ-aminobutyric acid type A receptor inverse agonist L-655,708.

    Science.gov (United States)

    Saab, Bechara J; Maclean, Ashley J B; Kanisek, Marijana; Zurek, Agnieszka A; Martin, Loren J; Roder, John C; Orser, Beverley A

    2010-11-01

    Memory blockade is an essential component of the anesthetic state. However, postanesthesia memory deficits represent an undesirable and poorly understood adverse effect. Inhibitory α5 subunit-containing γ-aminobutyric acid subtype A receptors (α5GABAA) are known to play a critical role in memory processes and are highly sensitive to positive modulation by anesthetics. We postulated that inhibiting the activity of α5GABAA receptors during isoflurane anesthesia would prevent memory deficits in the early postanesthesia period. Mice were pretreated with L-655,708, an α5GABAA receptor-selective inverse agonist, or vehicle. They were then exposed to isoflurane for 1 h (1.3%, or 1 minimum alveolar concentration, or air-oxygen control). Then, either 1 or 24 h later, mice were conditioned in fear-associated contextual and cued learning paradigms. In addition, the effect of L-655,708 on the immobilizing dose of isoflurane was studied. Motor coordination, sedation, anxiety, and the concentration of isoflurane in the brain at 5 min, 1 h, and 24 h after isoflurane were also examined. Motor and sensory function recovered within minutes after termination of isoflurane administration. In contrast, a robust deficit in contextual fear memory persisted for at least 24 h. The α5GABAA receptor inverse agonist, L-655,708, completely prevented memory deficits without changing the immobilizing dose of isoflurane. Trace concentrations of isoflurane were measured in the brain 24 h after treatment. Memory deficits occurred long after the sedative, analgesic, and anxiolytic effects of isoflurane subsided. L-655,708 prevented memory deficit, suggesting that an isoflurane interaction at α5GABAA receptors contributes to memory impairment during the early postanesthesia period.

  14. Low pH immobilizes and kills human leukocytes and prevents transmission of cell-associated HIV in a mouse model

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    Markham Richard B

    2005-09-01

    Full Text Available Abstract Background Both cell-associated and cell-free HIV virions are present in semen and cervical secretions of HIV-infected individuals. Thus, topical microbicides may need to inactivate both cell-associated and cell-free HIV to prevent sexual transmission of HIV/AIDS. To determine if the mild acidity of the healthy vagina and acid buffering microbicides would prevent transmission by HIV-infected leukocytes, we measured the effect of pH on leukocyte motility, viability and intracellular pH and tested the ability of an acidic buffering microbicide (BufferGel® to prevent the transmission of cell-associated HIV in a HuPBL-SCID mouse model. Methods Human lymphocyte, monocyte, and macrophage motilities were measured as a function of time and pH using various acidifying agents. Lymphocyte and macrophage motilities were measured using video microscopy. Monocyte motility was measured using video microscopy and chemotactic chambers. Peripheral blood mononuclear cell (PBMC viability and intracellular pH were determined as a function of time and pH using fluorescent dyes. HuPBL-SCID mice were pretreated with BufferGel, saline, or a control gel and challenged with HIV-1-infected human PBMCs. Results Progressive motility was completely abolished in all cell types between pH 5.5 and 6.0. Concomitantly, at and below pH 5.5, the intracellular pH of PBMCs dropped precipitously to match the extracellular medium and did not recover. After acidification with hydrochloric acid to pH 4.5 for 60 min, although completely immotile, 58% of PBMCs excluded ethidium homodimer-1 (dead-cell dye. In contrast, when acidified to this pH with BufferGel, a microbicide designed to maintain vaginal acidity in the presence of semen, only 4% excluded dye at 10 min and none excluded dye after 30 min. BufferGel significantly reduced transmission of HIV-1 in HuPBL-SCID mice (1 of 12 infected compared to saline (12 of 12 infected and a control gel (5 of 7 infected. Conclusion These

  15. The omega-6/omega-3 fatty acid ratio: health implications

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    Simopoulos Artemis P.

    2010-09-01

    Full Text Available Today, Western diets are characterized by a higher omega-6 and a lower omega-3 fatty acid intake, whereas during the Paleolithic period when human’s genetic profile was established, there was a balance between omega-6 and omega-3 fatty acids. Their balance is an important determinant for brain development and in decreasing the risk for coronary heart disease (CHD, hypertension, cancer, diabetes, arthritis, and other autoimmune and possibly neurodegenerative diseases. Both omega-6 and omega-3 fatty acids influence gene expression. Because of single nucleotide polymorphisms (SNPs in their metabolic pathways, blood levels of omega-6 and omega-3 fatty acids are determined by both endogenous metabolism and dietary intake making the need of balanced dietary intake essential for health and disease prevention. Whether an omega-6/omega-3 ratio of 3:1 to 4:1 could prevent the pathogenesis of many diseases induced by today’s Western diets (AFSSA, 2010, a target of 1:1 to 2:1 appears to be consistent with studies on evolutionary aspects of diet, neurodevelopment, and genetics. A target of omega-6/omega-3 fatty acid ratio of 1:1 to 2:1 appears to be consistent with studies on evolutionary aspects of diet, neurodevelopment and genetics. A balanced ratio of omega-6/omega-3 fatty acids is important for health and in the prevention of CHD and possibly other chronic diseases.

  16. Intake of fish oil, oleic acid, folic acid, and vitamins B-6 and E for 1 year decreases plasma C-reactive protein and reduces coronary heart disease risk factors in male patients in a cardiac rehabilitation program.

    Science.gov (United States)

    Carrero, Juan Jesús; Fonollá, Juristo; Marti, José Luis; Jiménez, Jesús; Boza, Julio J; López-Huertas, Eduardo

    2007-02-01

    Certain nutrients have been shown to be effective in preventing coronary heart disease. We hypothesized that a daily intake of low amounts of a number of these nutrients would exert beneficial effects on risk factors and clinical variables in patients that suffered from myocardial infarction (MI) and were following a cardiac rehabilitation program. Forty male MI patients were randomly allocated into 2 groups. The supplemented group consumed 500 mL/d of a fortified dairy product containing eicosapentaenoic acid, docosahexaenoic acid, oleic acid, folic acid, and vitamins A, B-6, D, and E. The control group consumed 500 mL/d of semi-skimmed milk with added vitamins A and D. The patients received supervised exercise training, lifestyle and dietary recommendations, and they were instructed to consume the products in addition to their regular diet. Blood extractions and clinical examinations were performed after 0, 3, 6, 9, and 12 mo. Plasma concentrations of eicosapentaenoic acid, docosahexaenoic acid, oleic acid, folic acid, vitamin B-6, and vitamin E increased after supplementation (Preactive protein concentrations decreased in the supplemented group (Pprogram comprising regular exercise and the intake of a combination of dietary nutrients, reduced a variety of risk factors in MI patients, which supports the rationale for nutritional programs in the secondary prevention of coronary heart disease.

  17. Docosahexaenoic acid affects arachidonic acid uptake in megakaryocytes

    International Nuclear Information System (INIS)

    Schick, P.K.; Webster, P.

    1987-01-01

    Dietary omega 3 fatty acids are thought to prevent atherosclerosis, possibly by modifying platelet (PT) function and arachidonic acid (20:4) metabolism. The study was designed to determine whether omega 3 fatty acids primarily affect 20:4 metabolism in megakaryocytes (MK), bone marrow precursors of PT, rather than in circulating PT. MK and PT were isolated from guinea pigs and incubated with [ 14 C]-20:4 (0.13uM). Docosahexaenoic acid (22:6) is a major omega 3 fatty acid in marine oils. The incubation of MK with 22:6 (0.1, 1.0 uM) resulted in the decrease of incorporation of [ 14 C]-20:4 into total MK phospholipids, 16% and 41% respectively. Alpha-linolenic acid (18:3), a major omega 3 fatty acid present in American diets, had no effect on 20:4 uptake in MK. 22:6 primarily affected the uptake of [ 14 C]-20:4 into phosphatidylethanolamine (PE) and phosphatidylserine (PS) in MK. In MK, 22:6 (0.1, 1.0 uM) caused a decrease of incorporation of [ 14 C]-20:4 into PE, 21% and 55% respectively; a decrease into PS, 16% and 48% respectively; but only a decrease of 4% and 18%, respectively, into phosphatidylcholine; and a decrease of 3% and 21% into phosphatidylinositol 22:6 (3.0 uM) had no effect on the uptake of AA into PT phospholipids. The study shows that 22:6 has a selective effect on AA uptake in MK and that the acylation or transacylation of PE and PS are primarily affected. 22:6 and other marine omega 3 fatty acids appear to primarily affect megakaryocytes which may result in the production of platelets with abnormal content and compartmentalization of AA

  18. Bile Acid Metabolism and Signaling

    Science.gov (United States)

    Chiang, John Y. L.

    2015-01-01

    Bile acids are important physiological agents for intestinal nutrient absorption and biliary secretion of lipids, toxic metabolites, and xenobiotics. Bile acids also are signaling molecules and metabolic regulators that activate nuclear receptors and G protein-coupled receptor (GPCR) signaling to regulate hepatic lipid, glucose, and energy homeostasis and maintain metabolic homeostasis. Conversion of cholesterol to bile acids is critical for maintaining cholesterol homeostasis and preventing accumulation of cholesterol, triglycerides, and toxic metabolites, and injury in the liver and other organs. Enterohepatic circulation of bile acids from the liver to intestine and back to the liver plays a central role in nutrient absorption and distribution, and metabolic regulation and homeostasis. This physiological process is regulated by a complex membrane transport system in the liver and intestine regulated by nuclear receptors. Toxic bile acids may cause inflammation, apoptosis, and cell death. On the other hand, bile acid-activated nuclear and GPCR signaling protects against inflammation in liver, intestine, and macrophages. Disorders in bile acid metabolism cause cholestatic liver diseases, dyslipidemia, fatty liver diseases, cardiovascular diseases, and diabetes. Bile acids, bile acid derivatives, and bile acid sequestrants are therapeutic agents for treating chronic liver diseases, obesity, and diabetes in humans. PMID:23897684

  19. Sodium 4-phenylbutyrate prevents murine dietary steatohepatitis caused by trans-fatty acid plus fructose.

    Science.gov (United States)

    Morinaga, Maki; Kon, Kazuyoshi; Saito, Hiroaki; Arai, Kumiko; Kusama, Hiromi; Uchiyama, Akira; Yamashina, Shunhei; Ikejima, Kenichi; Watanabe, Sumio

    2015-11-01

    Excess consumption of trans-fatty acid could increase the risk of non-alcoholic steatohepatitis (NASH); however, treatment targeting trans-fatty acid-induced NASH has not been examined. Here we focused on the influence of trans-fatty acid intake on endoplasmic reticulum (ER) stress in hepatocytes, so we investigated the effect of the chemical chaperone 4-phenylbutyric acid (PBA), on trans-fatty acid-caused steatohepatitis using diabetic KK-A(y) mice. Elaidic acid (EA, trans-fatty acid) alone did not cause definitive liver injury. In contrast, EA plus low-dose fructose induced extensive apoptosis in hepatocytes with severe fat accumulation. EA plus fructose significantly increased ER stress markers such as glucose-regulated protein 78 (GRP78), eukaryotic initiation factor 2α (eIF2α) and phosphorylated c-jun N-terminal kinase (JNK), while PBA significantly reduced this response. In vitro, EA promoted expression of GRP78 and phosphorylation of eIF2α in primary-cultured hepatocytes. EA also increased hepatocellular susceptibility to low-dose tert-butyl hydroperoxide. Treatment with PBA significantly reduced these responses. In conclusion, EA potentiates susceptibly to non-hazardous dose of fructose, and increases ER and oxidative stress. PBA improved steatohepatitis induced by EA plus fructose through amelioration of ER stress. Therefore, ER stress-targeted therapy using a chemical chaperone is a promising novel strategy for trans-fatty acid-induced steatohepatitis.

  20. Prenatal folic acid use associated with decreased risk of myelomeningocele: A case-control study offers further support for folic acid fortification in Bangladesh.

    Science.gov (United States)

    Kancherla, Vijaya; Ibne Hasan, Md Omar Sharif; Hamid, Rezina; Paul, Ligi; Selhub, Jacob; Oakley, Godfrey; Quamruzzaman, Quazi; Mazumdar, Maitreyi

    2017-01-01

    Neural tube defects contribute to severe morbidity and mortality in children and adults; however, they are largely preventable through maternal intake of folic acid before and during early pregnancy. We examined the association between maternal prenatal folic acid supplement intake and risk of myelomeningocele (a severe and common type of neural tube defect) in the offspring. We performed secondary analysis using data from a case-control study conducted at Dhaka Community Hospital, Bangladesh between April and November of 2013. Cases and controls included children with and without myelomeningocele, respectively, and their mothers. Cases were identified from local hospitals and rural health clinics served by Dhaka Community Hospital. Controls were selected from pregnancy registries located in the same region as the cases, and matched (1:1) to cases by age and sex. Myelomeningocele in the offspring was confirmed by a pediatrician with expertise in classifying neural tube defects. Maternal prenatal folic acid supplement intake was the main exposure of interest. We estimated crude and adjusted odds ratios (OR) and 95% confidence intervals (CI) using conditional logistic regression analysis. There were 53 pairs of matched cases and controls in our study. Overall, 51% of case mothers reported using folic acid supplements during pregnancy compared to 72% of control mothers (p = 0.03). Median plasma folate concentrations at the time of study visit were 2.79 ng/mL and 2.86 ng/mL among case and control mothers, respectively (p = 0.85). Maternal prenatal folic acid use significantly decreased the odds of myelomeningocele in the offspring (unadjusted OR = 0.42, 95% CI = 0.18-0.96). The association was slightly attenuated after adjusting for maternal age at the time of pregnancy (adjusted OR = 0.43, 95% CI = 0.18-1.02). Our study confirms the protective association between maternal prenatal folic acid supplement use and myelomeningocele among children born in Bangladesh. Our

  1. Prenatal folic acid use associated with decreased risk of myelomeningocele: A case-control study offers further support for folic acid fortification in Bangladesh.

    Directory of Open Access Journals (Sweden)

    Vijaya Kancherla

    Full Text Available Neural tube defects contribute to severe morbidity and mortality in children and adults; however, they are largely preventable through maternal intake of folic acid before and during early pregnancy. We examined the association between maternal prenatal folic acid supplement intake and risk of myelomeningocele (a severe and common type of neural tube defect in the offspring. We performed secondary analysis using data from a case-control study conducted at Dhaka Community Hospital, Bangladesh between April and November of 2013. Cases and controls included children with and without myelomeningocele, respectively, and their mothers. Cases were identified from local hospitals and rural health clinics served by Dhaka Community Hospital. Controls were selected from pregnancy registries located in the same region as the cases, and matched (1:1 to cases by age and sex. Myelomeningocele in the offspring was confirmed by a pediatrician with expertise in classifying neural tube defects. Maternal prenatal folic acid supplement intake was the main exposure of interest. We estimated crude and adjusted odds ratios (OR and 95% confidence intervals (CI using conditional logistic regression analysis. There were 53 pairs of matched cases and controls in our study. Overall, 51% of case mothers reported using folic acid supplements during pregnancy compared to 72% of control mothers (p = 0.03. Median plasma folate concentrations at the time of study visit were 2.79 ng/mL and 2.86 ng/mL among case and control mothers, respectively (p = 0.85. Maternal prenatal folic acid use significantly decreased the odds of myelomeningocele in the offspring (unadjusted OR = 0.42, 95% CI = 0.18-0.96. The association was slightly attenuated after adjusting for maternal age at the time of pregnancy (adjusted OR = 0.43, 95% CI = 0.18-1.02. Our study confirms the protective association between maternal prenatal folic acid supplement use and myelomeningocele among children born in

  2. The role of polyunsaturated fatty acids (n-3 PUFAs) on the pancreatic β-cells and insulin action.

    Science.gov (United States)

    Baynes, Habtamu Wondifraw; Mideksa, Seifu; Ambachew, Sintayehu

    2018-03-14

    Polyunsaturated Fatty acids have multiple effects in peripheral tissues and pancreatic beta cell function. The n-3 Polyunsaturated Fatty acids prevent and reverse high-fat-diet induced adipose tissue inflammation and insulin resistance. Insulin secretion is stimulated by glucose, amino acids, and glucagon- like peptide-1 in tissue containing high levels of n-3 Polyunsaturated Fatty acids than lower level of n-3 Polyunsaturated Fatty acids. Also, n-3 Polyunsaturated Fatty acids led to decreased production of prostaglandin, which in turn contributed to the elevation of insulin secretion. N-3 polyunsaturated fatty acids prevent cytokine-induced cell death in pancreatic islets. Supplementation of n-3 Polyunsaturated Fatty acids for human subjects prevent beta cell destruction and insulin resistance. It also enhances insulin secretion, reduction in lipid profiles and glucose concentration particularly in type II diabetes patients. Therefore there should be a focus on the treatment mechanism of insulin related obesity and diabetes by n-3 polyunsaturated fatty acids.

  3. Folic Acid and Birth Defects: A Case Study (Iran

    Directory of Open Access Journals (Sweden)

    Mohammad Bager Hosseini

    2011-01-01

    Full Text Available The aim of this study was to evaluate the impact of folic acid use in pregnancy for the reduction of neural tube defects (NTDs in the northwest region of Iran. We studied 243 women with pregnancies complicated by some forms of birth defect(s. These patients were identified by medical diagnostic tests as having a fetus with some types of congenital anomalies. The prevalence of NTDs among pregnant women who were referred for therapeutic termination of pregnancy was 24.7 percent. Consumption of folic acid prevented NTDs by 79 percent (Odds Ratio = 0.21, CI 95%: 0.12–0.40 and 94 percent (Odds Ratio = 0.06, CI 95%: 0.03–0.15 compared to pregnancies complicated by other anomalies and normal pregnancies, respectively. Hydrops fetalis, hydrocephaly, Down syndrome, and limb anomalies did not have any significant association with the folic acid use. Along with the advice for the consumption of folic acid for pregnant women, they should be offered prenatal screening or diagnostic tests to identify fetal abnormalities for possible termination of pregnancy.

  4. PPAR/RXR Regulation of Fatty Acid Metabolism and Fatty Acid -Hydroxylase (CYP4 Isozymes: Implications for Prevention of Lipotoxicity in Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    James P. Hardwick

    2009-01-01

    Full Text Available Fatty liver disease is a common lipid metabolism disorder influenced by the combination of individual genetic makeup, drug exposure, and life-style choices that are frequently associated with metabolic syndrome, which encompasses obesity, dyslipidemia, hypertension, hypertriglyceridemia, and insulin resistant diabetes. Common to obesity related dyslipidemia is the excessive storage of hepatic fatty acids (steatosis, due to a decrease in mitochondria -oxidation with an increase in both peroxisomal -oxidation, and microsomal -oxidation of fatty acids through peroxisome proliferator activated receptors (PPARs. How steatosis increases PPAR activated gene expression of fatty acid transport proteins, peroxisomal and mitochondrial fatty acid -oxidation and -oxidation of fatty acids genes regardless of whether dietary fatty acids are polyunsaturated (PUFA, monounsaturated (MUFA, or saturated (SFA may be determined by the interplay of PPARs and HNF4 with the fatty acid transport proteins L-FABP and ACBP. In hepatic steatosis and steatohepatitis, the -oxidation cytochrome P450 CYP4A gene expression is increased even with reduced hepatic levels of PPAR. Although numerous studies have suggested the role ethanol-inducible CYP2E1 in contributing to increased oxidative stress, Cyp2e1-null mice still develop steatohepatitis with a dramatic increase in CYP4A gene expression. This strongly implies that CYP4A fatty acid -hydroxylase P450s may play an important role in the development of steatohepatitis. In this review and tutorial, we briefly describe how fatty acids are partitioned by fatty acid transport proteins to either anabolic or catabolic pathways regulated by PPARs, and we explore how medium-chain fatty acid (MCFA CYP4A and long-chain fatty acid (LCFA CYP4F -hydroxylase genes are regulated in fatty liver. We finally propose a hypothesis that increased CYP4A expression with a decrease in CYP4F genes may promote the progression of steatosis to

  5. Gallic Acid Attenuates Postoperative Intra-Abdominal Adhesion by Inhibiting Inflammatory Reaction in a Rat Model

    Science.gov (United States)

    Wei, Guangbing; Wu, Yunhua; Gao, Qi; Shen, Cong; Chen, Zilu; Wang, Kang; Yu, Junhui

    2018-01-01

    Background Intra-abdominal adhesion is one of the most common complications after abdominal surgery. The efficacy of current treatments for intra-abdominal adhesion is unsatisfactory. In this study, we investigated the effect of gallic acid on the prevention and treatment of intra-abdominal adhesions after abdominal surgery using an intra-abdominal adhesion rat model. Material/Methods The experimental rats were randomly divided into the sham operation group, the control group, the chitosan group, and 3 gallic acid groups of different concentrations. All rats except those in the sham operation group received cecal abrasion to induce adhesion. From the first postoperative day, the rats in the gallic acid groups were administered different concentrations of gallic acid in a 2-ml gavage daily. All rats were sacrificed on postoperative day 7, and the degree of intra-abdominal adhesion was evaluated by the naked eye. The amount of collagen deposited between the injured peritoneal tissues was assessed by Sirius red staining. Serum levels of interleukin-6 (IL-6), tumor necrosis factor (TNF-α), and transforming growth factor-β (TGF-β) were measured by ELISA. Western blot was used to detect the level of NF-κB phosphorylation in the injured peritoneal or adhesion tissues of the rats. Results Compared with the control group, the scores of intra-abdominal adhesions in the rats treated with larger doses of gallic acid were significantly decreased, and the degree of inflammation and fibrosis was also significantly decreased. Gallic acid significantly reduced IL-6, TNF-α, and TGF-β1 serum levels. NF-κB phosphorylation in the higher gallic acid groups was significantly reduced. Conclusions Gallic acid inhibits the formation of postoperative intra-abdominal adhesions in rats by inhibiting the inflammatory reaction and fibrogenesis. Gallic acid is a promising drug for preventing intra-abdominal adhesions. PMID:29429982

  6. Implementing preventive iron-folic acid supplementation among women of reproductive age in some Western Pacific countries: possibilities and challenges.

    Science.gov (United States)

    Smitasiri, Suttilak; Solon, Florentino S

    2005-12-01

    Lack of effective implementation mechanisms is identified as a major obstacle in the prevention and control of iron-deficiency anemia. This paper discusses experiences gained from implementing iron-folic acid supplementation in the Philippines, Vietnam, and Cambodia. The understanding of contextual elements is proposed as a foundation for planning interventions. Moreover, it is suggested that a social marketing framework should provide a way of thinking about how to influence related behaviors. The application of a social marketing framework applied using a "5 P's" approach: public relations and collaboration, product, price, place, and promotion, is described, as well as enabling factors (possibilities) and inhibiting factors (challenges) of this approach. Although a program to improve iron nutrition among women of reproductive age may not be simple to implement, it is essential to enhancing health, human development, and economic advancement in developing countries.

  7. Paper-Based Microfluidic Device with a Gold Nanosensor to Detect Arsenic Contamination of Groundwater in Bangladesh

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    Mosfera A. Chowdury

    2017-03-01

    Full Text Available In this paper, we present a microfluidic paper-based analytical device (μPAD with a gold nanosensor functionalized with α-lipoic acid and thioguanine (Au–TA–TG to detect whether the arsenic level of groundwater from hand tubewells in Bangladesh is above or below the World Health Organization (WHO guideline level of 10 μg/L. We analyzed the naturally occurring metals present in Bangladesh groundwater and assessed the interference with the gold nanosensor. A method was developed to prevent interference from alkaline metals found in Bangladesh groundwater (Ca, Mg, K and Na by increasing the pH level on the μPADs to 12.1. Most of the heavy metals present in the groundwater (Ni, Mn, Cd, Pb, and Fe II did not interfere with the μPAD arsenic tests; however, Fe III was found to interfere, which was also prevented by increasing the pH level on the μPADs to 12.1. The μPAD arsenic tests were tested with 24 groundwater samples collected from hand tubewells in three different districts in Bangladesh: Shirajganj, Manikganj, and Munshiganj, and the predictions for whether the arsenic levels were above or below the WHO guideline level agreed with the results obtained from laboratory testing. The μPAD arsenic test is the first paper-based test validated using Bangladesh groundwater samples and capable of detecting whether the arsenic level in groundwater is above or below the WHO guideline level of 10 μg/L, which is a step towards enabling the villagers who collect and consume the groundwater to test their own sources and make decisions about where to obtain the safest water.

  8. Effectiveness of tranexamic acid for decreasing bleeding in prostate surgery: a systematic review and meta-analysis.

    Science.gov (United States)

    Mina, Sergio Hernando; Garcia-Perdomo, Herney Andres

    2018-01-01

    The objective of this study was to determine the effectiveness of tranexamic acid in decreasing bleeding in patients undergoing prostate surgery. All clinical experiments were included without language restrictions. The inclusion criteria were as follows: men over 18 years of age who underwent prostate surgery (transurethral, prostate adenectomy, and radical prostatectomy) and received tranexamic acid prior to prostate surgery as a preventive measure for perioperative hemorrhage. Prophylactic tranexamic acid vs. no intervention or placebo were compared. The primary outcomes were as follows: 1) intraoperative blood loss and 2) the need for red blood cell transfusion. A systematic search was performed in MEDLINE, EMBASE, CENTRAL and LILACS. Other sources were used to discover published and unpublished literature sources. The statistical analysis was performed in Review Manager v.5.3. Four studies were included with a total of 436 patients. Three of the four studies had small sample sizes. There was a low risk of attrition bias and reporting bias. Unclear risk of selection bias, performance bias, or detection bias was presented. A mean difference (MD) of -174.49 [95% CI (-248.43 to -100.56)] was found for perioperative blood loss (the primary outcome). At the end of the procedure, the hemoglobin concentration had a MD of -1.19 [95% CI (-4.37 to 1.99)]. Tranexamic acid is effective at preventing perioperative blood loss compared with the placebo in patients undergoing transurethral resection of the prostate (TURP). However, this treatment was not effective neither at preventing the need for transfusions nor at increasing hemoglobin values at the end of the procedure.

  9. Oral Metformin-Ascorbic Acid Co-Administration Ameliorates Alcohol ...

    African Journals Online (AJOL)

    Oral Metformin-Ascorbic Acid Co-Administration Ameliorates Alcohol-Induced Hepatotoxicity In Rats. ... Nigerian Quarterly Journal of Hospital Medicine ... the present in vivo animal study was to determine whether metformin-ascorbic acid co-administration also prevents alcoholic hepatotoxicity in chronic alcohol exposure.

  10. Cost-effectiveness of periconceptional supplementation of folic acid

    NARCIS (Netherlands)

    Postma, MJ; Londeman, J; Veenstra, M; de Walle, HEK; de Jong-van den Berg, LTW

    Background: Supplementation of folic acid prior to and in the beginning of pregnancy may prevent neural tube defects (NTDs) in newborns - such as spina bifida - and possibly other congenital malformations. Objective. To estimate cost effectiveness of periconceptional supplementation of folk: acid

  11. Miniaturized isothermal nucleic acid amplification, a review.

    Science.gov (United States)

    Asiello, Peter J; Baeumner, Antje J

    2011-04-21

    Micro-Total Analysis Systems (µTAS) for use in on-site rapid detection of DNA or RNA are increasingly being developed. Here, amplification of the target sequence is key to increasing sensitivity, enabling single-cell and few-copy nucleic acid detection. The several advantages to miniaturizing amplification reactions and coupling them with sample preparation and detection on the same chip are well known and include fewer manual steps, preventing contamination, and significantly reducing the volume of expensive reagents. To-date, the majority of miniaturized systems for nucleic acid analysis have used the polymerase chain reaction (PCR) for amplification and those systems are covered in previous reviews. This review provides a thorough overview of miniaturized analysis systems using alternatives to PCR, specifically isothermal amplification reactions. With no need for thermal cycling, isothermal microsystems can be designed to be simple and low-energy consuming and therefore may outperform PCR in portable, battery-operated detection systems in the future. The main isothermal methods as miniaturized systems reviewed here include nucleic acid sequence-based amplification (NASBA), loop-mediated isothermal amplification (LAMP), helicase-dependent amplification (HDA), rolling circle amplification (RCA), and strand displacement amplification (SDA). Also, important design criteria for the miniaturized devices are discussed. Finally, the potential of miniaturization of some new isothermal methods such as the exponential amplification reaction (EXPAR), isothermal and chimeric primer-initiated amplification of nucleic acids (ICANs), signal-mediated amplification of RNA technology (SMART) and others is presented.

  12. Omega-6 fatty acid biomarkers and incident type 2 diabetes

    NARCIS (Netherlands)

    Wu, Jason H.Y.; Marklund, Matti; Imamura, Fumiaki; Tintle, Nathan; Ardisson Korat, Andres V.; Goede, de Janette; Zhou, Xia; Yang, Wei Sin; Oliveira Otto, de Marcia C.; Kröger, Janine; Qureshi, Waqas; Virtanen, Jyrki K.; Bassett, Julie K.; Frazier-Wood, Alexis C.; Lankinen, Maria; Murphy, Rachel A.; Rajaobelina, Kalina; Gobbo, Del Liana C.; Forouhi, Nita G.; Luben, Robert; Khaw, Kay Tee; Wareham, Nick; Kalsbeek, Anya; Veenstra, Jenna; Luo, Juhua; Hu, Frank B.; Lin, Hung Ju; Siscovick, David S.; Boeing, Heiner; Chen, Tzu An; Steffen, Brian; Steffen, Lyn M.; Hodge, Allison; Eriksdottir, Gudny; Smith, Albert V.; Gudnason, Vilmunder; Harris, Tamara B.; Brouwer, Ingeborg A.; Berr, Claudine; Helmer, Catherine; Samieri, Cecilia; Laakso, Markku; Tsai, Michael Y.; Giles, Graham G.; Nurmi, Tarja; Wagenknecht, Lynne; Schulze, Matthias B.; Lemaitre, Rozenn N.; Chien, Kuo Liong; Soedamah-Muthu, Sabita S.; Geleijnse, Johanna M.; Sun, Qi; Harris, William S.; Lind, Lars; Ärnlöv, Johan; Riserus, Ulf; Micha, Renata; Mozaffarian, Dariush

    2017-01-01

    Background: The metabolic effects of omega-6 polyunsaturated fatty acids (PUFAs) remain contentious, and little evidence is available regarding their potential role in primary prevention of type 2 diabetes. We aimed to assess the associations of linoleic acid and arachidonic acid biomarkers with

  13. Farnesoid X Receptor Agonist Treatment Alters Bile Acid Metabolism but Exacerbates Liver Damage in a Piglet Model of Short-Bowel Syndrome.

    Science.gov (United States)

    Pereira-Fantini, Prue M; Lapthorne, Susan; Gahan, Cormac G M; Joyce, Susan A; Charles, Jenny; Fuller, Peter J; Bines, Julie E

    2017-07-01

    Options for the prevention of short-bowel syndrome-associated liver disease (SBS-ALDs) are limited and often ineffective. The farnesoid X receptor (FXR) is a newly emerging pharmaceutical target and FXR agonists have been shown to ameliorate cholestasis and metabolic disorders. The aim of this study was to assess the efficacy of obeticholic acid (OCA) treatment in preventing SBS-ALDs. Piglets underwent 75% small-bowel resection (SBS) or sham surgery (sham) and were assigned to either a daily dose of OCA (2.4 mg/kg/day) or were untreated. Clinical measures included weight gain and stool studies. Histologic features were assessed. Ultraperformance liquid chromatography tandem mass spectrometry was used to determine bile acid composition in end point bile and portal serum samples. Gene expression of key FXR targets was assessed in intestinal and hepatic tissues via quantitative polymerase chain reaction. OCA-treated SBS piglets showed decreased stool fat and altered liver histology when compared with nontreated SBS piglets. OCA prevented SBS-associated taurine depletion, however, further analysis of bile and portal serum samples indicated that OCA did not prevent SBS-associated alterations in bile acid composition. The expression of FXR target genes involved in bile acid transport and synthesis increased within the liver of SBS piglets after OCA administration whereas, paradoxically, intestinal expression of FXR target genes were decreased by OCA administration. Administration of OCA in SBS reduced fat malabsorption and altered bile acid composition, but did not prevent the development of SBS-ALDs. We postulate that extensive small resection impacts the ability of the remnant intestine to respond to FXR activation.

  14. A Randomized Clinical Trial of Preoperative Administration of Branched-Chain Amino Acids to Prevent Postoperative Ascites in Patients with Liver Resection for Hepatocellular Carcinoma.

    Science.gov (United States)

    Kikuchi, Yutaro; Hiroshima, Yukihiko; Matsuo, Kenichi; Kawaguchi, Daisuke; Murakami, Takashi; Yabushita, Yasuhiro; Endo, Itaru; Taguri, Masataka; Koda, Keiji; Tanaka, Kuniya

    2016-10-01

    Massive postoperative ascites remains a major threat that can lead to liver failure and other fatal complications, especially in patients with poor liver function. Branched-chain amino acid (BCAA) administration increases biosynthesis and secretion of albumin by hepatocytes and increases oncotic pressure by elevating blood albumin concentration, thereby decreasing peripheral edema, ascites, and pleural effusion. We randomly allocated consecutive patients undergoing major liver resection for hepatocellular carcinoma to either a group where oral BCAA administration was initiated 3 weeks before liver resection, or a non-BCAA group. The primary study endpoint was development of postoperative ascites. Overall, 39 patients were allocated to the BCAA group, while 38 were assigned to the non-BCAA group. No significant difference in the rate of refractory ascites, considered alone, was evident between the BCAA (5.1 %) and non-BCAA groups (13.2 %; p = 0.263). However, the occurrence of refractory ascites and/or pleural effusion was significantly less frequent in the BCAA group (5.1 %) than in the non-BCAA group (21.1 %; p = 0.047). Furthermore, the postoperative serum concentration of reduced-state albumin was greater immediately after liver resection in the BCAA group than in the non-BCAA group. Preoperative administration of BCAA did not significantly improve prevention of refractory ascites, but significant effectiveness in preventing ascites, pleural effusion, or both, as well as improving metabolism of albumin, was demonstrated [University Hospital Medical Information Network (UMIN) reference number 000004244].

  15. Low compliance with recommendations on folic acid use in relation to pregnancy: is there a need for fortification?

    DEFF Research Database (Denmark)

    Knudsen, Vibeke; Orozova-Bekkevold, Ivanka; Rasmussen, Lone Banke

    2004-01-01

    Objective: As a means to prevent neural tube defects (NTDs), women planning pregnancy in Denmark are recommended to take a dietary supplement of 400 mug folic acid daily during the periconceptional period. We examined compliance with this recommendation in a national survey. Design: Cohort study...... campaign events. However, even at the end of the period, only 22.3% of the women who had planned their pregnancy fully complied with the recommendation. No increase at all was seen in periconceptional folic acid use among women with unplanned pregnancies. Young age, low education and smoking were...... identified as factors that determined non-compliance. Conclusions: Alternative and more effective strategies are needed if the Danish population is to benefit fully from the knowledge that folic acid prevents NTDs. Future strategies should not only target vulnerable groups, such as the less educated...

  16. Global Burden of Neural Tube Defects, Risk Factors, and Prevention

    Directory of Open Access Journals (Sweden)

    Joseph E

    2014-11-01

    Full Text Available Neural tube defects (NTDs, serious birth defects of the brain and spine usually resulting in death or paralysis, affect an estimated 300,000 births each year worldwide. Although the majority of NTDs are preventable with adequate folic acid consumption during the preconception period and throughout the first few weeks of gestation, many populations, in particular those in low and middle resource settings, do not have access to fortified foods or vitamin supplements containing folic acid. Further, accurate birth defects surveillance data, which could help inform mandatory fortification and other NTD prevention initiatives, are lacking in many of these settings. The burden of birth defects in South East Asia is among the highest in the world. Expanding global neural tube defects prevention initiatives can support the achievement of the United Nations Millennium Development Goal 4 to reduce child mortality, a goal which many countries in South East Asia are currently not poised to reach, and the 63rd World Health Assembly Resolution on birth defects. More work is needed to develop and implement mandatory folic acid fortification policies, as well as supplementation programs in countries where the reach of fortification is limited.

  17. Aristolochic acid nephropathy: Harbinger of a global iatrogenic disease.

    Science.gov (United States)

    Grollman, Arthur P

    2013-01-01

    This review constitutes an overview of our investigations of aristolochic acid nephropathy, a chronic kidney disease associated with carcinomas of the upper urinary tract. Our studies began by confirming the hypothesis that chronic dietary poisoning by aristolochic acid was responsible for endemic (Balkan) nephropathy. A unique TP53 mutational signature in urothelial tumors and the presence of aristolactam-DNA adducts in the renal cortex, defined in the course of this research, proved to be robust biomarkers of exposure to this potent nephrotoxin and human carcinogen. Armed with this information, we used molecular epidemiologic approaches and novel mechanistic information to establish the causative role of aristolochic acid in upper urinary tract carcinoma in Taiwan, where one-third of the population had been prescribed herbal remedies containing Aristolochia, and the recorded incidence of upper urinary tract cancers is the highest in the world. As traditional Chinese medicine is practiced similarly in Taiwan and China, it is likely that upper urinary tract carcinomas and their attendant aristolochic acid nephropathy are prevalent in China and other Asian countries where Aristolochia herbs have been used for centuries in the treatment and prevention of disease, creating a potential public health problem of considerable magnitude. Copyright © 2012 Wiley Periodicals, Inc.

  18. Techniques to correct and prevent acid mine drainage: A review

    Directory of Open Access Journals (Sweden)

    Santiago Pozo-Antonio

    2014-01-01

    Full Text Available En la actualidad uno de los problemas medioambientales con mayor necesidad de actuación es la contaminación por la formación de drenajes ácidos de mina (AMD: “Acid Mine Drainage” procedentes de estériles de mina. Este es el término utilizado para describir el drenaje generado por la oxidación natural de sulfuros minerales que son expuestos a la acción combinada de agua y oxígeno atmosférico. Los minerales responsables de la generación de AMD son los sulfuros de hierro (pirita, FeS2 y en menor medida la pirrotita, Fe1-XS, los cuales son estables e insolubles mientras no se encuentren en contacto con agua y oxígeno atmosférico. Sin embargo, como consecuencia de la actividad minera, estos dos sulfuros son expuestos a condiciones ambientales oxidantes. La necesidad de prevenir la formación de AMD ha desarrollado numerosas investigaciones sobre los mecanismos de oxidación y su prevención. En el presente trabajo además de realizar una explicación y valoración teórica del proceso de oxidación de la pirita también se realiza un compendio de las medidas preventivas y correctoras más empleadas.

  19. Treating asthma with omega-3 fatty acids: where is the evidence? A systematic review

    Directory of Open Access Journals (Sweden)

    Sampson M

    2006-07-01

    Full Text Available Abstract Background Considerable interest exists in the potential therapeutic value of dietary supplementation with the omega-3 fatty acids. Given the interplay between pro-inflammatory omega-6 fatty acids, and the less pro-inflammatory omega-3 fatty acids, it has been thought that the latter could play a key role in treating or preventing asthma. The purpose was to systematically review the scientific-medical literature in order to identify, appraise, and synthesize the evidence for possible treatment effects of omega-3 fatty acids in asthma. Methods Medline, Premedline, Embase, Cochrane Central Register of Controlled Trials, CAB Health, and, Dissertation Abstracts were searched to April 2003. We included randomized controlled trials (RCT's of subjects of any age that used any foods or extracts containing omega-3 fatty acids as treatment or prevention for asthma. Data included all asthma related outcomes, potential covariates, characteristics of the study, design, population, intervention/exposure, comparators, and co interventions. Results Ten RCT's were found pertinent to the present report. Conclusion Given the largely inconsistent picture within and across respiratory outcomes, it is impossible to determine whether or not omega-3 fatty acids are an efficacious adjuvant or monotherapy for children or adults. Based on this systematic review we recommend a large randomized controlled study of the effects of high-dose encapsulated omega-3 fatty acids on ventilatory and inflammatory measures of asthma controlling diet and other asthma risk factors. This review was limited because Meta-analysis was considered inappropriate due to missing data; poorly or heterogeneously defined populations, interventions, intervention-comparator combinations, and outcomes. In addition, small sample sizes made it impossible to meaningfully assess the impact on clinical outcomes of co-variables. Last, few significant effects were found.

  20. Folic acid knowledge and use among expectant mothers in 1997: a comparison with 1996.

    LENUS (Irish Health Repository)

    McDonnell, R

    1999-04-01

    This study examined changes in folic acid knowledge and use among antenatal women in Dublin maternity hospitals between 1996 and 1997, following a campaign to improve the very low uptake of peri-conceptional folic acid. The results showed significant improvements between the two years. Almost 76% of respondents had heard of folic acid in 1997 compared with 54% in 1996 (p < 0.01), with a shift in the proportion of people hearing of folic acid from hospital doctors to general practitioners (GP). Almost 43% of respondents in 1997 knew that folic acid can prevent spina bifida compared with 21% in 1996 (p < 0.01). A higher proportion was taking folic acid prior to conception in 1997 (16% vs 6%, p < 0.01). We conclude that the improvements may have been in part due to the promotional campaign among health professionals, women\\'s groups and the media. However, less than a fifth of women were taking folic acid peri-conceptionally in 1997 and there is still scope for much improvement.