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Sample records for carnosine

  1. Carnosine, carnosinase and kidney diseases

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    Katarzyna Kiliś-Pstrusińska

    2012-04-01

    Full Text Available  Carnosine (beta-alanyl-L-histidine is an endogenously synthesized dipeptide which is present in different human tissues, including the kidney. Carnosine is hydrolyzed by the enzyme carnosinase. There are two carnosinase homologues: serum secreted carnosinase and non-specific cytosolic dipeptidase, encoded by the genes CNDP1 and CNDP2 respectively and located on chromosome 18q22.3. Carnosine functions as a radical oxygen species scavenger and as a natural angiotensin converting enzyme inhibitor. Carnosine inhibits advanced glycation end product formation and reduces the synthesis of matrix proteins such as fibronectin and collagen type VI of podocytes and mesangial cells. In experimental studies it was shown that carnosine reduces the level of proinflammatory and profibrotic cytokines. It is suggested that carnosine is a naturally occurring anti-aging substance in human organisms with a beneficial effect on the cardiovascular system.This paper reports the results of studies concerning carnosine’s role in kidney diseases, particularly in ischemia/reperfusion induced acute renal failure, diabetic nephropathy, gentamicin-induced nephrotoxicity and also in blood pressure regulation. The correlations between serum carnosine and serum carnosinase activity and polymorphism in the CNDP1 gene are analyzed. The role of CNDP1 gene polymorphism in the development of diabetic nephropathy and non-diabetic chronic kidney disease is discussed. Carnosine is engaged in different metabolic pathways. It has nephroprotective features. Further studies of carnosine metabolism and its biological properties, particularly those concerning the human organism, are required.

  2. Determinants of muscle carnosine content.

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    Harris, R C; Wise, J A; Price, K A; Kim, H J; Kim, C K; Sale, C

    2012-07-01

    The main determinant of muscle carnosine (M-Carn) content is undoubtedly species, with, for example, aerobically trained female vegetarian athletes [with circa 13 mmol/kg dry muscle (dm)] having just 1/10th of that found in trained thoroughbred horses. Muscle fibre type is another key determinant, as type II fibres have a higher M-Carn or muscle histidine containing dipeptide (M-HCD) content than type I fibres. In vegetarians, M-Carn is limited by hepatic synthesis of β-alanine, whereas in omnivores this is augmented by the hydrolysis of dietary supplied HCD's resulting in muscle levels two or more times higher. β-alanine supplementation will increase M-Carn. The same increase in M-Carn occurs with administration of an equal molar quantity of carnosine as an alternative source of β-alanine. Following the cessation of supplementation, M-Carn returns to pre-supplementation levels, with an estimated t1/2 of 5-9 weeks. Higher than normal M-Carn contents have been noted in some chronically weight-trained subjects, but it is unclear if this is due to the training per se, or secondary to changes in muscle fibre composition, an increase in β-alanine intake or even anabolic steroid use. There is no measureable loss of M-Carn with acute exercise, although exercise-induced muscle damage may result in raised plasma concentrations in equines. Animal studies indicate effects of gender and age, but human studies lack sufficient control of the effects of diet and changes in muscle fibre composition.

  3. Transport characteristics of L-carnosine and the anticancer derivative 4-toluenesulfonylureido-carnosine in a human epithelial cell line

    DEFF Research Database (Denmark)

    Nielsen, Carsten Uhd; Supuran, Claudiu T; Scozzafava, Andrea

    2002-01-01

    The aim of the present study was to evaluate whether the transepithelial transport of the anticancer compound 4-toluenesulfonylureido-carnosine (Ts-carnosine) and the dipeptide moiety L-carnosine was due to a hPepT1 carrier-mediated flux....

  4. Effectiveness of carnosine on disturbed electrolytes homeostasis ...

    African Journals Online (AJOL)

    We aimed to assess the effect of well known antioxidant carnosine on disturbed plasma and intraerythrocytes electrolytes and Na+-K+-ATPase activity by cisplatin. 24 male albino Wistar rats were selected and divided into 4 groups: Group I = untreated control; Group II = cisplatin control (received cisplatin at a dose of 3 mg/ ...

  5. Muscle Carnosine Is Associated with Cardiometabolic Risk Factors in Humans.

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    Barbora de Courten

    Full Text Available Carnosine is a naturally present dipeptide abundant in skeletal muscle and an over-the counter food additive. Animal data suggest a role of carnosine supplementation in the prevention and treatment of obesity, insulin resistance, type 2 diabetes and cardiovascular disease but only limited human data exists.Samples of vastus lateralis muscle were obtained by needle biopsy. We measured muscle carnosine levels (high-performance liquid chromatography, % body fat (bioimpedance, abdominal subcutaneous and visceral adiposity (magnetic resonance imaging, insulin sensitivity (euglycaemic hyperinsulinemic clamp, resting energy expenditure (REE, indirect calorimetry, free-living ambulatory physical activity (accelerometers and lipid profile in 36 sedentary non-vegetarian middle aged men (45±7 years with varying degrees of adiposity and glucose tolerance. Muscle carnosine content was positively related to % body fat (r = 0.35, p = 0.04 and subcutaneous (r = 0.38, p = 0.02 but not visceral fat (r = 0.17, p = 0.33. Muscle carnosine content was inversely associated with insulin sensitivity (r = -0.44, p = 0.008, REE (r = -0.58, p<0.001 and HDL-cholesterol levels (r = -0.34, p = 0.048. Insulin sensitivity and physical activity were the best predictors of muscle carnosine content after adjustment for adiposity.Our data shows that higher carnosine content in human skeletal muscle is positively associated with insulin resistance and fasting metabolic preference for glucose. Moreover, it is negatively associated with HDL-cholesterol and basal energy expenditure. Intervention studies targeting insulin resistance, metabolic and cardiovascular disease risk factors are necessary to evaluate its putative role in the prevention and management of type 2 diabetes and cardiovascular disease.

  6. Carnosine may reduce lung injury caused by radiation therapy.

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    Guney, Yildiz; Turkcu, Ummuhani Ozel; Hicsonmez, Ayse; Andrieu, Meltem Nalca; Guney, H Zafer; Bilgihan, Ayse; Kurtman, Cengiz

    2006-01-01

    Ionising radiation is known one of the most effective tools in the therapy of cancer but in many thoracic cancers, the total prescribed dose of radiation that can be safely administered to the target volume is limited by the risk of complications arising in the normal lung tissue. One of the major reasons for cellular injury after radiation is the formation of reactive oxygen species (ROS). Radiation pneumonitis is an acute phase side-effect which generally subsides after a few weeks and is followed by a chronic phase characterized by inflammation and fibrosis, that can develop months or years after irradiation. Carnosine is a dipeptide composed by the amino acids beta-histidine and l-alanine. The exact biological role of carnosine is not totally understood, but several studies have demonstrated that it possesses strong and specific antioxidant properties, protects against radiation damage,and promotes wound healing. The antioxidant mechanism of carnosine is attributed to its chelating effect against metal ions, superoxide dismutase (SOD)-like activity, ROS and free radicals scavenging ability . Either its antioxidant or anti-inflammatuar properties, we propose that carnosine ameliorates irradiation-induced lung injury. Thus, supplementing cancer patients to whom applied radiation therapy with carnosine, may provide an alleviation of the symptoms due to radiation-induced lung injury. This issue warrants further studies.

  7. A carnosine intervention study in overweight human volunteers: bioavailability and reactive carbonyl species sequestering effect

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    Regazzoni, Luca; de Courten, Barbora; Garzon, Davide; Altomare, Alessandra; Marinello, Cristina; Jakubova, Michaela; Vallova, Silvia; Krumpolec, Patrik; Carini, Marina; Ukropec, Jozef; Ukropcova, Barbara; Aldini, Giancarlo

    2016-06-01

    Carnosine is a natural dipeptide able to react with reactive carbonyl species, which have been recently associated with the onset and progression of several human diseases. Herein, we report an intervention study in overweight individuals. Carnosine (2 g/day) was orally administered for twelve weeks in order to evaluate its bioavailability and metabolic fate. Two carnosine adducts were detected in the urine samples of all subjects. Such adducts are generated from a reaction with acrolein, which is one of the most toxic and reactive compounds among reactive carbonyl species. However, neither carnosine nor adducts have been detected in plasma. Urinary excretion of adducts and carnosine showed a positive correlation although a high variability of individual response to carnosine supplementation was observed. Interestingly, treated subjects showed a significant decrease in the percentage of excreted adducts in reduced form, accompanied by a significant increase of the urinary excretion of both carnosine and carnosine-acrolein adducts. Altogether, data suggest that acrolein is entrapped in vivo by carnosine although the response to its supplementation is possibly influenced by individual diversities in terms of carnosine dietary intake, metabolism and basal production of reactive carbonyl species.

  8. Role of histidine/histamine in carnosine-induced neuroprotection during ischemic brain damage.

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    Bae, Ok-Nam; Majid, Arshad

    2013-08-21

    Urgent need exists for new therapeutic options in ischemic stroke. We recently demonstrated that carnosine, an endogenous dipeptide consisting of alanine and histidine, is robustly neuroprotective in ischemic brain injury and has a wide clinically relevant therapeutic time window. The precise mechanistic pathways that mediate this neuroprotective effect are not known. Following in vivo administration, carnosine is hydrolyzed into histidine, a precursor of histamine. It has been hypothesized that carnosine may exert its neuroprotective activities through the histidine/histamine pathway. Herein, we investigated whether the neuroprotective effect of carnosine is mediated by the histidine/histamine pathway using in vitro primary astrocytes and cortical neurons, and an in vivo rat model of ischemic stroke. In primary astrocytes, carnosine significantly reduced ischemic cell death after oxygen-glucose deprivation, and this effect was abolished by histamine receptor type I antagonist. However, histidine or histamine did not exhibit a protective effect on ischemic astrocytic cell death. In primary neuronal cultures, carnosine was found to be neuroprotective but histamine receptor antagonists had no effect on the extent of neuroprotection. The in vivo effect of histidine and carnosine was compared using a rat model of ischemic stroke; only carnosine exhibited neuroprotection. Taken together, our data demonstrate that although the protective effects of carnosine may be partially mediated by activity at the histamine type 1 receptor on astrocytes, the histidine/histamine pathway does not appear to play a critical role in carnosine induced neuroprotection. Copyright © 2013. Published by Elsevier B.V.

  9. Would carnosine or a carnivorous diet help suppress aging and associated pathologies?

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    Hipkiss, Alan R

    2006-05-01

    Carnosine (beta-alanyl-L-histidine) is found exclusively in animal tissues. Carnosine has the potential to suppress many of the biochemical changes (e.g., protein oxidation, glycation, AGE formation, and cross-linking) that accompany aging and associated pathologies. Glycation, generation of advanced glycosylation end-products (AGEs), and formation of protein carbonyl groups play important roles in aging, diabetes, its secondary complications, and neurodegenerative conditions. Due to carnosine's antiglycating activity, reactivity toward deleterious carbonyls, zinc- and copper-chelating activity and low toxicity, carnosine and related structures could be effective against age-related protein carbonyl stress. It is suggested that carnivorous diets could be beneficial because of their carnosine content, as the dipeptide has been shown to suppress some diabetic complications in mice. It is also suggested that carnosine's therapeutic potential should be explored with respect to neurodegeneration. Olfactory tissue is normally enriched in carnosine, but olfactory dysfunction is frequently associated with neurodegeneration. Olfactory administration of carnosine could provide a direct route to compromised tissue, avoiding serum carnosinases.

  10. L-Carnosine reduces telomere damage and shortening rate in cultured normal fibroblasts

    International Nuclear Information System (INIS)

    Shao Lan; Li Qinghuan; Tan Zheng

    2004-01-01

    Telomere is the repetitive DNA sequence at the end of chromosomes, which shortens progressively with cell division and limits the replicative potential of normal human somatic cells. L-Carnosine, a naturally occurring dipeptide, has been reported to delay the replicative senescence, and extend the lifespan of cultured human diploid fibroblasts. In this work, we studied the effect of carnosine on the telomeric DNA of cultured human fetal lung fibroblast cells. Cells continuously grown in 20 mM carnosine exhibited a slower telomere shortening rate and extended lifespan in population doublings. When kept in a long-term nonproliferating state, they accumulated much less damages in the telomeric DNA when cultured in the presence of carnosine. We suggest that the reduction in telomere shortening rate and damages in telomeric DNA made an important contribution to the life-extension effect of carnosine

  11. L-carnosine affects the growth of Saccharomyces cerevisiae in a metabolism-dependent manner.

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    Cartwright, Stephanie P; Bill, Roslyn M; Hipkiss, Alan R

    2012-01-01

    The dipeptide L-carnosine (β-alanyl-L-histidine) has been described as enigmatic: it inhibits growth of cancer cells but delays senescence in cultured human fibroblasts and extends the lifespan of male fruit flies. In an attempt to understand these observations, the effects of L-carnosine on the model eukaryote, Saccharomyces cerevisiae, were examined on account of its unique metabolic properties; S. cerevisiae can respire aerobically, but like some tumor cells, it can also exhibit a metabolism in which aerobic respiration is down regulated. L-Carnosine exhibited both inhibitory and stimulatory effects on yeast cells, dependent upon the carbon source in the growth medium. When yeast cells were not reliant on oxidative phosphorylation for energy generation (e.g. when grown on a fermentable carbon source such as 2% glucose), 10-30 mM L-carnosine slowed growth rates in a dose-dependent manner and increased cell death by up to 17%. In contrast, in media containing a non-fermentable carbon source in which yeast are dependent on aerobic respiration (e.g. 2% glycerol), L-carnosine did not provoke cell death. This latter observation was confirmed in the respiratory yeast, Pichia pastoris. Moreover, when deletion strains in the yeast nutrient-sensing pathway were treated with L-carnosine, the cells showed resistance to its inhibitory effects. These findings suggest that L-carnosine affects cells in a metabolism-dependent manner and provide a rationale for its effects on different cell types.

  12. Effect of beta-alanine and carnosine supplementation on muscle contractility in mice.

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    Everaert, Inge; Stegen, Sanne; Vanheel, Bert; Taes, Youri; Derave, Wim

    2013-01-01

    Enhanced carnosine levels have been shown to be ergogenic for high-intensity exercise performances, although the role of carnosine in the control of muscle function is poorly understood. Therefore, the aim of this study was to investigate the effect of long-term supplementation with increasing doses of carnosine and beta-alanine on muscle carnosine, anserine, and taurine levels and on in vitro contractility and fatigue in mice. Male Naval Medical Research Institute mice (n = 66) were control fed or supplemented with either carnosine (0.1%, 0.5%, or 1.8%) or beta-alanine (0.6 or 1.2%) in their drinking water for 8-12 wk. Soleus and extensor digitorum longus (EDL) were tested for in vitro contractile properties, and carnosine, anserine, and taurine content were measured in EDL and tibialis anterior by high-performance liquid chromatography. Only supplementation with 1.8% carnosine and 1.2% beta-alanine resulted in markedly higher carnosine (up to +160%) and anserine levels (up to +46%) compared with control mice. Beta-alanine supplementation (1.2%) resulted in increased fatigue resistance in the beginning of the fatigue protocol in soleus (+2%-4%) and a marked leftward shift of the force-frequency relation in EDL (10%-31% higher relative forces). Comparable with humans, beta-alanine availability seems to be the rate-limiting step for synthesis of muscle histidine-containing dipeptides in mice. Moreover, muscle histidine-containing dipeptides loading in mice moderately and muscle dependently affects excitation-contraction coupling and fatigue.

  13. Carnosine enhances diabetic wound healing in the db/db mouse model of type 2 diabetes.

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    Ansurudeen, Ishrath; Sunkari, Vivekananda Gupta; Grünler, Jacob; Peters, Verena; Schmitt, Claus Peter; Catrina, Sergiu-Bogdan; Brismar, Kerstin; Forsberg, Elisabete Alcantara

    2012-07-01

    Diabetes mellitus (DM) is a progressive disorder with severe late complications. Normal wound healing involves a series of complex and well-orchestrated molecular events dictated by multiple factors. In diabetes, wound healing is grossly impaired due to defective, and dysregulated cellular and molecular events at all phases of wound healing resulting in chronic wounds that fail to heal. Carnosine, a dipeptide of alanine and histidine and an endogenous antioxidant is documented to accelerate healing of wounds and ulcers. However, not much is known about its role in wound healing in diabetes. Therefore, we studied the effect of carnosine in wound healing in db/db mice, a mice model of Type 2 DM. Six millimeter circular wounds were made in db/db mice and analyzed for wound healing every other day. Carnosine (100 mg/kg) was injected (I.P.) every day and also applied locally. Treatment with carnosine enhanced wound healing significantly, and wound tissue analysis showed increased expression of growth factors and cytokines genes involved in wound healing. In vitro studies with human dermal fibroblasts and microvascular-endothelial cells showed that carnosine increases cell viability in presence of high glucose. These effects, in addition to its known role as an antioxidant and a precursor for histamine synthesis, provide evidence for a possible therapeutic use of carnosine in diabetic wound healing.

  14. Carnosine markedly ameliorates H9N2 swine influenza virus-induced acute lung injury.

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    Xu, Tong; Wang, Cunlian; Zhang, Ruihua; Xu, Mingju; Liu, Baojian; Wei, Dong; Wang, Guohua; Tian, Shufei

    2015-10-01

    Oxidative stress injury is an important pathogenesis of influenza virus in critically ill patients. The present study investigated the efficacy of carnosine, an antioxidant and free radical scavenger, on a model of acute lung injury (ALI) induced by H9N2 swine influenza virus. Female specific-pathogen-free BALB/c mice were randomized into four groups and treated as follows: (1) H9N2 group, (2) mock control group, (3) H9N2+carnosine group and (4) carnosine control group. The H9N2 group mice were inoculated intranasally with A/Swine/Hebei/012/2008/ (H9N2) virus (100 μl) in allantoic fluid (AF), whilst mock-infected animals were intranasally inoculated with non-infectious AF. Carnosine [10 mg (kg body mass)- 1] was administered orally (100 μl) for 7 days consecutively. The survival rate, lung water content, TNF-α and IL-1β levels, lung histopathology, myeloperoxidase (MPO) activity, and Toll-like receptor (TLR)-4 levels were determined at 2, 4, 6, 8 and 14 days after inoculation. Carnosine treatment effectively decreased the mortality (43 versus 75 %, P lungs and decreased the lung wet/dry mass ratio (P lungs of infected mice (P < 0.05), which supported the use of carnosine for managing severe influenza cases.

  15. Carnosine attenuates cyclophosphamide-induced bone marrow suppression by reducing oxidative DNA damage

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    Jie Deng

    2018-04-01

    Full Text Available Oxidative DNA damage in bone marrow cells is the main side effect of chemotherapy drugs including cyclophosphamide (CTX. However, not all antioxidants are effective in inhibiting oxidative DNA damage. In this study, we report the beneficial effect of carnosine (β-alanyl-l-histidine, a special antioxidant with acrolein-sequestering ability, on CTX-induced bone marrow cell suppression. Our results show that carnosine treatment (100 and 200 mg/kg, i.p. significantly inhibited the generation of reactive oxygen species (ROS and 8-hydroxy-2′-deoxyguanosine (8-oxo-dG, and decreased chromosomal abnormalities in the bone marrow cells of mice treated with CTX (20 mg/kg, i.v., 24 h. Furthermore, carnosine evidently mitigated CTX-induced G2/M arrest in murine bone marrow cells, accompanied by reduced ratios of p-Chk1/Chk1 and p-p53/p53 as well as decreased p21 expression. In addition, cell apoptosis caused by CTX was also suppressed by carnosine treatment, as assessed by decreased TUNEL-positive cell counts, down-regulated expressions of Bax and Cyt c, and reduced ratios of cleaved Caspase-3/Caspase-3. These results together suggest that carnosine can protect murine bone marrow cells from CTX-induced DNA damage via its antioxidant activity. Keywords: Carnosine, Cyclophosphamide, Oxidative DNA damage, Sister chromatid exchange, Apoptosis, Cell cycle arrest

  16. CARNOSINE CONTENT AND MUSCLE OXIDATIVE STABILITY OF MALE AND FEMALE BROILER CHICKENS

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    Gordana Kralik

    2011-12-01

    Full Text Available Carnosine is a dipeptide with antioxidative effects in broiler muscles. Its anti-ageing effect has also been determined recently, which is especially important for human health and vitality preservation. The research investigated concentration of carnosine in breast and thigh muscles of Cobb 500 broilers. It was carried out on 20 male and female broilers that were conventionally fattened for 42 days. Carnosine concentrations and TBARS values were measured on fresh breast and thigh muscles with respect to broiler sex. Content of carnosine was slightly higher in female broiler breast muscles than in male’s (1079.85 : 1012.66 μg/g tissue; P>0.05. Female broiler thigh muscle tissue also contained higher carnosine values than male’s (464.69 : 404.97 μg/g tissue; P>0.05. The research proved that carnosine was more deposited in breast muscle tissue than in thigh muscle tissue, regardless of broiler sex. Lipid peroxidation products measured as TBARS values (mg MDA/kg tissue did not statistically differ according to broiler sex or muscle type (P>0.05. Further research needs to be directed towards control of peroxidation products during meat storage.

  17. Histidine and carnosine alleviated hepatic steatosis in mice consumed high saturated fat diet.

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    Mong, Mei-chin; Chao, Che-yi; Yin, Mei-chin

    2011-02-25

    The effects of histidine, alanine and carnosine on activity and/or mRNA expression of lipogenic enzymes and sterol regulatory element-binding proteins (SREBPs) in liver and adipose tissue from high fat diet treated mice were examined. Histidine, alanine or carnosine, each agent at 1g/l was added into drinking water for 8-wk supplement. Histidine or carnosine supplement increased hepatic levels of alanine, histidine and carnosine. High fat diet evoked lipogenesis via raising the activity and mRNA expression of glucose-6-phosphate dehydrogenase, malic enzyme, fatty acid synthase (FAS), 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, SREBP-1a, -1c and -2 in liver and adipose tissue (Pmalic enzyme, FAS, HMG-CoA reductase, SREBP-1c and SREBP-2, which led to lower body weight, epididymal fat, and hepatic triglyceride and cholesterol levels (P<0.05). Mice consumed high fat diet exhibited hyper-insulinemia, hyper-leptinemia, hypo-adiponectinemia and hypo-ghrelinemia. Histidine or carnosine treatments significantly improved insulin sensitivity and attenuated hyper-insulinemia (P<0.05). These results support that histidine and carnosine are effective agents for mitigating high fat diet induced hepatic steatosis. Copyright © 2010 Elsevier B.V. All rights reserved.

  18. Radiochemical synthesis and preliminary in vivo evaluation of new radioactive platinum complexes with carnosine

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    Maurin, MichaL [Department of Radiopharmaceuticals, National Medicines Institute, 30/34 CheLmska Street, 00-725 Warsaw (Poland)], E-mail: mmaurin@il.waw.pl; Garnuszek, Piotr [Department of Radiopharmaceuticals, National Medicines Institute, 30/34 CheLmska Street, 00-725 Warsaw (Poland)

    2010-02-15

    Application of cross-linking agents such as SATA and 2-iminothiolane (2-IT) for radiochemical synthesis of new radioactive Pt(II) and Pt(IV) complexes with carnosine was investigated. The mixed-ligand Pt(II)([{sup 125}I]Hist)(Carnosine) complex has been synthesized in a multi-step reaction. First, carnosine was modified by the attachment of SATA. After chromatographic purification, the conjugate was unprotected to form a reactive sulfhydryl functional group, and then the modified carnosine was substituted to PtCl{sub 2}[{sup 125}I]Hist complex. The Pt(II)(IT-[{sup 125}I]Carnosine) and Pt(IV)(IT-[{sup 131}I]Carnosine) complexes were synthesized in a three-step reaction. First, carnosine was labeled with iodine radionuclide ({sup 125}I or {sup 131}I), followed by conjugation with 2-IT. The modified IT-[*I]Carnosine was complexed with tetrachloroplatinate or hexachloroplatinate. Comparative biodistribution studies were performed in normal Wistar rats and in Lewis rats with implanted (s.c.) rat pancreatic tumor cells (AR42J). The HPLC analysis showed a relatively fast formation of the new mixed-ligand Pt([{sup 125}I]Hist)(Carnosine) complex (yield ca. 50% after 20 h). Reaction of K{sub 2}PtCl{sub 4} with [{sup 125}I]Carnosine modified by 2-IT proceeded rapidly and with a high yield (>95% after 2 h). The synthesis of the Pt(IV)IT-[*I]Carnosine complex was the slower reaction in comparison to the analogous synthesis of the Pt(II) complex (yield ca. 70% after 12 h), thus a purification step was necessary. The biodistribution study proved the in vivo stability of the newly synthesized complexes (a low accumulation in thyroid gland and in GIT) and showed that the conjugation of the modified carnosine changes significantly biodistribution scheme of the Pt complexes comparing to the reference Pt(II)[*I]Hist and Pt(IV)([*I]Hist){sub 2} complexes. The mixed-ligand complex was rapidly excreted in urine and revealed the highest accumulation in kidneys (>5%ID/g). A very high

  19. Radiochemical synthesis and preliminary in vivo evaluation of new radioactive platinum complexes with carnosine

    International Nuclear Information System (INIS)

    Maurin, MichaL; Garnuszek, Piotr

    2010-01-01

    Application of cross-linking agents such as SATA and 2-iminothiolane (2-IT) for radiochemical synthesis of new radioactive Pt(II) and Pt(IV) complexes with carnosine was investigated. The mixed-ligand Pt(II)([ 125 I]Hist)(Carnosine) complex has been synthesized in a multi-step reaction. First, carnosine was modified by the attachment of SATA. After chromatographic purification, the conjugate was unprotected to form a reactive sulfhydryl functional group, and then the modified carnosine was substituted to PtCl 2 [ 125 I]Hist complex. The Pt(II)(IT-[ 125 I]Carnosine) and Pt(IV)(IT-[ 131 I]Carnosine) complexes were synthesized in a three-step reaction. First, carnosine was labeled with iodine radionuclide ( 125 I or 131 I), followed by conjugation with 2-IT. The modified IT-[*I]Carnosine was complexed with tetrachloroplatinate or hexachloroplatinate. Comparative biodistribution studies were performed in normal Wistar rats and in Lewis rats with implanted (s.c.) rat pancreatic tumor cells (AR42J). The HPLC analysis showed a relatively fast formation of the new mixed-ligand Pt([ 125 I]Hist)(Carnosine) complex (yield ca. 50% after 20 h). Reaction of K 2 PtCl 4 with [ 125 I]Carnosine modified by 2-IT proceeded rapidly and with a high yield (>95% after 2 h). The synthesis of the Pt(IV)IT-[*I]Carnosine complex was the slower reaction in comparison to the analogous synthesis of the Pt(II) complex (yield ca. 70% after 12 h), thus a purification step was necessary. The biodistribution study proved the in vivo stability of the newly synthesized complexes (a low accumulation in thyroid gland and in GIT) and showed that the conjugation of the modified carnosine changes significantly biodistribution scheme of the Pt complexes comparing to the reference Pt(II)[*I]Hist and Pt(IV)([*I]Hist) 2 complexes. The mixed-ligand complex was rapidly excreted in urine and revealed the highest accumulation in kidneys (>5%ID/g). A very high concentration in blood and in liver was observed for the

  20. Carnosine content in skeletal muscle is dependent on vitamin B6 status in rats

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    Sofya eSuidasari

    2016-01-01

    Full Text Available Carnosine, a histidine-containing dipeptide, is well known to be associated with skeletal muscle performance. However, there is limited information on the effect of dietary micronutrients on muscle carnosine level. Pyridoxal 5′-phosphate (PLP, the active form of vitamin B6, is involved in amino acid metabolisms in the body as a co-factor. We hypothesized that enzymes involved in β-alanine biosynthesis, the rate-limiting precursor of carnosine, may also be PLP-dependent. Thus, we examined the effects of dietary vitamin B6 on the muscle carnosine content of rats. Male and female rats were fed a diet containing 1, 7, or 35 mg pyridoxine HCl/kg for 6 weeks. Carnosine in skeletal muscles was quantified by ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS. In the gastrocnemius muscle of male rats, carnosine concentration was significantly higher in the 7 and 35 mg groups (+70% and +61%, respectively than in the 1 mg pyridoxine HCl/kg group, whereas that in the soleus muscle of male rats was significantly higher only in the 7 mg group (+43% than in the 1 mg pyridoxine HCl/kg group (P<0.05. In both muscles of female rats, carnosine concentration was significantly higher in the 7 and 35 mg groups (+32% ~ +226% than in the 1 mg pyridoxine HCl/kg group (P<0.05. We also found that compared to the 1 mg group, β-alanine concentrations in the 7 and 35 mg groups were markedly elevated in gastrocnemius muscles of male (+153% and +148%, respectively, P<0.05 and female (+381% and +437%, respectively, P<0.05 rats. Noteworthy, the concentrations of ornithine in the 7 and 35 mg groups were decreased in gastrocnemius muscles of male rats (−46% and −54%, respectively, P<0.05, which strongly inversely correlated with β-alanine concentration (r=−0.84, P<0.01. In humans, 19% lower muscle carnosine content was found in soleus muscle of women of the lower plasma PLP tertile, but this was not observed in gastrocnemius muscle

  1. Theoretical and experimental investigation of carnosine and its oxygenated adducts. The reaction with the nickel ion

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    Pavlos, Dimitrios; Petropouleas, Panayiotis; Hatzipanayioti, Despina, E-mail: stambaki@chem.uoa.gr

    2015-11-05

    Highlights: • Study on models of neutral cations and anions of carnosine at the B3LYP/TZVP level. • The {sup 1}O{sub 2}-adducts of these models resulted in oxygenated carnosine. • Theoretical parameters correlated to experimental results for carn and carn-H{sub 2}O{sub 2}. • Theoretical models of Nickel-carn complexes have been investigated. • Isolation and characterization of the solid [Ni(carn){sub 2}(H{sub 2}O){sub 5}] have been performed. - Abstract: DFT theoretical calculations at B3LYP/TZVP or LANL2DZ level of theory, for neutral, zwitterions, protonated and anionic carnosine, were performed. Energies, the structural and spectroscopic parameters were calculated in the gas phase and aqueous medium. Additional H-bonds stabilize the ionized forms of carnosine, creating “nests” into which metal ions or bio-molecules may be sheltered. Based on Fukui functions, the reactivity of the abovementioned forms of carnosine, with {sup 1}O{sub 2}, may lead to oxygenated species. The theoretical spectroscopic parameters have been correlated to our experimental results. The effect of H{sub 2}O{sub 2} and the electrochemistry of aqueous carnosine solutions were examined. Theoretical models containing Ni(II), carnosine and water were constructed. In the isolated mauve solid, formulated [Ni(carn){sub 2}(H{sub 2}O){sub 5}], the COO−, N{sub π} and/or NH{sub 2} were bonded. When H{sub 2}O{sub 2} was added, the imidazole NMR signals disappeared. A redox couple clearly indicates one electron process, the electron coming from either the oxidation of imidazole ring or the nickel(II)/Ni(III) couple.

  2. L-carnosine affects the growth of Saccharomyces cerevisiae in a metabolism-dependent manner.

    Directory of Open Access Journals (Sweden)

    Stephanie P Cartwright

    Full Text Available The dipeptide L-carnosine (β-alanyl-L-histidine has been described as enigmatic: it inhibits growth of cancer cells but delays senescence in cultured human fibroblasts and extends the lifespan of male fruit flies. In an attempt to understand these observations, the effects of L-carnosine on the model eukaryote, Saccharomyces cerevisiae, were examined on account of its unique metabolic properties; S. cerevisiae can respire aerobically, but like some tumor cells, it can also exhibit a metabolism in which aerobic respiration is down regulated. L-Carnosine exhibited both inhibitory and stimulatory effects on yeast cells, dependent upon the carbon source in the growth medium. When yeast cells were not reliant on oxidative phosphorylation for energy generation (e.g. when grown on a fermentable carbon source such as 2% glucose, 10-30 mM L-carnosine slowed growth rates in a dose-dependent manner and increased cell death by up to 17%. In contrast, in media containing a non-fermentable carbon source in which yeast are dependent on aerobic respiration (e.g. 2% glycerol, L-carnosine did not provoke cell death. This latter observation was confirmed in the respiratory yeast, Pichia pastoris. Moreover, when deletion strains in the yeast nutrient-sensing pathway were treated with L-carnosine, the cells showed resistance to its inhibitory effects. These findings suggest that L-carnosine affects cells in a metabolism-dependent manner and provide a rationale for its effects on different cell types.

  3. Carnosine supplementation protects rat brain tissue against ethanol-induced oxidative stress.

    Science.gov (United States)

    Ozel Turkcu, Ummuhani; Bilgihan, Ayşe; Biberoglu, Gursel; Mertoglu Caglar, Oznur

    2010-06-01

    Ethanol causes oxidative stress and tissue damage. The aim of this study was to investigate the effect of antioxidant carnosine on the oxidative stress induced by ethanol in the rat brain tissue. Forty male rats were divided equally into four groups as control, carnosine (CAR), ethanol (EtOH), and ethanol plus carnosine (EtOH + CAR). Rats in the control group (n = 10) were injected intraperitoneally (i.p.) with 0.9% saline; EtOH group (n = 10) with 2 g/kg/day ethanol, CAR group (n = 10) received carnosine at a dose of 1 mg/kg/day and EtOH + CAR group (n = 10) received carnosine (orally) and ethanol (i.p.). All animals were sacrificed using ketamine and brain tissues were removed. Malondialdehyde (MDA), protein carbonyl (PCO) and tissue carnosine levels, and superoxide dismutase (SOD) activities were measured. Endogenous CAR levels in the rat brain tissue specimens were significantly increased in the CAR and EtOH groups when compared to the control animals. MDA and PCO levels in the EtOH group were significantly increased as compared to the other groups (P < 0.05). CAR treatment also decreased MDA levels in the CAR group as compared to the control group. Increased SOD activities were obtained in the EtOH + CAR group as compared to the control (P < 0.05). CAR levels in the rat brain were significantly increased in the CAR, EtOH and CAR + EtOH groups when compared to the control animals. These findings indicated that carnosine may appear as a protective agent against ethanol-induced brain damage.

  4. Computational design of bio-inspired carnosine-based HOBr antioxidants

    Science.gov (United States)

    Sarrami, Farzaneh; Yu, Li-Juan; Karton, Amir

    2017-10-01

    During a respiratory burst the enzyme myeloperoxidase generates significant amounts of hypohalous acids (HOX, X = Cl and Br) in order to inflict oxidative damage upon invading pathogens. However, excessive production of these potent oxidants is associated with numerous inflammatory diseases. It has been suggested that the endogenous antioxidant carnosine is an effective HOCl scavenger. Recent computational and experimental studies suggested that an intramolecular Cl+ transfer from the imidazole ring to the terminal amine might play an important role in the antioxidant activity of carnosine. Based on high-level ab initio calculations, we propose a similar reaction mechanism for the intramolecular Br+ transfer in carnosine. These results suggest that carnosine may be an effective HOBr scavenger. On the basis of the proposed reaction mechanism, we proceed to design systems that share similar structural features to carnosine but with enhanced HOX scavenging capabilities for X = Cl and Br. We find that (i) elongating the β-alanyl-glycyl side chain by one carbon reduces the reaction barriers by up to 44%, and (ii) substituting the imidazole ring with strong electron-donating groups reduces the reaction barriers by similar amounts. We also show that the above structural and electronic effects are largely additive. In an antioxidant candidate that involves both of these effects the reaction barriers are reduced by 71%.

  5. Absolute quantification of carnosine in human calf muscle by proton magnetic resonance spectroscopy

    Science.gov (United States)

    Özdemir, Mahir S.; Reyngoudt, Harmen; DeDeene, Yves; Sazak, Hakan S.; Fieremans, Els; Delputte, Steven; D'Asseler, Yves; Derave, Wim; Lemahieu, Ignace; Achten, Eric

    2007-12-01

    Carnosine has been shown to be present in the skeletal muscle and in the brain of a variety of animals and humans. Despite the various physiological functions assigned to this metabolite, its exact role remains unclear. It has been suggested that carnosine plays a role in buffering in the intracellular physiological pHi range in skeletal muscle as a result of accepting hydrogen ions released in the development of fatigue during intensive exercise. It is thus postulated that the concentration of carnosine is an indicator for the extent of the buffering capacity. However, the determination of the concentration of this metabolite has only been performed by means of muscle biopsy, which is an invasive procedure. In this paper, we utilized proton magnetic resonance spectroscopy (1H MRS) in order to perform absolute quantification of carnosine in vivo non-invasively. The method was verified by phantom experiments and in vivo measurements in the calf muscles of athletes and untrained volunteers. The measured mean concentrations in the soleus and the gastrocnemius muscles were found to be 2.81 ± 0.57/4.8 ± 1.59 mM (mean ± SD) for athletes and 2.58 ± 0.65/3.3 ± 0.32 mM for untrained volunteers, respectively. These values are in agreement with previously reported biopsy-based results. Our results suggest that 1H MRS can provide an alternative method for non-invasively determining carnosine concentration in human calf muscle in vivo.

  6. Absolute quantification of carnosine in human calf muscle by proton magnetic resonance spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Oezdemir, Mahir S [Department of Electronics and Information Systems, MEDISIP, Ghent University-IBBT-IBiTech, De Pintelaan 185 block B, B-9000 Ghent (Belgium); Reyngoudt, Harmen [Department of Radiology, Ghent University Hospital, De Pintelaan 185, Ghent (Belgium); Deene, Yves de [Department of Radiotherapy, Ghent University Hospital, De Pintelaan 185, Ghent (Belgium); Sazak, Hakan S [Department of Statistics, Ege University, 35100 Bornova, Izmir (Turkey); Fieremans, Els [Department of Electronics and Information Systems, MEDISIP, Ghent University-IBBT-IBiTech, De Pintelaan 185 block B, B-9000 Ghent (Belgium); Delputte, Steven [Department of Electronics and Information Systems, MEDISIP, Ghent University-IBBT-IBiTech, De Pintelaan 185 block B, B-9000 Ghent (Belgium); D' Asseler, Yves [Department of Electronics and Information Systems, MEDISIP, Ghent University-IBBT-IBiTech, De Pintelaan 185 block B, B-9000 Ghent (Belgium); Derave, Wim [Department of Movement and Sports Science, Ghent University, Watersportlaan 2, Ghent (Belgium); Lemahieu, Ignace [Department of Electronics and Information Systems, MEDISIP, Ghent University-IBBT-IBiTech, De Pintelaan 185 block B, B-9000 Ghent (Belgium); Achten, Eric [Department of Radiology, Ghent University Hospital, De Pintelaan 185, Ghent (Belgium)

    2007-12-07

    Carnosine has been shown to be present in the skeletal muscle and in the brain of a variety of animals and humans. Despite the various physiological functions assigned to this metabolite, its exact role remains unclear. It has been suggested that carnosine plays a role in buffering in the intracellular physiological pH{sub i} range in skeletal muscle as a result of accepting hydrogen ions released in the development of fatigue during intensive exercise. It is thus postulated that the concentration of carnosine is an indicator for the extent of the buffering capacity. However, the determination of the concentration of this metabolite has only been performed by means of muscle biopsy, which is an invasive procedure. In this paper, we utilized proton magnetic resonance spectroscopy ({sup 1}H MRS) in order to perform absolute quantification of carnosine in vivo non-invasively. The method was verified by phantom experiments and in vivo measurements in the calf muscles of athletes and untrained volunteers. The measured mean concentrations in the soleus and the gastrocnemius muscles were found to be 2.81 {+-} 0.57/4.8 {+-} 1.59 mM (mean {+-} SD) for athletes and 2.58 {+-} 0.65/3.3 {+-} 0.32 mM for untrained volunteers, respectively. These values are in agreement with previously reported biopsy-based results. Our results suggest that {sup 1}H MRS can provide an alternative method for non-invasively determining carnosine concentration in human calf muscle in vivo.

  7. Effects of L- Carnosine Supplementation on Sleep Disorders and Disease Severity in Autistic Children: A Randomized, Controlled Clinical Trial.

    Science.gov (United States)

    Mehrazad-Saber, Zahra; Kheirouri, Sorayya; Noorazar, Seyyed-Gholamreza

    2018-02-11

    Sleep disorders are frequently reported in autistic patients. Evidences suggest that increased oxidative stress and reduced antioxidants may play a major role in the pathogenesis of these disorders. Carnosine acts as an antioxidant, antitoxic and neuroprotective agent. The aim of this trial study was to examine the effects of carnosine supplementation on the sleep disorders and severity of autism core symptoms in autistic patients. In this double-blind, randomized clinical trial, 43 autistic patients (31 boys and 12 girls; aged 4 to 16 years) were divided into two groups of carnosine and control that received 500 mg of carnosine and 500 mg of placebo per day for two months, respectively. Sleep disorders was measured using Children's Sleep Habits Questionnaires. Gilliam Autism Rating Scale 2 was used to assess the effects of carnosine supplementation on the autism severity. Carnosine supplementation did not change anthropometric indices (p>0.05) and showed no effect on autism severity (p>0.05), whereas it significantly reduced sleep duration (p=0.04), parasomnias (p=0.02) and total sleep disorders score by 7.59% (p=0.006) when compared with the control group. The results suggest that carnosine supplementation could be effective in improving sleep disturbances, in particular sleep duration and parasomnias subscales. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  8. Simple enzymatic procedure for l‐carnosine synthesis: whole‐cell biocatalysis and efficient biocatalyst recycling

    Science.gov (United States)

    Heyland, Jan; Antweiler, Nicolai; Lutz, Jochen; Heck, Tobias; Geueke, Birgit; Kohler, Hans‐Peter E.; Blank, Lars M.; Schmid, Andreas

    2010-01-01

    Summary β‐Peptides and their derivates are usually stable to proteolysis and have an increased half‐life compared with α‐peptides. Recently, β‐aminopeptidases were described as a new enzyme class that enabled the enzymatic degradation and formation of β‐peptides. As an alternative to the existing chemical synthesis routes, the aim of the present work was to develop a whole‐cell biocatalyst for the synthesis and production of β‐peptides using this enzymatic activity. For the optimization of the reaction system we chose the commercially relevant β,α‐dipeptide l‐carnosine (β‐alanine‐l‐histidine) as model product. We were able to show that different recombinant yeast and bacteria strains, which overexpress a β‐peptidase, could be used directly as whole‐cell biocatalysts for the synthesis of l‐carnosine. By optimizing relevant reaction conditions for the best‐performing recombinant Escherichia coli strain, such as pH and substrate concentrations, we obtained high l‐carnosine yields of up to 71%. Long‐time as well as biocatalyst recycling experiments indicated a high stability of the developed biocatalyst for at least five repeated batches. Application of the recombinant E. coli in a fed‐batch process enabled the accumulation of l‐carnosine to a concentration of 3.7 g l−1. PMID:21255308

  9. Carnosine reverses the aging-induced down regulation of brain regional serotonergic system.

    Science.gov (United States)

    Banerjee, Soumyabrata; Ghosh, Tushar K; Poddar, Mrinal K

    2015-12-01

    The purpose of the present investigation was to study the role of carnosine, an endogenous dipeptide biomolecule, on brain regional (cerebral cortex, hippocampus, hypothalamus and pons-medulla) serotonergic system during aging. Results showed an aging-induced brain region specific significant (a) increase in Trp (except cerebral cortex) and their 5-HIAA steady state level with an increase in their 5-HIAA accumulation and declination, (b) decrease in their both 5-HT steady state level and 5-HT accumulation (except cerebral cortex). A significant decrease in brain regional 5-HT/Trp ratio (except cerebral cortex) and increase in 5-HIAA/5-HT ratio were also observed during aging. Carnosine at lower dosages (0.5-1.0μg/Kg/day, i.t. for 21 consecutive days) didn't produce any significant response in any of the brain regions, but higher dosages (2.0-2.5μg/Kg/day, i.t. for 21 consecutive days) showed a significant response on those aging-induced brain regional serotonergic parameters. The treatment with carnosine (2.0μg/Kg/day, i.t. for 21 consecutive days), attenuated these brain regional aging-induced serotonergic parameters and restored towards their basal levels that observed in 4 months young control rats. These results suggest that carnosine attenuates and restores the aging-induced brain regional down regulation of serotonergic system towards that observed in young rats' brain regions. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  10. Creatine supplementation augments skeletal muscle carnosine content in senescence-accelerated mice (SAMP8).

    Science.gov (United States)

    Derave, Wim; Jones, Glenys; Hespel, Peter; Harris, Roger C

    2008-06-01

    The histidine-containing dipeptides (HCD) carnosine and anserine are found in high concentrations in mammalian skeletal muscle. Given its versatile biologic properties, such as antioxidative, antiglycation, and pH buffering capacity, carnosine has been implicated as a protective factor in the aging process. The present study aimed to systematically explore age-related changes in skeletal muscles HCD content in a murine model of accelerated aging. Additionally, we investigated the effect of lifelong creatine supplementation on muscle HCD content and contractile fatiguability. Male senescence-accelerated mice (SAMP8) were fed control or creatine-supplemented (2% of food intake) diet from the age of 10 to 60 weeks. At week 10, 25, and 60, tibialis anterior muscles were dissected and analysed for HCD and taurine content by HPLC. Soleus and EDL muscles were tested for in vitro contractile fatigue and recovery. From 10 to 60 weeks of age, muscular carnosine (-45%), taurine (-24%), and total creatine (-42%) concentrations gradually and significantly decreased. At 25 but not at 60 weeks, oral creatine supplementation significantly increased carnosine (+88%) and anserine (+40%) content compared to age-matched control-fed animals. Taurine and total creatine content were not affected by creatine supplementation at any age. Creatine-treated mice showed attenuated muscle fatigue (soleus) and enhanced force recovery (m. extensor digitorum longus [EDL]) compared to controls at 25 weeks, but not at 60 weeks. From the present study, we can conclude that skeletal muscle tissue exhibits a significant decline in HCD content at old age. Oral creatine supplementation is able to transiently but potently increase muscle carnosine and anserine content, which coincides with improved resistance to contractile fatigue.

  11. Aging-induced changes in brain regional serotonin receptor binding: Effect of Carnosine.

    Science.gov (United States)

    Banerjee, S; Poddar, M K

    2016-04-05

    Monoamine neurotransmitter, serotonin (5-HT) has its own specific receptors in both pre- and post-synapse. In the present study the role of carnosine on aging-induced changes of [(3)H]-5-HT receptor binding in different brain regions in a rat model was studied. The results showed that during aging (18 and 24 months) the [(3)H]-5-HT receptor binding was reduced in hippocampus, hypothalamus and pons-medulla with a decrease in their both Bmax and KD but in cerebral cortex the [(3)H]-5-HT binding was increased with the increase of its only Bmax. The aging-induced changes in [(3)H]-5-HT receptor binding with carnosine (2.0 μg/kg/day, intrathecally, for 21 consecutive days) attenuated in (a) 24-month-aged rats irrespective of the brain regions with the attenuation of its Bmax except hypothalamus where both Bmax and KD were significantly attenuated, (b) hippocampus and hypothalamus of 18-month-aged rats with the attenuation of its Bmax, and restored toward the [(3)H]-5-HT receptor binding that observed in 4-month-young rats. The decrease in pons-medullary [(3)H]-5-HT binding including its Bmax of 18-month-aged rats was promoted with carnosine without any significant change in its cerebral cortex. The [(3)H]-5-HT receptor binding with the same dosages of carnosine in 4-month-young rats (a) increased in the cerebral cortex and hippocampus with the increase in their only Bmax whereas (b) decreased in hypothalamus and pons-medulla with a decrease in their both Bmax and KD. These results suggest that carnosine treatment may (a) play a preventive role in aging-induced brain region-specific changes in serotonergic activity (b) not be worthy in 4-month-young rats in relation to the brain regional serotonergic activity. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  12. Management of the virulent influenza virus infection by oral formulation of nonhydrolized carnosine and isopeptide of carnosine attenuating proinflammatory cytokine-induced nitric oxide production.

    Science.gov (United States)

    Babizhayev, Mark A; Deyev, Anatoly I

    2012-01-01

    Inducible nitric oxide synthase (iNOS) plays an important role in mediating inflammation. In our studies, we found that iNOS-derived NO was significantly increased in the serum samples of 150 patients infected with influenza A virus in comparison with samples of 140 healthy individuals. In human lung epithelial cells, infection with influenza A virus or stimulation with poly(I:C) + interferon-gamma resulted in increased mRNA and protein levels of both interleukin-32 and iNOS, with subsequent release of NO. Activated macrophages are also a source of nitric oxide (NO), which is largely produced by iNOS in response to proinflammatory cytokines. In this review article, the presented findings have many important implications for understanding the Influenza A (H1N1) viral pathogenesis, prevention, and treatment. The direct viral cytotoxicity (referred cytopathic effect) is only a fraction of several types of events induced by virus infection. Nitric oxide and oxygen free radicals such as superoxide anion (O₂⁻˙) are generated markedly in influenza A (including H1N1) virus-infected host boosts, and these molecular species are identified as the potent pathogenic agents. The mutual interaction of NO with O₂⁻˙ resulting in formation of peroxynitrite is operative in the pathogenic mechanism of influenza virus pneumonia. The toxicity and reactivity of oxygen radicals, generated in excessive amounts mediate the overreaction of the host's immune response against the organs or tissues in which viruses are replicating, and this may explain the mechanism of tissue injuries observed in influenza virus infection of various types. The authors revealed the protection that carnosine and its bioavailable nonhydrolized forms provide against peroxynitrite damage and other types of viral injuries in which immunologic interactions are usually involved. Carnosine (beta-alanyl-L-histidine) shows the pharmacologic intracellular correction of NO release which might be one of the

  13. Carnosine: effect on aging-induced increase in brain regional monoamine oxidase-A activity.

    Science.gov (United States)

    Banerjee, Soumyabrata; Poddar, Mrinal K

    2015-03-01

    Aging is a natural biological process associated with several neurological disorders along with the biochemical changes in brain. Aim of the present investigation is to study the effect of carnosine (0.5-2.5μg/kg/day, i.t. for 21 consecutive days) on aging-induced changes in brain regional (cerebral cortex, hippocampus, hypothalamus and pons-medulla) mitochondrial monoamine oxidase-A (MAO-A) activity with its kinetic parameters. The results of the present study are: (1) The brain regional mitochondrial MAO-A activity and their kinetic parameters (except in Km of pons-medulla) were significantly increased with the increase of age (4-24 months), (2) Aging-induced increase of brain regional MAO-A activity including its Vmax were attenuated with higher dosages of carnosine (1.0-2.5μg/kg/day) and restored toward the activity that observed in young, though its lower dosage (0.5μg/kg/day) were ineffective in these brain regional MAO-A activity, (3) Carnosine at higher dosage in young rats, unlike aged rats significantly inhibited all the brain regional MAO-A activity by reducing their only Vmax excepting cerebral cortex, where Km was also significantly enhanced. These results suggest that carnosine attenuated the aging-induced increase of brain regional MAO-A activity by attenuating its kinetic parameters and restored toward the results of MAO-A activity that observed in corresponding brain regions of young rats. Copyright © 2014 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

  14. Unfolding the mechanism of cisplatin induced pathophysiology in spleen and its amelioration by carnosine.

    Science.gov (United States)

    Banerjee, Sharmistha; Sinha, Krishnendu; Chowdhury, Sayantani; Sil, Parames C

    2018-01-05

    cis-Diamminedichloroplatinum (cisplatin) is an effective chemotherapeutic and is widely used for the treatment of various types of solid tumors. Bio-distribution of cisplatin to other organs due to poor targeting towards only cancer cells constitutes the backbone of cisplatin-induced toxicity. The adverse effect of this drug on spleen is not well characterized so far. Therefore, we have set our goal to explore the mechanism of the cisplatin-induced pathophysiology of the spleen and would also like to evaluate whether carnosine, an endogenous neurotransmitter and antioxidant, can ameliorate this pathophysiological response. We found a dose and time-dependent increase of the pro-inflammatory cytokine, TNF-α, in the spleen tissue of the experimental mice exposed to 10 and 20 mg/kg body weight of cisplatin. The increase in inflammatory cytokine can be attributed to the activation of the transcription factor, NF-ĸB. This also aids in the transcription of other pro-inflammatory cytokines and cellular adhesion molecules. Exposure of animals to cisplatin at both the doses resulted in ROS and NO production leading to oxidative stress. The MAP Kinase pathway, especially JNK activation, was also triggered by cisplatin. Eventually, the persistence of inflammatory response and oxidative stress lead to apoptosis through extrinsic pathway. Carnosine has been found to restore the expression of inflammatory molecules and catalase to normal levels through inhibition of pro-inflammatory cytokines, oxidative stress, NF-ĸB and JNK. Carnosine also protected the splenic cells from apoptosis. Our study elucidated the detailed mechanism of cisplatin-induced spleen toxicity and use of carnosine as a protective agent against this cytotoxic response. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Role of Carnosine and Melatonin in Ameliorating Cardiotoxicity of Titanium Dioxide Nanoparticles in the Rats

    Directory of Open Access Journals (Sweden)

    Nouf Al-Rasheed

    2015-08-01

    Full Text Available The aim of this work was to study the possible cardiotoxicity of two different doses of 50 nm nano titanium dioxide (n-TiO2 and the possible modulating effects of the use of two natural antioxidants carnosine and melatonin. The results showed that TiO2- NPs produced deleterious effects on rat cardiac tissue as confirmed by the increased levels of serum myoglobin, troponin-T and CK-MB. Increased levels of serum Inflammatory markers represented by the tumor necrosis factor alpha (TNF-α and Interleukin-6 (IL-6 was also noticed. Caspase3 and IGg were elevated compared to the control group in a dose dependant manner. treatment of the rats with Carnosine or melatonin. along with TiO2- NPs administration significantly improved most of the elevated biochemical markers. It was concluded that the use of Carnosine or melatonin could play a beneficial role against deleterious effects of TiO2- NPs

  16. Bioaccessibility of the Bioactive Peptide Carnosine during in Vitro Digestion of Cured Beef Meat.

    Science.gov (United States)

    Marcolini, Elena; Babini, Elena; Bordoni, Alessandra; Di Nunzio, Mattia; Laghi, Luca; Maczó, Anita; Picone, Gianfranco; Szerdahelyi, Emoke; Valli, Veronica; Capozzi, Francesco

    2015-05-27

    A bioactive compound is a food component that may have an impact on health. Its bioaccessibility, defined as the fraction released from the food matrix into the gastrointestinal tract during digestion, depends on compound stability, interactions with other food components, and supramolecular organization of food. In this study, the effect of pH on the bioaccessibility of the bioactive dipeptide carnosine was evaluated in two commercial samples of the Italian cured beef meat bresaola at two key points of digestion: before the gastric and after the duodenal phases. The digestion process was simulated using an in vitro static system, whereas capillary zone electrophoresis (CZE) and (1)H nuclear magnetic resonance (NMR) were used for quantitative analysis. The gap between the total carnosine content, measured by CZE, and its free diffusible fraction observable by NMR spectroscopy, was 11 and 19% for two independent bresaola products, where such percentages represent the fraction of carnosine not accessible for intestinal absorption because it was adsorbed to the food matrix dispersed in the digestion fluid.

  17. Optimizing Carnosine Containing Extract Preparation from Chicken Breast for Anti-glycating agents.

    Science.gov (United States)

    Kim, Seung-Ki; Kwon, Dodan; Kwon, Da-Ae; Paik, In Kee; Auh, Joong-Hyuck

    2014-01-01

    Optimization of carnosine and anserine extraction from chicken breast was performed using response surface methodology (RSM) to obtain the maximized physiological activities for anti-glycation and anti-oxidation. The optimum extraction conditions were water extraction for 1.6 h in the case of the 20-wk laying hen muscle and water extraction for 2.12 h in the case of 90-wk laying hen muscle. Higher carnosine and anserine contents were measured in the 20-wk laying hen muscle, along with higher physiological activities, which increased in direct proportion with the dipeptide contents. The extracts prepared from the 20-wk laying hen under optimum conditions showed 57% inhibition of advanced glycated end-product formation, 64% inhibition of lipid peroxidation, and 61% of DPPH radical scavenging effects. On the other hand, 52% inhibition of AGE formation, 62% inhibition of lipid peroxidation, and 53% of DPPH radical scavenging effect were demonstrated within the 90-wk laying hen. In addition, the ratio of carnosine was a key indicator for the physiological activities of the extracts.

  18. Carnosine protects brain microvascular endothelial cells against rotenone-induced oxidative stress injury through histamine H₁ and H₂ receptors in vitro.

    Science.gov (United States)

    Zhang, Luyi; Yao, Ke; Fan, Yanying; He, Ping; Wang, Xiaofen; Hu, Weiwei; Chen, Zhong

    2012-12-01

    Although it is believed that carnosine has protective effects on various cell types, its effect on microvascular endothelial cells has not been well defined. In the present study, we investigated the protective effects of carnosine in microvascular endothelial cells using an in vitro rotenone-induced oxidative stress model. Mouse brain microvascular endothelial cells were exposed to 1 μmol/L rotenone for 18 h. In some experiments, carnosine (100 nmol/L-1 mmol/L) was added 30 min prior to rotenone exposure. When used, histamine receptor antagonists (100 nmol/L-10 μmol/L) were added 15 min before carnosine treatment. After rotenone exposure, apoptosis of microvascular cells was analysed by Hoechst 33342 staining, whereas mitochondrial membrane potential was assessed by JC-1 staining. Intracellular carnosine and histamine levels were determined using HPLC or ultra-HPLC. Over the range 1 μmol/L-1 mmol/L, carnosine concentration-dependently decreased the number of apoptotic cells after 18 h exposure to rotenone. This effect was reversed by the histamine H1 receptor antagonists pyrilamine and diphenhydramine (1 and 10 μmol/L) and the H2 receptor antagonists cimetidine (100 nmol/L-10 μmol/L) and zolatidine (10 μmol/L). α-Fluoromethylhistidine (100 μmol/L), a selective and irreversible inhibitor of histidine decarboxylase, also significantly inhibited the protective effects of carnosine. At 0.1 mmol/L, carnosine restored the decrease in mitochondrial membrane potential after 6 h exposure to 1 μmol/L rotenone and this effect was also reversed by the H1 and H2 receptor antagonists. Moreover, intracellular carnosine levels increased as early as 1 h after carnosine treatment, whereas intracellular histamine levels increased 18 h after carnosine treatment. The results of the present study indicate that carnosine protects brain microvascular endothelial cells against rotenone-induced oxidative stress injury via histamine H1 and H2 receptors. The

  19. Laccase mediated-synthesis of hydroxycinnamoyl-peptide from ferulic acid and carnosine.

    Science.gov (United States)

    Aljawish, Abdulhadi; Chevalot, Isabelle; Madad, Nidal; Paris, Cédric; Muniglia, Lionel

    2016-06-10

    Carnosine (CAR) dipeptide was functionalized with ferulic acid (FA) as substrate using laccase from Myceliophtora thermophila as biocatalyst. The enzymatic reaction was performed in aqueous medium under mild conditions (pH 7.5, 30°C) as an eco-friendly procedure. Results showed that this enzymatic process led to the synthesis of two new derivatives (P1, P2), from the coupling between CAR and FA derived products. Conditions allowing a high production of P1, P2 derivatives were determined with an optimal ratio of (FA: CAR) of (1:1.6) at optimal time reaction of 8h. Under these optimal conditions, the coupling between CAR and FA-products was demonstrated, resulting in the decrease of -NH2 groups (almost 50%) as quantified via derivatization. Due to the presence of FA in the structure of these new derivatives, they exhibited higher hydrophobic property than carnosine. Structural analyses by mass spectrometry showed that P1 and P2 (FA-CAR) derivatives exhibited the same molecular mass (MM 770g/mol) containing one CAR-molecule and three FA-molecules but with different chemical structures. Furthermore, these derivatives presented improved antioxidant (almost 10 times) and anti-proliferative (almost 18 times) properties in comparison with CAR. Moreover, P1 derivative exhibited higher antioxidant and anti-proliferative activities than P2 derivative, which confirmed the different structures of P1 and P2. These results suggested that the oxidized phenols coupling with carnosine is a promising process to enhance the CAR-properties. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Sensitive determination of carnosine in urine by high-performance liquid chromatography using 4-(5,6-dimethoxy-2-phthalimidinyl)-2-methoxyphenylsulfonyl chloride as a fluorescent labeling reagent.

    OpenAIRE

    鶴田, 泰人; 丸山, 潔; 井上, 裕文; 古謝, 景子; 伊達, 有子; 岡村, 信幸; 江藤, 精二; 小嶋, 英二朗

    2010-01-01

    A simple and highly sensitive high-performance liquid chromatography procedure was developed for the determination of carnosine in urine. Carnosine was derivatized with 4-(5,6-dimethoxy-2-phthalimidinyl)-2-methoxyphenylsulfonyl chloride at 70 degrees C for 15 min in borate buffer (20 mmol l(-1), pH 9.0) to produce fluorescent sulfonamides. After hydrolysis of the reaction mixture with formic acid at 100 degrees C for 15 min, the fluorescent derivative of carnosine was separated on a reversed-...

  1. Carnosine Attenuates the Development of both Type 2 Diabetes and Diabetic Nephropathy in BTBR ob/ob Mice

    NARCIS (Netherlands)

    Albrecht, Thomas; Schilperoort, Maaike; Zhang, Shiqi; Braun, Jana D.; Qiu, Jiedong; Rodriguez, Angelica; Pastene, Diego O.; Kraemer, Bernhard K.; Koeppel, Hannes; Baelde, Hans; de Heer, Emile; Altomare, Alessandra Anna; Regazzoni, Luca; Denisi, Alessandra; Aldini, Giancarlo; van den Born, Jacob; Yard, Benito A.; Hauske, Sibylle J.

    2017-01-01

    We previously demonstrated that polymorphisms in the carnosinase-1 gene (CNDP1) determine the risk of nephropathy in type 2 diabetic patients. Carnosine, the substrate of the enzyme encoded by this gene, is considered renoprotective and could possibly be used to treat diabetic nephropathy (DN). In

  2. Hyperglycemia Does Not Affect Iron Mediated Toxicity of Cultured Endothelial and Renal Tubular Epithelial Cells : Influence of L-Carnosine

    NARCIS (Netherlands)

    Zhang, Shiqi; Ntasis, Emmanouil; Kabtni, Sarah; van den Born, Jaap; Navis, Gerjan; Bakker, Stephan J. L.; Kraemer, Bernhard K.; Yard, Benito A.; Hauske, Sibylle J.

    2016-01-01

    Iron has been suggested to affect the clinical course of type 2 diabetes (T2DM) as accompanying increased intracellular iron accumulation may provide an alternative source for reactive oxygen species (ROS). Although carnosine has proven its therapeutic efficacy in rodent models of T2DM, little is

  3. On the Anticataractogenic Effects of L-Carnosine: Is It Best Described as an Antioxidant, Metal-Chelating Agent or Glycation Inhibitor?

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    Hamdy Abdelkader

    2016-01-01

    Full Text Available Purpose. L-Carnosine is a naturally occurring dipeptide which recently gained popularity as an anticataractogenic agent due to its purported antioxidant activities. There is a paucity of research and conclusive evidence to support such claims. This work offers compelling data that help clarify the mechanism(s behind the anticataract properties of L-carnosine. Methods. Direct in vitro antioxidant free radical scavenging properties were assayed using three different antioxidant (TEAC, CUPRAC, and DPPH assays. Indirect in vitro and ex vivo antioxidant assays were studied by measuring glutathione bleaching capacity and total sulfhydryl (SH capacity of bovine lens homogenates as well as hydrogen-peroxide-stress assay using human lens epithelial cells. Whole porcine lenses were incubated in high galactose media to study the anticataract effects of L-carnosine. MTT cytotoxicity assays were conducted on human lens epithelial cells. Results. The results showed that L-carnosine is a highly potent antiglycating agent but with weak metal chelating and antioxidant properties. There were no significant decreases in lens epithelial cell viability compared to negative controls. Whole porcine lenses incubated in high galactose media and treated with 20 mM L-carnosine showed a dramatic inhibition of advanced glycation end product formation as evidenced by NBT and boronate affinity chromatography assays. Conclusion. L-Carnosine offers prospects for investigating new methods of treatment for diabetic cataract and any diseases that are caused by glycation.

  4. Determination of carnosine, anserine, homocarnosine, pentosidine and thiobarbituric acid reactive substances contents in meat from different animal species.

    Science.gov (United States)

    Peiretti, Pier Giorgio; Medana, Claudio; Visentin, Sonja; Giancotti, Valeria; Zunino, Valentina; Meineri, Giorgia

    2011-06-15

    The aim of this research was to determine the content of the histidinic antioxidants, advanced glycation end products (pentosidine) and thiobarbituric acid reactive substance (TBARS) in the meat from different animal species. Carnosine, anserine, homocarnosine and pentosidine were quantified by HPLC/MS, while TBARS was determined by photometric measurements. The total CRCs (carnosine+anserine+homocarnosine) content was in the increasing order: beef

  5. Carnosine and anserine homeostasis in skeletal muscle and heart is controlled by β‐alanine transamination

    Science.gov (United States)

    Blancquaert, Laura; Baba, Shahid P.; Kwiatkowski, Sebastian; Stautemas, Jan; Stegen, Sanne; Barbaresi, Silvia; Chung, Weiliang; Boakye, Adjoa A.; Hoetker, J. David; Bhatnagar, Aruni; Delanghe, Joris; Vanheel, Bert; Veiga‐da‐Cunha, Maria; Derave, Wim

    2016-01-01

    Key points Using recombinant DNA technology, the present study provides the first strong and direct evidence indicating that β‐alanine is an efficient substrate for the mammalian transaminating enzymes 4‐aminobutyrate‐2‐oxoglutarate transaminase and alanine‐glyoxylate transaminase.The concentration of carnosine and anserine in murine skeletal and heart muscle depends on circulating availability of β‐alanine, which is in turn controlled by degradation of β‐alanine in liver and kidney.Chronic oral β‐alanine supplementation is a popular ergogenic strategy in sports because it can increase the intracellular carnosine concentration and subsequently improve the performance of high‐intensity exercises. The present study can partly explain why the β‐alanine supplementation protocol is so inefficient, by demonstrating that exogenous β‐alanine can be effectively routed toward oxidation. Abstract The metabolic fate of orally ingested β‐alanine is largely unknown. Chronic β‐alanine supplementation is becoming increasingly popular for improving high‐intensity exercise performance because it is the rate‐limiting precursor of the dipeptide carnosine (β‐alanyl‐l‐histidine) in muscle. However, only a small fraction (3–6%) of the ingested β‐alanine is used for carnosine synthesis. Thus, the present study aimed to investigate the putative contribution of two β‐alanine transamination enzymes, namely 4‐aminobutyrate‐2‐oxoglutarate transaminase (GABA‐T) and alanine‐glyoxylate transaminase (AGXT2), to the homeostasis of carnosine and its methylated analogue anserine. We found that, when transfected into HEK293T cells, recombinant mouse and human GABA‐T and AGXT2 are able to transaminate β‐alanine efficiently. The reaction catalysed by GABA‐T is inhibited by vigabatrin, whereas both GABA‐T and AGXT2 activity is inhibited by aminooxyacetic acid (AOA). Both GABA‐T and AGXT2 are highly expressed in the mouse liver and

  6. Multitarget trehalose-carnosine conjugates inhibit Aβ aggregation, tune copper(II) activity and decrease acrolein toxicity.

    Science.gov (United States)

    Grasso, Giuseppa Ida; Bellia, Francesco; Arena, Giuseppe; Satriano, Cristina; Vecchio, Graziella; Rizzarelli, Enrico

    2017-07-28

    Increasing evidence is accumulating, showing that neurodegenerative disorders are somehow associated with the toxicity of amyloid aggregates, metal ion dyshomeostasis as well as with products generated by oxidative stress. Within the biological oxidation products, acrolein does have a prominent role. A promising strategy to deal with the above neurogenerative disorders is to use multi-functions bio-molecules. Herein, we show how a class of bio-conjugates takes advantage of the antiaggregating, antioxidant and antiglycating properties of trehalose and carnosine. Their ability to sequester acrolein and to inhibit both self- and metal-induced aggregation is here reported. The copper(II) coordination properties of a new trehalose-carnosine conjugate and the relative antioxidant effects have also been investigated. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  7. Effects of beta-alanine supplementation on brain homocarnosine/carnosine signal and cognitive function: an exploratory study.

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    Marina Yazigi Solis

    Full Text Available Two independent studies were conducted to examine the effects of 28 d of beta-alanine supplementation at 6.4 g d(-1 on brain homocarnosine/carnosine signal in omnivores and vegetarians (Study 1 and on cognitive function before and after exercise in trained cyclists (Study 2.In Study 1, seven healthy vegetarians (3 women and 4 men and seven age- and sex-matched omnivores undertook a brain 1H-MRS exam at baseline and after beta-alanine supplementation. In study 2, nineteen trained male cyclists completed four 20-Km cycling time trials (two pre supplementation and two post supplementation, with a battery of cognitive function tests (Stroop test, Sternberg paradigm, Rapid Visual Information Processing task being performed before and after exercise on each occasion.In Study 1, there were no within-group effects of beta-alanine supplementation on brain homocarnosine/carnosine signal in either vegetarians (p = 0.99 or omnivores (p = 0.27; nor was there any effect when data from both groups were pooled (p = 0.19. Similarly, there was no group by time interaction for brain homocarnosine/carnosine signal (p = 0.27. In study 2, exercise improved cognitive function across all tests (P 0.05 of beta-alanine supplementation on response times or accuracy for the Stroop test, Sternberg paradigm or RVIP task at rest or after exercise.28 d of beta-alanine supplementation at 6.4 g d(-1 appeared not to influence brain homocarnosine/carnosine signal in either omnivores or vegetarians; nor did it influence cognitive function before or after exercise in trained cyclists.

  8. Biological activities of the natural imidazole-containing peptidomimetics n-acetylcarnosine, carcinine and L-carnosine in ophthalmic and skin care products.

    Science.gov (United States)

    Babizhayev, Mark A

    2006-04-11

    Apart from genetically programmed cell aging, different external aggressors related to oxidative stress and lipid peroxidation (LPO) can accelerate the skin aging phenomenon. Oxidative stress associated with the formation of lipid peroxides is suggested to contribute to pathological processes in aging and systemic diseases known as the risk factors for cataract. Despite the fact that L-carnosine-related peptidomimetics N-acetylcarnosine (N-acetyl-beta-alanyl-L-histidine) (NAC) and carcinine (beta-alanylhistamine) are metabolically related to L-carnosine and have been demonstrated to occur in tissues of many vertebrates, including humans, these compounds were shown resistant toward enzymatic hydrolysis. A series of related biocompatible imidazole-containing peptidomimetics were synthesized in order to confer resistance to enzymatic hydrolysis and ex vivo improvement of protective antioxidative properties related to L-carnosine. The included findings revealed a greater role of N-acetylcarnosine (NAC) and carcinine ex vivo in the prolongation and potentiation of physiological responses to the therapeutical and cosmetics treatments with L-carnosine as antioxidant. 3-D molecular conformation studies proposed the antioxidant activity of peptidomimetics (carcinine, L-prolylhistamine, N-acetylcarnosine, L-carnosine) for metal ion binding, quenching of a number free radicals, and binding of hydroperoxide or aldehyde (including dialdehyde LPO products) in an imidazole-peroxide adducts. NAC can act as a time release (carrier) stable version of L-carnosine during application in ophthalmic pharmaceutical and cosmetics formulations which include lubricants. Carcinine, L-prolylhistamine show efficient deactivation of lipid hydroperoxides monitored by HPLC and protection of membrane phospholipids and water soluble proteins from the lipid peroxides-induced damages. This activity is superior over the lipophilic antioxidant vitamin E. The biologically significant applications of

  9. Effect of carnosine supplementation on apoptosis and irisin, total oxidant and antioxidants levels in the serum, liver and lung tissues in rats exposed to formaldehyde inhalation.

    Science.gov (United States)

    Aydin, Suna; Ogeturk, Murat; Kuloglu, Tuncay; Kavakli, Ahmet; Aydin, Suleyman

    2015-02-01

    The main objective of the study has been to show whether carnosine has positive effects on liver and lung tissues of rats exposed to a range of formaldehyde concentrations, and to explore how irisin expression and antioxidant capacity are altered in these tissues by carnosine supplementation. Sprague-Dawley type male rats were divided into 8 groups with 6 animals in each: (I) Control; no chemical supplementation); (II) sham (100mg/kg/day carnosine); (III) low dose formaldehyde (LDFA) for 5 days/week; (IV) LDFA for 5 days/week and carnosine); (V) moderate dose formaldehyde (MDFA) for 5 days/week); (VI) MDFA for 5 days/week and carnosine; (VII) high dose formaldehyde (HDFA) for 5 days/week; (VIII) and HDFA for 5 days/week and carnosine. Sham and control groups were exposed to normal air. Irisin levels of the serum, liver and lung tissue supernatants were analyzed by ELISA, while the REL method was used to determine total oxidant/antioxidant capacity. Irisin production by the tissues was detected immunohistochemically. Increasing doses of FA decreased serum/tissue irisin and total antioxidant levels relative to the controls, as also to increases in TUNEL expressions, total oxidant level, oxidant and apoptosis index. Irisin expression was detected in hepatocyte and sinusoidal cells of the liver and parenchymal cells of the lung. In conclusion, while FA exposure reduces irisin and total oxidant in the serum, liver and lung tissues in a dose-dependent manner and increases the total antioxidant capacity, carnosine supplementation reduces the oxidative stress and restores the histopathological and biochemical signs. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Glycotoxins: Dietary and Metabolic Origins; Possible Amelioration of Neurotoxicity by Carnosine, with Special Reference to Parkinson's Disease.

    Science.gov (United States)

    Hipkiss, Alan R

    2018-02-07

    There is a strong association between neurodegeneration and protein glycation; possible origins of neurotoxic glycated protein, also called glycotoxins, include (i) diet (i.e., proteins cooked at high temperatures), (ii) protein glycation in the gut, and (iii) intracellular reaction of proteins with deleterious aldehydes, especially methylglyoxal (MG). It is likely that excessive glycolysis provokes increased generation of dihydroxyacetone phosphate which decomposes into MG due to activity-induced deamidation of certain asparagine residues in the glycolytic enzyme triose-phosphate isomerase (TPI). It is suggested that, following hyperglycemia, erythrocytes (i) possibly participate in MG distribution throughout the body and (ii) could provide a source of glycated alpha-synuclein which also accumulates in PD brains as Lewy bodies. The dipeptide carnosine, recently shown to be present in erythrocytes, could help to protect against MG reactivity by scavenging the reactive bicarbonyl, especially if glyoxalase activity is insufficient, as often occurs during aging. By reacting with MG, carnosine may also prevent generation of the neurotoxin 1-acetyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (ADTIQ), which accumulates in PD and diabetic brains. It is suggested that carnosine's therapeutic potential could be explored via nasal administration in order to avoid the effects of serum carnosinase. The possibility that some glycated proteins (e.g., alpha-synuclein) could possess prion-like properties is also considered.

  11. L-carnosine enhanced reproductive potential of the Saccharomyces cerevisiae yeast growing on medium containing glucose as a source of carbon.

    Science.gov (United States)

    Kwolek-Mirek, Magdalena; Molon, Mateusz; Kaszycki, Pawel; Zadrag-Tecza, Renata

    2016-08-01

    Carnosine is an endogenous dipeptide composed of β-alanine and L-histidine, which occurs in vertebrates, including humans. It has a number of favorable properties including buffering, chelating, antioxidant, anti-glycation and anti-aging activities. In our study we used the Saccharomyces cerevisiae yeast as a model organism to examine the impact of L-carnosine on the cell lifespan. We demonstrated that L-carnosine slowed down the growth and decreased the metabolic activity of cells as well as prolonged their generation time. On the other hand, it allowed for enhancement of the yeast reproductive potential and extended its reproductive lifespan. These changes may be a result of the reduced mitochondrial membrane potential and decreased ATP content in the yeast cells. However, due to reduction of the post-reproductive lifespan, L-carnosine did not have an influence on the total lifespan of yeast. In conclusion, L-carnosine does not extend the total lifespan of S. cerevisiae but rather it increases the yeast's reproductive capacity by increasing the number of daughter cells produced.

  12. Characterization of dioxygenated cobalt(II)-carnosine complexes by Raman and IR spectroscopy.

    Science.gov (United States)

    Torreggiani, A; Taddei, P; Fini, G

    2002-01-01

    Raman and IR studies are carried out on carnosine (beta-alanyl-L-histidine, Carnos) and its complexes with cobalt(II) at different metal/ligand ratios and basic pH. Binuclear complexes that bind molecular oxygen are formed and information regarding the O-O bridge is obtained from the Raman spectra. When the Co(II)/Carnos ratio is complexes are the predominant species and two forms (monobridged and dibridged) are identified by the presence of two Raman peaks in the nuO-O region (750-850 cm(-1)). These peroxo complexes can be oxidized to yield a superoxo complex when the metal slightly exceeds the Carnos concentration, and there are consequent shifts of the nuO-O band to higher wavenumbers. In addition, the chelated species in the 2 : 1 Co(II)/Carnos system is found to bind oxygen to a lesser degree. With respect to the coordination sites, each Co(II) ion of the binuclear dioxygenated complexes is bound to one oxygen atom and four nitrogen atoms: N(pi) and N(tau) of two Carnos molecules, the peptide, and the terminal amino nitrogen atoms. Conversely, when the metal/ligand ratio is 2, in addition to the dioxygenated complexes, a complex is formed in which the imidazole moiety of Carnos binds two different cobalt ions because the N(pi) and N(tau) nitrogens are both deprotonated. Copyright 2002 John Wiley & Sons, Inc.

  13. The anti-proliferative effect of L-carnosine correlates with a decreased expression of hypoxia inducible factor 1 alpha in human colon cancer cells.

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    Barbara Iovine

    Full Text Available In recent years considerable attention has been given to the use of natural substances as anticancer drugs. The natural antioxidant dipeptide L-carnosine belongs to this class of molecules because it has been proved to have a significant anticancer activity both in vitro and in vivo. Previous studies have shown that L-carnosine inhibits the proliferation of human colorectal carcinoma cells by affecting the ATP and Reactive Oxygen Species (ROS production. In the present study we identified the Hypoxia-Inducible Factor 1α (HIF-1α as a possible target of L-carnosine in HCT-116 cell line. HIF-1α protein is over-expressed in multiple types of human cancer and is the major cause of resistance to drugs and radiation in solid tumours. Of particular interest are experimental data supporting the concept that generation of ROS provides a redox signal for HIF-1α induction, and it is known that some antioxidants are able to suppress tumorigenesis by inhibiting HIF-1α. In the current study we found that L-carnosine reduces the HIF-1α protein level affecting its stability and decreases the HIF-1 transcriptional activity. In addition, we demonstrated that L-carnosine is involved in ubiquitin-proteasome system promoting HIF-1α degradation. Finally, we compared the antioxidant activity of L-carnosine with that of two synthetic anti-oxidant bis-diaminotriazoles (namely 1 and 2, respectively. Despite these three compounds have the same ability in reducing intracellular ROS, 1 and 2 are more potent scavengers and have no effect on HIF-1α expression and cancer cell proliferation. These findings suggest that an analysis of L-carnosine antioxidant pathway will clarify the mechanism underlying the anti-proliferative effects of this dipeptide on colon cancer cells. However, although the molecular mechanism by which L-carnosine down regulates or inhibits the HIF-1α activity has not been yet elucidated, this ability may be promising in treating hypoxia

  14. The detox strategy in smoking comprising nutraceutical formulas of non-hydrolyzed carnosine or carcinine used to protect human health.

    Science.gov (United States)

    Babizhayev, Mark A

    2014-03-01

    The increased oxidative stress in patients with smoking-associated disease, such as chronic obstructive pulmonary disease, is the result of an increased burden of inhaled oxidants as well as increased amounts of reactive oxygen species generated by various inflammatory, immune and epithelial cells of the airways. Nicotine sustains tobacco addiction, a major cause of disability and premature death. In addition to the neurochemical effects of nicotine, behavioural factors also affect the severity of nicotine withdrawal symptoms. For some people, the feel, smell and sight of a cigarette and the ritual of obtaining, handling, lighting and smoking a cigarette are all associated with the pleasurable effects of smoking. For individuals who are motivated to quit smoking, a combination of pharmacotherapy and behavioural therapy has been shown to be most effective in controlling the symptoms of nicotine withdrawal. In the previous studies, we proposed the viability and versatility of the imidazole-containing dipeptide-based compounds in the nutritional compositions as the telomere protection targeted therapeutic system for smokers in combination with in vitro cellular culture techniques being an investigative tool to study telomere attrition in cells induced by cigarette smoke (CS) and smoke constituents. Our working therapeutic concept is that imidazole-containing dipeptide-based compounds (non-hydrolyzed carnosine and carcinine) can modulate the telomerase activity in the normal cells and can provide the redox regulation of the cellular function under the terms of environmental and oxidative stress and in this way protect the length and the structure of telomeres from attrition. The detoxifying system of non-hydrolyzed carnosine or carcinine can be applied in the therapeutic nutrition formulations or installed in the cigarette filter. Patented specific oral formulations of non-hydrolyzed carnosine and carcinine provide a powerful manipulation tool for targeted therapeutic

  15. Carnosine, anserine, creatine, and inosine 5'-monophosphate contents in breast and thigh meats from 5 lines of Korean native chicken.

    Science.gov (United States)

    Jung, Samooel; Bae, Young Sik; Kim, Hyun Joo; Jayasena, Dinesh D; Lee, Jun Heon; Park, Hee Bok; Heo, Kang Nyung; Jo, Cheorun

    2013-12-01

    The aim of this study was to examine the effect of chicken line on the contents of endogenous compounds, including carnosine, anserine, creatine, and inosine 5'-monophosphate (IMP), in breast and thigh meats from 5 lines of Korean native chicken for the development of high-quality meat breeds. Additionally, the effects of sex (male or female) and meat type (breast or thigh meat) were examined. In total, 595 F1 progeny [black: 90 (male: 45, female: 45); gray-brown: 110 (male: 52, female: 58); red-brown: 136 (male: 68, female: 68); white: 126 (male: 63, female: 63); and yellow-brown: 133 (male: 62, female: 71)] from 70 full-sib families were used. The male chicken from the red-brown line and the female chicken from the black line showed the highest BW among the 5 lines. Carnosine content was higher in female chicken and breast meat than in male chicken and thigh meat, respectively. Breast meat contained higher anserine content compared with thigh meat. The sex effect on anserine was not consistent between breast and thigh meat. Creatine content was not consistently influenced by sex between breast and thigh meat, and no meat type effect was observed. The IMP contents were higher in female chicken and breast meat compared with male chicken and thigh meat, respectively. In addition, we clearly observed line effects by the comparison of the contents of carnosine, anserine, creatine, and IMP for each meat type according to each sex. These data are useful for selection and development of high-quality, meat-type chicken breeds.

  16. The zinc form of carnosine dipeptidase 2 (CN2) has dipeptidase activity but its substrate specificity is different from that of the manganese form.

    Science.gov (United States)

    Okumura, Nobuaki; Takao, Toshifumi

    2017-12-16

    Carnosine dipeptidase II (CN2), a metallopeptidase present in the cytosol of various vertebrate tissues, catalyzes the hydrolysis of carnosine and several other dipeptides in the presence of Mn 2+ . Although the metal-binding center of mouse CN2 is also able to associate with Zn 2+ in vitro, it was not known whether the zinc form of CN2 has any enzymatic activity. In the present study, we show that Zn 2+ has a higher affinity for binding to CN2 than Mn 2+ , as evidenced by native mass spectrometry. The issue of whether the zinc form of CN2 has enzymatic activity was also examined using various dipeptides as substrates. The findings indicate that the zinc form of CN2 catalyzes the hydrolysis of several different dipeptides including Leu-His, Met-His and Ala-His at a reaction rate comparable to that for its manganese form. On the other hand, the zinc form of CN2 did not catalyze the hydrolysis of carnosine and several other dipeptides that are hydrolyzed by the manganese form of CN2. Substrate specificity was also examined in HEK293T cells expressing CN2, and the findings indicate that Leu-His, Met-His, but not carnosine, were hydrolyzed in the cell culture. These results suggest that the zinc form of CN2 is an active enzyme, but with a different substrate specificity from that of the manganese form. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. THE EFFECT OF L-CARNOSINE ON ERYTHROCYTE DEFORMABILITY AND AGGREGATION ACCORDING TO THE CELL AGE IN YOUNG AND AGED RATS

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    Gülten Erken

    2013-01-01

    Full Text Available This study aimed to investigate alterations in hemorheology induced by L-carnosine, an anti- oxidant dipeptide, and to determine their relationship to oxidative stress in density-separated erythrocytes of aged and young rats. 28 male Sprague Dawley rats were divided into 4 groups as aged (Aca, young (Yca L-carnosine groups (250 mg/kg L-carnosine, i.p. and aged (As, young (Ys control groups (saline, i.p.. Density separation was further performed to these groups in order to separate erythrocytes according to their age. Blood samples were used for the determination of erythrocyte deformability, aggregation; and oxidative stress parameters. Erythrocyte deformability of Yca group measured at 0.53 Pa was lower than Aca group. Similarly, deformability of least-dense (young erythrocytes of Yca group was decreased compared to least-dense erythrocytes of Aca groups. Total antioxidant capacity (TAC of Aca group was higher and oxidative stress index (OSI lower than As group. Although L-carnosine resulted in an enhancement in TAC of aged rats, this favorable effect was not observed in erythrocyte deformability and aggregation in the dose applied in this study.

  18. Effect of cooking method on carnosine and its homologues, pentosidine and thiobarbituric acid-reactive substance contents in beef and turkey meat.

    Science.gov (United States)

    Peiretti, Pier Giorgio; Medana, Claudio; Visentin, Sonja; Dal Bello, Federica; Meineri, Giorgia

    2012-05-01

    Commercial samples of beef and turkey meat were prepared by commonly used cooking methods with standard cooking times: (1) broiled at 200°C for 10min, (2) broiled at a medium temperature (140°C) for 10min, (3) cooked by microwave (MW) for 3min and then grilled (MW/grill) for 7min, (4) cooked in a domestic microwave oven for 10min, and (5) boiled in water for 10min. The raw and cooked meats were then analysed to determine the carnosine, anserine, homocarnosine, pentosidine, and thiobarbituric acid-reactive substance (TBARS) contents. It was observed that boiling beef caused a loss of approximately 50% of the carnosine, probably because of the high water solubility of carnosine and its homologues; cooking by microwave caused a medium loss of the anti-oxidants of approximately 20%; cooking by MW/grill led to a reduction in carnosine of approximately 10%. As far as the anserine and homocarnosine contents were concerned, a greater loss was observed for the boiling method (approximately 70%) while, for the other cooking methods, the value ranged from 30% to 70%. The data oscillate more for the turkey meat: the minimum carnosine decrease was observed in the cases of MW/grill and broiling at high temperature (25%). Analogously, the anserine and homocarnosine contents decreased slightly in the case of MW/grill and broiling at a high temperature (2-7%) and by 10-30% in the other cases. No analysed meat sample showed any traces of pentosidine above the instrumental determination limits. The cooked beef showed an increased TBARS value compared to the raw meat, and the highest values were found when the beef was broiled at a high temperature, cooked by microwave or boiled in water. The TBARS value of the turkey meat decreased for all the cooking methods in comparison to the TBARS value of the fresh meat. Copyright © 2011 Elsevier Ltd. All rights reserved.

  19. The Expression of Carnosine and Its Effect on the Antioxidant Capacity of Muscle in Finishing Pigs Exposed to Constant Heat Stress

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    Peige Yang

    2014-12-01

    Full Text Available The objective of this study was to assess the effects of constant high ambient temperatures on meat quality, antioxidant capacity, and carnosine expression in longissimus dorsi muscle of finishing pigs. Castrated 24 male DLY (crossbreeds between Landrace×Yorkshire sows and Duroc boars pigs were allocated to one of three treatments: constant ambient temperature at 22°C and ad libitum feeding (CON, n = 8; constant high ambient temperature at 30°C and ad libitum feeding (H30, n = 8; and constant ambient temperature at 22°C and pair-fed with H30 (PF, n = 8. Meat quality, malondialdehyde (MDA content, antioxidant capacity, carnosine content, and carnosine synthetase (CARNS1 mRNA expression in longissimus dorsi muscle were measured after three weeks. The results revealed that H30 had lower pH24 h, redness at 45 min, and yellowness at 24 h post-mortem (p<0.05, and higher drip loss at 48 h and lightness at 24 h post-mortem (p<0.01. Constant heat stress disrupted the pro-oxidant/antioxidant balance in longissimus dorsi muscle with higher MDA content (p<0.01 and lower antioxidant capacity (p<0.01. Carnosine content and CARNS1 mRNA expression in longissimus dorsi muscle of H30 pigs were significantly decreased (p<0.01 after three weeks at 30°C. In conclusion, constant high ambient temperatures affect meat quality and antioxidant capacity negatively, and the reduction of muscle carnosine content is one of the probable reasons.

  20. Antioxidant, Anti-inflammatory, and Genomic Stability Enhancement Effects of Zinc l-carnosine: A Potential Cancer Chemopreventive Agent?

    Science.gov (United States)

    Ooi, Theng Choon; Chan, Kok Meng; Sharif, Razinah

    2017-01-01

    Cancer is one of the major causes of death worldwide, and the incidence and mortality rates of cancer are expected to rise tremendously in the near future. Despite a better understanding of cancer biology and advancement in cancer management, current strategies in cancer treatment remain costly and ineffective. Hence, instead of putting more efforts to search for new cancer cures, attention has now been shifted to the development of cancer chemopreventive agents as a preventive measure for cancer formation. It is well known that neoplastic transformation of cells is multifactorial, and the occurrence of oxidative stress, chronic inflammation, and genomic instability events has been implicated in the carcinogenesis of cells. Zinc l-carnosine (ZnC), which is clinically used as gastric ulcer treatment in Japan, has been suggested to have the potential in preventing cancer development. Multiple studies have revealed that ZnC possesses potent antioxidant, anti-inflammatory, and genomic stability enhancement effects. Thus, this review provides some mechanistic insight into the antioxidant, anti-inflammatory, and genomic stability enhancement effects of ZnC in relevance to its chemopreventive potential.

  1. The effect of production system and age on levels of iron, taurine, carnosine, coenzyme Q(10), and creatine in beef muscles and liver.

    Science.gov (United States)

    Purchas, R W; Busboom, J R

    2005-08-01

    Samples of longissimus (LL) and triceps brachii (TB) muscles from Angus-cross heifers finished either on a high-concentrate ration in Washington, USA, (US cattle, n=15) or on pasture in New Zealand (NZ cattle, n=16) were assessed for composition characteristics. Half of the NZ cattle were of a similar age to the US cattle (NZAge) and half were of a similar weight (NZWt). Iron concentration was higher in TB (20.9 vs. 17.5μgg(-1); Pmuscle were higher than for LL or TB, and liver levels were 66% higher than cheek muscle. The proportion of haem iron, however, was lowest in liver (55.3%) and was lower in cheek muscle (78.4%) than LL or TB. Relative to LL, TB had higher levels of taurine and coenzyme Q(10), but lower levels of carnosine, creatine and creatinine, as expected for a muscle with a more aerobic metabolism. These differences were magnified for the even more aerobic cheek muscle. Differences between the two NZ groups were small, but muscles from the US cattle contained less taurine, carnosine, coenzyme Q(10), and creatinine. Reasons for these differences in various meat components for similar cattle from different production systems are not clear.

  2. An "enigmatic" L-carnosine (β-alanyl-L-histidine)? Cell proliferative activity as a fundamental property of a natural dipeptide inherent to traditional antioxidant, anti-aging biological activities: balancing and a hormonally correct agent, novel patented oral therapy dosage formulation for mobility, skeletal muscle power and functional performance, hypothalamic-pituitary- brain relationship in health, aging and stress studies.

    Science.gov (United States)

    Babizhayev, Mark A; Yegorov, Yegor E

    2015-01-01

    Hypothalamic releasing and inhibiting hormones are major neuroendocrine regulators of human body metabolism being driven directly to the anterior pituitary gland via hypothalamic-hypophyseal portal veins. The alternative physiological or therapeutic interventions utilizing the pharmaco-nutritional boost of imidazole-containing dipeptides (non-hydrolized oral form of carnosine, carcinine, N-acetylcarnosine lubricant eye drops) can maintain health, enhance physical exercise performance and prevent ageing. Carnosine (β-alanyl-L-histidine) is synthesized in mammalian skeletal muscle. There is an evidence that the release of carnosine from the skeletal muscle sarcomeres moieties during physical exercise affects autonomic neurotransmission and physiological functions. Carnosine released from skeletal muscle during exercise acts as a powerful afferent physiological signaling stimulus for hypothalamus, may be transported into the hypothalamic tuberomammillary nucleus (TMN), specifically to TMN-histamine neurons and hydrolyzed herewith via activities of carnosine-degrading enzyme (carnosinase 2) localized in situ. Through the colocalized enzymatic activity of Histidine decarboxylase in the histaminergic neurons, the resulting L-histidine may subsequently be converted into histamine, which could be responsible for the effects of carnosine on neurotransmission and physiological function. Carnosine and its imidazole-containing dipeptide derivatives are renowned for their anti-aging, antioxidant, membrane protective, metal ion chelating, buffering, anti-glycation/ transglycating activities used to prevent and treat a spectrum of age-related and metabolic diseases, such as neurodegenerative disease, sight threatening eye diseases, Diabetes mellitus and its complications, cancers and other disorders due to their wide spectrum biological activities. The precursor of carnosine (and related imidazole containing compounds) synthesis in skeletal muscles beta-alanine is used as the

  3. Evidence for a dipolar-coupled AM system in carnosine in human calf muscle from in vivo 1H NMR spectroscopy

    Science.gov (United States)

    Schröder, Leif; Bachert, Peter

    2003-10-01

    Spin systems with residual dipolar couplings such as creatine, taurine, and lactate in skeletal muscle tissue exhibit first-order spectra in in vivo 1H NMR spectroscopy at 1.5 T because the coupled protons are represented by (nearly) symmetrized eigenfunctions. The imidazole ring protons (H2, H4) of carnosine are suspected to form also a coupled system. The ring's stiffness could enable a connectivity between these anisochronous protons with the consequence of second-order spectra at low field strength. Our purpose was to study whether this deviation from the Paschen-Back condition can be used to detect the H2-H4 coupling in localized 1D 1H NMR spectra obtained at 1.5 T (64 MHz) from the human calf in a conventional whole-body scanner. As for the hydrogen hyperfine interaction, a Breit-Rabi equation was derived to describe the transition from Zeeman to Paschen-Back regime for two dipolar-coupled protons. The ratio of the measurable coupling strength ( Sk) and the difference in resonance frequencies of the coupled spins (Δ ω) induces quantum-state mixing of various degree upon definition of an appropriate eigenbase of the coupled spin system. The corresponding Clebsch-Gordan coefficients manifest in characteristic energy corrections in the Breit-Rabi formula. These additional terms were used to define an asymmetry parameter of the line positions as a function of Sk and Δ ω. The observed frequency shifts of the resonances were found to be consistent with this parameter within the accuracy achievable in in vivo NMR spectroscopy. Thus it was possible to identify the origin of satellite peaks of H2, H4 and to describe this so far not investigated type of residual dipolar coupling in vivo.

  4. An high-performance liquid chromatographic method for the simultaneous analysis of acetylcarnitine taurinate, carnosine, asparagine and potassium aspartate and for the analysis of phosphoserine in alimentary supplements.

    Science.gov (United States)

    Gatti, R; Andreatta, P; Boschetti, S

    2013-07-12

    A RP-HPLC method with pre-column derivatization was developed and validated for the simultaneous quantification of carnosine (Carn), acetylcarnitine taurinate (AC-Tau), asparagine (Asn), potassium aspartate (Asp) and for the determination of phosphoserine (p-Ser) in new and commercial alimentary supplements. The effect of complex matrices was evaluated by the study of the amino acid derivatization reaction with 2,4-dinitrofluorobenzene (DNFB) both in standard and placebo solutions. The reaction was carried out for 20 min at 70 °C in alkaline medium (pH10) for p-Ser analysis, whereas for 60 min in the case of Carn, AC-Tau, Asn and Asp analysis. The adducts have been separated on a Discovery RP Amide C16 (250 mm×4.6mm, i.d.) column using a mobile phase consisting of acetonitrile (ACN) and triethylammonium (TEA) phosphate buffer (pH 3, 0.05 M) under gradient elution conditions at a flow-rate of 0.8 mL/min. Detection was set at λ=360 nm. The validation parameters such as linearity, sensitivity, accuracy, precision and specificity were found to be highly satisfactory. Linear responses were observed by placebo solutions (determination coefficient ≤0.9996). Intra-day precision (relative standard deviation, RSD) was ≤1.06% for corrected peak area and ≤0.99% for retention times (tR) without significant differences between intra- and inter-day data. Recovery studies showed good results for all examined compounds (from 97.7% to 101.5%) with RSD ranging from 0.5% to 1.3%). The high stability of derivatized compound solutions at room temperature means an undoubted advantage of the method allowing the simultaneous preparation of a large number of samples and consecutive chromatographic analyses by the use of an autosampler. The developed method can be considered suitable for the quality control of new and commercial products. Copyright © 2013 Elsevier B.V. All rights reserved.

  5. Evaluation of radioprotective effect of carnosine (beta- alanyl-1- histidine on the wound healing in rats Avaliação do efeito radioprotetor da carnosina (beta-alanil-1- histidina no processo de cicatrização em ratos

    Directory of Open Access Journals (Sweden)

    Rosana Aramaki Tanaka

    2005-09-01

    Full Text Available The purpose of this study was to evaluate the radioprotective effect of carnosine (beta- alanyl-1-histidine on the wound healing in rats. Therefore, 48 male rats were submitted to a surgical procedure to perform a rectangular wound in the anterior-dorsal region. The animals were divided into 4 experimental groups randomly chosen: control; irradiated; carnosine irradiated and carnosine group. The irradiated and carnosine irradiated group were exposed to a dose (6Gy of gamma irradiation, in the whole body, 72 hours after surgery. The carnosine and carnosine irradiated groups, in addition to the surgical procedure and the irradiation, received two doses of carnosine aqueous solution, the first one being injected 48 hours after surgery, and the second one 1 hour and 30 minutes before irradiation. The tissue repair of the 4 groups was evaluated at 4, 7, 14, and 21 days after inflicting the wound, by morphological, histochemical and histophysical methods. At all examined periods, it could be observed that the animals from the carnosine irradiated group presented a better developed granulation tissue than the irradiated group and closely similar to that of the control group. Thus, under the experimental conditions used, it was possible to conclude that carnosine is an effective radioprotective substance.O objetivo deste estudo foi avaliar o efeito radioprotetor da carnosina (beta-alanil-1-histidina no processo de cicatrização em ratos. Para isto, 48 ratos machos foram submetidos a um procedimento cirúrgico para realização de uma ferida retangular na região dorsal anterior. Os animais foram divididos aleatoriamente em 4 grupos experimentais: controle, irradiado, carnosina irradiado e carnosina. Os grupos carnosina e carnosina irradiado foram exposto a uma dose de corpo todo de 6 Gy de radiação gama, 72 horas após a cirurgia para confecção da ferida. O grupo carnosina e carnosina irradiado, adicionalmente, ao procedimento cirúrgico e a

  6. A Dietary Supplement Containing Cinnamon, Chromium and Carnosine Decreases Fasting Plasma Glucose and Increases Lean Mass in Overweight or Obese Pre-Diabetic Subjects: A Randomized, Placebo-Controlled Trial

    Science.gov (United States)

    Liu, Yuejun; Cotillard, Aurélie; Vatier, Camille; Bastard, Jean-Philippe; Fellahi, Soraya; Stévant, Marie; Allatif, Omran; Langlois, Clotilde; Bieuvelet, Séverine; Brochot, Amandine; Guilbot, Angèle; Clément, Karine; Rizkalla, Salwa W.

    2015-01-01

    Background Preventing or slowing the progression of prediabetes to diabetes is a major therapeutic issue. Objectives Our aim was to evaluate the effects of 4-month treatment with a dietary supplement containing cinnamon, chromium and carnosine in moderately obese or overweight pre-diabetic subjects, the primary outcome being change in fasting plasma glucose (FPG) level. Other parameters of plasma glucose homeostasis, lipid profile, adiposity and inflammatory markers were also assessed. Methods In a randomized, double-blind, placebo-controlled study, 62 subjects with a FPG level ranging from 5.55 to 7 mmol/L and a body mass index ≥25 kg/m2, unwilling to change their dietary and physical activity habits, were allocated to receive a 4-month treatment with either 1.2 g/day of the dietary supplement or placebo. Patients were followed up until 6 months post-randomization. Results Four-month treatment with the dietary supplement decreased FPG compared to placebo (-0.24±0.50 vs +0.12±0.59 mmol/L, respectively, p = 0.02), without detectable significant changes in HbA1c. Insulin sensitivity markers, plasma insulin, plasma lipids and inflammatory markers did not differ between the treatment groups. Although there were no significant differences in changes in body weight and energy or macronutrient intakes between the two groups, fat-free mass (%) increased with the dietary supplement compared to placebo (p = 0.02). Subjects with a higher FPG level and a milder inflammatory state at baseline benefited most from the dietary supplement. Conclusions Four-month treatment with a dietary supplement containing cinnamon, chromium and carnosine decreased FPG and increased fat-free mass in overweight or obese pre-diabetic subjects. These beneficial effects might open up new avenues in the prevention of diabetes. Trial Registration ClinicalTrials.gov NCT01530685 PMID:26406981

  7. A Dietary Supplement Containing Cinnamon, Chromium and Carnosine Decreases Fasting Plasma Glucose and Increases Lean Mass in Overweight or Obese Pre-Diabetic Subjects: A Randomized, Placebo-Controlled Trial.

    Directory of Open Access Journals (Sweden)

    Yuejun Liu

    Full Text Available Preventing or slowing the progression of prediabetes to diabetes is a major therapeutic issue.Our aim was to evaluate the effects of 4-month treatment with a dietary supplement containing cinnamon, chromium and carnosine in moderately obese or overweight pre-diabetic subjects, the primary outcome being change in fasting plasma glucose (FPG level. Other parameters of plasma glucose homeostasis, lipid profile, adiposity and inflammatory markers were also assessed.In a randomized, double-blind, placebo-controlled study, 62 subjects with a FPG level ranging from 5.55 to 7 mmol/L and a body mass index ≥ 25 kg/m(2, unwilling to change their dietary and physical activity habits, were allocated to receive a 4-month treatment with either 1.2 g/day of the dietary supplement or placebo. Patients were followed up until 6 months post-randomization.Four-month treatment with the dietary supplement decreased FPG compared to placebo (-0.24 ± 0.50 vs +0.12 ± 0.59 mmol/L, respectively, p = 0.02, without detectable significant changes in HbA1c. Insulin sensitivity markers, plasma insulin, plasma lipids and inflammatory markers did not differ between the treatment groups. Although there were no significant differences in changes in body weight and energy or macronutrient intakes between the two groups, fat-free mass (% increased with the dietary supplement compared to placebo (p = 0.02. Subjects with a higher FPG level and a milder inflammatory state at baseline benefited most from the dietary supplement.Four-month treatment with a dietary supplement containing cinnamon, chromium and carnosine decreased FPG and increased fat-free mass in overweight or obese pre-diabetic subjects. These beneficial effects might open up new avenues in the prevention of diabetes.ClinicalTrials.gov NCT01530685.

  8. Preparation, Spectrochemical, and Computational Analysis of L-Carnosine (2-[(3-Aminopropanoylamino]-3-(1H-imidazol-5-ylpropanoic Acid and Its Ruthenium (II Coordination Complexes in Aqueous Solution

    Directory of Open Access Journals (Sweden)

    Myalo Sabela

    2011-12-01

    Full Text Available This study reports the synthesis and characterization of novel ruthenium (II complexes with the polydentate dipeptide, L-carnosine (2-[(3-aminopropanoylamino]-3-(1H-imidazol-5-ylpropanoic acid. Mixed-ligand complexes with the general composition [MLp(Clq(H2Or]·xH2O (M = Ru(II; L = L-carnosine; p = 3 − q; r = 0–1; and x = 1–3 were prepared by refluxing aqueous solutions of the ligand with equimolar amounts of ruthenium chloride (black-alpha form at 60 °C for 36 h. Physical properties of the complexes were characterized by elemental analysis, DSC/TGA, and cyclic voltammetry. The molecular structures of the complexes were elucidated using UV-Vis, ATR-IR, and heteronuclear NMR spectroscopy, then confirmed by density function theory (DFT calculations at the B3LYP/LANL2DZ level. Two-dimensional NMR experiments (1H COSY, 13C gHMBC, and 15N gHMBC were also conducted for the assignment of chemical shifts and calculation of relative coordination-induced shifts (RCIS by the complex formed. According to our results, the most probable coordination geometries of ruthenium in these compounds involve nitrogen (N1 from the imidazole ring and an oxygen atom from the carboxylic acid group of the ligand as donor atoms. Additional thermogravimetric and electrochemical data suggest that while the tetrahedral-monomer or octahedral-dimer are both possible structures of the formed complexes, the metal in either structure occurs in the (2+ oxidation state. Resulting RCIS values indicate that the amide-carbonyl, and the amino-terminus of the dipeptide are not involved in chelation and these observations correlate well with theoretical shift predictions by DFT.

  9. Non-hydrolyzed in digestive tract and blood natural L-carnosine peptide ("bioactivated Jewish penicillin") as a panacea of tomorrow for various flu ailments: signaling activity attenuating nitric oxide (NO) production, cytostasis, and NO-dependent inhibition of influenza virus replication in macrophages in the human body infected with the virulent swine influenza A (H1N1) virus.

    Science.gov (United States)

    Babizhayev, Mark A; Deyev, Anatoliy I; Yegorov, Yegor E

    2013-01-01

    in excessive amounts mediate the overreaction of the host's immune response against the organs or tissues in which viruses are replicating, and this may explain the mechanism of tissue injuries observed in influenza virus infection of various types. In this article, the types of protection of carnosine in its bioavailable non-hydrolyzed forms in formulations are considered against reactive oxygen radical species-dependent injury, peroxynitrite damage, and other types of viral injuries in which impaired immune responses to viral pathogens are usually involved. Carnosine (β-alanyl-L-histidine) shows the pharmacological intracellular correction of NO release, which might be one of the important factors of natural immunity in controlling the initial stages of influenza A virus infection (inhibition of virus replication) and virus-induced regulation of cytokine gene expression. The protective effects of orally applied non-hydrolyzed formulated species of carnosine include at least the direct interaction with NO, inhibition of cytotoxic NO-induced proinflammatory condition, and attenuation of the effects of cytokines and chemokines that can exert profound effects on inflammatory cells. These data are consistent with the hypothesis that natural products, such as chicken soup and chicken breast extracts rich in carnosine and its derivative anserine (β-alanyl-1-methyl-L-histidine), could contribute to the pathogenesis and prevention of influenza virus infections and cold but have a limitation due to the susceptibility to enzymatic hydrolysis of dipeptides with serum carnosinase and urine excretion after oral ingestion of a commercial chicken extract. The formulations of non-hydrolyzed in digestive tract and blood natural carnosine peptide and isopeptide (γ-glutamyl-carnosine) products, manufactured at the cGMP-certified facility and patented by the authors, have promise in the control and prevention of influenza A (H1N1) virus infection, cough, and cold.

  10. CCl 4 -Induced Hepatotoxicity: Protective Effects of Carnosine on ...

    African Journals Online (AJOL)

    Hepatotoxicity was assessed by measurement of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities. Hepatic peroxisome proliferator-activated receptor gamma (PPARy) mRNA expression, glutathione-S-transferase (GST) activity, paraoxonase 1 (PON1) activity, xantheine oxidase (XO) ...

  11. A Military Relevant Model of Closed Concussive Head Injury: Longitudinal Studies Characterizing and Validating Single and Repetitive mTBI

    Science.gov (United States)

    2015-10-01

    metabolic homeostasis associated with repeated concussion versus a single concussion. More specifically, 3×PCIs resulted in increased levels of glycogen ...carnosine is an endogenous neuroprotector against free radicals. Cell Mol Neurobiol, 17(2), 259-271. 3. Borges, N., Cerejo, A., Santos, A., Sarmento, A

  12. Central administration of dipeptides, beta-alanyl-BCAAs, induces hyperactivity in chicks

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    Denbow D Michael

    2007-05-01

    Full Text Available Abstract Background Carnosine (β-alanyl-L-histidine is a putative neurotransmitter and has a possible role in neuron-glia cell interactions. Previously, we reported that carnosine induced hyperactivity in chicks when intracerebroventricularly (i.c.v. administered. In the present study, we focused on other β-alanyl dipeptides to determine if they have novel functions. Results In Experiment 1, i.c.v. injection of β-alanyl-L-leucine, but not β-alanyl-glycine, induced hyperactivity behavior as observed with carnosine. Both carnosine and β-alanyl-L-leucine stimulated corticosterone release. Thus, dipeptides of β-alanyl-branched chain amino acids were compared in Experiment 2. The i.c.v. injection of β-alanyl-L-isoleucine caused a similar response as β-alanyl-L-leucine, but β-alanyl-L-valine was somewhat less effective than the other two dipeptides. β-Alanyl-L-leucine strongly stimulated, and the other two dipeptides tended to stimulate, corticosterone release. Conclusion These results suggest that central β-alanyl-branched chain amino acid stimulates activity in chicks through the hypothalamus-pituitary-adrenal axis. We named β-alanyl-L-leucine, β-alanyl-L-isoleucine and β-alanyl-L-valine as Excitin-1, Excitin-2 and Excitin-3, respectively.

  13. Author Details

    African Journals Online (AJOL)

    Soliman, NA. Vol 32, No 1 (2014) - Articles CCl4-Induced Hepatotoxicity: Protective Effects of Carnosine on Peroxisome Proliferator-Activated Receptor Gamma Gene Expression, Genotoxicity and Oxidant/Antioxidant Status in Rats Abstract. ISSN: 1687-1502. AJOL African Journals Online. HOW TO USE AJOL.

  14. Biochemical, Biomedical and Metabolic Aspects of Imidazole-Containing Dipeptides with the Inherent Complexity to Neurodegenerative Diseases and Various States of Mental Well-Being: A Challenging Correction and Neurotherapeutic Pharmaceutical Biotechnology for Treating Cognitive Deficits, Depression and Intellectual Disabilities.

    Science.gov (United States)

    Babizhayev, Mark A

    2014-01-01

    The activities of carnosine (β-alanyl-L-histidine), carnosine imidazole containing dipeptide based derivatives (N-acetylcarnosine, carcinine, homocarnosine) and a carnosine degrading enzyme (serum carnosinase (EC 3.4.13.20); [human tissue carnosinase (EC 3.4.13.3), CN2 (CNDP2)] ) activities have been discrepantly linked to neuropathophysiological processes. Approximately 82% of the U.S. population will experience normal age-related cognitive decline, as compared to the precipitous losses that are associated with dementing disorders. Interventions designed to promote health and function through everyday activity and specific pharmaco-nutritional therapeutic treatments may enhance brain plasticity in key regions that support executive function. Cognitive health is multidimensional cascade of functions. It encompasses an array of functions, including general intellectual ability, memory, language, allowing a person to interact effectively and appropriately with the environment. The risk factors for reduced physical and cognitive functions in elderly people, as identified in longitudinal studies, relate to comorbidities, critical care situations, physical and psychosocial health, environmental conditions, social circumstances, nutrition, and lifestyle. Depression and dementia are both common in older adults; cognitive functioning declines slightly with normal aging; depression itself can be associated with cognitive impairment and dementia. In this study the role of carnosine and related neuron specific naturally-occurring endogenous imidazole-containing dipeptide pharmacoperones (N-acetylcarnosine, carcinine) is revealed presently in a surprisingly large amounts in long-lived human tissues to correct conformational abnormalities leading to distinct neurodegeneration and age-related disease states, treating cognitive deficits, depression and intellectual disabilities. Carnosine serves as a physiological buffering agent and a metal ion (e.g., zinc and copper) chelator

  15. A new method for non-invasive estimation of human muscle fiber type composition.

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    Audrey Baguet

    Full Text Available BACKGROUND: It has been established that excellence in sports with short and long exercise duration requires a high proportion of fast-twitch (FT or type-II fibers and slow-twitch (ST or type-I fibers, respectively. Until today, the muscle biopsy method is still accepted as gold standard to measure muscle fiber type composition. Because of its invasive nature and high sampling variance, it would be useful to develop a non-invasive alternative. METHODOLOGY: Eighty-three control subjects, 15 talented young track-and-field athletes, 51 elite athletes and 14 ex-athletes volunteered to participate in the current study. The carnosine content of all 163 subjects was measured in the gastrocnemius muscle by proton magnetic resonance spectroscopy ((1H-MRS. Muscle biopsies for fiber typing were taken from 12 untrained males. PRINCIPAL FINDINGS: A significant positive correlation was found between muscle carnosine, measured by (1H-MRS, and percentage area occupied by type II fibers. Explosive athletes had ∼30% higher carnosine levels compared to a reference population, whereas it was ∼20% lower than normal in typical endurance athletes. Similar results were found in young talents and ex-athletes. When active elite runners were ranked according to their best running distance, a negative sigmoidal curve was found between logarithm of running distance and muscle carnosine. CONCLUSIONS: Muscle carnosine content shows a good reflection of the disciplines of elite track-and-field athletes and is able to distinguish between individual track running distances. The differences between endurance and sprint muscle types is also observed in young talents and former athletes, suggesting this characteristic is genetically determined and can be applied in early talent identification. This quick method provides a valid alternative for the muscle biopsy method. In addition, this technique may also contribute to the diagnosis and monitoring of many conditions and

  16. Biopolymeric receptor for peptide recognition by molecular imprinting approach—Synthesis, characterization and application

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Lav Kumar; Singh, Monika; Singh, Meenakshi, E-mail: meenakshi_s4@rediffmail.com

    2014-12-01

    The present work is focused on the development of a biocompatible zwitterionic hydrogel for various applications in analytical chemistry. Biopolymer chitosan was derivatized to obtain a series of zwitterionic hydrogel samples. Free amino groups hanging on the biopolymeric chain were reacted with γ-butyrolactone to quaternize the N-centers of polymeric chain. N,N-methylene-bis-acrylamide acts as a crosslinker via Michael-type addition in the subsequent step and facilitated gelation of betainized chitosan. These biopolymeric hydrogel samples were fully characterized by FTIR, {sup 1}H NMR, {sup 13}C NMR spectra, SEM and XRD. Hydrogels were further characterized for their swelling behavior at varying parameters. The extent of swelling was perceived to be dictated by solvent composition such as pH, ionic strength and temperature. This valuable polymeric format is herein chosen to design an artificial receptor for dipeptide ‘carnosine’, which has adequate societal significance to be analytically determined, by molecular imprinting. Electrostatic interactions along with complementary H-bonding and other hydrophobic interactions inducing additional synergetic effect between the template (carnosine) and the imprinted polymer led to the formation of imprinted sites. The MIP was able to selectively and specifically take up carnosine from aqueous solution quantitatively. Thus prepared MIPs were characterized by FTIR spectroscopy, SEM providing evidence for the quality and quantity of imprinted gels. The binding studies showed that the MIP illustrated good recognition for carnosine as compared to non-imprinted polymers (NIPs). Detection limit was estimated as 3.3 μg mL{sup −1}. Meanwhile, selectivity experiments demonstrated that imprinted gel had a high affinity to carnosine in the presence of close structural analogues (interferrants). - Highlights: • Development of a biocompatible zwitterionic hydrogel • A series of chitosan-derived zwitterionic hydrogel samples

  17. Study of molecular mechanisms of UV-induced aggregation of crystallins and possibility of maintaining eye lens transparency

    Science.gov (United States)

    Soustov, L. V.; Chelnokov, E. V.; Bityurin, N. M.; Kiselev, A. L.; Nemov, V. V.; Sergeev, Yu. V.; Ostrovsky, M. A.

    2006-03-01

    The effect of D-pantethine and L-carnosine on the rate of UV-induced (XeC1 laser λ = 308 nm) aggregation of a mixture of βL-crystallin and α-crystallin is studied. We also demonstrate that the suggested by us combination of short-chain peptides shows better protective properties with respect to UV-induced aggregation than known anti-cataract agents.

  18. Muscle histidine-containing dipeptides are elevated by glucose intolerance in both rodents and men.

    Directory of Open Access Journals (Sweden)

    Sanne Stegen

    Full Text Available Muscle carnosine and its methylated form anserine are histidine-containing dipeptides. Both dipeptides have the ability to quench reactive carbonyl species and previous studies have shown that endogenous tissue levels are decreased in chronic diseases, such as diabetes.Rodent study: Skeletal muscles of rats and mice were collected from 4 different diet-intervention studies, aiming to induce various degrees of glucose intolerance: 45% high-fat feeding (male rats, 60% high-fat feeding (male rats, cafeteria feeding (male rats, 70% high-fat feeding (female mice. Body weight, glucose-tolerance and muscle histidine-containing dipeptides were assessed. Human study: Muscle biopsies were taken from m. vastus lateralis in 35 males (9 lean, 8 obese, 9 prediabetic and 9 newly diagnosed type 2 diabetic patients and muscle carnosine and gene expression of muscle fiber type markers were measured.Diet interventions in rodents (cafeteria and 70% high-fat feeding induced increases in body weight, glucose intolerance and levels of histidine-containing dipeptides in muscle. In humans, obese, prediabetic and diabetic men had increased muscle carnosine content compared to the lean (+21% (p>0.1, +30% (p<0.05 and +39% (p<0.05, respectively. The gene expression of fast-oxidative type 2A myosin heavy chain was increased in the prediabetic (1.8-fold, p<0.05 and tended to increase in the diabetic men (1.6-fold, p = 0.07, compared to healthy lean subjects.Muscle histidine-containing dipeptides increases with progressive glucose intolerance, in male individuals (cross-sectional. In addition, high-fat diet-induced glucose intolerance was associated with increased muscle histidine-containing dipeptides in female mice (interventional. Increased muscle carnosine content might reflect fiber type composition and/or act as a compensatory mechanism aimed at preventing cell damage in states of impaired glucose tolerance.

  19. Mechanical Stress Promotes Cisplatin-Induced Hepatocellular Carcinoma Cell Death

    Science.gov (United States)

    Riad, Sandra; Bougherara, Habiba

    2015-01-01

    Cisplatin (CisPt) is a commonly used platinum-based chemotherapeutic agent. Its efficacy is limited due to drug resistance and multiple side effects, thereby warranting a new approach to improving the pharmacological effect of CisPt. A newly developed mathematical hypothesis suggested that mechanical loading, when coupled with a chemotherapeutic drug such as CisPt and immune cells, would boost tumor cell death. The current study investigated the aforementioned mathematical hypothesis by exposing human hepatocellular liver carcinoma (HepG2) cells to CisPt, peripheral blood mononuclear cells, and mechanical stress individually and in combination. HepG2 cells were also treated with a mixture of CisPt and carnosine with and without mechanical stress to examine one possible mechanism employed by mechanical stress to enhance CisPt effects. Carnosine is a dipeptide that reportedly sequesters platinum-based drugs away from their pharmacological target-site. Mechanical stress was achieved using an orbital shaker that produced 300 rpm with a horizontal circular motion. Our results demonstrated that mechanical stress promoted CisPt-induced death of HepG2 cells (~35% more cell death). Moreover, results showed that CisPt-induced death was compromised when CisPt was left to mix with carnosine 24 hours preceding treatment. Mechanical stress, however, ameliorated cell death (20% more cell death). PMID:25685789

  20. State of the art clinical efficacy and safety evaluation of N-acetylcarnosine dipeptide ophthalmic prodrug. Principles for the delivery, self-bioactivation, molecular targets and interaction with a highly evolved histidyl-hydrazide structure in the treatment and therapeutic management of a group of sight-threatening eye diseases.

    Science.gov (United States)

    Babizhayev, Mark A; Kasus-Jacobi, Anne

    2009-01-01

    The exact biological functions of the aminoacyl-histidine dipeptides in ophthalmology are still unknown but they are the subject of intensive research activities at Innovative Vision Products, Inc. (IVP). Numerous studies have demonstrated, both at the tissue and organelle levels, that naturally occuring imidazole containing peptidomimetics possess strong and specific antioxidant properties, by preventing and reducing the accumulation of oxidised products derived from the lipid peroxidation (LPO) of biological membranes. Carnosine has been shown to act as a competitive inhibitor of the non-enzymatic glycosylation of proteins.Thus, carnosine may prevent and reverse (de-link) the formation of the advanced glycation end-products (AGEs), whose accumulation in the ocular tissues has been proposed to play a direct role in the etiology and pathogenesis of cataract and diabetic ocular complications (DOC). Besides, histidine-containing dipeptides are believed to act as cytosolic buffering agents. To compare the efficacy of L-carnosine and derivatives in inhibiting/reversing oxidative stress-induced reactions relevant for cataract pathogenesis. To assess the transglycation activity of carnosine versus representatives of a new group of synthetic carnosine histidyl-hydrazide analogs. To test the clinical efficacy of N-acetylcarnosine prodrug eye drops, developed by IVP's scientists, in decreasing the symptoms of age-related cataract. Antioxidant activity of L-carnosine and N-acetylcarnosine was studied in liposomes, a model of lipid membranes. Iron/ascorbate was used for induction of LPO and peroxidation products were measured. Second-generation carnosine analogs were synthesized and tested vs. L-carnosine for their ability to reverse the glycation process, ultimately resulting in the formation of the AGEs. Visual acuity and glare sensitivity was measured before and after 9-month of topical administration of N-acetylcarnosine eye drops in a randomized placebo-controlled cohort

  1. Effects of beta-alanine supplementation and interval training on physiological determinants of severe exercise performance.

    Science.gov (United States)

    Gross, Micah; Boesch, Chris; Bolliger, Christine S; Norman, Barbara; Gustafsson, Thomas; Hoppeler, Hans; Vogt, Michael

    2014-02-01

    We aimed to manipulate physiological determinants of severe exercise performance. We hypothesized that (1) beta-alanine supplementation would increase intramuscular carnosine and buffering capacity and dampen acidosis during severe cycling, (2) that high-intensity interval training (HIT) would enhance aerobic energy contribution during severe cycling, and (3) that HIT preceded by beta-alanine supplementation would have greater benefits. Sixteen active men performed incremental cycling tests and 90-s severe (110 % peak power) cycling tests at three time points: before and after oral supplementation with either beta-alanine or placebo, and after an 11-days HIT block (9 sessions, 4 × 4 min), which followed supplementation. Carnosine was assessed via MR spectroscopy. Energy contribution during 90-s severe cycling was estimated from the O2 deficit. Biopsies from m. vastus lateralis were taken before and after the test. Beta-alanine increased leg muscle carnosine (32 ± 13 %, d = 3.1). Buffering capacity and incremental cycling were unaffected, but during 90-s severe cycling, beta-alanine increased aerobic energy contribution (1.4 ± 1.3 %, d = 0.5), concurrent with reduced O2 deficit (-5.0 ± 5.0 %, d = 0.6) and muscle lactate accumulation (-23 ± 30 %, d = 0.9), while having no effect on pH. Beta-alanine also enhanced motivation and perceived state during the HIT block. There were no between-group differences in adaptations to the training block, namely increased buffering capacity (+7.9 ± 11.9 %, p = 0.04, d = 0.6, n = 14) and glycogen storage (+30 ± 47 %, p = 0.04, d = 0.5, n = 16). Beta-alanine did not affect buffering considerably, but has beneficial effects on severe exercise metabolism as well as psychological parameters during intense training phases.

  2. Changes in urinary amino acids excretion in relationship with muscle activity markers over a professional cycling stage race: in search of fatigue markers.

    Science.gov (United States)

    Corsetti, Roberto; Barassi, Alessandra; Perego, Silvia; Sansoni, Veronica; Rossi, Alessandra; Damele, Clara Anna Linda; Melzi D'Eril, Gianlodovico; Banfi, Giuseppe; Lombardi, Giovanni

    2016-01-01

    The aim of this study was to identify the relationship between metabolic effort, muscular damage/activity indices, and urinary amino acids profile over the course of a strenuous prolonged endurance activity, as a cycling stage race is, in order to identify possible fatigue markers. Nine professional cyclists belonging to a single team, competing in the Giro d'Italia cycling stage race, were anthropometrically characterized and sampled for blood and urine the day before the race started, and on days 12 and 23 of the race. Diet was kept the same over the race, and power output and energy expenditure were recorded. Sera were assayed for muscle markers (lactate dehydrogenase, aspartate aminotransferase, and creatine kinase activities, and blood urea nitrogen), and creatinine, all corrected for plasma volume changes. Urines were profiled for amino acid concentrations, normalized on creatinine excretion. Renal function, in terms of glomerular filtration rate, was monitored by MDRD equation corrected on body surface area. Creatine kinase activity and blood urea were increased during the race as did serum creatinine while kidney function remained stable. Among the amino acids, taurine, glycine, cysteine, leucine, carnosine, 1-methyl histidine, and 3-methyl histidine showed a net decreased, while homocysteine was increased. Taurine and the dipeptide carnosine (β-alanyl-L-histidine) were significantly correlated with the muscle activity markers and the indices of effort. In conclusion, the metabolic profile is modified strikingly due to the effort. Urinary taurine and carnosine seem useful tools to evaluate the muscle damage and possibly the fatigue status on a long-term basis.

  3. β-Alanine supplemented diets enhance behavioral resilience to stress exposure in an animal model of PTSD.

    Science.gov (United States)

    Hoffman, Jay R; Ostfeld, Ishay; Stout, Jeffrey R; Harris, Roger C; Kaplan, Zeev; Cohen, Hagit

    2015-06-01

    This study investigated the effects of β-alanine (BA) ingestion on the behavioral and neuroendocrine response of post-traumatic stress disorder (PTSD) in a murine model. Animals were fed a normal diet with or without (PL) BA supplementation (100 mg kg(-1)) for 30 days. Animals were then exposed to a predator-scent stress (PSS) or a sham (UNEX). Behaviors were evaluated using an elevated plus maze (EPM) and acoustic startle response (ASR) 7 days following exposure to the PSS. Corticosterone concentrations (CS), expression of brain-derived neurotrophic factor (BDNF), and brain carnosine concentrations were analyzed a day later. Animals in PSS+PL spent significantly less time in the open arms and in the number of entries in the EPM than PSS+BA, UNEX+BA, or UNEX+PL. Animals in PSS+BA had comparable scores to UNEX+BA. Anxiety index was higher (p PSS+PL compared to PSS+BA or animals that were unexposed. ASR and freezing were greater (p PSS compared to animals unexposed. CS expression was higher (p PSS compared to unexposed animals. Brain carnosine concentrations in the hippocampus and other brain sections were significantly greater in animals supplemented with BA compared to PL. BDNF expression in the CA1 and DG subregions of the hippocampus was lower (p < 0.05) in animals exposed and fed a normal diet compared to animals exposed and supplemented with BA, or animals unexposed. In conclusion, BA supplementation in rats increased brain carnosine concentrations and resulted in a reduction in PTSD-like behavior, which may be mediated in part by maintaining BDNF expression in the hippocampus.

  4. Metabolomic elucidation of pork from different crossbreds

    DEFF Research Database (Denmark)

    Bertram, Hanne Christine S.; Straadt, Ida Krestine; Clausen, Morten Rahr

    , and correlations between individual metabolites and sensory attributes were elucidated. A high content of carnosine in the meat was associated with a low value of many sensory attributes related to meat flavor/taste. Surprsingly, IMP and inosine were in general not correlated with sensory attributes related...... to meat flavor/taste. Water-holding capacity and oxygen radical absorbance capacity (ORAC) of the meat were determined to elucidate the correlations between individual metabolites and these two parameters that are of importance for the technological meat quality. In conclusion, the present study reveals...

  5. Localized proton NMR spectroscopy using stimulated echoes: applications to human skeletal muscle in vivo.

    Science.gov (United States)

    Bruhn, H; Frahm, J; Gyngell, M L; Merboldt, K D; Hänicke, W; Sauter, R

    1991-01-01

    Localized proton NMR spectroscopy using stimulated echoes (STEAM) has been used to study metabolites in different proximal skeletal muscles of normal volunteers at rest. Single scan water-suppressed proton NMR spectra obtained at 1.5 and 2.0 T (Siemens Magnetom) from a 64-ml volume-of-interest (VOI) yield resonances due to triglycerides, phosphocreatine plus a minor contribution from creatine, and betaines comprising carnitine and choline-containing compounds. The observation of the pH-dependent resonances of carnosine required multiple acquisitions and echo times as short as 20 ms. T1 and T2 relaxation times of muscle metabolites were obtained by varying the repetition time and echo time of the STEAM sequence, respectively. Although rather long T2 values such as 180 ms for (phospho-) creatine correspond to natural resonance linewidths of only 2 Hz, the observed linewidths of typically 10-12 Hz are entirely determined by the short T2 relaxation times (25-30 ms) of the water protons used for shimming. The spectroscopic results from 24 muscle studies on 17 young male volunteers show remarkable intra- and interindividual differences in the absolute signal intensities of mobile lipids. Further metabolic variations were observed for the relative concentrations of betaines (by a factor of 2) and carnosine (by a factor of 3) when total creatine is assumed to be constant.

  6. The potential of a niacinamide dominated cosmeceutical formulation on fibroblast activity and wound healing in vitro.

    Science.gov (United States)

    Wessels, Quenton; Pretorius, Etheresia; Smith, Celeste M; Nel, Hugo

    2014-04-01

    Knowledge on the intrinsic mechanisms involved in wound healing provides opportunity for various therapeutic strategies. The manipulation of dermal fibroblast proliferation and differentiation might prove to beneficially augment wound healing. This study evaluated the combined effects of niacinamide, L-carnosine, hesperidin and Biofactor HSP(®) on fibroblast activity. The effects on fibroblast collagen production, cellular proliferation, migration and terminal differentiation were assessed. In addition, the authors determined the effects on in vitro wound healing. The optimal concentrations of actives were determined in vitro. Testing parameters included microscopic morphological cell analysis, cell viability and proliferation determination, calorimetric collagen detection and in vitro wound healing dynamics. Results show that 0·31 mg/ml niacinamide, 0·10 mg/ml L-carnosine, 0·05 mg/ml hesperidin and 5·18 µg/ml Biofactor HSP® proved optimal in vitro. The results show that fibroblast collagen synthesis was increased alongside with cellular migration and proliferation. © 2012 The Authors. International Wound Journal © 2012 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

  7. Glycyl-alanyl-histidine protects PC12 cells against hydrogen peroxide toxicity.

    Science.gov (United States)

    Shimura, Hideki; Tanaka, Ryota; Shimada, Yoshiaki; Yamashiro, Kazuo; Hattori, Nobutaka; Urabe, Takao

    2017-11-22

    Peptides with cytoprotective functions, including antioxidants and anti-infectives, could be useful therapeutics. Carnosine, β-alanine-histidine, is a dipeptide with anti-oxidant properties. Tripeptides of Ala-His-Lys, Pro-His-His, or Tyr-His-Tyr are also of interest in this respect. We synthesized several histidine-containing peptides including glycine or alanine, and tested their cytoprotective effects on hydrogen peroxide toxicity for PC12 cells. Of all these peptides (Gly-His-His, Ala-His-His, Ala-His-Ala, Ala-Ala-His, Ala-Gly-His, Gly-Ala-His (GAH), Ala-His-Gly, His-Ala-Gly, His-His-His, Gly-His-Ala, and Gly-Gly-His), GAH was found to have the strongest cytoprotective activity. GAH decreased lactate dehydrogenase (LDH) leakage, apoptosis, morphological changes, and nuclear membrane permeability changes against hydrogen peroxide toxicity in PC12 cells. The cytoprotective activity of GAH was superior to that of carnosine against hydrogen peroxide toxicity in PC12 cells. GAH also protected PC12 cells against damage caused by actinomycin D and staurosporine. Additionally, it was found that GAH also protected SH-SY5Y and Jurkat cells from damage caused by hydrogen peroxide, as assessed by LDH leakage. Thus, a novel tripeptide, GAH, has been identified as having broad cytoprotective effects against hydrogen peroxide-induced cell damage.

  8. How much chicken is food? Questioning the definition of food by analyzing amino acid composition of modern convenience products.

    Science.gov (United States)

    Hermanussen, M; Gonder, U; Stegemann, D; Wesolowski, M; Ulewicz-Magulska, B; Wartensleben, H; Hoffmann, G F

    2012-01-01

    Substantial differences exist between traditionally cooked and chemically designed ready-to-serve products and raise questions about the general principles and requirements of current food law. Differences in amino acid patterns were analyzed in four examples of chicken preparations (boiled chicken meat, traditionally prepared broth from whole chicken, and two commercial chicken broths), and four examples of vegetable broth (traditionally prepared, two commercial products one of which was claimed a BIO-product, and the classic German bouillon cube). Chicken meat contained 284 mg of free amino acids in 100 ml of the boiled meat homogenate, with physiological peaks of glutamate (14.5 mg/100 ml), glutamine (8.5 mg/100 ml), anserine (88 mg/100 ml) and carnosine (55 mg/100 ml). The patterns significantly differ in industrially designed chicken soups with elevated peaks of glutamate, and missing anserine or carnosine. Similar results were obtained in vegetable broths. In the classic German bouillon cube, glutamate accounts for 96% of all free amino acids. The amino acid composition of modern ready-to-serve chicken soups and vegetable broths are far from being similar to any natural composition. We need to question current legal definitions of food, and consider its impact on eating habits, appetite regulation and obesity.

  9. The Effect of Chicken Extract on Mood, Cognition and Heart Rate Variability

    Directory of Open Access Journals (Sweden)

    Hayley Young

    2015-01-01

    Full Text Available Chicken extract, which is rich in anserine and carnosine, has been widely taken in Asian countries as a traditional remedy with various aims, including attenuation of psychological fatigue. The effects of consuming BRAND’S Essence of Chicken (EOC or a placebo on 46 young adults’ responses to a standard psychological “stressor” were considered. Heart rate variability (HRV, cortisol responses, mood and cognition were measured at baseline and after ten days supplementation. EOC resulted in feeling less anxious, depressed and confused and more agreeable and clearheaded. A decrease in HRV was observed after EOC but only in females. Cognition and cortisol levels were not influenced by EOC. Findings suggest that EOC may be a promising supplement to improve mood in a healthy population.

  10. Improving meat quality through cattle feed enriched with mate extract

    DEFF Research Database (Denmark)

    de Zawadzki, Andressa

    The use of plant extracts in animal feeding trials has been considered as a potential alternative to improve the redox stability of meat. Bioactive compounds from plant extracts can provide the antioxidative mechanisms required to improve animal health and welfare and, to protect meat against...... oxidation. Pharmacological properties and antioxidant effects have been associated to the extract of hops and to the extracts of yerba mate. However, the effects of hops and yerba mate as dietary supplement for animal feeding on the metabolic profile and the redox stability of meat have not been reported...... yet. Addition of extract of mate to a standard maize/soy feed at a level of 0.5, 1.0 or 1.5% to the diet of feedlot for cattle resulted in an increased level of inosine monophosphate, creatine, carnosine and of conjugated linoleic acid in the fresh meat. The tendency to radical formation in meat...

  11. Meat and meat products as a source of bioactive peptides

    Directory of Open Access Journals (Sweden)

    Alfonso Totosaus

    2016-12-01

    Full Text Available Meat is a high protein content food, with great nutritional and biological value. Meat protein hydrolysis begins with the muscle to meat conversion, during meat ageing. After slaughter, endogen enzymes are responsible of meat softening since myofibrillar anchorage proteins are degraded. Protein hydrolysis continues during food preparation. When meat reaches the stomach, pepsin is the first enzyme to interact. As the food travel trough out gastrointestinal tract, pancreatic enzymes degraded the remained protein and the peptidases made the final proteolysis process. The small proteins or peptides are the absorbed to the circulatory system and distributed to the rest of the body. Bioactive peptides activity of meat and meat products is anti-hypertensive mainly, where histidine, carnosine and anserine are the main peptides identified. Another peptide with anti-oxidant activity is glutathione. The content depends on animal species.

  12. Aldehyde-sequestering drugs: tools for studying protein damage by lipid peroxidation products.

    Science.gov (United States)

    Burcham, Philip C; Kaminskas, Lisa M; Fontaine, Frank R; Petersen, Dennis R; Pyke, Simon M

    2002-12-27

    Elevated levels of reactive alpha,beta-unsaturated aldehydes (e.g. malondialdehyde, 4-hydroxynonenal and acrolein) in the affected tissues of various degenerative conditions suggest these substances are active propagators of the disease process. One experimental approach to attenuating damage by these intermediates employs 'aldehyde-sequestering drugs' as sacrificial nucleophiles, thereby sparing cell macromolecules and perhaps slowing disease progression. Drugs with demonstrated trapping activity toward lipid-derived aldehydes include various amine compounds such as aminoguanidine, carnosine and pyridoxamine. We have focused on identifying scavengers of acrolein, perhaps the most toxic aldehyde formed during lipid peroxidation cascades. Various phthalazine compounds (hydralazine and dihydralazine) were found to trap acrolein readily, forming hydrazone derivatives in a rapid Schiff-type reaction. These compounds strongly protect against acrolein-mediated toxicity in isolated hepatocytes.

  13. Functional foods, herbs and nutraceuticals: towards biochemical mechanisms of healthy aging.

    Science.gov (United States)

    Ferrari, Carlos K B

    2004-01-01

    Aging is associated with mitochondrial dysfunctions, which trigger membrane leakage, release of reactive species from oxygen and nitrogen and subsequent induction of peroxidative reactions that result in biomolecules' damaging and releasing of metals with amplification of free radicals discharge. Free radicals induce neuronal cell death increasing tissue loss, which could be associated with memory detriment. These pathological events are involved in cardiovascular, neurodegenerative and carcinogenic processes. Dietary bioactive compounds from different functional foods, herbs and nutraceuticals (ginseng, ginkgo, nuts, grains, tomato, soy phytoestrogens, curcumin, melatonin, polyphenols, antioxidant vitamins, carnitine, carnosine, ubiquinone, etc.) can ameliorate or even prevent diseases. Protection from chronic diseases of aging involves antioxidant activities, mitochondrial stabilizing functions, metal chelating activities, inhibition of apoptosis of vital cells, and induction of cancer cell apoptosis. Functional foods and nutraceuticals constitute a great promise to improve health and prevent aging-related chronic diseases.

  14. 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.

  15. Behavioral and inflammatory response in animals exposed to a low-pressure blast wave and supplemented with β-alanine.

    Science.gov (United States)

    Hoffman, Jay R; Zuckerman, Amitai; Ram, Omri; Sadot, Oren; Stout, Jeffrey R; Ostfeld, Ishay; Cohen, Hagit

    2017-05-01

    This study investigated the benefit of β-alanine (BA) supplementation on behavioral and cognitive responses relating to mild traumatic brain injury (mTBI) and post-traumatic stress disorder (PTSD) in rats exposed to a low-pressure blast wave. Animals were fed a normal diet with or without (PL) BA supplementation (100 mg kg -1 ) for 30-day, prior to being exposed to a low-pressure blast wave. A third group of animals served as a control (CTL). These animals were fed a normal diet, but were not exposed to the blast. Validated cognitive-behavioral paradigms were used to assess both mTBI and PTSD-like behavior on days 7-14 following the blast. Brain-derived neurotrophic factor (BDNF), neuropeptide Y, glial fibrillary acidic protein (GFAP) and tau protein expressions were analyzed a day later. In addition, brain carnosine and histidine content was assessed as well. The prevalence of animals exhibiting mTBI-like behavior was significantly lower (p = 0.044) in BA than PL (26.5 and 46%, respectively), but no difference (p = 0.930) was noted in PTSD-like behavior between the groups (10.2 and 12.0%, respectively). Carnosine content in the cerebral cortex was higher (p = 0.048) for BA compared to PL, while a trend towards a difference was seen in the hippocampus (p = 0.058) and amygdala (p = 0.061). BDNF expression in the CA1 subregion of PL was lower than BA (p = 0.009) and CTL (p animals exposed to a low-pressure blast wave.

  16. [PHENOTYPICAL CHARACTERISTICS AND GENETICAL DETERMINANTS OF PATHOGENICITY OF STAPHYLOCOCCUS AUREUS, ISOLATED FROM BACTERIAL CARRIERS, RESIDING ON THE TERRITORIES WITH VARIOUS LEVELS OF ANTHROPOGENIC POLLUTION OF AIR ENVIRONMENT].

    Science.gov (United States)

    Utkina, T M; Popova, L P; Kartashova, O L; Khazeeva, G D; Khaliullina, A A

    2015-01-01

    Comparative phenotypical and genetical evaluation of pathogenic potential of Staphylococcus aureus strains, isolated from resident bacterial carriers, residing on the territories with anthropogenic pollution of air environment of varying intensity. S. aureus, isolated 3 times from mucous membrane of the anterior of nose from 210 children, were the object of the study. Anti-carnosine activity and biofilm formation was determined by a photometric method, antibiotics resistance--by a disc diffusion method. lukS, lukF, sec 3, clfA, clfB, agr and mecA gene detection, that are associated with S. aureus, was carried out by PCR. S. aureus strains, isolated from children, residing on the territories with a high level of anthropogenic pollution of air environment, were characterized by antibiotics resistance, higher values of anti-carnosine activity, 2 times more frequently formed biofilms with higher values of the parameter. clfA and clfB genes, that determine colonization of mucous membranes, and agr gene were detected in all the studied S. aureus strains, lukF and sec 3 genes were detected in 20-40% of the strains, isolated from children, residing on both territories. mecA and lukS genetical determinants were not detected. S. aureus, isolated from children, residing on the territories with high levels of anthropogenic pollution of air environment; were characterized by higher values of the studied factors of persistence and stability against antibiotics. Genetical determinants of pathogenicity were not detected in S. aureus, isolated from individuals, residing on both territories.

  17. High Levels of Dietary Supplement Vitamins A, C and E are Absorbed in the Small Intestine and Protect Nutrient Transport Against Chronic Gamma Irradiation

    Science.gov (United States)

    Azzam, Edouard I.; Ferraris, Ronaldo P.; Howell, Roger W.

    2015-01-01

    We examined nutrient transport in the intestines of mice exposed to chronic low-LET 137Cs gamma rays. The mice were whole-body irradiated for 3 days at dose rates of 0, 0.13 and 0.20 Gy/h, for total dose delivery of 0, 9.6 or 14.4 Gy, respectively. The mice were fed either a control diet or a diet supplemented with high levels of vitamins A, C and E. Our results showed that nutrient transport was perturbed by the chronic irradiation conditions. However, no apparent alteration of the macroscopic intestinal structures of the small intestine were observed up to day 10 after initiating irradiation. Jejunal fructose uptake measured in vitro was strongly affected by the chronic irradiation, whereas uptake of proline, carnosine and the bile acid taurocholate in the ileum was less affected. D-glucose transport did not appear to be inhibited significantly by either 9.6 or 14.4 Gy exposure. In the 14.4 Gy irradiated groups, the diet supplemented with high levels of vitamins A, C and E increased intestinal transport of fructose compared to the control diet (day 10; t test, P = 0.032), which correlated with elevated levels of vitamins A, C and E in the plasma and jejunal enterocytes. Our earlier studies with mice exposed acutely to 137Cs gamma rays demonstrated significant protection for transport of fructose, glucose, proline and carnosine. Taken together, these results suggest that high levels of vitamins A, C and E dietary supplements help preserve intestinal nutrient transport when intestines are irradiated chronically or acutely with low-LET gamma rays. PMID:26484399

  18. Antioxidant status of turkey breast meat and blood after feeding a diet enriched with histidine.

    Science.gov (United States)

    Kopec, W; Wiliczkiewicz, A; Jamroz, D; Biazik, E; Pudlo, A; Hikawczuk, T; Skiba, T; Korzeniowska, M

    2016-01-01

    The objective of this study was to investigate the effects of 1) spray dried blood cells rich in histidine and 2) pure histidine added to feed on the antioxidant status and concentration of carnosine related components in the blood and breast meat of female turkeys. The experiment was performed on 168 Big7 turkey females randomly assigned to 3 dietary treatments: control; control with the addition of 0.18% L-histidine (His); and control with the addition of spray dried blood cells (SDBC). Birds were raised for 103 d on a floor with sawdust litter, with drinking water and feed ad libitum. The antioxidant status of blood plasma and breast muscle was analyzed by ferric reducing ability (FRAP) and by 2,2-Azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 1,1-Diphenyl-2-picrylhydrazyl (DPPH) radicals scavenging ability. The activity of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) was analyzed in the blood and breast meat, with the content of carnosine and anserine quantified by HPLC. Proximate analysis as well as amino acid profiling were carried out for the feed and breast muscles. Growth performance parameters also were calculated. Histidine supplementation of the turkey diet resulted in increased DPPH radical scavenging capacity in the breast muscles and blood, but did not result in higher histidine dipeptide concentrations. The enzymatic antioxidant system of turkey blood was affected by the diet with SDBC. In the plasma, the SDBC addition increased both SOD and GPx activity, and decreased GPx activity in the erythrocytes. Feeding turkeys with an SDBC containing diet increased BW and the content of isoleucine and valine in breast muscles. © 2015 Poultry Science Association Inc.

  19. Physiological and performance responses to a preseason altitude-training camp in elite team-sport athletes.

    Science.gov (United States)

    McLean, Blake D; Buttifant, David; Gore, Christopher J; White, Kevin; Liess, Carsten; Kemp, Justin

    2013-07-01

    Little research has been done on the physiological and performance effects of altitude training on team-sport athletes. Therefore, this study examined changes in 2000-m time-trial running performance (TT), hemoglobin mass (Hbmass), and intramuscular carnosine content of elite Australian Football (AF) players after a preseason altitude camp. Thirty elite AF players completed 19 days of living and training at either moderate altitude (~2130 m; ALT, n = 21) or sea level (CON, n = 9). TT performance and Hbmass were assessed preintervention (PRE) and postintervention (POST1) in both groups and at 4 wk after returning to sea level (POST2) in ALT only. Improvement in TT performance after altitude was likely 1.5% (± 4.8-90%CL) greater in ALT than in CON, with an individual responsiveness of 0.8%. Improvements in TT were maintained at POST2 in ALT. Hbmass after altitude was very likely increased in ALT compared with CON (2.8% ± 3.5%), with an individual responsiveness of 1.3%. Hbmass returned to baseline at POST2. Intramuscular carnosine did not change in either gastrocnemius or soleus from PRE to POST1. A preseason altitude camp improved TT performance and Hbmass in elite AF players to a magnitude similar to that demonstrated by elite endurance athletes undertaking altitude training. The individual responsiveness of both TT and Hbmass was approximately half the group mean effect, indicating that most players gained benefit. The maintenance of running performance for 4 wk, despite Hbmass returning to baseline, suggests that altitude training is a valuable preparation for AF players leading into the competitive season.

  20. N-Acetylcarnosine sustained drug delivery eye drops to control the signs of ageless vision: Glare sensitivity, cataract amelioration and quality of vision currently available treatment for the challenging 50,000-patient population

    Directory of Open Access Journals (Sweden)

    Mark A Babizhayev

    2008-10-01

    Full Text Available Mark A Babizhayev1, Leslie Burke2, Philip Micans3, Stuart P Richer4,51Innovative Vision Products, Inc., County of New Castle, Delaware, USA; 2Wise Choice Products LLC, London, England, United Kingdom; 3IAS Group, Sark, United Kingdom; 4Eye Clinic DVA Medical Center, North Chicago, Illinois, USA; 5Department of Family and Preventive Medicine, Rosalind Franklin University of Medicine and Science, North Chicago, Illinois, USABackground: Innovative Vision Products, Inc. (IVP’s scientists developed the lubricant eye drops (Can-C™ designed as 1% N-acetylcarnosine (NAC prodrug of L-carnosine containing a mucoadhesive cellulose-based compound combined with corneal absorption promoters in a sustained drug delivery system. Only the natural L-isomeric form of NAC raw material was specifically synthesized at the cGMP facility and employed for the manufacturing of Can-C™ eye drops.Objective and study design: In the present clinical study the authors assessed vision before and after 9 month term of topical ocular administration of NAC lubricant eye drops or placebo in 75 symptomatic patients with age-related uncomplicated cataracts in one or both eyes, with acuity in one eye of 20/40 or worse (best-corrected distance, and no previous cataract surgery in either eye and no other ocular abnormality and 72 noncataract subjects ranged in age from 54 to 78 years.Setting: Subjects in these subsample groups have reported complaints of glare and wanted to administer eye drops to get quick eye relief and quality of vision for their daily activities including driving and computer works. Following 9 months of treatment with NAC lubricant eye drops, most patients’ glare scores were improved or returned to normal in disability glare tests with Halometer DG. Improvement in disability glare was accompanied with independent improvement in acuity. Furthermore, patients with the poorest pretreatment vision were as likely to regain certain better visual function after 9

  1. Redefining face contour with a novel anti-aging cosmetic product: an open-label, prospective clinical study

    Directory of Open Access Journals (Sweden)

    Garre A

    2017-11-01

    Full Text Available Aurora Garre,1 Gemma Martinez-Masana,1 Jaime Piquero-Casals,2 Corinne Granger1 1Innovation and Development, ISDIN S.A., Barcelona, Spain; 2Dermik Clinic, Barcelona, Spain Background: Skin aging is accelerated by multiple extrinsic factors: ultraviolet radiation, smoking and pollution increase oxidative activity, damaging cellular and extracellular components such as DNA, proteins, and lipids. With age, collagen and hyaluronic acid levels decline, resulting in loss of elasticity and moisture of the skin. Over time this damage leads to characteristic signs that make the skin look older: altered facial contour, sagging skin, wrinkles, and an uneven complexion. This study evaluated the anti-aging effects of a new facial cream formulated with carnosine, Alteromonas ferment extract, crosspolymer hyaluronic acid, and a tripeptide. Methods: An open-label intra-individual study to assess the anti-aging efficacy of the investigational product in 33 women aged 45 to 65 years. The product was applied twice daily for 56 days. Facial contour and skin deformation, elasticity, hydration, and complexion were measured with specialized equipment at baseline and days 28 and 56. Additionally, subjects completed questionnaires at days 28 and 56 on the perceived efficacy and cosmetic characteristics of the product. Results: After 56 days of use of the investigational product, a redefining effect was observed, with a significant decrease in sagging jawline (7%. Skin was significantly more hydrated (12%, firmer (29%, and more elastic (20% (P<0.001 for all. On complexion assessment, skin texture (a measure of skin smoothness and spots (brown and red skin lesions also improved significantly (12% and 6% decrease, respectively. In the subjective self-evaluation, the majority of subjects reported that the skin was visibly tightened and more elastic, flexible, and moisturized (91%, 88%, 91%, and 90%, respectively. The product was well tolerated with no adverse events reported

  2. β-alanine supplementation to improve exercise capacity and performance: a systematic review and meta-analysis.

    Science.gov (United States)

    Saunders, Bryan; Elliott-Sale, Kirsty; Artioli, Guilherme G; Swinton, Paul A; Dolan, Eimear; Roschel, Hamilton; Sale, Craig; Gualano, Bruno

    2017-04-01

    To conduct a systematic review and meta-analysis of the evidence on the effects of β-alanine supplementation on exercise capacity and performance. This study was designed in accordance with PRISMA guidelines. A 3-level mixed effects model was employed to model effect sizes and account for dependencies within data. 3 databases (PubMed, Google Scholar, Web of Science) were searched using a number of terms ('β-alanine' and 'Beta-alanine' combined with 'supplementation', 'exercise', 'training', 'athlete', 'performance' and 'carnosine'). Inclusion/exclusion criteria limited articles to double-blinded, placebo-controlled studies investigating the effects of β-alanine supplementation on an exercise measure. All healthy participant populations were considered, while supplementation protocols were restricted to chronic ingestion. Cross-over designs were excluded due to the long washout period for skeletal muscle carnosine following supplementation. A single outcome measure was extracted for each exercise protocol and converted to effect sizes for meta-analyses. 40 individual studies employing 65 different exercise protocols and totalling 70 exercise measures in 1461 participants were included in the analyses. A significant overall effect size of 0.18 (95% CI 0.08 to 0.28) was shown. Meta-regression demonstrated that exercise duration significantly (p=0.004) moderated effect sizes. Subgroup analyses also identified the type of exercise as a significant (p=0.013) moderator of effect sizes within an exercise time frame of 0.5-10 min with greater effect sizes for exercise capacity (0.4998 (95% CI 0.246 to 0.753)) versus performance (0.1078 (95% CI -0.201 to 0.416)). There was no moderating effect of training status (p=0.559), intermittent or continuous exercise (p=0.436) or total amount of β-alanine ingested (p=0.438). Co-supplementation with sodium bicarbonate resulted in the largest effect size when compared with placebo (0.43 (95% CI 0.22 to 0.64)). β-alanine had a

  3. Variability in the contents of pork meat nutrients and how it may affect food composition databases.

    Science.gov (United States)

    Reig, Milagro; Aristoy, M-Concepción; Toldrá, Fidel

    2013-10-01

    Pork meat is generally recognised as a food with relevant nutritional properties because of its content in high biological value proteins, group B vitamins, minerals especially heme iron, trace elements and other bioactive compounds. But pork meat also contributes to the intake of fat, saturated fatty acids, cholesterol, and other substances that, in inappropriate amounts, may result in negative physiologically effects. However, there are relevant factors affecting the content of many of these substances and somehow such variability should be taken into consideration. So, genetics, age and even type of muscle have a relevant influence on the amount of fat and the contents in heme iron. Also the composition in fatty acids of triacylglycerols is very sensitive to the contents of cereals in the feed; for instance, polyunsaturated fatty acids may range from 10% to 22% in pork meat. The content of other nutrients, like vitamins E and A, are also depending on the type of feed. Some bioactive substances like coenzyme Q10, taurine, glutamine, creatine, creatinine, carnosine and anserine show a large dependence on the type of muscle. This manuscript describes the main factors affecting the composition of pork meat nutrients and how these changes may affect the general food composition databases. Copyright © 2012 Elsevier Ltd. All rights reserved.

  4. Radiation-induced changes in the patterns of free ninhydrin-reactive substances of meat

    International Nuclear Information System (INIS)

    Partmann, W.; Keskin, S.

    1979-01-01

    Samples of minced lean beef and pork, breast muscle of chicken, and white meat of carp packed in polyethylene/Hostaphan bags were irradiated in the presence of air at about 25 0 C with 10-MeV electrons. The doses applied were for beef 0.5-20 Mrad, and for other meat samples 10 Mrad. In the dose range of 0-5 Mrad, no statistically significant changes in the composition of the free amino acids and similar compounds usually present in beef were found. In the dose range between 10 and 20 Mrad a tendency towards small losses in such components became obvious. In beef samples irradiated at doses >= 0.5 Mrad a new substance (Y) appeared distinctly in the zone of the basic amino-acids. This compound was detected by two independent methods, column chromatography and high-voltage electrophoresis. The yellow colour of the band appearing above carnosine in the pherogram was striking. Substance Y was also found after irradiation of pork and chicken meat. At a dose of 10 Mrad the concentration of Y in white chicken meat was nearly three times higher than in beef and pork. After irradiation of white carp muscle no Y, but another new basic compound (X) was observed. In the pherograms it appeared as a brwonish-red band above β-alanine. (orig./AJ) [de

  5. Enhancing antioxidant activity of sesamol at frying temperature by addition of additives through reducing volatility.

    Science.gov (United States)

    Hwang, Hong-Sik; Winkler-Moser, Jill K; Vermillion, Karl; Liu, Sean X

    2014-11-01

    Additives were evaluated to investigate their effects on volatility of sesamol at frying temperature with the hypothesis that the interaction between an additive and sesamol would reduce sesamol volatility. Twenty-two additive : sesamol combinations were examined by thermogravimetric analysis (TGA) under nitrogen in neat form and in soybean oil. The results indicate that these additives could bind to or interact with sesamol and consequently reduced its volatility. (1) H NMR study provided evidence for hydrogen bonding between sesamol and a hydroxyl group, an amino group, and ether groups. Subsequent heating tests were conducted to investigate the effect of the reduced volatility of sesamol on antioxidant activity in soybean oil at 180 °C. Oxidation of soybean oil was monitored with gel permeation chromatography for formation of polymerized triacylglycerols and with (1) H NMR for loss of olefinic and bisallylic protons. Sesamol retained in soybean oil during the heating process was determined by high-performance liquid chromatography. A strong correlation between the retained sesamol and the antioxidant activity was observed. The mixture of 830 ppm sesamol and mono-/diglycerides, polysorbate 20 or l-carnosine showed much improved antioxidant activity compared to sesamol itself and slightly better antioxidant activity than 200 ppm tert-butylhydroquinone. It is believed that this method can also be used for many other antioxidants for which volatility is a problem. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

  6. Metabolomic approach for identifying and visualizing molecular tissue markers in tadpoles of Xenopus tropicalis by mass spectrometry imaging

    Directory of Open Access Journals (Sweden)

    Naoko Goto-Inoue

    2016-09-01

    Full Text Available In developmental and cell biology it is crucial to evaluate the dynamic profiles of metabolites. An emerging frog model system using Xenopus tropicalis, whose genome sequence and inbred strains are available, is now ready for metabolomics investigation in amphibians. In this study we applied matrix-assisted laser desorption/ionization (MALDI-mass spectrometry imaging (MSI analysis to identify and visualize metabolomic molecular markers in tadpoles of Xenopus tropicalis. We detected tissue-specific peaks and visualized their distribution in tissues, and distinguished 19 tissues and their specific peaks. We identified, for the first time, some of their molecular localizations via tandem mass spectrometric analysis: hydrocortisone in artery, L-DOPA in rhombencephalon, taurine in eye, corticosterone in gill, heme in heart, inosine monophosphate and carnosine in muscle, dopamine in nerves, and phosphatidylethanolamine (16:0/20:4 in pharynx. This is the first MALDI-MSI study of X. tropicalis tadpoles, as in small tadpoles it is hard to distinguish and dissect the various organs. Furthermore, until now there has been no data about the metabolomic profile of each organ. Our results suggest that MALDI-MSI is potentially a powerful tool for examining the dynamics of metabolomics in metamorphosis as well as conformational changes due to metabolic changes.

  7. Role of Histamine and Its Receptors in Cerebral Ischemia

    Science.gov (United States)

    2012-01-01

    Histamine is recognized as a neurotransmitter or neuromodulator in the brain, and it plays a major role in the pathogenic progression after cerebral ischemia. Extracellular histamine increases gradually after ischemia, and this may come from histaminergic neurons or mast cells. Histamine alleviates neuronal damage and infarct volume, and it promotes recovery of neurological function after ischemia; the H1, H2, and H3 receptors are all involved. Further studies suggest that histamine alleviates excitotoxicity, suppresses the release of glutamate and dopamine, and inhibits inflammation and glial scar formation. Histamine may also affect cerebral blood flow by targeting to vascular smooth muscle cells, and promote neurogenesis. Moreover, endogenous histamine is an essential mediator in the cerebral ischemic tolerance. Due to its multiple actions, affecting neurons, glia, vascular cells, and inflammatory cells, histamine is likely to be an important target in cerebral ischemia. But due to its low penetration of the blood-brain barrier and its wide actions in the periphery, histamine-related agents, like H3 antagonists and carnosine, show potential for cerebral ischemia therapy. However, important questions about the molecular aspects and pathophysiology of histamine and related agents in cerebral ischemia remain to be answered to form a solid scientific basis for therapeutic application. PMID:22860191

  8. Metabolic signatures associated with environmental pollution by metals in Doñana National Park using P. clarkii as bioindicator.

    Science.gov (United States)

    Gago-Tinoco, Amanda; González-Domínguez, Raúl; García-Barrera, Tamara; Blasco-Moreno, Julián; Bebianno, M J; Gómez-Ariza, José-Luis

    2014-12-01

    Bioindicators can reflect the effects of pollutants on their metabolism, being widely used to assess environmental stress. In this sense, the crab Procambarus clarkii has been previously proposed to monitor the contamination in Doñana National Park (southwest Spain) using conventional biomarkers. In this work, a metabolomic approach based on direct infusion mass spectrometry, which allows an easy and quick study of a large number of metabolites in a single run, was used for pollution assessment of this area, considering the biological response of this organism to contamination. In addition, metal accumulation in crab tissues was determined. Thus, the integrated analysis of metabolomic and metallomic data enabled the study of metabolic response of the organism against pollution. Several metabolites were discovered as potential biomarkers of pollution, such as decreased levels of carnosine, alanine, niacinamide, acetoacetate, pantothenic acid, ascorbate, glucose-6-phosphate, arginine, glucose, lactate, phospholipids, and tryglicerides, as well as elevated levels of acetyl carnitine, phosphocholine, choline, and uric acid. In this way, metal-induced toxicity could be related to metabolic impairments, principally oxidative stress, metabolic dysfunction, and dyslipidemia.

  9. Fortified Extract of Red Berry, Ginkgo biloba, and White Willow Bark in Experimental Early Diabetic Retinopathy

    Directory of Open Access Journals (Sweden)

    Claudio Bucolo

    2013-01-01

    Full Text Available Diabetic retinopathy is a complex condition where inflammation and oxidative stress represent crucial pathways in the pathogenesis of the disease. Aim of the study was to investigate the effects of a fortified extract of red berries, Ginkgo biloba and white willow bark containing carnosine and α-lipoic acid in early retinal and plasma changes of streptozotocin-induced diabetic rats. Diabetes was induced by a single streptozotocin injection in Sprague Dawley rats. Diabetics and nondiabetic (control rats were treated daily with the fortified extract for the ten days. Retina samples were collected and analyzed for their TNF-α and VEGF content. Moreover, plasma oxidative stress was evaluated by thiobarbituric acid reacting substances (TBARS. Increased TNF-α and VEGF levels were observed in the retina of diabetic rats. Treatment with the fortified extract significantly lowered retinal cytokine levels and suppressed diabetes-related lipid peroxidation. These data demonstrate that the fortified extract attenuates the degree of retinal inflammation and plasma lipid peroxidation preserving the retina in early diabetic rats.

  10. Effects of Rice Bran, Flax Seed, and Sunflower Seed on Growth Performance, Carcass Characteristics, Fatty Acid Composition, Free Amino Acid and Peptide Contents, and Sensory Evaluations of Native Korean Cattle (Hanwoo

    Directory of Open Access Journals (Sweden)

    Chang Bon Choi

    2016-02-01

    Full Text Available This study was conducted to evaluate the effect of dietary supplementation with rice bran, flax seed, or sunflower seed to finishing native Korean cattle (Hanwoo on growth performances, carcass characteristics, fatty acid composition, free amino acid and peptide contents, and sensory evaluations of Longissimus muscle (LM. A total of 39 Hanwoo steers (average age of 22.2 mo and average body weight (BW of 552.2 kg were randomly divided into Control, rice bran (RB, flax seed (FS, or Sunflower seed (SS groups. The steers were group fed for 273 d until they reached an average age of 31.2 mo. Final BW was 768.2, 785.8, 786.2, and 789.0 kg, and average daily gain was 0.79, 0.85, 0.82, and 0.84 kg for the Control, RS, FS, and SS groups, respectively (p>0.05. Fat thickness of the FS group (19.8 mm was greater (p0.05 scores for flavor, umami, and overall palatability in sensory evaluations. In conclusion, supplementation of flax seed to diets of finishing Hanwoo steers improved sensory evaluations which might have been caused by increases in flavor related amino acids such as methionine, glutamic acid and α-AAA and peptides, anserine and carnosine, and their complex reactions.

  11. THE EVALUATION OF PEPTIDE/HISTIDINE TRANSPORTER 1 (PHT1) FUNCTION: UPTAKE KINETICS UTILIZING A COS-7 STABLY TRANSFECTED CELL LINE.

    Science.gov (United States)

    Lindley, David J; Carl, Stephen M; Mowery, Stephanie A; Knipp, Gregory T

    2011-10-01

    There have been relatively few studies focused on the proton-dependent oligopeptide transporter (POT) superfamily member, Peptide/Histidine Transporter 1 (PHT1), with respect to its contribution to the ADME of peptides and peptide-based drugs. These studies were conducted to determine hPHT1-mediated, H + -dependent uptake kinetics of histidine, carnosine, Gly-Sar and valacyclovir in stably transfected hPHT1-COS-7 cells comparative to kinetics determined in an empty vector (Mock) stably transfected cell line. The results suggest that Gly-Sar appears to be a substrate for PHT1 based on efflux from the stably transfected hPHT1 COS-7 cells. Histidine and Gly-Sar concentration- and time-dependent studies suggest mixed-uptake kinetics. These studies suggest that stably transfected hPHT1-COS-7 cells exhibit different uptake kinetics than those observed in our previous studies and illustrate the requirement for experiments to delineate the physiological role of hPHT1.

  12. Common variants in CNDP1 and CNDP2, and risk of nephropathy in type 2 diabetes.

    Science.gov (United States)

    Ahluwalia, T S; Lindholm, E; Groop, L C

    2011-09-01

    Several genome-wide linkage studies have shown an association between diabetic nephropathy and a locus on chromosome 18q harbouring two carnosinase genes, CNDP1 and CNDP2. Carnosinase degrades carnosine (β-alanyl-L-histidine), which has been ascribed a renal protective effect as a scavenger of reactive oxygen species. We investigated the putative associations of genetic variants in CNDP1 and CNDP2 with diabetic nephropathy (defined either as micro- or macroalbuminuria) and estimated GFR in type 2 diabetic patients from Sweden. We genotyped nine single nucleotide polymorphisms (SNPs) and one trinucleotide repeat polymorphism (D18S880, five to seven leucine repeats) in CNDP1 and CNDP2 in a case-control set-up including 4,888 unrelated type 2 diabetic patients (with and without nephropathy) from Sweden (Scania Diabetes Registry). Two SNPs, rs2346061 in CNDP1 and rs7577 in CNDP2, were associated with an increased risk of diabetic nephropathy (rs2346061 p = 5.07 × 10(-4); rs7577 p = 0.021). The latter was also associated with estimated GFR (β = -0.037, p = 0.014), particularly in women. A haplotype including these SNPs (C-C-G) was associated with a threefold increased risk of diabetic nephropathy (OR 2.98, 95% CI 2.43-3.67, p < 0.0001). These data suggest that common variants in CNDP1 and CNDP2 play a role in susceptibility to kidney disease in patients with type 2 diabetes.

  13. Importance of nanoparticle size in colorimetric and SERS-based multimodal trace detection of Ni(II) ions with functional gold nanoparticles.

    Science.gov (United States)

    Krpetić, Zeljka; Guerrini, Luca; Larmour, Iain A; Reglinski, John; Faulds, Karen; Graham, Duncan

    2012-03-12

    Colorimetric detection of analytes using gold nanoparticles along with surface-enhanced Raman spectroscopy (SERS) are areas of intense research activity since they both offer sensing of very low concentrations of target species. Multimodal detection promotes the simultaneous detection of a sample by a combination of different techniques; consequently, surface chemistry design in the development of multimodal nanosensors is important for rapid and sensitive evaluation of the analytes by diverse analytical methods. Herein it is shown that nanoparticle size plays an important role in the design of functional nanoparticles for colorimetric and SERS-based sensing applications, allowing controlled nanoparticle assembly and tunable sensor response. The design and preparation of robust nanoparticle systems and their assembly is reported for trace detection of Ni(II) ions as a model system in an aqueous solution. The combination of covalently attached nitrilotriacetic acid moieties along with the L-carnosine dipeptide on the nanoparticle surface represents a highly sensitive platform for rapid and selective detection of Ni(II) ions. This systematic study demonstrates that significantly lower detection limits can be achieved by finely tuning the assembly of gold nanoparticles of different core sizes. The results clearly demonstrate the feasibility and usefulness of a multimodal approach. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Enhanced topical delivery of tacrolimus by a carbomer hydrogel formulation with transcutol P.

    Science.gov (United States)

    Lee, Sang Gon; Kang, Jong Bu; Kim, Sung Rae; Kim, Chae Jin; Yeom, Dong Woo; Yoon, Ho Yub; Kwak, Seong Shin; Choi, Young Wook

    2016-10-01

    Tacrolimus (TAC), a non-steroidal anti-inflammatory and immunosuppressive agent, is used for the treatment of atopic dermatitis (AD) and skin immune diseases. TAC-loaded topical hydrogel formulations composed of carbomer, carnosine, transcutol P (diethylene glycol monoethyl ether) and humectant were prepared. For comparison, TAC-loaded topical cream-type formulations were also prepared and commercially available TAC ointment was used as a reference. A drug release study in vitro revealed that the total amount of TAC released from hydrogels over 24 h was approximately 30 times greater than that for the reference formulation. Compared to the reference ointment and creams, carbomer gel formulations showed higher skin permeation and retention of TAC (significantly different at p < 0.05), especially those with more than 10% of transcutol P. Therefore, carbomer gel formulations with sufficient levels of transcutol P are good candidates for skin delivery of TAC and have potential as therapeutic agents for the treatment of AD or immune skin disorders.

  15. Tocopheryl phosphate mixture (TPM) as a novel lipid-based transdermal drug delivery carrier: formulation and evaluation.

    Science.gov (United States)

    Gavin, Paul D; El-Tamimy, Mahmoud; Keah, Hooi Hong; Boyd, Ben J

    2017-02-01

    Transdermal drug delivery is a useful route of administration that avoids first-pass metabolism and more invasive delivery options. However, many drugs require enhancers to enable sufficient drug absorption to reach therapeutic effect. Alpha-tocopheryl phosphate (TP) and di-alpha-tocopheryl phosphate (T2P) are two phosphorylated forms of vitamin E which form tocopheryl phosphate mixture (TPM) when combined, and have been proposed to enhance the dermal and transdermal delivery of actives of interest. Here, we report the physicochemical characteristics and morphological properties of TPM formulations, including particle size, deformability and morphology, and its ability to facilitate the transport of carnosine, vitamin D3, CoEnzyme Q10 and caffeine into, and across, the skin. Results demonstrate that TPM self-assembles to form vesicular structures in hydroethanolic solutions ranging in mean size from 101 to 162 nM depending on the amount of TPM and ethanol present in the formulation. The ratio of TP to T2P in TPM formulations altered vesicle size and elasticity, with vesicles high in TP found to be more deformable than those rich in T2P. TPM produced a significant (p TPM delivery platform was able to deliver a diverse range of actives with differing size and solubility profiles and therefore has significant potential to expand the number and types of drugs available for topical application and transdermal delivery.

  16. Hyperfine structure analysis in magnetic resonance spectroscopy: from astrophysical measurements towards endogenous biosensors in human tissue; Hyperfeinstruktur-Analyse in der Magnetresonanzspektroskopie: von astrophysikalischen Messungen zu endogenen Biosensoren in menschlichem Gewebe

    Energy Technology Data Exchange (ETDEWEB)

    Schroeder, L. [Deutsches Krebsforschungszentrum, Heidelberg (Germany). Medizinische Physik in der Radiologie; California Univ., Berkeley, CA (United States). Dept. of Chemistry; Lawrence Berkeley National Lab., Berkeley, CA (United States). Dept. of Chemistry

    2007-07-01

    The hyperfine interaction of two spins is a well studied effect in atomic systems. Magnetic resonance experiments demonstrate that the detectable dipole transitions are determined by the magnetic moments of the constituents and the external magnetic field. Transferring the corresponding quantum mechanics to molecular bound nuclear spins allows for precise prediction of NMR spectra obtained from metabolites in human tissue. This molecular hyperfine structure has been neglected so far in in vivo NMR spectroscopy but contains useful information, especially when studying molecular dynamics. This contribution represents a review of the concept of applying the Breit-Rabi formalism to coupled nuclear spins and discusses the immobilization of different metabolites in anisotropic tissue revealed by 1H NMR spectra of carnosine, phosphocreatine and taurine. Comparison of atomic and molecular spin systems allows for statements on the biological constraints for direct spin-spin interactions. Moreover, the relevance of hyperfine effects on the line shapes of multiplets of indirectly-coupled spin systems with more than two constituents can be predicted by analyzing quantum mechanical parameters. As an example, the superposition of eigenstates of the AMX system of adenosine 5'-triphosphate and its application for better quantification of 31P-NMR spectra will be discussed. (orig.)

  17. Controlled drug release from cross-linked κ-carrageenan/hyaluronic acid membranes.

    Science.gov (United States)

    El-Aassar, M R; El Fawal, G F; Kamoun, Elbadawy A; Fouda, Moustafa M G

    2015-01-01

    In this work, hydrogel membrane composed of; kappa carrageenan (κC) and hyaluronic acid (HA) crosslinked with epichlorohydrine is produced. The optimum condition has been established based on their water absorption properties. Tensile strength (TS) and elongation (E%) for the formed films are evaluated. The obtained films were characterized by FTIR, scanning electron microscopy (SEM) and thermal analysis. All membranes were loaded with l-carnosine as a drug model. The swelling properties and kinetics of the release of the model drug from the crosslinked hydrogel membrane were monitored in buffer medium at 37°C. The equilibrium swelling of films showed fair dependency on the high presence of HA in the hydrogel. Moreover, the cumulative release profile increased significantly and ranged from 28% to 93%, as HA increases. SEM explored that, the porosity increased by increasing HA content; consequently, drug release into the pores and channels of the membranes is facilitated. In addition, water uptake % increased as well. A slight change in TS occurred by increasing the HA% to κC, while the highest value of strain for κC membrane was 498.38% by using 3% HA. The thermal stability of the κC/HA was higher than that of HA. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Are fish fed with cyanobacteria safe, nutritious and delicious? A laboratory study

    Science.gov (United States)

    Liang, Hualei; Zhou, Wenshan; Zhang, Yulei; Qiao, Qin; Zhang, Xuezhen

    2015-10-01

    Toxic cyanobacterial blooms, which produce cyclic heptapeptide toxins known as microcystins, are worldwide environmental problems. On the other hand, the cyanobacteria protein (30-50%) has been recommended as substitute protein for aquaculture. The present laboratory study verified the feasibility of cyanobacteria protein substitution and risk assessment. Goldfish were fed diets supplemented lyophilised cyanobacteria powder for 16 weeks with the various doses: 0% (control), 10%, 20%, 30% and 40%. Low doses (10% and 20%) promoted growth whereas high doses (30% and 40%) inhibited growth. In cyanobacteria treated fish, the proximate composition of ash, crude fat content and crude protein content decreased in 16 weeks; the saturated fatty acid (SFA) content significantly increased; the n-3 polyunsaturated fatty acid content, collagen content and muscle pH significantly decreased; cooking loss percents increased significantly. Muscle fiber diameter and myofibril length were negatively correlation. Additionally, flavour compounds (e.g., amino acids, nucleotides, organic acids and carnosine) changed significantly in the treated fish, and odour compounds geosmin and 2-methylisoborneol increased significantly. The estimated daily intake (EDI) of microcystins in muscle was close to or exceeded the World Health Organization (WHO) tolerable daily intake (TDI), representing a great health risk. Cyanobacterie is not feasible for protein sources use in aquaculture.

  19. Metabolomic study of plasma from female mink (Neovison vison) with low and high residual feed intake during restrictive and ad libitum feeding.

    Science.gov (United States)

    Hedemann, Mette Skou; Damgaard, Birthe Marie

    2012-12-01

    Metabolite profiling may elucidate changes in metabolic pathways under various physiological or nutritional conditions. In the present study two groups of female mink characterised as having a high (16 mink) or low (14 mink) residual feed intake were investigated during restrictive and ad libitum feeding. Blood samples were collected three times during the experimental period; during restrictive feeding, and four days and three weeks after the change to ad libitum feeding. Plasma samples were subjected to liquid chromatography mass spectrometry non-targeted metabolomics. Subjecting data to principal component analysis showed that there was no grouping of the data according to the residual feed intake. In contrast, data were clearly grouped according to feeding level. Identification of the metabolites responsible for this grouping showed that the plasma level of metabolites related to mobilisation of energy was high during restrictive feeding, e.g. betaine, carnitine, and creatine. During ad libitum feeding the plasma level of metabolites that can be characterised as biomarkers of meat intake (creatinine, carnosine, 1- and 3 methylhistidine) was high. The plasma level of lysophosphatidylcholine species was highest after four days of ad libitum feeding suggesting a short term imbalance in the transport or metabolism of these metabolites when changing the feeding level. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. Nutraceutical intervention improves older adults' cognitive functioning.

    Science.gov (United States)

    Small, Brent J; Rawson, Kerri S; Martin, Christina; Eisel, Sarah L; Sanberg, Cyndy D; McEvoy, Cathy L; Sanberg, Paul R; Shytle, R Douglas; Tan, Jun; Bickford, Paula C

    2014-02-01

    Interventions to improve the cognitive health of older adults are of critical importance. In the current study, we conducted a double-blind, placebo-controlled clinical trial using a pill-based nutraceutical (NT-020) that contained a proprietary formulation of blueberry, carnosine, green tea, vitamin D3, and Biovin to evaluate the impact on changes in multiple domains of cognitive functioning. One hundred and five cognitively intact adults aged 65-85 years of age (M=73.6 years) were randomized to receive NT-020 (n=52) or a placebo (n=53). Participants were tested with a battery of cognitive performance tests that were classified into six broad domains--episodic memory, processing speed, verbal ability, working memory, executive functioning, and complex speed at baseline and 2 months later. The results indicated that persons taking NT-020 improved significantly on two measures of processing speed across the 2-month test period in contrast to persons on the placebo whose performance did not change. None of the other cognitive ability measures were related to intervention group. The results also indicated that the NT-020 was well tolerated by older adults, and the presence of adverse events or symptoms did not differ between the NT-020 and placebo groups. Overall, the results of the current study were promising and suggest the potential for interventions like these to improve the cognitive health of older adults.

  1. Capillary electrophoresis of free amino acids in physiological fluids without derivatization employing direct or indirect absorbance detection.

    Science.gov (United States)

    Zunić, Gordana D; Spasić, Slavica; Jelić-Ivanović, Zorana

    2012-01-01

    Whole blood and/or plasma amino acids are useful for monitoring whole body protein and amino acid metabolism in an organism under various physiological and pathophysiological conditions. Various methodological procedures are in use for their measurement in biological fluids. From the time when capillary electrophoresis was introduced as a technology offering rapid separation of various ionic and/or ionizable compounds with low sample and solvent consumption, there were many attempts to use it for the measurement of amino acids present in physiological fluids. As a rule, these methods require derivatization procedures for detection purposes.Here, we present two protocols for the analysis of free amino acids employing free zone capillary electrophoresis. Main advantage of both methods is an absence of any derivatization procedures that permits the analysis of free amino acid in physiological fluids. The method using direct detection and carrier electrolyte consisting of disodium monophosphate (10 mM at pH 2.90) permits determination of compounds that absorb in UV region (aromatic and sulfur containing amino acids, as well as some peptides, such as carnosine, reduced and oxidized glutathione). The other method uses indirect absorbance detection, employing 8 mM p-amino salicylic acid buffered with sodium carbonate at pH 10.2 as running electrolyte. It permits quantification of 30 underivatized physiological amino acids and peptides. In our experience, factorial design represents a useful tool for final optimization of the electrophoretic conditions if it is necessary.

  2. Changes in chemical components in the freshwater apple snail, Pomacea canaliculata (Gastropoda: Ampullariidae), in relation to the development of its cold hardiness.

    Science.gov (United States)

    Matsukura, Keiichiro; Tsumuki, Hisaaki; Izumi, Yohei; Wada, Takashi

    2008-04-01

    The apple snail, Pomacea canaliculata, is an invasive freshwater snail. It increases its cold hardiness before winter. However, the physiological mechanism of cold hardiness in molluscs is poorly understood, especially in freshwater molluscs. In this study, we examined the changes in low molecular weight compounds, glycogen and lipids, in the body of P. canaliculata in association with the development of cold hardiness. When snails without cold hardiness were experimentally cold-acclimated, the amount of glycerol, glutamine, and carnosine increased, while glycogen and phenylalanine decreased. Overwintering cold-tolerant snails collected from a drained paddy field in November also showed increased glycerol in their bodies with decreasing glycogen concentration, compared to summer snails collected from a submerged field. Water content also decreased during the cold acclimation, although the water loss was minimal. These results indicate that the freshwater snail, P. canaliculata enhances cold hardiness by accumulation of some kinds of low molecular weight compounds in its body as some insects do. However, the actual function of each low molecular compound is still unknown.

  3. Patterns of free amino acids in German convenience food products: marked mismatch between label information and composition.

    Science.gov (United States)

    Hermanussen, M; Gonder, U; Jakobs, C; Stegemann, D; Hoffmann, G

    2010-01-01

    Free amino acids affect food palatability. As information on amino acids in frequently purchased pre-packaged food is virtually absent, we analyzed free amino acid patterns of 17 frequently purchased ready-to-serve convenience food products, and compared them with the information obtained from the respective food labels. Quantitative amino acid analysis was performed using ion-exchange chromatography. gamma-Aminobutyric acid (GABA) concentrations were verified using a stable isotope dilution gas chromatography/mass spectrometry (GC-MS) method. The patterns of free amino acids were compared with information obtained from food labels. An obvious mismatch between free amino acid patterns and food label information was detected. Even on considering that tomatoes and cereal proteins are naturally rich in glutamate, the concentrations of free glutamate outranged the natural concentration of this amino acid in several products, and strongly suggested artificial enrichment. Free glutamate was found to be elevated even in dishes that explicitly state 'no glutamate added'. Arginine was markedly elevated in lentils. Free cysteine was generally low, possibly reflecting thermal destruction of this amino acid during food processing. The meat and brain-specific dipeptide carnosine (CARN) was present in most meat-containing products. Some products did not contain detectable amounts of CARN in spite of meat content being claimed on the food labels. We detected GABA at concentrations that contribute significantly to the taste sensation. This investigation highlights a marked mismatch between food label information and food composition.

  4. Photochemical reaction of 2-(3-benzoylphenyl)propionic acid (ketoprofen) with basic amino acids and dipeptides.

    Science.gov (United States)

    Suzuki, Tadashi; Shinoda, Mio; Osanai, Yohei; Isozaki, Tasuku

    2013-08-22

    Photoreaction of 2-(3-benzoylphenyl)propionic acid (ketoprofen, KP) with basic amino acids (histidine, lysine, and arginine) and dipeptides (carnosine and anserine) including a histidine moiety in phosphate buffer solution (pH 7.4) has been investigated with transient absorption spectroscopy. With UV irradiation KP(-) gave rise to a carbanion through a decarboxylation reaction, and the carbanion easily abstracted a proton from the surrounding molecule to yield a 3-ethylbenzophenone ketyl biradical (EBPH). The dipeptides as well as the basic amino acids were found to accelerate the proton transfer reaction whereas alanine and glycine had no effect on the reaction, revealing that these amino acids having a protonated side chain act as a proton donor. The formation quantum yield of EBPH was estimated to be fairly large by means of an actinometrical method with benzophenone, and the bimolecular reaction rate constant for the proton transfer between the carbanion and the protonated basic amino acids or the protonated dipeptides was successfully determined. It has become apparent that the bimolecular reaction rate constant for the proton transfer depended on the acid dissociation constant for the side chain of the amino acids for the first time. This reaction mechanism was interpreted by difference of the heat of reaction for each basic amino acid based on the thermodynamical consideration. These results strongly suggest that the side chain of the basic amino acid residue in protein should play an important role for photochemistry of KP in vivo.

  5. Non-Targeted Metabolomics Analysis of Golden Retriever Muscular Dystrophy-Affected Muscles Reveals Alterations in Arginine and Proline Metabolism, and Elevations in Glutamic and Oleic Acid In Vivo

    Directory of Open Access Journals (Sweden)

    Muhammad Abdullah

    2017-07-01

    Full Text Available Background: Like Duchenne muscular dystrophy (DMD, the Golden Retriever Muscular Dystrophy (GRMD dog model of DMD is characterized by muscle necrosis, progressive paralysis, and pseudohypertrophy in specific skeletal muscles. This severe GRMD phenotype includes atrophy of the biceps femoris (BF as compared to unaffected normal dogs, while the long digital extensor (LDE, which functions to flex the tibiotarsal joint and serves as a digital extensor, undergoes the most pronounced atrophy. A recent microarray analysis of GRMD identified alterations in genes associated with lipid metabolism and energy production. Methods: We, therefore, undertook a non-targeted metabolomics analysis of the milder/earlier stage disease GRMD BF muscle versus the more severe/chronic LDE using GC-MS to identify underlying metabolic defects specific for affected GRMD skeletal muscle. Results: Untargeted metabolomics analysis of moderately-affected GRMD muscle (BF identified eight significantly altered metabolites, including significantly decreased stearamide (0.23-fold of controls, p = 2.89 × 10−3, carnosine (0.40-fold of controls, p = 1.88 × 10−2, fumaric acid (0.40-fold of controls, p = 7.40 × 10−4, lactamide (0.33-fold of controls, p = 4.84 × 10−2, myoinositol-2-phosphate (0.45-fold of controls, p = 3.66 × 10−2, and significantly increased oleic acid (1.77-fold of controls, p = 9.27 × 10−2, glutamic acid (2.48-fold of controls, p = 2.63 × 10−2, and proline (1.73-fold of controls, p = 3.01 × 10−2. Pathway enrichment analysis identified significant enrichment for arginine/proline metabolism (p = 5.88 × 10−4, FDR 4.7 × 10−2, where alterations in L-glutamic acid, proline, and carnosine were found. Additionally, multiple Krebs cycle intermediates were significantly decreased (e.g., malic acid, fumaric acid, citric/isocitric acid, and succinic acid, suggesting that altered energy metabolism may be underlying the observed GRMD BF muscle

  6. Redefining face contour with a novel anti-aging cosmetic product: an open-label, prospective clinical study.

    Science.gov (United States)

    Garre, Aurora; Martinez-Masana, Gemma; Piquero-Casals, Jaime; Granger, Corinne

    2017-01-01

    Skin aging is accelerated by multiple extrinsic factors: ultraviolet radiation, smoking and pollution increase oxidative activity, damaging cellular and extracellular components such as DNA, proteins, and lipids. With age, collagen and hyaluronic acid levels decline, resulting in loss of elasticity and moisture of the skin. Over time this damage leads to characteristic signs that make the skin look older: altered facial contour, sagging skin, wrinkles, and an uneven complexion. This study evaluated the anti-aging effects of a new facial cream formulated with carnosine, Alteromonas ferment extract, crosspolymer hyaluronic acid, and a tripeptide. An open-label intra-individual study to assess the anti-aging efficacy of the investigational product in 33 women aged 45 to 65 years. The product was applied twice daily for 56 days. Facial contour and skin deformation, elasticity, hydration, and complexion were measured with specialized equipment at baseline and days 28 and 56. Additionally, subjects completed questionnaires at days 28 and 56 on the perceived efficacy and cosmetic characteristics of the product. After 56 days of use of the investigational product, a redefining effect was observed, with a significant decrease in sagging jawline (7%). Skin was significantly more hydrated (12%), firmer (29%), and more elastic (20%) ( P <0.001 for all). On complexion assessment, skin texture (a measure of skin smoothness) and spots (brown and red skin lesions) also improved significantly (12% and 6% decrease, respectively). In the subjective self-evaluation, the majority of subjects reported that the skin was visibly tightened and more elastic, flexible, and moisturized (91%, 88%, 91%, and 90%, respectively). The product was well tolerated with no adverse events reported during the study. This new cosmetic product demonstrated anti-aging effects after 56 days of use, most notably a redefined facial contour and improved complexion. It is a safe and effective anti-aging product.

  7. Radiation-induced changes in the patterns of free ninhydrin-reactive substances of meat

    International Nuclear Information System (INIS)

    Partmann, W.; Keskin, S.

    1979-01-01

    Samples of minced lean beef and pork, breast muscle of chicken, and white meat of carp packed in polyethylene/Hostaphan bags were irradiated in the presence of air at about 25 0 C with 10-MeV electrons. The doses applied were for beef 0.5-20 Mrad, and for other meat samples 10 Mrad. In the dose range of 0-5 Mrad, no statistically significant changes in the composition of the free amino acids and similar compounds usually present in beef were found. In the dose range between 10 and 20 Mrad a tendency towards small losses in such components became obvious. In beef samples irradiated at doses >= 0.5 Mrad a new substance (Y) appeared distinctly in the zone of the basic amino-acids. This compound was detected by two independent methods, column chromatography and high-voltage electrophoresis. The yellow colour of the band appearing above carnosine in the pherogram was striking. Substance Y was also found after irradiation of pork and chicken meat. At a dose of 10 Mrad the concentration of Y in white chicken meat was nearly three times higher than in beef and pork. After irradiation of white carp muscle no Y, but another new basic compound (X) was observed. In the pherograms it appeared as a brownish-red band above β-alanine. The irradiation products X and Y may be used to find out whether meat of animals as used in this investigation had been exposed to radiation, if doses of 0.5 Mrad or higher were applied. (orig.) [de

  8. Lipid Peroxide-Derived Short-Chain Carbonyls Mediate Hydrogen Peroxide-Induced and Salt-Induced Programmed Cell Death in Plants1[OPEN

    Science.gov (United States)

    Biswas, Md. Sanaullah; Mano, Jun’ichi

    2015-01-01

    Lipid peroxide-derived toxic carbonyl compounds (oxylipin carbonyls), produced downstream of reactive oxygen species (ROS), were recently revealed to mediate abiotic stress-induced damage of plants. Here, we investigated how oxylipin carbonyls cause cell death. When tobacco (Nicotiana tabacum) Bright Yellow-2 (BY-2) cells were exposed to hydrogen peroxide, several species of short-chain oxylipin carbonyls [i.e. 4-hydroxy-(E)-2-nonenal and acrolein] accumulated and the cells underwent programmed cell death (PCD), as judged based on DNA fragmentation, an increase in terminal deoxynucleotidyl transferase dUTP nick end labeling-positive nuclei, and cytoplasm retraction. These oxylipin carbonyls caused PCD in BY-2 cells and roots of tobacco and Arabidopsis (Arabidopsis thaliana). To test the possibility that oxylipin carbonyls mediate an oxidative signal to cause PCD, we performed pharmacological and genetic experiments. Carnosine and hydralazine, having distinct chemistry for scavenging carbonyls, significantly suppressed the increase in oxylipin carbonyls and blocked PCD in BY-2 cells and Arabidopsis roots, but they did not affect the levels of ROS and lipid peroxides. A transgenic tobacco line that overproduces 2-alkenal reductase, an Arabidopsis enzyme to detoxify α,β-unsaturated carbonyls, suffered less PCD in root epidermis after hydrogen peroxide or salt treatment than did the wild type, whereas the ROS level increases due to the stress treatments were not different between the lines. From these results, we conclude that oxylipin carbonyls are involved in the PCD process in oxidatively stressed cells. Our comparison of the ability of distinct carbonyls to induce PCD in BY-2 cells revealed that acrolein and 4-hydroxy-(E)-2-nonenal are the most potent carbonyls. The physiological relevance and possible mechanisms of the carbonyl-induced PCD are discussed. PMID:26025050

  9. Antioxidants can extend lifespan of Brachionus manjavacas (Rotifera), but only in a few combinations

    Science.gov (United States)

    Fields, Allison M.; Johnston, Rachel K.

    2013-01-01

    Animal cells are protected from oxidative damage by an antioxidant network operating as a coordinated system, with strong synergistic interactions. Lifespan studies with whole animals are expensive and laborious, so there has been little investigation of which antioxidant interactions might be useful for life extension. Animals in the phylum Rotifera are particularly promising models for aging studies because they are small (0.1–1 mm), have short, two-week lifespan, display typical patterns of animal aging, and have well characterized, easy to measure phenotypes of aging and senescence. One class of interventions that has consistently produced significant rotifer life extension is antioxidants. Although the mechanism of antioxidant effects on animal aging remains controversial, the ability of some antioxidant supplements to extend rotifer lifespan was unequivocal. We found that exposing rotifers to certain combinations of antioxidant supplements can produce up to about 20% longer lifespan, but that most antioxidants have no effect. We performed life table tests with 20 single antioxidants and none yielded significant rotifer life extension. We tested 60 two-way combinations of selected antioxidants and only seven (12%) produced significant rotifer life extension. None of the 20 three- and four-way antioxidant combinations tested yielded significant rotifer life extension. These observations suggest that dietary exposure of antioxidants can extend rotifer lifespan, but most antioxidants do not. We observed significant rotifer life extension only when antioxidants were paired with trolox, N-acetyl cysteine, l-carnosine, or EUK-8. This illustrates that antioxidant treatments capable of rotifer life extension are patchily distributed in the parameter space, so large regions must be searched to find them. It furthermore underscores the value of the rotifer model to conduct rapid, facile life table experiments with many treatments, which makes such a search feasible

  10. A review of traditional and novel treatments for seizures in autism spectrum disorder: Findings from a systematic review and expert panel.

    Directory of Open Access Journals (Sweden)

    Richard Eugene Frye

    2013-09-01

    Full Text Available Despite the fact that seizures are commonly associated with autism spectrum disorder (ASD, the effectiveness of treatments for seizures has not been well studied in individuals with ASD. This manuscript reviews both traditional and novel treatments for seizures associated with ASD. Studies were selected by systematically searching major electronic databases and by a panel of experts that treat ASD individuals. Only a few anti-epileptic drugs (AEDs have undergone carefully controlled trials in ASD, but these trials examined outcomes other than seizures. Several lines of evidence point to valproate, lamotrigine and levetiracetam as the most effective and tolerable AEDs for individuals with ASD. Limited evidence supports the use of traditional non-AED treatments, such as the ketogenic and modified Atkins diet, multiple subpial transections and immunomodulation and neurofeedback treatments. Although specific treatments may be more appropriate for specific genetic and metabolic syndromes associated with ASD and seizures, there are few studies which have documented the effectiveness of treatments for seizures for specific syndromes. Limited evidence supports L-carnitine, multivitamins and N-acetyl-L-cysteine in mitochondrial disease and dysfunction, folinic acid in cerebral folate abnormalities and early treatment with vigabatrin in tuberous sclerosis complex. Finally, there is limited evidence for a number of novel treatments, particularly magnesium with pyridoxine, omega-3 fatty acids, the gluten-free casein-free diet and transcranial magnetic simulation. Zinc and L-carnosine are potential novel treatments supported by basic research but not clinical studies. This review demonstrates the wide variety of treatments used to treat seizures in individuals with ASD as well as the striking lack of clinical trials performed to support the use these treatments. Additional studies concerning these treatments for controlling seizures in individuals with ASD

  11. Water-structuring technology with the molecular chaperone proteins: indicated application of the α-crystallin domains and imidazole-containing peptidomimetics in cosmetic skin care systems or dermatological therapeutic drug carrier formulations.

    Science.gov (United States)

    Babizhayev, Mark A; Nikolayev, Gennady M; Nikolayeva, Juliana G; Yegorov, Yegor E

    2011-01-01

    Changes in structural proteins and hydration during aging are responsible for altered skin morphologic and mechanical properties manifested as wrinkling, sagging, loss of elasticity, and apparent dryness. Impairment in protein hydration may add to the ultrastructural, mechanical, and biochemical changes in structural proteins in the aged skin. At Innovative Vision Products, Inc., we have pioneered a molecular chaperone protein-activated therapeutic or cosmetic platform to enable simultaneous analysis of water-binding and structuring characteristics for biology-related or skin aging and skin disease-related pathways. This cutting-edge technology has changed the hydration of proteins in photoaged skin which so that they are more compact and interact with water to limited degree. The mechanisms of skin diseases, aging, and cellular and signaling pathways mediated by targeting with molecular chaperone protein(s) are considered. Skin lesions that are growing, spreading, or pigmented, and those that occur on exposed areas of skin are likely to be treated by these emerging pharmacological chaperones that could have cosmetic or dermatological benefits. Examples of such chaperones are anti-/trans-glycation-imidazole-containing peptidomimetic(s) (natural L-carnosine derivatives and mimetics) combined with the molecular chaperone protein α-crystallin derived from a natural source, brine shrimp (Artemia franciscana) cysts, or with recombinant human αA-crystallin. This patented biotechnology represents an efficient tool with which to mitigate the consequences of free radical-induced skin damage. The article is organized to provide in one place all of the relevant technical information, such as high-performance nuclear magnetic resonance and electron spin resonance application tools, and to describe the entire process from sample preparation to data analysis, which is moving from biological studies to biotechnology batches of the product. The proposed biotechnology results in

  12. Cloning and nucleotide sequence analysis of pepV, a carnosinase gene from Lactobacillus delbrueckii subsp. lactis DSM 7290, and partial characterization of the enzyme.

    Science.gov (United States)

    Vongerichten, K F; Klein, J R; Matern, H; Plapp, R

    1994-10-01

    Cell extracts of Lactobacillus delbrueckii subsp. lactis DSM 7290 were found to exhibit unique peptolytic ability against unusual beta-alanyl-dipeptides. In order to clone the gene encoding this activity, designated pepV, a gene library of strain DSM 7290 genomic DNA, prepared in the low-copy-number plasmid pLG339, was screened for heterologous expression in Escherichia coli. Recombinant clones harbouring pepV were identified by their ability to allow the utilization of carnosine (beta-alanyl-histidine) as a source of histidine by the E. coli mutant strain UK197 (pepD, hisG). Complementation was observed in a colony harbouring a recombinant plasmid (pKV101), carrying pepV. A 2.4 kb fragment containing pepV was subcloned and its nucleotide sequence revealed an open reading frame (ORF) of 1413 nucleotides, corresponding to a protein with predicted molecular mass of 51998 Da. A single transcription initiation site 71 bp upstream of the ATG translational start codon was identified by primer extension. No significant homology was detected between pepV or its deduced amino acid sequence with any entry in the databases. The only similarity was found in a region conserved in the ArgE/DapE/CPG2/YscS family of proteins. This observation, and protease inhibitor studies, indicated that pepV is of the metalloprotease type. A second ORF present in the sequenced fragment showed extensive homology to a variety of amino acid permeases from E. coli and Saccharomyces cerevisiae.

  13. Nutraceuticals and Dietary Supplements to Improve Quality of Life and Outcomes in Heart Failure Patients.

    Science.gov (United States)

    Cicero, Arrigo F G; Colletti, Alessandro

    2017-01-01

    Heart failure (HF) is a complex clinical syndrome that can result from any structural or functional cardiac disorder that impairs the ability of the ventricle to fill or eject blood. It represents a major public health issue, with a prevalence of over 23 million worldwide. The lifetime risk of developing HF is one in five and the most important risk factors identified are ischemic heart disease, hypertension, smoking, obesity and diabetes. Preventive approaches are based on improvements of lifestyle, associated with pharmacological therapy. Several nutraceuticals have shown interesting clinical results in prevention of HF as well as in the treatment of the early stages of the disease, alone or in association with pharmacological therapy. The aim of this review is to resume the available clinical evidence on phytochemicals effect on HF prevention and/or treatment. A systematic search strategy was developed to identify trials in PubMed (January 1980 to April 2016). The terms 'nutraceuticals', 'dietary supplements', 'herbal drug' and 'heart failure' were incorporated into an electronic search strategy. Clinical trials reported that the intake of some nutraceuticals (hawthorn, coenzyme Q10, L-carnitine, Dribose, Carnosine, Vitamin D, Some probiotics, Omega-3 PUFAs, Beet nitrates) is associated with improvements in functional parameters such as ejection fraction, stroke volume and cardiac output in HF patients, with minimal side effects. These findings were sometimes reinforced by subsequent meta-analyses, which further concluded that benefits tended to be greater in earlier stage HF. The main mechanisms involved are antioxidant, antinflammatory, anti-ischemic and antiaggregant effects. Evidence suggests that the supplementation with nutraceuticals may be a useful option for effective management of HF, with the advantage of excellent clinical tolerance. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  14. Acute effects of taurine on sarcoplasmic reticulum Ca2+ accumulation and contractility in human type I and type II skeletal muscle fibers.

    Science.gov (United States)

    Dutka, T L; Lamboley, C R; Murphy, R M; Lamb, G D

    2014-10-01

    Taurine occurs in high concentrations in muscle and is implicated in numerous physiological processes, yet its effects on many aspects of contractility remain unclear. Using mechanically skinned segments of human vastus lateralis muscle fibers, we characterized the effects of taurine on sarcoplasmic reticulum (SR) Ca2+ accumulation and contractile apparatus properties in type I and type II fibers. Prolonged myoplasmic exposure (>10 min) to taurine substantially increased the rate of accumulation of Ca2+ by the SR in both fiber types, with no change in the maximum amount accumulated; no such effect was found with carnosine. SR Ca2+ accumulation was similar with 10 or 20 mM taurine, but was significantly slower at 5 mM taurine. Cytoplasmic taurine (20 mM) had no detectable effects on the responsiveness of the Ca2+ release channels in either fiber type. Taurine caused a small increase in Ca2+ sensitivity of the contractile apparatus in type I fibers, but type II fibers were unaffected; maximum Ca(2+)-activated force was unchanged in both cases. The effects of taurine on SR Ca2+ accumulation (1) only became apparent after prolonged cytoplasmic exposure, and (2) persisted for some minutes after complete removal of taurine from the cytoplasm, consistent with the hypothesis that the effects were due to an action of taurine from inside the SR. In summary, taurine potentiates the rate of SR Ca2+ uptake in both type I and type II human fibers, possibly via an action from within the SR lumen, with the degree of potentiation being significantly reduced at low physiological taurine levels. Copyright © 2014 the American Physiological Society.

  15. Polaprezinc attenuates cyclophosphamide-induced cystitis and related bladder pain in mice

    Directory of Open Access Journals (Sweden)

    Masahiro Murakami-Nakayama

    2015-02-01

    Full Text Available Cav3.2 T-type Ca2+ channels targeted by H2S, a gasotransmitter, participate in cyclophosphamide-induced cystitis and bladder pain. Given that zinc selectively inhibits Cav3.2 among T-channel isoforms and also exhibits antioxidant activity, we examined whether polaprezinc (zinc-l-carnosine, a medicine for peptic ulcer treatment and zinc supplementation, reveals preventive or therapeutic effects on bladder inflammation and/or pain in the mouse with cyclophosphamide-induced cystitis, a model for interstitial cystitis. Systemic administration of cyclophosphamide caused cystitis-related symptoms including increased bladder weight and vascular permeability, and histological signs of bladder edema, accompanied by bladder pain-like nociceptive behavior/referred hyperalgesia. All these symptoms were significantly attenuated by oral preadministration of polaprezinc at 400 mg/kg. The same dose of polaprezinc also prevented the increased malondialdehyde level, an indicator of lipid peroxidation, and protein upregulation of cystathionine-γ-lyase, an H2S-generating enzyme, but not occludin, a tight junction-related membrane protein, in the bladder tissue of cyclophosphamide-treated mice. Oral posttreatment with polaprezinc at 30–100 mg/kg reversed the nociceptive behavior/referred hyperalgesia in a dose-dependent manner without affecting the increased bladder weight. Together, our data show that zinc supplementation with polaprezinc prevents the cyclophosphamide-induced cystitis probably through the antioxidant activity, and, like T-channel blockers, reverses the established cystitis-related bladder pain in mice, suggesting novel therapeutic usefulness of polaprezinc.

  16. Vegan diets: practical advice for athletes and exercisers.

    Science.gov (United States)

    Rogerson, David

    2017-01-01

    With the growth of social media as a platform to share information, veganism is becoming more visible, and could be becoming more accepted in sports and in the health and fitness industry. However, to date, there appears to be a lack of literature that discusses how to manage vegan diets for athletic purposes. This article attempted to review literature in order to provide recommendations for how to construct a vegan diet for athletes and exercisers. While little data could be found in the sports nutrition literature specifically, it was revealed elsewhere that veganism creates challenges that need to be accounted for when designing a nutritious diet. This included the sufficiency of energy and protein; the adequacy of vitamin B12, iron, zinc, calcium, iodine and vitamin D; and the lack of the long-chain n -3 fatty acids EPA and DHA in most plant-based sources. However, via the strategic management of food and appropriate supplementation, it is the contention of this article that a nutritive vegan diet can be designed to achieve the dietary needs of most athletes satisfactorily. Further, it was suggested here that creatine and β-alanine supplementation might be of particular use to vegan athletes, owing to vegetarian diets promoting lower muscle creatine and lower muscle carnosine levels in consumers. Empirical research is needed to examine the effects of vegan diets in athletic populations however, especially if this movement grows in popularity, to ensure that the health and performance of athletic vegans is optimised in accordance with developments in sports nutrition knowledge.

  17. β-alanine supplementation improves isometric endurance of the knee extensor muscles

    Directory of Open Access Journals (Sweden)

    Sale Craig

    2012-06-01

    Full Text Available Abstract Background We examined the effect of four weeks of β-alanine supplementation on isometric endurance of the knee extensors at 45% maximal voluntary isometric contraction (MVIC. Methods Thirteen males (age 23 ± 6 y; height 1.80 ± 0.05 m; body mass 81.0 ± 10.5 kg, matched for pre-supplementation isometric endurance, were allocated to either a placebo (n = 6 or β-alanine (n = 7; 6.4 g·d-1 over 4 weeks supplementation group. Participants completed an isometric knee extension test (IKET to fatigue, at an intensity of 45% MVIC, before and after supplementation. In addition, two habituation tests were completed in the week prior to the pre-supplementation test and a further practice test was completed in the week prior to the post-supplementation test. MVIC force, IKET hold-time, and impulse generated were recorded. Results IKET hold-time increased by 9.7 ± 9.4 s (13.2% and impulse by 3.7 ± 1.3 kN·s-1 (13.9% following β-alanine supplementation. These changes were significantly greater than those in the placebo group (IKET: t(11 = 2.9, p ≤0.05; impulse: t(11 = 3.1, p ≤ 0.05. There were no significant changes in MVIC force in either group. Conclusion Four weeks of β-alanine supplementation at 6.4 g·d-1 improved endurance capacity of the knee extensors at 45% MVIC, which most likely results from improved pH regulation within the muscle cell as a result of elevated muscle carnosine levels.

  18. Dietary supplementation with cholesterol and docosahexaenoic acid affects concentrations of amino acids in tissues of young pigs

    Science.gov (United States)

    Li, Peng; Kim, Sung Woo; Li, Xilong; Datta, Sujay; Pond, Wilson G.

    2013-01-01

    Cholesterol and docosahexaenoic acid (DHA) are important nutrients for neural development of infants. However, little is known about the effect of cholesterol or DHA on concentrations of amino acids (AA) in neonatal tissues. This study was conducted with the piglet (an established model for studying human infant nutrition) to test the hypothesis that dietary supplementation with the lipids may modulate AA availability in tissues. Sixteen newborn pigs were nursed by sows for 24 h and then assigned to one of four treatment groups, representing supplementation with 0.0% (control), 0.2% cholesterol, 0.2% DHA, or cholesterol plus DHA to the basal milk-formula. All piglets were euthanized at 49 days of age. In brain, cholesterol supplementation reduced (P < 0.05) concentrations of glutamate, serine, glutamine, threonine, β-alanine, alanine, methionine, isoleucine, leucine, and γ-aminobutyrate but increased (P < 0.05) concentrations of glycine and lysine, whereas DHA supplementation similarly affected (P < 0.05) concentrations of the same AA (except for isoleucine and lysine) and taurine. In addition, concentrations of most AA in liver, muscle and plasma were substantially altered by dietary supplementation of cholesterol and DHA in a tissue-dependent manner. Further, DHA reduced concentrations of carnosine in skeletal muscle, as well as ammonia in both plasma and brain. The results reveal that cholesterol and DHA can regulate AA metabolism and availability in various tissues of piglets. These novel findings have important implications for designing the next generation of infant formula to optimize neonatal growth and development. PMID:18972185

  19. β-Alanine supplementation for athletic performance: an update.

    Science.gov (United States)

    Bellinger, Phillip M

    2014-06-01

    β-alanine supplementation has become a common practice among competitive athletes participating in a range of different sports. Although the mechanism by which chronic β-alanine supplementation could have an ergogenic effect is widely debated, the popular view is that β-alanine supplementation augments intramuscular carnosine content, leading to an increase in muscle buffer capacity, a delay in the onset of muscular fatigue, and a facilitated recovery during repeated bouts of high-intensity exercise. β-alanine supplementation appears to be most effective for exercise tasks that rely heavily on ATP synthesis from anaerobic glycolysis. However, research investigating its efficacy as an ergogenic aid remains equivocal, making it difficult to draw conclusions as to its effectiveness for training and competition. The aim of this review was to update, summarize, and critically evaluate the findings associated with β-alanine supplementation and exercise performance with the most recent research available to allow the development of practical recommendations for coaches and athletes. A critical review of the literature reveals that when significant ergogenic effects have been found, they have been generally shown in untrained individuals performing exercise bouts under laboratory conditions. The body of scientific data available concerning highly trained athletes performing single competition-like exercise tasks indicates that this type of population receives modest but potentially worthwhile performance benefits from β-alanine supplementation. Recent data indicate that athletes may not only be using β-alanine supplementation to enhance sports performance but also as a training aid to augment bouts of high-intensity training. β-alanine supplementation has also been shown to increase resistance training performance and training volume in team-sport athletes, which may allow for greater overload and superior adaptations compared with training alone. The ergogenic

  20. Coupled Ca2+/H+ transport by cytoplasmic buffers regulates local Ca2+ and H+ ion signaling.

    Science.gov (United States)

    Swietach, Pawel; Youm, Jae-Boum; Saegusa, Noriko; Leem, Chae-Hun; Spitzer, Kenneth W; Vaughan-Jones, Richard D

    2013-05-28

    Ca(2+) signaling regulates cell function. This is subject to modulation by H(+) ions that are universal end-products of metabolism. Due to slow diffusion and common buffers, changes in cytoplasmic [Ca(2+)] ([Ca(2+)]i) or [H(+)] ([H(+)]i) can become compartmentalized, leading potentially to complex spatial Ca(2+)/H(+) coupling. This was studied by fluorescence imaging of cardiac myocytes. An increase in [H(+)]i, produced by superfusion of acetate (salt of membrane-permeant weak acid), evoked a [Ca(2+)]i rise, independent of sarcolemmal Ca(2+) influx or release from mitochondria, sarcoplasmic reticulum, or acidic stores. Photolytic H(+) uncaging from 2-nitrobenzaldehyde also raised [Ca(2+)]i, and the yield was reduced following inhibition of glycolysis or mitochondrial respiration. H(+) uncaging into buffer mixtures in vitro demonstrated that Ca(2+) unloading from proteins, histidyl dipeptides (HDPs; e.g., carnosine), and ATP can underlie the H(+)-evoked [Ca(2+)]i rise. Raising [H(+)]i tonically at one end of a myocyte evoked a local [Ca(2+)]i rise in the acidic microdomain, which did not dissipate. The result is consistent with uphill Ca(2+) transport into the acidic zone via Ca(2+)/H(+) exchange on diffusible HDPs and ATP molecules, energized by the [H(+)]i gradient. Ca(2+) recruitment to a localized acid microdomain was greatly reduced during intracellular Mg(2+) overload or by ATP depletion, maneuvers that reduce the Ca(2+)-carrying capacity of HDPs. Cytoplasmic HDPs and ATP underlie spatial Ca(2+)/H(+) coupling in the cardiac myocyte by providing ion exchange and transport on common buffer sites. Given the abundance of cellular HDPs and ATP, spatial Ca(2+)/H(+) coupling is likely to be of general importance in cell signaling.

  1. Characteristic metabolism of free amino acids in cetacean plasma: cluster analysis and comparison with mice.

    Directory of Open Access Journals (Sweden)

    Kazuki Miyaji

    Full Text Available From an evolutionary perspective, the ancestors of cetaceans first lived in terrestrial environments prior to adapting to aquatic environments. Whereas anatomical and morphological adaptations to aquatic environments have been well studied, few studies have focused on physiological changes. We focused on plasma amino acid concentrations (aminograms since they show distinct patterns under various physiological conditions. Plasma and urine aminograms were obtained from bottlenose dolphins, pacific white-sided dolphins, Risso's dolphins, false-killer whales and C57BL/6J and ICR mice. Hierarchical cluster analyses were employed to uncover a multitude of amino acid relationships among different species, which can help us understand the complex interrelations comprising metabolic adaptations. The cetacean aminograms formed a cluster that was markedly distinguishable from the mouse cluster, indicating that cetaceans and terrestrial mammals have quite different metabolic machinery for amino acids. Levels of carnosine and 3-methylhistidine, both of which are antioxidants, were substantially higher in cetaceans. Urea was markedly elevated in cetaceans, whereas the level of urea cycle-related amino acids was lower. Because diving mammals must cope with high rates of reactive oxygen species generation due to alterations in apnea/reoxygenation and ischemia-reperfusion processes, high concentrations of antioxidative amino acids are advantageous. Moreover, shifting the set point of urea cycle may be an adaptation used for body water conservation in the hyperosmotic sea water environment, because urea functions as a major blood osmolyte. Furthermore, since dolphins are kept in many aquariums for observation, the evaluation of these aminograms may provide useful diagnostic indices for the assessment of cetacean health in artificial environments in the future.

  2. Brain type carnosinase in dementia: a pilot study

    Directory of Open Access Journals (Sweden)

    Papaioannou Alexandra

    2007-11-01

    Full Text Available Abstract Background The pathological processes underlying dementia are poorly understood and so are the markers which identify them. Carnosinase is a dipeptidase found almost exclusively in brain and serum. Carnosinase and its substrate carnosine have been linked to neuropathophysiological processes. Methods Carnosinase activity was measured by a flourometric method in 37 patients attending a Geriatric Outpatient Clinic. There were 17 patients without dementia, 13 had Alzheimer's disease (AD and 7 had mixed dementia (MD. Results The range of serum carnosinase activity for patients without dementia was 14.5 – 78.5 μmol/ml/h. There was no difference in carnosinase activity between patients without dementia (40.3 ± 15.2 μmol/ml/h and patients with AD (44.4 ± 12.4 μmol/ml/h or MD (26.6 ± 15 μmol/ml/h. However, levels in the MD group were significantly lower than the AD group (p = 0.01. This difference remained significant after adjusting for gender, MMSE score, exercise, but not age, one at a time and all combined. The effect of other medical conditions did not remove the significance between the AD and MD groups. The MD group, but not the AD group, demonstrated a significant trend with carnosinase activity decreasing with duration of disease (from first recorded date of diagnosis to date of blood collection (r = -0.76, p = 0.049. There was no association with carnosinase activity and MMSE score in the AD or MD group. Both AD and MD patients on any dementia medication (donepezil, galantamine, memantine had higher carnosinase activity compared to those not taking a dementia medication. Carnosinase activity was higher in patients who regularly exercised (n = 20 compared to those who did not exercise regularly (n = 17(p = 0.006. Conclusion This exploratory study has shown altered activities of the enzyme carnosinase in patients with dementia.

  3. Lipid Peroxide-Derived Short-Chain Carbonyls Mediate Hydrogen Peroxide-Induced and Salt-Induced Programmed Cell Death in Plants.

    Science.gov (United States)

    Biswas, Md Sanaullah; Mano, Jun'ichi

    2015-07-01

    Lipid peroxide-derived toxic carbonyl compounds (oxylipin carbonyls), produced downstream of reactive oxygen species (ROS), were recently revealed to mediate abiotic stress-induced damage of plants. Here, we investigated how oxylipin carbonyls cause cell death. When tobacco (Nicotiana tabacum) Bright Yellow-2 (BY-2) cells were exposed to hydrogen peroxide, several species of short-chain oxylipin carbonyls [i.e. 4-hydroxy-(E)-2-nonenal and acrolein] accumulated and the cells underwent programmed cell death (PCD), as judged based on DNA fragmentation, an increase in terminal deoxynucleotidyl transferase dUTP nick end labeling-positive nuclei, and cytoplasm retraction. These oxylipin carbonyls caused PCD in BY-2 cells and roots of tobacco and Arabidopsis (Arabidopsis thaliana). To test the possibility that oxylipin carbonyls mediate an oxidative signal to cause PCD, we performed pharmacological and genetic experiments. Carnosine and hydralazine, having distinct chemistry for scavenging carbonyls, significantly suppressed the increase in oxylipin carbonyls and blocked PCD in BY-2 cells and Arabidopsis roots, but they did not affect the levels of ROS and lipid peroxides. A transgenic tobacco line that overproduces 2-alkenal reductase, an Arabidopsis enzyme to detoxify α,β-unsaturated carbonyls, suffered less PCD in root epidermis after hydrogen peroxide or salt treatment than did the wild type, whereas the ROS level increases due to the stress treatments were not different between the lines. From these results, we conclude that oxylipin carbonyls are involved in the PCD process in oxidatively stressed cells. Our comparison of the ability of distinct carbonyls to induce PCD in BY-2 cells revealed that acrolein and 4-hydroxy-(E)-2-nonenal are the most potent carbonyls. The physiological relevance and possible mechanisms of the carbonyl-induced PCD are discussed. © 2015 American Society of Plant Biologists. All Rights Reserved.

  4. Expression of HSP72 in the gastric mucosa is regulated by gastric acid in rats-Correlation of HSP72 expression with mucosal protection

    International Nuclear Information System (INIS)

    Wada, Isao; Otaka, Michiro; Jin, Mario; Odashima, Masaru; Komatsu, Koga; Konishi, Noriaki; Matsuhashi, Tamotsu; Horikawa, Youhei; Ohba, Reina; Itoh, Hideaki; Watanabe, Sumio

    2006-01-01

    Background and aim: The real mechanism of adaptive cytoprotection in the gastric mucosa is not well established. In the present study, we investigated the effect of acid suppressing agents on a 72-kDa heat shock protein (HSP72) expression, which is known as endogenous cytoprotective factor, in the gastric mucosa. Also, the association of gastric mucosal protective function against HCl-challenge was compared between HSP72-induced and -reduced group. Materials and methods: Expression of HSP72 was measured by Western blotting in the gastric mucosa before and after administration of famotidine or omeprazole. The gastric mucosal protective function against 0.6 N HCl was compared between control group and HSP72-reduced group. Also, the effect of increased expression of gastric HSP72 by additional administration of zinc sulfate or zinc L-carnosine, which is known as HSP72-inducer, on mucosal protective function was studied. Results: HSP72 expression in the gastric mucosa was reduced by acid suppressing agents. The lowest expression level of HSP72 was observed 12 h (famotidine, H2-receptor antagonist) or 48 h (omeprazole, proton pump inhibitor) after administration. The gastric mucosal protective ability against 0.6 N HCl was also reduced when HSP72 expression was decreased by famotidine or omeprazole. This phenomenon was reversed by HSP72 induction by additional administration of zinc derivatives. Conclusion: Our results might indicate that the expression of HSP72 in the gastric mucosa is physiologically regulated by gastric acid, and that HSP72 induction could be important in view of mucosal protection especially when HSP72 expression is reduced by administration of acid suppressing agents such as proton pump inhibitor or H2 receptor antagonist

  5. Influence of different histidine sources and zinc supplementation of broiler diets on dipeptide content and antioxidant status of blood and meat.

    Science.gov (United States)

    Kopeć, W; Jamroz, D; Wiliczkiewicz, A; Biazik, E; Pudlo, A; Hikawczuk, T; Skiba, T; Korzeniowska, M

    2013-01-01

    1. The objective of this study was to investigate how a diet containing spray-dried blood cells (SDBC) (4%) with or without zinc (Zn) would affect the concentration of two histidine heterodipeptides and the antioxidant status of broiler blood and breast muscles. 2. The study was carried out on 920 male Flex chickens randomly assigned to 4 dietary treatments: I - control, II - diet I with SDBC, III - diet I with SDBC and supplemented with Zn and IV - diet I supplemented with L-histidine. Birds were raised on floor littered with wood shavings, given free access to water and fed ad libitum. Performance indices were measured on d 1, 21 and 42. 3. The activity of antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase was analysed in plasma, erythrocytes and muscle tissue. The total antioxidant capacity of plasma and breast muscles was measured by 2,2-azinobis-(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging ability, as well as by ferric reducing antioxidant power (FRAP). Carnosine/anserine content of meat and plasma were determined using HPLC. Diets and breast muscles were analysed for amino acid profile and selected microelement content. 4. Histidine supplementation of the diet increased glutathione peroxidase activity in plasma and superoxide dismutase activity in erythrocytes. Moreover, the addition of SDBC or pure histidine in the diet increased histidine dipeptide content and activated enzymatic and non-enzymatic antioxidant systems in chicken blood and muscles. However, it led to lower growth performance indices. 5. The enrichment of broiler diets with Zn increased the antioxidant potential and the activity of superoxide dismutase in plasma, which was independent of the histidine dipeptide concentration. Zn supplementation combined with SDBC in a broiler diet led to the increase of superoxide dismutase and glutathione peroxidase activity, but it did not affect the radical

  6. Effect of taking chicken essence on stress and cognition of human volunteers.

    Science.gov (United States)

    Zain, Azhar Md; Syedsahiljamalulail, Syedmohsin

    2003-03-01

    Stress is a common phenomenon. Every individual experiences it. There are many ways of combating stress. Stress is necessary for preparation against challenging situations and danger. It is necessary to have stress before a test so that we are prepared. For instance, stress actually motivates students to prepare for examination but excessive stress can lead to poor performance. This study evaluates the effect of a commercial essence of chicken (CEC) on the various parameters related to stress and cognition of human volunteers. CEC is produced by a hot-water extraction process from chicken meat under high pressure condition. It contains concentrated amounts of proteins, amino acids and peptides such as carnosine compared to homemade traditional chicken soup. Due to the unique extraction process, it has been postulated that readily absorbed amino acids and bioactive peptides are present in CEC. In this experiment, we evaluated the effect of CEC in comparison with a placebo and carageenan on a group of stressed medical students before their examinations. Students were divided into three groups at random and given either CEC, placebo or a carageenan drink daily for two weeks. Before and after the two weeks, the students were given a series of tests to assess their mental and physical well-being as well as attention and memory. The tests were the general health questionnaire (GHQ), SF36, digit span, construction of figures, 3-min memory test, comprehension and mental arithmetic. The students who ingested essence of chicken fared significantly better than the other two groups of students. The ability of essence of chicken to control anxiety by distraction and promoting attention and memory is discussed.

  7. Six weeks of β-alanine supplementation did not enhance repeated-sprint ability or technical performances in young elite basketball players.

    Science.gov (United States)

    Milioni, Fabio; Redkva, Paulo E; Barbieri, Fabio A; Zagatto, Alessandro M

    2017-06-01

    Supplementation with β-alanine plays an important role as a precursor of carnosine, the most effective intramuscular buffer, and has been seen as a potential ergogenic aid, especially for high-intensity modalities such as basketball. Thus, the aim of the present study was to investigate the effects of 6 weeks of β-alanine supplementation on repeated sprint ability (RSA) and technical performances in young elite Brazilian basketball players. In total, 27 young basketball players (17±1 years) were randomized into a β-alanine group (Gβ - 6.4 g day -1 of β-alanine) and a placebo group (GP - 6.4 g day -1 of dextrose). Before and after the supplementation period the athletes performed a RSA test composed of ten 30 m sprints with two 180° changes of direction interspaced by 30 s of recovery. During the recovery period (i.e., after the sprints) the athletes performed a countermovement jump (CMJ) and a set of three free throws. After 48 h they performed a Yo-Yo intermittent recovery test level 1 (Yo-Yo IR1). Both groups increased the distance covered in the Yo-Yo IR1 after the supplementation period ( p = 0.001). On the other hand, both groups presented impairment in RSA time-performance (total time, best time, and mean time, p ≤ 0.04), while no significant changes were observed for technical task performances (i.e., CMJ and free throws) ( p ≥ 0.07). No between-group interactions were observed for any variable measured ( p ≥ 0.31). Thus, 6 weeks of β-alanine supplementation did not improve RSA or technical performances in young elite basketball players.

  8. Heat shock protein 70-dependent protective effect of polaprezinc on acetylsalicylic acid-induced apoptosis of rat intestinal epithelial cells.

    Science.gov (United States)

    Qin, Ying; Naito, Yuji; Handa, Osamu; Hayashi, Natsuko; Kuki, Aiko; Mizushima, Katsura; Omatsu, Tatsushi; Tanimura, Yuko; Morita, Mayuko; Adachi, Satoko; Fukui, Akifumi; Hirata, Ikuhiro; Kishimoto, Etsuko; Nishikawa, Taichiro; Uchiyama, Kazuhiko; Ishikawa, Takeshi; Takagi, Tomohisa; Yagi, Nobuaki; Kokura, Satoshi; Yoshikawa, Toshikazu

    2011-11-01

    Protection of the small intestine from mucosal injury induced by nonsteroidal anti-inflammatory drugs including acetylsalicylic acid is a critical issue in the field of gastroenterology. Polaprezinc an anti-ulcer drug, consisting of zinc and L-carnosine, provides gastric mucosal protection against various irritants. In this study, we investigated the protective effect of polaprezinc on acetylsalicylic acid-induced apoptosis of the RIE1 rat intestinal epithelial cell line. Confluent rat intestinal epithelial cells were incubated with 70 µM polaprezinc for 24 h, and then stimulated with or without 15 mM acetylsalicylic acid for a further 15 h. Subsequent cellular viability was quantified by fluorometric assay based on cell lysis and staining. Acetylsalicylic acid-induced cell death was also qualified by fluorescent microscopy of Hoechst33342 and propidium iodide. Heat shock proteins 70 protein expression after adding polaprezinc or acetylsalicylic acid was assessed by western blotting. To investigate the role of Heat shock protein 70, Heat shock protein 70-specific small interfering RNA was applied. Cell viability was quantified by fluorometric assay based on cell lysis and staining and apoptosis was analyzed by fluorescence-activated cell sorting. We found that acetylsalicylic acid significantly induced apoptosis of rat intestinal epithelial cells in a dose- and time-dependent manner. Polaprezinc significantly suppressed acetylsalicylic acid-induced apoptosis of rat intestinal epithelial cells at its late phase. At the same time, polaprezinc increased Heat shock protein 70 expressions of rat intestinal epithelial cells in a time-dependent manner. However, in Heat shock protein 70-silenced rat intestinal epithelial cells, polaprezinc could not suppress acetylsalicylic acid -induced apoptosis at its late phase. We conclude that polaprezinc-increased Heat shock protein 70 expression might be an important mechanism by which polaprezinc suppresses acetylsalicylic

  9. CURRENT STATE OF POULTRY BREEDING AND ITS FUTURE TRENDS

    Directory of Open Access Journals (Sweden)

    Gordana Kralik

    2013-06-01

    Full Text Available Poultry production in eastern Croatia is developed by individual producers mainly in semi intensive way, and within the organized poultry systems where the process is organized in a modern, intensive way. There is a tradition of breeding hens and geese in this area. Poultry products - meat and eggs are important in supplying the population with animal protein, minerals and vitamins. Modern hybrid hens are used for egg production and for meat production in the intensive production. Today geese breeding in these areas are completely neglected. Croatia as a member of European Union, has possibility of the placement of autochthonous breeds of poultry such as Hrvatica hen, Zagorje turkey and Podravian goose. Financial supports at the national level are allocated for the first two autochthonous breeds of poultry because these breeds can, with good production traits, represent genetic resources and strategic reserves in the future development of domestic poultry genotypes. Poultry production is especial emphasis in accordance with the criteria of welfare and health of poultry. This paper discusses further development of poultry in terms of production of poultry meat and eggs as a functional food. The composition and content of nutricines in meat and eggs can be affected by feed composition. Desired nutricines are installed in muscular tissue of poultry by using feed and adding some components. Consumption of eggs and poultry meat enriched by selenium, lutein and omega-3 fatty acids affects the improvement of the quality of the human diet. The recent researches show that chicken can effectively be enriched in carnosine - ingredients that are now taught as “anti-aging” factor. Enrichment of poultry products with nutricines gives greater importance to these foods in the diet of the population than the former one, mainly based on the nutritional aspect. Greater selection of quality poultry products can be a significant factor in the development of

  10. Spirulina promotes stem cell genesis and protects against LPS induced declines in neural stem cell proliferation.

    Science.gov (United States)

    Bachstetter, Adam D; Jernberg, Jennifer; Schlunk, Andrea; Vila, Jennifer L; Hudson, Charles; Cole, Michael J; Shytle, R Douglas; Tan, Jun; Sanberg, Paul R; Sanberg, Cyndy D; Borlongan, Cesario; Kaneko, Yuji; Tajiri, Naoki; Gemma, Carmelina; Bickford, Paula C

    2010-05-05

    Adult stem cells are present in many tissues including, skin, muscle, adipose, bone marrow, and in the brain. Neuroinflammation has been shown to be a potent negative regulator of stem cell and progenitor cell proliferation in the neurogenic regions of the brain. Recently we demonstrated that decreasing a key neuroinflammatory cytokine IL-1beta in the hippocampus of aged rats reversed the age-related cognitive decline and increased neurogenesis in the age rats. We also have found that nutraceuticals have the potential to reduce neuroinflammation, and decrease oxidative stress. The objectives of this study were to determine if spirulina could protect the proliferative potential of hippocampal neural progenitor cells from an acute systemic inflammatory insult of lipopolysaccharide (LPS). To this end, young rats were fed for 30 days a control diet or a diet supplemented with 0.1% spirulina. On day 28 the rats were given a single i.p. injection of LPS (1 mg/kg). The following day the rats were injected with BrdU (50 mg/kg b.i.d. i.p.) and were sacrificed 24 hours after the first injection of BrdU. Quantification of the BrdU positive cells in the subgranular zone of the dentate gyrus demonstrated a decrease in proliferation of the stem/progenitor cells in the hippocampus as a result of the LPS insult. Furthermore, the diet supplemented with spirulina was able to negate the LPS induced decrease in stem/progenitor cell proliferation. In a second set of studies we examined the effects of spirulina either alone or in combination with a proprietary formulation (NT-020) of blueberry, green tea, vitamin D3 and carnosine on the function of bone marrow and CD34+ cells in vitro. Spirulina had small effects on its own and more than additive effects in combination with NT-020 to promote mitochondrial respiration and/or proliferation of these cells in culture. When examined on neural stem cells in culture spirulina increased proliferation at baseline and protected against the

  11. Spirulina promotes stem cell genesis and protects against LPS induced declines in neural stem cell proliferation.

    Directory of Open Access Journals (Sweden)

    Adam D Bachstetter

    Full Text Available Adult stem cells are present in many tissues including, skin, muscle, adipose, bone marrow, and in the brain. Neuroinflammation has been shown to be a potent negative regulator of stem cell and progenitor cell proliferation in the neurogenic regions of the brain. Recently we demonstrated that decreasing a key neuroinflammatory cytokine IL-1beta in the hippocampus of aged rats reversed the age-related cognitive decline and increased neurogenesis in the age rats. We also have found that nutraceuticals have the potential to reduce neuroinflammation, and decrease oxidative stress. The objectives of this study were to determine if spirulina could protect the proliferative potential of hippocampal neural progenitor cells from an acute systemic inflammatory insult of lipopolysaccharide (LPS. To this end, young rats were fed for 30 days a control diet or a diet supplemented with 0.1% spirulina. On day 28 the rats were given a single i.p. injection of LPS (1 mg/kg. The following day the rats were injected with BrdU (50 mg/kg b.i.d. i.p. and were sacrificed 24 hours after the first injection of BrdU. Quantification of the BrdU positive cells in the subgranular zone of the dentate gyrus demonstrated a decrease in proliferation of the stem/progenitor cells in the hippocampus as a result of the LPS insult. Furthermore, the diet supplemented with spirulina was able to negate the LPS induced decrease in stem/progenitor cell proliferation. In a second set of studies we examined the effects of spirulina either alone or in combination with a proprietary formulation (NT-020 of blueberry, green tea, vitamin D3 and carnosine on the function of bone marrow and CD34+ cells in vitro. Spirulina had small effects on its own and more than additive effects in combination with NT-020 to promote mitochondrial respiration and/or proliferation of these cells in culture. When examined on neural stem cells in culture spirulina increased proliferation at baseline and protected

  12. NT-020, a natural therapeutic approach to optimize spatial memory performance and increase neural progenitor cell proliferation and decrease inflammation in the aged rat.

    Science.gov (United States)

    Acosta, S; Jernberg, J; Sanberg, C D; Sanberg, P R; Small, Brent J; Gemma, Carmelina; Bickford, Paula C

    2010-10-01

    The process of aging is linked to oxidative stress, microglial activation, and proinflammatory factors, which are known to decrease cell proliferation and limit neuroplasticity. These factors may lead the transition from normal aging to more severe cognitive dysfunction associated with neurodegenerative diseases. We have shown that natural compounds such as polyphenols from blueberry and green tea and amino acids like carnosine are high in antioxidant and antiinflammatory activity that decreases the damaging effects of reactive oxygen species (ROS), in the blood, brain, and other tissues of the body. Furthermore, we have shown that the combination of these nutrients (called NT-020) creates a synergistic effect that promotes the proliferation of stem cells in vitro and in vivo. In the current study, we examined the effects of NT-020 on neurogenesis and performance on a Morris water maze (MWM). Aged (20-month-old) male Fischer 344 rats were treated with 135.0 mg/kg per day (n = 13) of NT-020. Young (3-month-old) (n = 10) and aged (20-month-old) (n = 13) control male Fischer 344 rats were treated with water by oral gavage. All groups were treated for a period of 4 weeks. Although there was no difference in performance in the MWM when comparing all aged rats, when the data for aged impaired rats were compared, there was a significant difference between groups on the last day of training with the treatment group performing better than controls. Using the cell cycle-regulating protein (Ki67), doublecortin (DCX), and OX6 antibody markers, cell proliferation, neurogenesis, and microglial activation were estimated in the dentate gyrus (DG) of young and aged animals. Cell proliferation was also examined in the subventricular zone (SVZ). A decreased number of OX6 MHC II-positive cells, increased neurogenesis, and increased number of proliferating cells were found in rats treated with NT-020 in comparison with aged control rats. In sum, NT-020 may promote health, proliferation

  13. Reactive Carbonyl Species Activate Caspase-3-Like Protease to Initiate Programmed Cell Death in Plants.

    Science.gov (United States)

    Biswas, Md Sanaullah; Mano, Jun'ichi

    2016-07-01

    Reactive oxygen species (ROS)-triggered programmed cell death (PCD) is a typical plant response to biotic and abiotic stressors. We have recently shown that lipid peroxide-derived reactive carbonyl species (RCS), downstream products of ROS, mediate oxidative signal to initiate PCD. Here we investigated the mechanism by which RCS initiate PCD. Tobacco Bright Yellow-2 cultured cells were treated with acrolein, one of the most potent RCS. Acrolein at 0.2 mM caused PCD in 5 h (i.e. lethal), but at 0.1 mM it did not (sublethal). Specifically, these two doses caused critically different effects on the cells. Both lethal and sublethal doses of acrolein exhausted the cellular glutathione pool in 30 min, while the lethal dose only caused a significant ascorbate decrease and ROS increase in 1-2 h. Prior to such redox changes, we found that acrolein caused significant increases in the activities of caspase-1-like protease (C1LP) and caspase-3-like protease (C3LP), the proteases which trigger PCD. The lethal dose of acrolein increased the C3LP activity 2-fold more than did the sublethal dose. In contrast, C1LP activity increments caused by the two doses were not different. Acrolein and 4-hydroxy-(E)-2-nonenal, another RCS, activated both proteases in a cell-free extract from untreated cells. H 2 O 2 at 1 mM added to the cells increased C1LP and C3LP activities and caused PCD, and the RCS scavenger carnosine suppressed their activation and PCD. However, H 2 O 2 did not activate the proteases in a cell-free extract. Thus the activation of caspase-like proteases, particularly C3LP, by RCS is an initial biochemical event in oxidative signal-stimulated PCD in plants. © The Author 2016. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  14. Smoking and health: association between telomere length and factors impacting on human disease, quality of life and life span in a large population-based cohort under the effect of smoking duration.

    Science.gov (United States)

    Babizhayev, Mark A; Yegorov, Yegor E

    2011-08-01

    Reactive oxygen species (ROS) are of primary importance as they cause damage to lipids, proteins, and DNA either endogenously by cellular mechanism, or through exogenous exposure to environmental injury factors, including oxidation insult factors, such as tobacco smoke. Currently 46.3 million adults (25.7 percent of the population) are smokers. This includes 24 million men (28.1 percent of the total) and more than 22 million women (23.5 percent). The prevalence is highest among persons 25-44 years of age. Cigarette smokers have a higher risk of developing several chronic disorders. These include fatty buildups in arteries, several types of cancer and chronic obstructive pulmonary disease (lung problems). As peripheral leukocytes have been the main target of human telomere research, most of what is known about human telomere dynamics in vivo is based on these cells. Leukocyte telomere length (TL) is a complex trait that is shaped by genetic, epigenetic, and environmental determinants. In this article, we consider that smoking modifies leukocyte TL in humans and contributes to its variability among individuals, although the smoking effect on TL and its relation with other metabolic indices may accelerate biological aging and development of smoking-induced chronic diseases in a large human population-based cohorts with smoking behavior. Recent studies confirmed that individuals with shorter telomeres present a higher prevalence of arterial lesions and higher risk of cardiovascular disease mortality. This study originally suggests that efficient therapeutic protection of TL and structure in response to stresses that are known to reduce TL, such as oxidative damage or inflammation associated with tobacco smoking, would lead to better telomere maintenance. Recently, we have discovered the potential use of telomere-restorative imidazole-containing dipeptide (non-hydrolized carnosine, carcinine) based therapy for better survival of smokers. We conclude that a better

  15. Radioprotectors in Radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Nair, C.K.K. [Bhabha Atomic Research Centre, Mumbai (India); Parida, D.K.; Nomura, Taisei

    2001-03-01

    , orientin, and vicinin), DNA-binding ligands (Hoechst 33342), and other compounds (melatonin, carnosin, tempace, and tempol). The article also briefly explains the mechanisms of radiation protection (e.g., suppression of the formation of reactive species, detoxification of radiation-induced species, target stabilization, and enhancement of the repair and recovery processes) and of DNA repair and cell recovery processes. Although a large number of radioprotective compounds have been identified over the last 50 years, most of them have failed to make the transition from laboratory to clinic. Acute toxicity and inability to differentiate between tumor and normal cells are the main reasons for their failure to be applied clinically. The authors conclude the article by describing some approaches to overcoming problems associated with the toxicity of radioprotective agents. Future searches for effective radioprotectors may be directed at compounds that protect normoxic cells but afford no protection in a hypoxic environment, which is a common feature of all solid tumors. Other eandidates are compounds that are enzymatically converted to toxic derivatives in hypoxic tumor cells while remaining unchanged and protecting normal cells. (K.H.). 120 refs.

  16. Molecular dynamics and information on possible sites of interaction of intramyocellular metabolites in vivo from resolved dipolar couplings in localized 1H NMR spectra

    Science.gov (United States)

    Schröder, Leif; Schmitz, Christian; Bachert, Peter

    2004-12-01

    Proton NMR resonances of the endogenous metabolites creatine and phosphocreatine ((P)Cr), taurine (Tau), and carnosine (Cs, β-alanyl- L-histidine) were studied with regard to residual dipolar couplings and molecular mobility. We present an analysis of the direct 1H- 1H interaction that provides information on motional reorientation of subgroups in these molecules in vivo. For this purpose, localized 1H NMR experiments were performed on m. gastrocnemius of healthy volunteers using a 1.5-T clinical whole-body MR scanner. We evaluated the observable dipolar coupling strength SD0 ( S = order parameter) of the (P)Cr-methyl triplet and the Tau-methylene doublet by means of the apparent line splitting. These were compared to the dipolar coupling strength of the (P)Cr-methylene doublet. In contrast to the aliphatic protons of (P)Cr and Tau, the aromatic H2 ( δ = 8 ppm) and H4 ( δ = 7 ppm) protons of the imidazole ring of Cs exhibit second-order spectra at 1.5 T. This effect is the consequence of incomplete transition from Zeeman to Paschen-Back regime and allows a determination of SD0 from H2 and H4 of Cs as an alternative to evaluating the multiplet splitting which can be measured directly in high-resolution 1H NMR spectra. Experimental data showed striking differences in the mobility of the metabolites when the dipolar coupling constant D0 (calculated with the internuclear distance known from molecular geometry in the case of complete absence of molecular dynamics and motion) is used for comparison. The aliphatic signals involve very small order parameters S ≈ (1.4 - 3) × 10 -4 indicating rapid reorientation of the corresponding subgroups in these metabolites. In contrast, analysis of the Cs resonances yielded S ≈ (113 - 137) × 10 -4. Thus, the immobilization of the Cs imidazole ring owing to an anisotropic cellular substructure in human m. gastrocnemius is much more effective than for (P)Cr and Tau subgroups. Furthermore, 1H NMR experiments on aqueous model