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Sample records for delta-aminolaevulinic acid ala

  1. Photodynamic Detection of Peritoneal Metastases Using 5-Aminolevulinic Acid (ALA

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    Yutaka Yonemura

    2017-03-01

    Full Text Available In the past, peritoneal metastasis (PM was considered as a terminal stage of cancer. From the early 1990s, however, a new comprehensive treatment consisting of cytoreductive surgery and perioperative chemotherapy has been established to improve long-term survival for selected patients with PM. Among prognostic indicators after the treatment, completeness of cytoreduction is the most independent predictors of survival. However, peritoneal recurrence is a main cause of recurrence, even after complete cytoreduction. As a cause of peritoneal recurrence, small PM may be overlooked at the time of cytoreductive surgery (CRS, therefore, development of a new method to detect small PM is desired. Recently, photodynamic diagnosis (PDD was developed for detection of PM. The objectives of this review were to evaluate whether PDD using 5-aminolevulinic acid (ALA could improve detection of small PM.

  2. Impact of charged amino acid substitution in the transmembrane domain of L-alanine exporter, AlaE, of Escherichia coli on the L-alanine export.

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    Kim, Seryoung; Ihara, Kohei; Katsube, Satoshi; Ando, Tasuke; Isogai, Emiko; Yoneyama, Hiroshi

    2017-01-01

    The Escherichia coli alaE gene encodes the L-alanine exporter, AlaE, that catalyzes active export of L-alanine using proton electrochemical potential. The transporter comprises only 149 amino acid residues and four predicted transmembrane domains (TMs), which contain three charged amino acid residues. The AlaE-deficient L-alanine non-metabolizing cells (ΔalaE cells) appeared hypersusceptible to L-alanyl-L-alanine showing a minimum inhibitory concentration (MIC) of 2.5 µg/ml for the dipeptide due to a toxic accumulation of L-alanine. To elucidate the mechanism by which AlaE exports L-alanine, we replaced charged amino acid residues in the TMs, glutamic acid-30 (TM-I), arginine-45 (TM-II), and aspartic acid-84 (TM-III) with their respective charge-conserved amino acid or a net neutral cysteine. The ΔalaE cells producing R45K or R45C appeared hypersusceptible to the dipeptide, indicating that arginine-45 is essential for AlaE activity. MIC of the dipeptide in the ΔalaE cells expressing E30D and E30C was 156 µg/ml and >10,000 µg/ml, respectively, thereby suggesting that a negative charge at this position is not essential. The ΔalaE cells expressing D84E or D84C showed an MIC >10,000 and 78 µg/ml, respectively, implying that a negative charge is required at this position. These results were generally consistent with that of the L-alanine accumulation experiments in intact cells. We therefore concluded that charged amino acid residues (R45 and D84) in the AlaE transmembrane domain play a pivotal role in L-alanine export. Replacement of three cysteine residues at C22, C28 (both in TM-I), and C135 (C-terminal region) with alanine showed only a marginal effect on L-alanine export.

  3. In vitro evaluation of 5-aminolevulinic acid (ALA loaded PLGA nanoparticles

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    Shi L

    2013-07-01

    Full Text Available Lei Shi,1 Xiuli Wang,1 Feng Zhao,2 Hansen Luan,2 Qingfeng Tu,1 Zheng Huang,3 Hao Wang,2 Hongwei Wang1,41Shanghai Skin Disease Hospital, Shanghai, People's Republic of China; 2National Pharmaceutical Engineering Research Center, China State Institute of Pharmaceutical Industry, Shanghai, People's Republic of China; 3Ministry of Education (MOE Key Laboratory of OptoElectronic Science and Technology for Medicine, Fujian Normal University, Fuzhou, People's Republic of China; 4Huadong Hospital, Fudan University, Shanghai, People's Republic of ChinaBackground: 5-Aminolevulinic acid (ALA is a prodrug for topical photodynamic therapy. The effectiveness of topical ALA can be limited by its bioavailability. The aim of this study was to develop a novel ALA delivery approach using poly(lactic-co-glycolic acid (PLGA nanoparticles (NPs.Methods: A modified double emulsion solvent evaporation method was used to prepare ALA loaded PLGA NPs (ALA PLGA NPs. The characteristics, uptake, protoporphyrin IX fluorescence kinetics, and cytotoxicity of ALA PLGA NPs toward a human skin squamous cell carcinoma cell line were examined.Results: The mean particle size of spherical ALA PLGA NPs was 65.6 nm ± 26 nm with a polydispersity index of 0.62. The encapsulation efficiency was 65.8% ± 7.2% and ALA loading capacity was 0.62% ± 0.27%. When ALA was dispersed in PLGA NPs, it turned into an amorphous phase. ALA PLGA NPs could be taken up by squamous cell carcinoma cells and localized in the cytoplasm. The protoporphyrin IX fluorescence kinetics and 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay showed that ALA PLGA NPs were more effective than free ALA of the same concentration.Conclusion: PLGA NPs provide a promising ALA delivery strategy for topical ALA-photodynamic therapy of skin squamous cell carcinoma.Keywords: 5-Aminolevulinic acid (ALA, nanoparticles, poly(lactic-co-glycolic acid (PLGA, skin squamous cell carcinoma, photodynamic therapy (PDT

  4. Novel development of 5-aminolevurinic acid (ALA) in cancer diagnoses and therapy.

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    Ishizuka, Masahiro; Abe, Fuminori; Sano, Yuki; Takahashi, Kiwamu; Inoue, Katsushi; Nakajima, Motowo; Kohda, Takeo; Komatsu, Naoki; Ogura, Shun-ichiro; Tanaka, Tohru

    2011-03-01

    Early detection and intervention are needed for optimal outcomes in cancer therapy. Improvements in diagnostic technology, including endoscopy, photodynamic diagnosis (PDD), and photodynamic therapy (PDT), have allowed substantial progress in the treatment of cancer. 5-Aminolevulinic acid (ALA) is a natural, delta amino acid biosynthesized by animal and plant mitochondria. ALA is a precursor of porphyrin, heme, and bile pigments, and it is metabolized into protoporphyrin IX (PpIX) in the course of heme synthesis. PpIX preferentially accumulates in tumor cells resulting in a red fluorescence following irradiation with violet light and the formation of singlet oxygen. This reaction, utilized to diagnose and treat cancer, is termed ALA-induced PDD and PDT. In this review, the biological significance of heme metabolites, the mechanism of PpIX accumulation in tumor cells, and the therapeutic potential of ALA-induced PDT alone and combined with hyperthermia and immunotherapy are discussed.

  5. Delta-aminolevulinic acid dehydratase (ALAD) polymorphism in lead exposed Bangladeshi children and its effect on urinary aminolevulinic acid (ALA)

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    Tasmin, Saira, E-mail: rimzim1612@yahoo.com [Department of Human Ecology, School of International Health, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan); Furusawa, Hana [Department of Human Ecology, School of International Health, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan); Ahmad, Sk. Akhtar [Department of Occupational and Environmental Health, Bangladesh Institute of Health Sciences, 125/1, Darus Salam, Mirpur, Dhaka 1216 (Bangladesh); Faruquee, M.H. [Department of Public Health, State University of Bangladesh, 77 Satmasjid Road, Dhanmondi, Dhaka 1205 (Bangladesh); Watanabe, Chiho [Department of Human Ecology, School of International Health, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan)

    2015-01-15

    Background and objective: Lead has long been recognized as a harmful environmental pollutant. People in developing countries like Bangladesh still have a higher risk of lead exposure. Previous research has suggested that the delta-aminolevulinic acid dehydratase (ALAD) genotype can modify lead toxicity and individual susceptibility. As children are more susceptible to lead-induced toxicity, this study investigated whether the ALAD genotype influenced urinary excretion of delta-aminolevulinic acid (U-ALA) among children exposed to environmental lead in Bangladesh. Methods: Subjects were elementary schoolchildren from a semi-urban industrialized area in Bangladesh. A total of 222 children were studied. Blood and urine were collected to determine ALAD genotypes, blood lead levels and urinary aminolevulinic acid (U-ALA). Results: The mean BPb level was 9.7 µg/dl for the study children. BPb was significantly positively correlated with hemoglobin (p<0.01). In total, allele frequency for ALAD 1 and 2 was 0.83 and 0.17 respectively. The mean U-ALA concentration was lower in ALAD1-2/2-2 carriers than ALAD1-1 carriers for boys (p=0.001). But for girls, U-ALA did not differ significantly by genotype (p=0.26). When U-ALA was compared by genotype at the same exposure level in a multiple linear regression analysis, boys who were ALAD1-2/2-2 carriers still had a lower level of U-ALA compared to ALAD1-1carriers. Conclusion: This study provides information about the influence of ALAD polymorphism and its association with U-ALA in Bangladeshi children. Our results indicate that the ALAD1-2/2-2 genotype may have a protective effect in terms of U-ALA for environmentally lead exposed boys. - Highlights: • High blood lead level for the environmentally exposed schoolchildren. • BPb was significantly correlated with U-ALA and Hb. • Effect of ALAD genotype on U-ALA is differed by sex. • Lower U-ALA in ALAD2 than ALAD1 carriers only for boys at same exposure.

  6. The neuroprotective benefit from pioglitazone (PIO) addition on the alpha lipoic acid (ALA)-based treatment in experimental diabetic rats.

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    Jin, Heung Yong; Lee, Kyung Ae; Wu, Jin Zu; Baek, Hong Sun; Park, Tae Sun

    2014-12-01

    In this study, we investigated the combined effect of pioglitazone (PIO) with alpha lipoic acid (ALA) on the peripheral nerves of diabetic rats. Animals were divided into 8 groups (N = 6-8) and designated according to ALA (100 mg/kg/day) and PIO (10 mg/kg/day) treatment: Normal, Normal + ALA, Normal + PIO, Normal + ALA + PIO, DM, DM + ALA, DM + PIO, and DM + ALA + PIO. After 24 weeks, current perception threshold, mechanical allodynia, oxidative stresses, intraepidermal nerve fiber density (IENFD), and axonal morphology in the sciatic nerve were compared among groups. IENFD in the DM + ALA + PIO group was significantly less reduced than in other DM groups (7.61 ± 0.52 vs. 5.62 ± 0.96, 5.56 ± 0.60, and 7.10 ± 0.70 for DM, DM + ALA, and DM + PIO, respectively P diabetes. Moreover, PIO can be preferentially considered when additional glucose-lowering agent is required in DPN patients treated with ALA.

  7. Rolled-Up Nanotech: Illumination-Controlled Hydrofluoric Acid Etching of AlAs Sacrificial Layers

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    Costescu Ruxandra

    2009-01-01

    Full Text Available Abstract The effect of illumination on the hydrofluoric acid etching of AlAs sacrificial layers with systematically varied thicknesses in order to release and roll up InGaAs/GaAs bilayers was studied. For thicknesses of AlAs below 10 nm, there were two etching regimes for the area under illumination: one at low illumination intensities, in which the etching and releasing proceeds as expected and one at higher intensities in which the etching and any releasing are completely suppressed. The “etch suppression” area is well defined by the illumination spot, a feature that can be used to create heterogeneously etched regions with a high degree of control, shown here on patterned samples. Together with the studied self-limitation effect, the technique offers a way to determine the position of rolled-up micro- and nanotubes independently from the predefined lithographic pattern.

  8. Rolled-Up Nanotech: Illumination-Controlled Hydrofluoric Acid Etching of AlAs Sacrificial Layers

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    Costescu, Ruxandra M.; Deneke, Christoph; Thurmer, Dominic J.; Schmidt, Oliver G.

    2009-12-01

    The effect of illumination on the hydrofluoric acid etching of AlAs sacrificial layers with systematically varied thicknesses in order to release and roll up InGaAs/GaAs bilayers was studied. For thicknesses of AlAs below 10 nm, there were two etching regimes for the area under illumination: one at low illumination intensities, in which the etching and releasing proceeds as expected and one at higher intensities in which the etching and any releasing are completely suppressed. The “etch suppression” area is well defined by the illumination spot, a feature that can be used to create heterogeneously etched regions with a high degree of control, shown here on patterned samples. Together with the studied self-limitation effect, the technique offers a way to determine the position of rolled-up micro- and nanotubes independently from the predefined lithographic pattern.

  9. Photodynamic diagnosis following intravesical instillation of aminolevulinic acid (ALA): first clinical experiences in urology

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    Baumgartner, Reinhold; Kriegmair, M.; Stepp, Herbert G.; Lumper, W.; Heil, Peter; Riesenberg, Rainer; Stocker, Susanne; Hofstetter, Alfons G.

    1993-06-01

    Delta Aminolevulinic acid (ALA), a precursor of Protoporphyrin IX (PP IX) in hem biosynthesis has been topically applied in urinary bladders in order to study its potential as fluorescent tumor marker. Preclinical experiments have been performed on chemically induced tumors in rats, revealing a ratio of PP IX-fluorescence intensity up to 20:1 in tumors as compared to healthy urothelium. Synthesis of PP IX has been stimulated in 56 patients by intravesical instillation of a pH-neutral ALA-solution. After an incubation time of two to four hours strong red fluorescence was endoscopically observed even in tiny superficial tumors. Brightness and contrast allows visualization of early stage urothelial diseases with naked eyes and without the necessity suppressing background fluorescence or violet excitation light.

  10. Association of serum uric acid with Pro12Ala polymorphism in PPAR-γ2 among Chinese nonagenarians/centenarians.

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    Zhou, Yan; Huang, Chang-Quan; Lu, Zhen-Chan; Dong, Bi-Rong

    2012-04-01

    In previous studies, Pro12Ala polymorphism in peroxisome proliferator- activated receptors gamma 2 (PPAR-γ2) was shown to be associated with both longevity and metabolic syndrome, which was closely related with hyperuricemia. We examined long-lived subjects (≥90 years), to ascertain whether the polymorphism is associated with the level of serum uric acid (SUA). The present study analysed data from a survey conducted in 2005 on all residents aged 90 years or more in a district with 2,311,709 inhabitants. The sample comprised 669 unrelated Chinese participants (aged 90-108 years, mean: 93.54±3.53 years; 67.2% women). The genotype frequencies of the Pro12Ala polymorphism were 0% Ala12Ala and 9.0% Pro12Ala, 91.0% Pro12Pro. Between men or women, and between subjects who were or were not 12Ala carriers, neither in SUA levels nor the prevalence of hyperuricemia were significant. Between subjects with and without hyperuricemia, the difference in prevalence of 12Ala carriers was also non-significant. Unadjusted and adjusted multiple logistic regressions showed that the odds ratios (OR) for hyperuricemia were not associated with Pro12Ala polymorphism in PPAR-γ2. In Chinese nonagenarians and centenarians, SUA levels are not associated with polymorphism in PPAR-γ2.

  11. Ambulant photodynamic therapy of superficial malignomas with 5-ALA in combination with folic acid and use of noncoherent light.

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    Jindra, R H; Kubin, A; Kolbabek, H; Alth, G; Dobrowsky, W

    1999-01-01

    This study reports our first results of ambulant photodynamic treatment with 5-aminolevulinic acid (5-ALA) in combination with folic acid and subsequent illumination with a noncoherent light source. The compound was topically applied to avoid total body skin sensitivity which occurs in the case of systemic administration. If no therapeutic response could be proved, we added folic acid to 5-ALA for a further treatment attempt. Illumination was performed by broad band red thermic light to also excitate reaction products with absorption bands located near to that of the sensitizer. As a result, we observed a response in all cases, however, in some cases only after the addition of folic acid.

  12. Short-term supplementation of low-dose gamma-linolenic acid (GLA), alpha-linolenic acid (ALA), or GLA plus ALA does not augment LCP omega 3 status of Dutch vegans to an appreciable extent

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    Fokkema, M R; Brouwer, D A; Hasperhoven, M B; Martini, I A; Muskiet, F A

    2000-01-01

    Vegans do not consume meat and fish and have therefore low intakes of long chain polyunsaturated fatty acids (LCP). They may consequently have little negative feedback inhibition from dietary LCP on conversion of alpha -linolenic acid (ALA) to the LCP omega 3 eicosapentaenoic (EPA) and docosahexaeno

  13. Short-term supplementation of low-dose gamma-linolenic acid (GLA), alpha-linolenic acid (ALA), or GLA plus ALA does not augment LCP omega 3 status of Dutch vegans to an appreciable extent

    NARCIS (Netherlands)

    Fokkema, M R; Brouwer, D A; Hasperhoven, M B; Martini, I A; Muskiet, F A

    2000-01-01

    Vegans do not consume meat and fish and have therefore low intakes of long chain polyunsaturated fatty acids (LCP). They may consequently have little negative feedback inhibition from dietary LCP on conversion of alpha -linolenic acid (ALA) to the LCP omega 3 eicosapentaenoic (EPA) and

  14. Brain docosahexaenoic acid (DHA levels of young rats are related to alpha-linolenic acid (ALA levels and fat matrix of the diet: impact of dairy fat*

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    Delplanque Bernadette

    2011-11-01

    Full Text Available Dososahexaenoate (DHA is highly concentrated in mammalian nervous and visual systems and its deficiency during gestation, lactation and early life, could have dramatic impacts on brain functions and mental health. Achieving an appropriate DHA status in the neonatal brain is an important goal of neonatal nutrition. We evaluated how a-linolenic acid (ALA provided by different dietary fat matrices improved DHA content in the brains of both young male and female rats. Young rats born from dams fed during gestation and lactation with a low ALA diet (0.4% of fatty acids were subjected for 6 weeks after weaning to an anhydrous dairy fat blend-based diet that provided 1.5% ALA or to a palm oil blend-based diet that provided the same ALA level: either 1.5% ALA or 1.5% ALA and 0.12% DHA with 0.4% arachidonic acid (ARA. With each diet the n-6/ n-3 ratio was similar (10 to follow the values generally recommended for infant formula. Fatty acids analysis in whole brain showed that 1.5% ALA dairy fat blend was superior to both 1.5% ALA palm-oil blends, supplemented or not with dietary DHA, for increasing brain DHA. Females compared to males had significantly higher brain DHA with the 1.5% ALA palm-blend diet, but the dietary supplementation with DHA smoothed the differences by a specific increase of males DHA brain. In conclusion, dairy fat blend enriched with ALA appear to be an interesting strategy for achieving optimal DHA levels in the brain of post-weaning rats. Inclusion of dairy fat in infant formulas should be reconsidered.

  15. Intestinal fatty acid binding protein Ala54Thr polymorphism is associated with peripheral atherosclerosis combined with type 2 diabetes mellitus.

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    Khattab, Salma A; Abo-Elmatty, Dina M; Ghattas, Maivel H; Mesbah, Noha M; Mehanna, Eman T

    2017-09-01

    Intestinal fatty acid-binding protein 2 (FABP2) is expressed in enterocytes and binds saturated and unsaturated long-chain fatty acids. The FABP2 Ala54Thr polymorphism has been reported to effect lipid metabolism. The aim of the present study was to assess the relationship between this polymorphism and peripheral atherosclerosis combined with type 2 diabetes mellitus (T2DM) in an Egyptian population. The study was performed on 100 T2DM patients with peripheral atherosclerosis and 100 control subjects. The Ala54Thr polymorphism was analyzed by polymerase chain reaction-restriction fragment length polymorphism, whereas serum FABP2 levels were determined using ELISA. Fasting blood glucose, fasting serum insulin concentrations, HbA1c, lipid profile, body mass index (BMI) and systolic and diastolic blood pressure (SBP and DBP, respectively) were determined. There was a higher frequency of the Thr54 allele among the patient group (P = 0.002). In Ala54/Thr54 heterozygotes and carriers of the rare Thr54/Thr54 genotype, there were significant increases in BMI and FABP2. Those with the Thr54/Thr54 genotype had significantly decreased high-density lipoprotein cholesterol (HDL-C) concentrations; in addition, those with the Thr54/Thr54 genotype had significantly higher SBP and DBP than subjects with the Ala54/Ala54 and Ala54/Thr54 genotypes. There was a positive correlation between FABP2 levels and BMI, SBP and DBP, and a negative correlation with HDL-C. The Thr54 allele of the FABP2 Ala54Thr polymorphism was associated with an increased incidence of peripheral atherosclerosis combined with T2DM in the population studied. © 2016 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

  16. The influence of photodynamic therapy (PDT) with δ-aminolevulinic acid (ALA) on J-774A.1 macrophage cell line

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    Kawczyk-Krupka, Aleksandra; Czuba, Zenon; Ledwon, Aleksandra; Latos, Wojciech; Sliszka, Ewelina; Mianowska, Marta; Krol, Wojciech; Sieron, Aleksander

    2008-02-01

    Introduction. The whole mechanism of the cellular level of tumor destruction by photodynamic therapy (PDT) is still unknown. Despite necrotic and apoptotic ways of cell death, there is a variety of events leading to and magnifying the inactivation of tumor cells. Material and methods. J-774A.1 were incubated with δ-aminolevulinic acid (ALA) at different concentrations (125, 250, 500, 1000 μM) and then irradiated with VIS (400 - 750 nm) at the dose of 5,10 and 30 J/cm2 delivered from the incoherent light source. The effects of the application of ALA-PDT were evaluated on the basis of cell viability, nitric oxide (NO), tumor necrosis factor α- (TNF-α) and interleukin-1β (IL-1β) produced by the J-774A.1 cells. Results. The cell viability (assessed using MTT test) was comparable with control group at 5,10 and 30 J/cm2. At these doses of energy using different concentrations of ALA we have observed that at the higher energy doses, the greater increase of TNF-α release, lowering of the level of IL-1β production and decrease of NO release were observed. There was also observed the dependence of the secretional activity of the cells on the ALA concentrations. Conclusion. The cell viability and production of cytokines depended on ALA concentrations and energy doses of the light. The higher some cytokines' release after PDT could be an additional factor for the complete eradication of tumor.

  17. Lead in Missouri Streams: Monitoring Pollution from Mining with an Assay for Erythrocyte [delta]-Aminolevulinic Acid Dehydratase (ALA-D) in Fish Blood

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    US Fish and Wildlife Service, Department of the Interior — The activity of the erythrocyte enzyme d-aminolevulinic acid dehydratase (ALA-D) has long been used as a biomarker of lead exposure in humans and waterfowl and, more...

  18. Adsorption of Amino Acids (Ala, Cys, His, Met) on Zeolites: Fourier Transform Infrared and Raman Spectroscopy Investigations

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    Carneiro, Cristine E. A.; de Santana, Henrique; Casado, Clara; Coronas, Joaquin; Zaia, Dimas A. M.

    2011-06-01

    Minerals adsorb more amino acids with charged R-groups than amino acids with uncharged R-groups. Thus, the peptides that form from the condensation of amino acids on the surface of minerals should be composed of amino acid residues that are more charged than uncharged. However, most of the amino acids (74%) in today's proteins have an uncharged R-group. One mechanism with which to solve this paradox is the use of organophilic minerals such as zeolites. Over the range of pH (pH 2.66-4.50) used in these experiments, the R-group of histidine (His) is positively charged and neutral for alanine (Ala), cysteine (Cys), and methionine (Met). In acidic hydrothermal environments, the pH could be even lower than those used in this study. For the pH range studied, the zeolites were negatively charged, and the overall charge of all amino acids was positive. The conditions used here approximate those of prebiotic Earth. The most important finding of this work is that the relative concentrations of each amino acid (X=His, Met, Cys) to alanine (X/Ala) are close to 1.00. This is an important result with regard to prebiotic chemistry because it could be a solution for the paradox stated above. Pore size did not affect the adsorption of Cys and Met on zeolites, and the Si/Al ratio did not affect the adsorption of Cys, His, and Met. ZSM-5 could be used for the purification of Cys from other amino acids (Student-Newman-Keuls test, phydrophobic Van der Waals interaction between zeolites and Cys is too weak to produce any structural changes in the Cys groups (amine, carboxylic, sulfhydryl, etc.); thus, the FT-IR and Raman spectra are the same as those of solid Cys.

  19. Endoscopic fluorescence of gastrointestinal neoplasia after sensitization with 5-aminolaevulinic acid (ALA) or Photofrin

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    Messmann, Helmut; Mlkvy, Peter; Montan, Sune; Wang-Nordman, Ingrid; Nilsson, Annika M.; Svanberg, Katarina; Svanberg, Sune; MacRobert, Alexander J.; Bown, Stephen G.

    1995-03-01

    Fluorescence after photosensitization has the potential to identify lesions not visible on conventional endoscopy. We assessed 12 patients at high risk of or with established GI cancers (u ulcerative colitis, 1 colon polyp, 2 familial polyposis with duodenal polyps, 2 early oesophageal cancers). Fluorescence images (excitation 390 nm) were recorded with endoscopic equipment and additional spot measurements (optical multichannel analyzer). Patients were given 10 - 60 mg/kg ALA orally or 2 mg/kg Photofrin i.v. 60 mg/kg ALA gave high levels of PP IX (proto-porphyrin IX) in all areas, but 10 - 15 mg/kg resulted in selectivity in macroscopically inflamed colon. Photofrin gave oesophageal tumors selectivity at 4 and 48 hours. Photofrin patients subsequently had PDT. Photobleaching was documented in 3. We conclude that these techniques have potential as `optical biopsy tools' and for screening for early neoplastic changes.

  20. Ala54Thr fatty acid-binding protein 2 (FABP2 polymorphism in recurrent depression: associations with fatty acid concentrations and waist circumference.

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    Roel J T Mocking

    Full Text Available BACKGROUND: Fatty acid (FA-alterations may mediate the mutual association between Major Depressive Disorder (MDD and cardiovascular disease (CVD. However, etiology of observed FA-alterations in MDD and CVD remains largely unclear. An interesting candidate may be a mutation in the fatty acid-binding protein 2 (FABP2-gene, because it regulates dietary FA-uptake. Therefore, we aimed to test the hypotheses that in MDD-patients the FABP2 Ala54Thr-polymorphism would be (I more prevalent than in sex- and age-matched controls, (II associated with observed alterations in FA-metabolism, and (III associated with CVD-risk factor waist circumference. METHODS: We measured concentrations of 29 different erythrocyte FAs, FABP2-genotype, and waist circumference in recurrent MDD-patients and matched never-depressed controls. RESULTS: FABP2-genotype distribution did not significantly differ between the 137 MDD-patients and 73 matched controls. However, patients with the Ala54Thr-polymorphism had (I higher concentrations of especially eicosadienoic acid (C20:2ω6; P=.009 and other 20-carbon FAs, and associated (II lower waist circumference (P=.019. In addition, FABP2-genotype effects on waist circumference in patients seemed (I mediated by its effect on C20:2ω6, and (II different from controls. CONCLUSIONS: Although Ala54Thr-polymorphism distribution was not associated with recurrent MDD, our results indicate that FABP2 may play a role in the explanation of observed FA-alterations in MDD. For Ala54Thr-polymorphism patients, potentially adaptive conversion of increased bioavailable dietary precursors into eicosadienoic acid instead of arachidonic acid might be related to a low waist circumference. Because this is the first investigation of these associations, replication is warranted, preferably by nutrigenetic studies applying lipidomics and detailed dietary assessment.

  1. Adsorption of amino acids (ALA, CYS, HIS, MET) on zeolites: fourier transform infrared and Raman spectroscopy investigations.

    Science.gov (United States)

    Carneiro, Cristine E A; de Santana, Henrique; Casado, Clara; Coronas, Joaquin; Zaia, Dimas A M

    2011-06-01

    Minerals adsorb more amino acids with charged R-groups than amino acids with uncharged R-groups. Thus, the peptides that form from the condensation of amino acids on the surface of minerals should be composed of amino acid residues that are more charged than uncharged. However, most of the amino acids (74%) in today's proteins have an uncharged R-group. One mechanism with which to solve this paradox is the use of organophilic minerals such as zeolites. Over the range of pH (pH 2.66-4.50) used in these experiments, the R-group of histidine (His) is positively charged and neutral for alanine (Ala), cysteine (Cys), and methionine (Met). In acidic hydrothermal environments, the pH could be even lower than those used in this study. For the pH range studied, the zeolites were negatively charged, and the overall charge of all amino acids was positive. The conditions used here approximate those of prebiotic Earth. The most important finding of this work is that the relative concentrations of each amino acid (X=His, Met, Cys) to alanine (X/Ala) are close to 1.00. This is an important result with regard to prebiotic chemistry because it could be a solution for the paradox stated above. Pore size did not affect the adsorption of Cys and Met on zeolites, and the Si/Al ratio did not affect the adsorption of Cys, His, and Met. ZSM-5 could be used for the purification of Cys from other amino acids (Student-Newman-Keuls test, pzeolites through the [Formula: see text] group, and methionine-zeolite interactions involve the COO, [Formula: see text], and CH(3) groups. FT-IR spectra show that the interaction between the zeolites and His is weak. Cys showed higher adsorption on all zeolites; however, the hydrophobic Van der Waals interaction between zeolites and Cys is too weak to produce any structural changes in the Cys groups (amine, carboxylic, sulfhydryl, etc.); thus, the FT-IR and Raman spectra are the same as those of solid Cys.

  2. Differences between β-Ala and Gly-Gly in the design of amino acids-based hydrogels

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    Andreea Pasc

    2010-10-01

    Full Text Available Despite the continuous interest in organogels and hydrogels of low molecular weight gelators (LMWG, establishing the relationship between the molecular structure and the gelation mechanism is still a challenge. In this paper our interest focuses on the consequences of slight molecular modifications on the self-assembling behaviour of β-Ala vs Gly-Gly-based hydrogelators. Previously, in our group, amino acid based amphiphiles i.e. Gly-Gly-His-EO2-Alk, a trimodular amphiphile (containing three domains: H-bond donor and acceptor/hydrophilic/hydrophobic domain, respectively were reported to act as hydrogelators and that the gelation properties were related to hydrogen bonding, hydrophobic interactions and π-π stacking. Herein, β-Ala-His-EO2-Alk was fully characterised by FT-IR, NMR, SAXS and SEM and the gelation mechanism is discussed. It appears that the number of amide groups determines the self-assembling behaviour into 1D or 2D/3D networks as a result of intimate interactions between gelator molecules.

  3. Influence of Ala54Thr polymorphism of fatty acid-binding protein 2 on histological alterations and insulin resistance of non alcoholic fatty liver disease.

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    Aller, R; De Luis, D A; Fernandez, L; Calle, F; Velayos, B; Izaola, O; Gonzalez Sagrado, M; Conde, R; Gonzalez, J M

    2009-01-01

    A transition G to A at codon 54 of fatty acid binding protein type 2 (FABP2) produces an amino acid substitution (Ala 54 to Thr 54). This amino acid substitution was associated with modifications of insulin resistance, adipokines and insulin concentrations. The aim of this study was to evaluate the influence of Ala54Thr polymorphism in the FABP2 gene on the histological alterations of non-alcoholic fatty liver disease (NAFLD) and insulin resistance. Thirty subjects with the presence of biopsy-proven NAFLD were enrolled for this study. Glucose, Insulin, Insulin resistance (HOMA), total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, resistin, leptin, adiponectin, interleukin-6 and TNF-alfa serum levels were measured at basal time. A tetrapolar bioimpedance, BMI, waist circumference, waist to hip ratio, blood pressure and a prospective serial assessment of nutritional intake with 3 days written food records were examined. Genotype of Ala54Thr FABP2 gene polymorphism was studied. The mean age was 41.6 +/- 11 years and the mean BMI 29.2 +/- 6.6 with 24 males (80%) and 6 females (20%). Fifteen patients (50%) had the genotype Ala54/Ala54 (wild type group) and 15 (50%) patients Ala54/Thr54 (13 patients) or Thr54/Thr54 (2 patients) (mutant type group). Both genotype groups have the similar anthropometric parameters. Serum aspartate aminotransferase and alcaline phosfatase were higher in wild type group than mutant type group, with an unclear explanation. Dietary intake was similar in both groups. A non-statistical significant low levels of adiponectin in mutant group was observed. No differences were detected among other adipokines. There were no differences between genotypes in histological results of inflammation (portal or lobular inflammation) or grade of steatosis or fibrosis. In conclusion, the present study demonstrates that the polymorphism Ala54Thr of FABP in patients with NAFLD doesn't predict liver histological changes, nor both insulin resistance

  4. Nuclear receptor 5A (NR5A) family regulates 5-aminolevulinic acid synthase 1 (ALAS1) gene expression in steroidogenic cells.

    Science.gov (United States)

    Ju, Yunfeng; Mizutani, Tetsuya; Imamichi, Yoshitaka; Yazawa, Takashi; Matsumura, Takehiro; Kawabe, Shinya; Kanno, Masafumi; Umezawa, Akihiro; Kangawa, Kenji; Miyamoto, Kaoru

    2012-11-01

    5-Aminolevulinic acid synthase 1 (ALAS1) is a rate-limiting enzyme for heme biosynthesis in mammals. Heme is essential for the catalytic activities of P450 enzymes including steroid metabolic enzymes. Nuclear receptor 5A (NR5A) family proteins, steroidogenic factor-1 (SF-1), and liver receptor homolog-1 (LRH-1) play pivotal roles in regulation of steroidogenic enzymes. Recently, we showed that expression of SF-1/LRH-1 induces differentiation of mesenchymal stem cells into steroidogenic cells. In this study, genome-wide analysis revealed that ALAS1 was a novel SF-1-target gene in differentiated mesenchymal stem cells. Chromatin immunoprecipitation and reporter assays revealed that SF-1/LRH-1 up-regulated ALAS1 gene transcription in steroidogenic cells via binding to a 3.5-kb upstream region of ALAS1. The ALAS1 gene was up-regulated by overexpression of SF-1/LRH-1 in steroidogenic cells and down-regulated by knockdown of SF-1 in these cells. Peroxisome proliferator-activated receptor-γ coactivator-1α, a coactivator of nuclear receptors, also strongly coactivated expression of NR5A-target genes. Reporter analysis revealed that peroxisome proliferator-activated receptor-γ coactivator-1α strongly augmented ALAS1 gene transcription caused by SF-1 binding to the 3.5-kb upstream region. Finally knockdown of ALAS1 resulted in reduced progesterone production by steroidogenic cells. These results indicate that ALAS1 is a novel NR5A-target gene and participates in steroid hormone production.

  5. Photodynamic therapy (PDT) and photodiagnosis (PD) using endogenous photosensitization induced by 5-aminolevulinic acid (ALA): current clinical and development status

    Science.gov (United States)

    Marcus, Stuart L.; Sobel, Russel S.; Golub, Allyn L.; Carroll, Ronald L.; Lundahl, Scott L.; Shulman, D. Geoffrey

    1996-04-01

    Exogenous provision of ALA to many tissues results in the accumulation of sufficient quantities of the endogenous photosensitizer protoporphyrin IX, (PpIX), to produce a photodynamic effect. Therefore, ALA may be considered the only current PDT agent in clinical development which is a biochemical precursor of a photosensitizer. Topical ALA application, followed by exposure to activating light (ALA PDT), has been reported effective for the treatment of a variety of dermatologic diseases including cutaneous T-cell lymphoma, superficial basal cell carcinoma, Bowen's disease, and actinic (solar) keratoses, and is also being examined for treatment of acne and hirsutism. PpIX induced by ALA application also may serve as a fluorescence detection marker for photodiagnosis (PD) of malignant and pre- malignant conditions of the urinary bladder and other organs. Local internal application of ALA has also been used for selective endometrial ablation in animal model systems and is beginning to be examined in human clinical studies. Systemic, oral administration of ALA has been used for ALA PDT of superficial head and neck cancer, various gastrointestinal cancers, and the condition known as Barrett's esophagus. This brief paper reviews the current clinical and development status of ALA PDT.

  6. Synthesis of the C-terminal octapeptide of pig oxyntomodulin. Lys-Arg-Asn-Lys-Asn-Asn-Ile-Ala: a potent inhibitor of pentagastrin-induced acid secretion.

    Science.gov (United States)

    Audousset-Puech, M P; Jarrousse, C; Dubrasquet, M; Aumelas, A; Castro, B; Bataille, D; Martinez, J

    1985-10-01

    The synthesis of Lys-Arg-Asn-Lys-Asn-Asn-Ile-Ala representing the C-terminal octapeptide of oxyntomodulin isolated from pig intestine is described. Its structure was confirmed by its 360-MHz 1H NMR spectra. The octapeptide was tested for its ability to inhibit pentagastrin-induced acid secretion, in the anaesthetized rat, in the conscious rat with chronic gastric fistula, and in the conscious cat with gastric chronic fistula. The octapeptide inhibits pentagastrin-induced acid secretion in all three models. Compared to oxyntomodulin, the parent hormone, the synthetic peptide was approximately 150 times less potent but has the same efficacy. Biological data are presented and discussed.

  7. Docosahexaenoic Acid-Rich Fish Oil Supplementation Improves Body Composition without Influence of the PPARγ Pro12Ala Polymorphism in Patients with Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

    Science.gov (United States)

    Mansoori, Anahita; Sotoudeh, Gity; Djalali, Mahmoud; Eshraghian, Mohammad-Reza; Keramatipour, Mohammad; Nasli-Esfahani, Ensieh; Shidfar, Farzad; Alvandi, Ehsan; Toupchian, Omid; Koohdani, Fariba

    2015-01-01

    The aims of this research were to investigate (1) the impact of docosahexaenoic acid (DHA)-rich fish oil supplementation on body composition, plasma adiponectin level, and peroxisome proliferator-activated receptor γ (PPARγ) gene expression, and (2) whether the effect of DHA-rich fish oil supplementation on the aforementioned variables is modulated by PPARγ Pro12Ala polymorphism. We genotyped PPARγ Pro12Ala polymorphism in subjects with type 2 diabetes mellitus (T2DM). Ala carriers and non-Ala carriers were randomly assigned to DHA-rich fish oil or placebo intake for 8 weeks. Glycemic control was not affected by the intervention. The supplementation with DHA-rich fish oil decreased waist circumference (p Pro12Ala polymorphism did not influence the changes in the desired variables. © 2016 S. Karger AG, Basel.

  8. A Thr94Ala mutation in human liver fatty acid-binding protein contributes to reduced hepatic glycogenolysis and blunted elevation of plasma glucose levels in lipid-exposed subjects.

    Science.gov (United States)

    Weickert, Martin O; Loeffelholz, Christian V; Roden, Michael; Chandramouli, Visvanathan; Brehm, Attila; Nowotny, Peter; Osterhoff, Martin A; Isken, Frank; Spranger, Jochen; Landau, Bernard R; Pfeiffer, Andreas F H; Möhlig, Matthias

    2007-10-01

    Liver fatty acid-binding protein (L-FABP) is a highly conserved key factor in lipid metabolism. Amino acid replacements in L-FABP might alter its function and thereby affect glucose metabolism in lipid-exposed subjects, as indicated by studies in L-FABP knockout mice. Amino acid replacements in L-FABP were investigated in a cohort of 1,453 Caucasian subjects. Endogenous glucose production (EGP), gluconeogenesis, and glycogenolysis were measured in healthy carriers of the only common Thr(94)-to-Ala amino acid replacement (Ala/Ala(94)) vs. age-, sex-, and BMI-matched wild-type (Thr/Thr(94)) controls at baseline and after 320-min lipid/heparin-somatostatin-insulin-glucagon clamps (n = 18). Whole body glucose disposal was further investigated (subset; n = 13) using euglycemic-hyperinsulinemic clamps without and with lipid/heparin infusion. In the entire cohort, the only common Ala/Ala(94) mutation was significantly associated with reduced body weight, which is in agreement with a previous report. In lipid-exposed, individually matched subjects there was a genotype vs. lipid-treatment interaction for EGP (P = 0.009) driven mainly by reduced glycogenolysis in Ala/Ala(94) carriers (0.46 +/- 0.05 vs. 0.59 +/- 0.05 mgxkg(-1)xmin(-1), P = 0.013). The lipid-induced elevation of plasma glucose levels was smaller in Ala/Ala(94) carriers compared with wild types (P glycogenolysis and less severe hyperglycemia in lipid-exposed humans and was further associated with reduced body weight in a large cohort. Data clearly show that investigation of L-FABP phenotypes in the basal overnight-fasted state yielded incomplete information, and a challenge test was essential to detect phenotypical differences in glucose metabolism between L-FABP genotypes.

  9. Thr202Ala in thyA Is a Marker for the Latin American Mediterranean Lineage of the Mycobacterium tuberculosis Complex Rather than Para-Aminosalicylic Acid Resistance

    KAUST Repository

    Feuerriegel, S.

    2010-08-30

    Single nucleotide polymorphisms (SNPs) involved in the development of resistance represent powerful markers for the rapid detection of first- and second-line resistance in clinical Mycobacterium tuberculosis complex (MTBC) isolates. However, the association between particular mutations and phenotypic resistance is not always clear-cut, and phylogenetic SNPs have been misclassified as resistance markers in the past. In the present study, we investigated the utility of a specific polymorphism in thyA (Thr202Ala) as a marker for resistance to para-aminosalicyclic acid (PAS). Sixty-three PAS-susceptible MTBC strains comprising all major phylogenetic lineages, reference strain H37Rv, and 135 multidrug-resistant (MDR) strains from Germany (comprising 8 PAS-resistant isolates) were investigated for the presence of Thr202Ala. In both strain collections, the Thr202Ala SNP was found exclusively in strains of the Latin American Mediterranean (LAM) lineage irrespective of PAS resistance. Furthermore, PAS MICs (0.5 mg/liter) for selected LAM strains (all containing the SNP) and non-LAM strains (not containing the SNP), as well as the results of growth curve analyses performed in liquid 7H9 medium in the presence of increasing PAS concentrations (0 to 2.0 mg/liter), were identical. In conclusion, our data demonstrate that the Thr202Ala polymorphism in thyA is not a valid marker for PAS resistance but, instead, represents a phylogenetic marker for the LAM lineage of the M. tuberculosis complex. These findings challenge some of the previous understanding of PAS resistance and, as a consequence, warrant further in-depth investigations of the genetic variation in PAS-resistant clinical isolates and spontaneous mutants.

  10. Evaluation of the hepatic bioconversion of α-linolenic acid (ALA to eicosapentaenoic acid (EPA and docosahexaenoic acid (DHA in rats fed with oils from chia (Salvia hispánica or rosa mosqueta (Rosa rubiginosa

    Directory of Open Access Journals (Sweden)

    Tapia O., G.

    2012-03-01

    Full Text Available The high dietary intake of n-6 fatty acids in relation to n-3 fatty acids generates health disorders, such as cardiovascular diseases, inflammatory diseases and other chronic diseases. The consumption of fish, which is rich in n-3 fatty acids, is low in Latin America and it is necessary to seek other alternatives, such as chia oil (CO or rosa mosqueta oil (RMO, which are rich in α-linolenic acid (ALA, the precursor of the n -3 fatty acids, eicosapentaenoic acid (EPA and docosahexaenoic acid (DHA. This study evaluates the hepatic bioconversion of ALA to EPA and DHA and the damage to the liver (histology and transaminase in Sprague- Dawley rats fed different vegetable oils. Four experimental groups (n = 9 animals each group were fed the following dietary supplements for 21 days: a sunflower oil (SFO, b RMO, c CO d olive oil with fish oil added (EPA and DHA (OO/FO. RMO and CO increased the hepatic levels of ALA, EPA and DHA and decreased the n-6/n-3 ratio compared to SFO (p El elevado aporte en la dieta de ácidos grasos omega- 6, en relación a los ácidos grasos omega-3, genera alteraciones de la salud cardiovascular, inflamación y otras patologías crónicas no transmisibles. Por otro lado, el pescado rico en ácidos grasos omega-3 es de bajo consumo en Latinoamérica, siendo necesario buscar otras alternativas de aporte de ácidos grasos omega-3, como lo son el aceite de chía (CO o el de rosa mosqueta (RMO, ricos en ácido α-linolénico (ALA, que es el precursor de los ácidos grasos omega-3, eicosapentaenoico (EPA y docosahexaenoico (DHA. Este trabajo evaluó en forma preliminar la bioconversión hepática del ALA en EPA y DHA y el daño hepático (histología y transaminasas en ratas Sprague-Dawley alimentadas con diferentes aceites vegetales. Se conformaron cuatro grupos experimentales (n = 9 animales por grupo que recibieron durante 21 días: a aceite de girasol (SFO; b RMO, c CO y d aceite de oliva adicionado de aceite de pescado (EPA

  11. The feeding route (enteral or parenteral) affects the plasma response of the dipetide Ala-Gln and the amino acids glutamine, citrulline and arginine, with the administration of Ala-Gln in preoperative patients.

    Science.gov (United States)

    Melis, Gerdien C; Boelens, Petra G; van der Sijp, Joost R M; Popovici, Theodora; De Bandt, Jean-Pascal; Cynober, Luc; van Leeuwen, Paul A M

    2005-07-01

    Enhancement of depressed plasma concentrations of glutamine and arginine is associated with better clinical outcome. Supplementation of glutamine might be a way to provide the patient with glutamine, and also arginine, because glutamine provides the kidney with citrulline, from which the kidney produces arginine when plasma levels of arginine are low. The aim of the present study was to investigate the parenteral and enteral response of the administered dipeptide Ala-Gln, glutamine, citrulline and arginine. Therefore, seven patients received 20 g Ala-Gln, administered over 4 h, parenterally or enterally, on two separate occasions. Arterial blood samples were taken before and during the administration of Ala-Gln. ANOVA and a paired t test were used to test differences (Pglutamine was observed with parenteral infusion of the dipeptide, although enteral infusion also significantly increased plasma levels of glutamine. The highest plasma response of citrulline was observed with the enteral administration of the dipeptide, although parenteral administration also increased plasma levels of citrulline. Plasma arginine increased significantly with parenteral infusion, but not with enteral administration of Ala-Gln. In conclusion, administrations of Ala-Gln, parenteral or enteral, resulted in an increased plasma glutamine response, as compared with baseline. Interestingly, in spite of the high availability of citrulline with enteral administration of the dipeptide, only parenteral infusion of Ala-Gln increased plasma arginine concentration.

  12. Preliminary Validation of a High Docosahexaenoic Acid (DHA) and -Linolenic Acid (ALA) Dietary Oil Blend: Tissue Fatty Acid Composition and Liver Proteome Response in Atlantic Salmon (Salmo salar) Smolts

    Science.gov (United States)

    Nuez-Ortín, Waldo G.; Carter, Chris G.; Wilson, Richard; Cooke, Ira; Nichols, Peter D.

    2016-01-01

    Marine oils are important to human nutrition as the major source of docosahexaenoic acid (DHA), a key omega-3 long-chain (≥C20) polyunsaturated fatty acid (n-3 LC-PUFA) that is low or lacking in terrestrial plant or animal oils. The inclusion of fish oil as main source of n-3 LC-PUFA in aquafeeds is mostly limited by the increasing price and decreasing availability. Fish oil replacement with cheaper terrestrial plant and animal oils has considerably reduced the content of n-3 LC-PUFA in flesh of farmed Atlantic salmon. Novel DHA-enriched oils with high alpha-linolenic acid (ALA) content will be available from transgenic oilseeds plants in the near future as an alternative for dietary fish oil replacement in aquafeeds. As a preliminary validation, we formulated an oil blend (TOFX) with high DHA and ALA content using tuna oil (TO) high in DHA and the flaxseed oil (FX) high in ALA, and assessed its ability to achieve fish oil-like n-3 LC-PUFA tissue composition in Atlantic salmon smolts. We applied proteomics as an exploratory approach to understand the effects of nutritional changes on the fish liver. Comparisons were made between fish fed a fish oil-based diet (FO) and a commercial-like oil blend diet (fish oil + poultry oil, FOPO) over 89 days. Growth and feed efficiency ratio were lower on the TOFX diet. Fish muscle concentration of n-3 LC-PUFA was significantly higher for TOFX than for FOPO fish, but not higher than for FO fish, while retention efficiency of n-3 LC-PUFA was promoted by TOFX relative to FO. Proteomics analysis revealed an oxidative stress response indicative of the main adaptive physiological mechanism in TOFX fish. While specific dietary fatty acid concentrations and balances and antioxidant supplementation may need further attention, the use of an oil with a high content of DHA and ALA can enhance tissue deposition of n-3 LC-PUFA in relation to a commercially used oil blend. PMID:27556399

  13. Transporter-Mediated Drug Interaction Strategy for 5-Aminolevulinic Acid (ALA-Based Photodynamic Diagnosis of Malignant Brain Tumor: Molecular Design of ABCG2 Inhibitors

    Directory of Open Access Journals (Sweden)

    Toshihisa Ishikawa

    2011-09-01

    Full Text Available Photodynamic diagnosis (PDD is a practical tool currently used in surgical operation of aggressive brain tumors, such as glioblastoma. PDD is achieved by a photon-induced physicochemical reaction which is induced by excitation of protoporphyrin IX (PpIX exposed to light. Fluorescence-guided gross-total resection has recently been developed in PDD, where 5-aminolevulinic acid (ALA or its ester is administered as the precursor of PpIX. ALA induces the accumulation of PpIX, a natural photo-sensitizer, in cancer cells. Recent studies provide evidence that adenosine triphosphate (ATP-binding cassette (ABC transporter ABCG2 plays a pivotal role in regulating the cellular accumulation of porphyrins in cancer cells and thereby affects the efficacy of PDD. Protein kinase inhibitors are suggested to potentially enhance the PDD efficacy by blocking ABCG2-mediated porphyrin efflux from cancer cells. It is of great interest to develop potent ABCG2-inhibitors that can be applied to PDD for brain tumor therapy. This review article addresses a pivotal role of human ABC transporter ABCG2 in PDD as well as a new approach of quantitative structure-activity relationship (QSAR analysis to design potent ABCG2-inhibitors.

  14. Substitution of Ala564 in the first zinc cluster of the deoxyribonucleic acid (DNA)-binding domain of the androgen receptor by Asp, Asn, or Leu exerts differential effects on DNA binding

    NARCIS (Netherlands)

    H.T. Brüggenwirth (Hennie); A.L.M. Boehmer (Annemie); J.M. Lobaccaro; L. Chiche; C. Sultan; J. Trapman (Jan); A.O. Brinkmann (Albert)

    1998-01-01

    textabstractIn the androgen receptor of a patient with androgen insensitivity, the alanine residue at position 564 in the first zinc cluster of the DNA-binding domain was substituted by aspartic acid. In other members of the steroid receptor family, either valine or ala

  15. PPARgamma2 Pro12Ala polymorphism in relation to free fatty acids concentration and composition in lean healthy Czech individuals with and without family history of diabetes type 2.

    Science.gov (United States)

    Bendlová, B; Vejrazková, D; Vcelák, J; Lukásová, P; Burkonová, D; Kunesová, M; Vrbíková, J; Dvoráková, K; Vondra, K; Vanková, M

    2008-01-01

    Free fatty acids (FFAs) are natural ligands of the PPARgamma2 receptor. FFA plasma concentration and composition may represent one of the factors accounting for high heterogeneity of conclusions concerning the effect of the Pro12Ala on BMI, insulin sensitivity or diabetes type 2 (DM2) susceptibility. Our objective was to investigate the relation and possible interactions between the Pro12Ala polymorphism and FFA status, metabolic markers, and body composition in 324 lean nondiabetic subjects (M/F: 99/225; age 32+/-11 years; BMI 23.9+/-4.0 kg/m(2)) with and without family history of DM2. Family history of DM2 was associated with lower % PUFA and slightly higher % MUFA. The presence of Pro12Ala polymorphism was not associated with fasting plasma FFA concentration or composition, anthropometric or metabolic markers of glucose and lipid metabolism in tested population. However, the interaction of carriership status with FFA levels influenced the basal glucose levels, insulin sensitivity and disposition indices, triglycerides, HDL-cholesterol and leptin levels, especially in women. The metabolic effects of 12Ala carriership were influenced by FFA levels - the beneficial role of 12Ala was seen only in the presence of low concentration of plasma FFA. Surprisingly, a high PUFA/SFA ratio was associated with lower insulin sensitivity, the protective effect of 12Ala allele was apparent in subjects with family history of DM2. On the basis of our findings and published data we recommend the genotyping of diabetic patients for Pro12Ala polymorphism of the PPARgamma2 gene before treatment with thiazolidinediones and education of subjects regarding diet and physical activity, which modulate metabolic outcomes.

  16. Impact of the superoxide dismutase 2 Val16Ala polymorphism on the relationship between valproic acid exposure and elevation of γ-glutamyltransferase in patients with epilepsy: a population pharmacokinetic-pharmacodynamic analysis.

    Directory of Open Access Journals (Sweden)

    Naoki Ogusu

    Full Text Available BACKGROUND: There has been accumulating evidence that there are associations among γ-glutamyltransferase (γ-GT elevation and all-cause mortality, cardiovascular diseases and metabolic diseases, including nonalcoholic fatty liver disease. The primary objective of this study was to evaluate the impact of the most common and potentially functional polymorphisms of antioxidant enzyme genes, i.e. superoxide dismutase 2 (SOD2, glutathione S-transferase M1 and glutathione S-transferase T1, on the γ-GT elevation during valproic acid (VPA therapy. METHODS AND FINDINGS: This retrospective study included 237 and 169 VPA-treated Japanese patients with epilepsy for population pharmacokinetic and pharmacokinetic-pharmacodynamic analyses, respectively. A nonlinear mixed-effect model represented the pharmacokinetics of VPA and the relationships between VPA exposure and γ-GT elevation. A one-compartment model of the pharmacokinetic parameters of VPA adequately described the data; while the model for the probability of the γ-GT elevation was fitted using a logistic regression model, in which the logit function of the probability was a linear function of VPA exposure. The SOD2 Val16Ala polymorphism and complication with intellectual disability were found to be significant covariates influencing the intercept of the logit function for the probability of an elevated γ-GT level. The predicted mean percentages of the subjects with γ-GT elevation were about 2- to 3-fold, 3- to 4-fold and 4- to 8-fold greater in patients with the SOD2 Val/Val genotype but without any intellectual disability, those with the SOD2 Val/Ala or Ala/Ala genotype and intellectual disability and those with the SOD2 Val/Val genotype and intellectual disability, respectively, compared to those with the SOD2 Val/Ala or Ala/Ala genotype without intellectual disability. CONCLUSION: Our results showed that the SOD2 Val16Ala polymorphism has an impact on the relationship between VPA exposure and

  17. 5-氨基酮戊酸光动力疗法(ALA-PDT)治疗Bowen病的临床分析%Clinical analysis of 5-aminolevulinic acid photodynamic therapy (ALA-PDT)in the treatment of Bowen disease

    Institute of Scientific and Technical Information of China (English)

    熊林; 张晓燕; 张文娟; 陆延娜; 周晓凤; 万静; 魏亚东

    2012-01-01

    目的 分析5-氨基酮戊酸(ALA)光动力学疗法(PDT)治疗Bowen病的临床近期效果.方法 选择经病理组织学检查确诊为Bowen病患者23例,随机分为治疗组12例和对照组11例.治疗组皮损处局部外用20%ALA霜,3h后行红光照射,剂量为(100~120)J/cm2,照射时间约20~30 min,4周内每周照射1次.对照组每日外用5-氟尿嘧啶软膏(5-FU软膏)2次,用药4周.比较两组患者的临床疗效.结果 治疗组完全有效率91.67%,总有效率100%;对照组完全有效率27.27%,总有效率90.91%.治疗组的完全有效率明显优于对照组,两组间差异有统计学意义(P<0.01).结论 ALA-PDT治疗Bowen病简单有效、耐受性好,且无严重副作用,值得临床推广.

  18. ALA Pretreatment Improves Waterlogging Tolerance of Fig Plants.

    Directory of Open Access Journals (Sweden)

    Yuyan An

    Full Text Available 5-aminolevulinic acid (ALA, a natural and environmentally friendly plant growth regulator, can improve plant tolerance to various environmental stresses. However, whether ALA can improve plant waterlogging tolerance is unknown. Here, we investigated the effects of ALA pretreatment on the waterlogging-induced damage of fig (Ficus carica Linn. plants, which often suffer from waterlogging stress. ALA pretreatment significantly alleviated stress-induced morphological damage, increased leaf relative water content (RWC, and reduced leaf superoxide anion ([Formula: see text] production rate and malonaldehyde (MDA content in fig leaves, indicating ALA mitigates waterlogging stress of fig plants. We further demonstrated that ALA pretreatment largely promoted leaf chlorophyll content, photosynthetic electron transfer ability, and photosynthetic performance index, indicating ALA significantly improves plant photosynthetic efficiency under waterlogging stress. Moreover, ALA pretreatment significantly increased activities of leaf superoxide dismutase (SOD and peroxidase (POD, root vigor, and activities of root alcohol dehydrogenase (ADH, and lactate dehydrogenase (LDH, indicating ALA also significantly improves antioxidant ability and root function of fig plants under waterlogging stress. Taken together, ALA pretreatment improves waterlogging tolerance of fig plants significantly, and the promoted root respiration, leaf photosynthesis, and antioxidant ability may contribute greatly to this improvement. Our data firstly shows that ALA can improve plant waterlogging tolerance.

  19. Evaluation of the hepatic bioconversion of α-linolenic acid (ALA) to eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in rats fed with oils from chia (Salvia hispánica) or rosa mosqueta (Rosa rubiginosa)

    OpenAIRE

    Tapia O., G.; Valenzuela B., A.; Cornejo Z., P.; Vizcarra, M.; Masson S., L.; Gormáz, J. G.; Valenzuela B., R.

    2012-01-01

    The high dietary intake of n-6 fatty acids in relation to n-3 fatty acids generates health disorders, such as cardiovascular diseases, inflammatory diseases and other chronic diseases. The consumption of fish, which is rich in n-3 fatty acids, is low in Latin America and it is necessary to seek other alternatives, such as chia oil (CO) or rosa mosqueta oil (RMO), which are rich in α-linolenic acid (ALA), the precursor of the n -3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic ac...

  20. A single amino acid substitution (Trp(666)-->Ala) in the interbox1/2 region of the interleukin-6 signal transducer gp130 abrogates binding of JAK1, and dominantly impairs signal transduction.

    Science.gov (United States)

    Haan, C; Hermanns, H M; Heinrich, P C; Behrmann, I

    2000-07-01

    gp130 is the common signal-transducing receptor chain of interleukin (IL)-6-type cytokines. Here we describe, for the first time, a single amino acid substitution (Trp(666)-->Ala) in the membrane-proximal interbox1/2 region that abrogates activation of STAT (signal transducer and activator of transcription) transcription factors and the proliferative response of pro-B-cell transfectants. Moreover, association of the Janus kinase JAK1 is prevented. No signalling of heterodimeric IL-5 receptor (IL-5R)/gp130 chimaeras occurs in COS-7 cells, even when only a single cytoplasmic chain of a gp130 dimer contains the Trp(666)Ala mutation, indicating that it acts dominantly.

  1. Ala54Thr fatty acid-binding protein 2 (FABP2) polymorphism in recurrent depression : associations with fatty acid concentrations and waist circumference

    NARCIS (Netherlands)

    Mocking, Roel J T; Lok, Anja; Assies, Johanna; Koeter, Maarten W J; Visser, Ieke; Ruhe, Eric; Bockting, Claudi L H; Schene, Aart H

    2013-01-01

    BACKGROUND: Fatty acid (FA)-alterations may mediate the mutual association between Major Depressive Disorder (MDD) and cardiovascular disease (CVD). However, etiology of observed FA-alterations in MDD and CVD remains largely unclear. An interesting candidate may be a mutation in the fatty acid-bindi

  2. Antitumor effect of conditioned media derived from murine MSCs and 5-aminolevulinic acid (5-ALA) mediated photodynamic therapy in breast cancer in vitro.

    Science.gov (United States)

    Mohammadpour, Hemn; Majidzadeh-A, Keivan

    2015-06-01

    Mesenchymal stem cells are multi-potent progenitor cells that inhibit tumor growth by some ligands and releasing factors including TRAIL, DKK-1 and DKK-3. On other hands, photodynamic therapy is commonly used for treatment of different types of cancer. The aims of this study are to investigate of MSCs conditioned media and ALA mediated photodynamic therapy in breast cancer. Condition media was derived after documentation of mouse adipose derived MSCs. For photodynamic therapy (PDT), ALA was used at the final concentrations of 1mM for 4-h followed by exposure to red light with a peak wave length of 632-nm, delivered from diode laser located at 2 cm to achieve a total light dose of 5 Joules (J)/cm(2). Apoptosis and growth of 4T1 cancer cells were analyzed in different groups including MSCs derived condition media, PDT and MSCs derived condition media plus PDT by flow cytometry. Growth of cancer cells were assessed using MTT test. Our findings showed expression of TRAIL on mouse adipose-derived MSCs surfaces. Furthermore, treatment of 4T1 cancer cells with MSCs conditioned media cause to inhibit the cancer cells growth. Also, MSCs conditioned media with PDT have significantly synergic effects to induce apoptosis in breast cancer cells (P photodynamic therapy. This study showed that MSCs conditioned media combined with PDT may be useful as a novel treatment modality into the development of therapeutic strategies for treatment of breast cancer. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. THE ASSOCIATION OF Ala54Thr VARIANT OF INTESTINAL FATTY ACID BINDING PROTEIN GENE WITH GENERAL AND REGIONAL ADIPOSE TISSUE DEPOTS

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    Objective. To ascertain the relationship between the Ala54Thr variation of FABP2 gene and general as well as regional adipose tissue depots.Subjects. 165 subjects, in which 86 were subjects with normal glucose tolerance (NGT) [age 54.45±9.80, male/female 1.05,body mass index (BMI)26.48±4.01] and 79 were subjects with non-insulin-dependent diabetes mellitus (NIDDM)(age 55.86±10.00,male/female 1.08,BMI 26.75±3.30).Design and measurements. An association study of FABP2-Ala54Thr variation detected by PCR/HhaI digestion with general and regional adipose tissue depots determined by BMI and magnetic resonance imaging [abdominal subcutaneous and visceral adipose tissue area (SA and VA) and femoral subcutaneous adipose tissue area (FA)].Results. The geneotype and allele frequencies of FABP2-Ala54Thr variation in Chinese were quite close to the frequencies in American Caucasians and Pima Indians reported in the literature. Significant difference in genotype frequency distribution was observed between FA subgroups comparisons (FA≥75cm2 versus FA<75cm2)in NIDDM subjects (X2=11.460,P=0.003),with significantly increased in Thr54-carrier[Thr54(+)]genotype frequency and Thr54 allele frequency in NIDDM subject with FA<75cm2(odd ratio for genotype was 4.62,X2=10.112,P=0.001;and for allele=2.36,X2=5.379,P=0.020).The FA in NIDDM-Thr54(+)subgroup was significantly lower than that in subjects with NIDDM-Thr54(-)sugroup(61.19±21.51cm2 versus 75.36±31.70cm2,P=0.021). Stepwise regression analysis revealed that FABP2-Thr54 genotype variation was an independent factor contributing to the variation of FA in NIDDM(P=0.003).Conclusion. FABP2 is associated with regional adipose tissue depot.The decreased femoral subcutaneous adipose tissue depot in NIDDM subjects is related to FABP2-Thr54 variant.

  4. Topical aminolaevulinic acid- based photodynamic therapy as a treatment option for psoriasis? Results of a randomized, observer-blinded study%局部ALA-PDT是银屑病的一种治疗选择吗?随机双盲观察研究结果

    Institute of Scientific and Technical Information of China (English)

    Radakovic S-F; Blecha-Thalhammer; Schleyer V; 蔡宏

    2006-01-01

    @@ 背景与目的 银屑病是一种慢性、炎症性、增殖性皮肤疾病.原则上来说,由于氨基酮戊酸(aminolevulinic acid,ALA)光动力学疗法没有长期的副作用,如果该方法有效而且患者能够很好耐受,将是银屑病局部治疗的可选方法.本文的目的旨在探讨局部ALA-PDT治疗银屑病的可行性.

  5. ALA Conference 2009: Chicago Hope

    Science.gov (United States)

    Berry, John N., III

    2009-01-01

    There is joy among those who have the funds to go to Chicago for the American Library Association (ALA) annual conference, July 9-15. Every librarian knows there is nothing better than a Chicago gathering, with the city's wonderful haunts, museums, restaurants, and fine memories of past conferences. The conference program covers nearly every…

  6. Meie maa - Rehemaa / Terje Alas

    Index Scriptorium Estoniae

    Alas, Terje

    2005-01-01

    Aiakujundaja Toomas Türk ning käsitööõpetaja ja aiakujundaja Terje Alas on kolinud oma perega elama Raplamaale Rehemaa tallu ja vahendavad vana talu elluäratamist oma uueks koduks. Talukoha valikust, hoonetest, aiast ja esimestest sammudest aia uuendamisel. 7 ill

  7. Evidence for a Contribution of ALA Synthesis to Plastid-To-Nucleus Signaling

    Energy Technology Data Exchange (ETDEWEB)

    Czarnecki, Olaf; Gläßer, Christine; Chen, Jin-Gui; Mayer, Klaus F. X.; Grimm, Bernhard

    2012-01-01

    The formation of 5-aminolevulinic acid (ALA) in tetrapyrrole biosynthesis is widely controlled by environmental and metabolic feedback cues that determine the influx into the entire metabolic path. Because of its central role as the rate-limiting step, we hypothesized a potential role of ALA biosynthesis in tetrapyrrole-mediated retrograde signaling and exploited the direct impact of ALA biosynthesis on nuclear gene expression (NGE) by using two different approaches. Firstly, the Arabidopsis gun1, hy1 (gun2), hy2 (gun3), gun4 mutants showing uncoupled NGE from the physiological state of chloroplasts were thoroughly examined for regulatory modifications of ALA synthesis and transcriptional control in the nucleus. We found that reduced ALA-synthesizing capacity is common to analyzed gun mutants. Inhibition of ALA synthesis by gabaculine (GAB) that inactivates glutamate-1-semialdehyde aminotransferase and ALA feeding of wild-type and mutant seedlings corroborate the expression data of gun mutants. Transcript level of photosynthetic marker genes were enhanced in norflurazon (NF)-treated seedlings upon additional GAB treatment, while enhanced ALA amounts diminish these RNA levels in NF-treated wild-type in comparison to the solely NF-treated seedlings. Secondly, the impact of posttranslationally down-regulated ALA synthesis on NGE was investigated by global transcriptome analysis of GAB-treated Arabidopsis seedlings and the gun4-1 mutant, which is also characterized by reduced ALA formation. A common set of significantly modulated genes was identified indicating ALA synthesis as a potential signal emitter. The over-represented gene ontology categories of genes with decreased or increased transcript abundance highlight a few biological processes and cellular functions, which are remarkably affected in response to plastid-localized ALA biosynthesis. These results support the hypothesis that ALA biosynthesis correlates with retrograde signaling-mediated control of NGE.

  8. Evidence for a Contribution of ALA Synthesis to Plastid-To-Nucleus Signalling

    Directory of Open Access Journals (Sweden)

    Olaf eCzarnecki

    2012-10-01

    Full Text Available The formation of 5-aminolevulinic acid (ALA in tetrapyrrole biosynthesis is widely controlled by environmental and metabolic feedback cues that determine the influx into the entire metabolic path. Because of its central role as the rate-limiting step, we hypothesised a potential role of ALA biosynthesis in tetrapyrrole-mediated retrograde signalling and exploited the direct impact of ALA biosynthesis on nuclear gene expression (NGE by using two different approaches. Firstly, the Arabidopsis gun1, hy1 (gun2, hy2 (gun3, gun4 mutants showing uncoupled NGE from the physiological state of chloroplasts were thoroughly examined for regulatory modifications of ALA synthesis and transcriptional control in the nucleus. We found that reduced ALA-synthesising capacity is common to analysed gun mutants. Inhibition of ALA synthesis by gabaculine (GAB that inactivates glutamate-1-semialdhyde aminotransferase and ALA feeding of wild-type and mutant seedlings corroborate the expression data of gun mutants. Transcript level of photosynthetic marker genes were enhanced in norflurazon (NF-treated seedlings upon additional GAB treatment, while enhanced ALA amounts diminish these RNA levels in NF-treated wild-type in comparison to the solely NF-treated seedlings. Secondly, the impact of posttranslationally down-regulated ALA synthesis on NGE was investigated by global transcriptome analysis of GAB-treated Arabidopsis seedlings and the gun4-1 mutant, which is also characterized by reduced ALA formation. A common set of significantly modulated genes was identified indicating ALA synthesis as a potential signal emitter. The overrepresented gene ontology categories of genes with decreased or increased transcript abundance highlight a few biological processes and cellular functions, which are remarkably affected in response to plastid-localised ALA biosynthesis. These results support the hypothesis that ALA biosynthesis correlates with retrograde signalling

  9. Paradox of mistranslation of serine for alanine caused by AlaRS recognition dilemma.

    Science.gov (United States)

    Guo, Min; Chong, Yeeting E; Shapiro, Ryan; Beebe, Kirk; Yang, Xiang-Lei; Schimmel, Paul

    2009-12-10

    Mistranslation arising from confusion of serine for alanine by alanyl-tRNA synthetases (AlaRSs) has profound functional consequences. Throughout evolution, two editing checkpoints prevent disease-causing mistranslation from confusing glycine or serine for alanine at the active site of AlaRS. In both bacteria and mice, Ser poses a bigger challenge than Gly. One checkpoint is the AlaRS editing centre, and the other is from widely distributed AlaXps-free-standing, genome-encoded editing proteins that clear Ser-tRNA(Ala). The paradox of misincorporating both a smaller (glycine) and a larger (serine) amino acid suggests a deep conflict for nature-designed AlaRS. Here we show the chemical basis for this conflict. Nine crystal structures, together with kinetic and mutational analysis, provided snapshots of adenylate formation for each amino acid. An inherent dilemma is posed by constraints of a structural design that pins down the alpha-amino group of the bound amino acid by using an acidic residue. This design, dating back more than 3 billion years, creates a serendipitous interaction with the serine OH that is difficult to avoid. Apparently because no better architecture for the recognition of alanine could be found, the serine misactivation problem was solved through free-standing AlaXps, which appeared contemporaneously with early AlaRSs. The results reveal unconventional problems and solutions arising from the historical design of the protein synthesis machinery.

  10. Role of Fatty Acid-Binding Protein 2 Ala54Thr Genotype on Weight Loss and Cardiovascular Risk Factors after a High-Protein/Low-Carbohydrate versus a Standard Hypocaloric Diet during 9 Months.

    Science.gov (United States)

    de Luis, Daniel Antonio; Izaola, Olatz; de la Fuente, Beatriz; Primo, David; Romero, Enrique

    2015-01-01

    It has been found that the expression of fatty acid-binding protein 2 gene mRNA is under dietary control. The polymorphism Ala54Thr of this protein was associated with high insulin resistance. The aim of our study was to investigate the influence of Thr54 polymorphism on metabolic response, weight loss and serum adipokine levels secondary to high-protein/low-carbohydrate vs. standard hypocaloric diets during 9 months. A population of 193 obese subjects was analyzed in a randomized trial. A nutritional evaluation was performed at the beginning and at the end of a 9-month period in which subjects received 1 of 2 diets (diet HP: high-protein/low-carbohydrate vs. diet S: standard diet). With both diets and in both genotype groups, body mass index, weight, fat mass, waist circumference, systolic blood pressure and leptin levels decreased. With both diets and only in wild genotype (diet HP vs. diet S), glucose (-6.2 ± 2.1 vs. -4.9 ± 2.0 mg/dl; p metabolic response after weight loss than wild type non-A carriers obese, with a lack of decrease of LDL-cholesterol, glucose, insulin levels and HOMA-R. © 2015 S. Karger AG, Basel.

  11. The Ala/Ala genotype of PPARY Pro12 Ala polymorphism is associated with late onset of multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Lukić N.

    2013-01-01

    Full Text Available The function of peroxisome proliferator-activated receptor γ (PPARγ in immune regulation, as well as in antiinflammatory and anti-proliferative actions towards T lymphocytes, has been reported. A potential role of PPARs in multiple sclerosis (MS was suggested. The aim of this study was to investigate if there is an association of PPARγ-2 Pro12Ala polymorphism with MS in 361 patients from Serbia. The genotype and allele frequencies of Pro12Ala polymorphism were not significantly different between controls and patients, or between females and males. In contrast to controls, we detected a rare Ala/Ala genotype in patients with MS. We found that there is a significant association of Ala/Ala genotype with older age at onset (ANOVA, p=0.07; LSD post-hoc, Ala/Ala vs. Pro/Ala, p=0.03, Ala/Ala vs. Pro/Pro p=0.02. It would be useful to validate our results in other populations, as well as to perform follow-up of the disease progression in regard to PPARγ genotypes. [Projekat Ministarstva nauke Republike Srbije, br. 175085

  12. On the ALA Membership Pyramid

    Directory of Open Access Journals (Sweden)

    Emily Ford

    2008-10-01

    Full Text Available “…i [sic] only renew [my ALA membership] out of a sense of professional obligation, and also because of the fear that i’ll [sic] put it on my resume and get busted as not being a member.” –c-dog Membership in the American Library Association means professionals are bound together by the tenets of librarianship. Technically, this [...

  13. 5-ALA based photodynamic management of glioblastoma

    Science.gov (United States)

    Rühm, Adrian; Stepp, Herbert; Beyer, Wolfgang; Hennig, Georg; Pongratz, Thomas; Sroka, Ronald; Schnell, Oliver; Tonn, Jörg-Christian; Kreth, Friedrich-Wilhelm

    2014-03-01

    Objective: Improvement of the clinical outcome of glioblastoma (GBM) patients by employment of fluorescence and photosensitization on the basis of 5-aminolevulinic acid (5-ALA) induced protoporphyrin IX (PpIX). Methods: In this report the focus is laid on the use of tumor selective PpIX fluorescence for stereotactic biopsy sampling and intra-operative treatment monitoring. In addition, our current concept for treatment planning is presented. For stereotactic interstitial photodynamic therapy (iPDT), radial diffusers were implanted into the contrast enhancing tumor volume. Spectroscopic measurements of laser light transmission and fluorescence between adjacent fibers were performed prior, during and post PDT. Results: PpIX concentrations in primary glioblastoma tissue show high intra- and inter-patient variability, but are usually sufficient for an effective PDT. During individual treatment attempts with 5-ALA based GBM-iPDT, transmission and fluorescence measurements between radial diffusers gave the following results: 1. In some cases, transmission after PDT is considerably reduced compared to the value before PDT, which may be attributable to a depletion of oxygenated hemoglobin and/or diffuse bleeding. 2. PpIX fluorescence is efficiently photobleached during PDT in all cases. Conclusion: iPDT with assessment of PpIX fluorescence and photobleaching is a promising treatment option. Individualization of treatment parameters appears to bear a potential to further improve clinical outcomes.

  14. Fluorescence-Guided Resection of Malignant Glioma with 5-ALA

    Directory of Open Access Journals (Sweden)

    Sadahiro Kaneko

    2016-01-01

    Full Text Available Malignant gliomas are extremely difficult to treat with no specific curative treatment. On the other hand, photodynamic medicine represents a promising technique for neurosurgeons in the treatment of malignant glioma. The resection rate of malignant glioma has increased from 40% to 80% owing to 5-aminolevulinic acid-photodynamic diagnosis (ALA-PDD. Furthermore, ALA is very useful because it has no serious complications. Based on previous research, it is apparent that protoporphyrin IX (PpIX accumulates abundantly in malignant glioma tissues after ALA administration. Moreover, it is evident that the mechanism underlying PpIX accumulation in malignant glioma tissues involves an abnormality in porphyrin-heme metabolism, specifically decreased ferrochelatase enzyme activity. During resection surgery, the macroscopic fluorescence of PpIX to the naked eye is more sensitive than magnetic resonance imaging, and the alert real time spectrum of PpIX is the most sensitive method. In the future, chemotherapy with new anticancer agents, immunotherapy, and new methods of radiotherapy and gene therapy will be developed; however, ALA will play a key role in malignant glioma treatment before the development of these new treatments. In this paper, we provide an overview and present the results of our clinical research on ALA-PDD.

  15. Non-Conserved Residues in Clostridium acetobutylicum tRNAAla Contribute to tRNA Tuning for Efficient Antitermination of the alaS T Box Riboswitch

    Directory of Open Access Journals (Sweden)

    Liang-Chun Liu

    2015-09-01

    Full Text Available The T box riboswitch regulates expression of amino acid-related genes in Gram-positive bacteria by monitoring the aminoacylation status of a specific tRNA, the binding of which affects the folding of the riboswitch into mutually exclusive terminator or antiterminator structures. Two main pairing interactions between the tRNA and the leader RNA have been demonstrated to be necessary, but not sufficient, for efficient antitermination. In this study, we used the Clostridium acetobutylicum alaS gene, which encodes alanyl-tRNA synthetase, to investigate the specificity of the tRNA response. We show that the homologous C. acetobutylicum tRNAAla directs antitermination of the C. acetobutylicum alaS gene in vitro, but the heterologous Bacillus subtilis tRNAAla (with the same anticodon and acceptor end does not. Base substitutions at positions that vary between these two tRNAs revealed synergistic and antagonistic effects. Variation occurs primarily at positions that are not conserved in tRNAAla species, which indicates that these non-conserved residues contribute to optimal antitermination of the homologous alaS gene. This study suggests that elements in tRNAAla may have coevolved with the homologous alaS T box leader RNA for efficient antitermination.

  16. Enhanced photodynamic efficacy of PLGA-encapsulated 5-ALA nanoparticles in mice bearing Ehrlich ascites carcinoma

    Science.gov (United States)

    Shaker, Maryam N.; Ramadan, Heba S.; Mohamed, Moustafa M.; El khatib, Ahmed M.; Roston, Gamal D.

    2014-10-01

    Nanoparticles (NPs) fabricated from the biodegradable copolymer poly(lactic- co-glycolic acid) (PLGA) were investigated as a drug delivery system to enhance the photodynamic efficacy of 5-aminolevulinic acid (5-ALA) in mice bearing Ehrlich ascites carcinoma. The PLGA-encapsulated 5-ALA NPs were prepared using binary organic solvent diffusion method and characterized in terms of shape and particle size. The in vivo photodynamic efficiency in Ehrlich ascites-bearing mice was studied. The obtained particles were uniform in size with spherical shape of mean size of 249.5 nm as obtained by particle size analyzer and the in vitro release studies demonstrated a controlled release profile of 5-ALA. Tumor-bearing mice injected with PLGA-encapsulated 5-ALA NPs exhibited significantly smaller mean tumor volume, increased tumor growth delay compared with the control group and the group injected with free 5-ALA during the time course of the experiment. Histopathological examination of tumor from mice treated with PLGA-encapsulated 5-ALA NPs showed regression of tumor cells, in contrast to those obtained from mice treated with free 5-ALA. The results indicate that PLGA-encapsulated 5-ALA NPs are a successful delivery system for improving photodynamic activity in the target tissue.

  17. Cold-knife conization versus photodynamic therapy with topical 5-aminolevulinic acid (5-ALA) in cervical intraepithelial neoplasia (CIN) II with associated human papillomavirus infection: a comparison of preliminary results.

    Science.gov (United States)

    Bodner, Klaus; Bodner-Adler, Barbara; Wierrani, Franz; Kubin, Andreas; Szölts-Szölts, Josef; Spängler, Babette; Grünberger, Werner

    2003-01-01

    The optimal treatment of preinvasive cervical lesions is still not clear as all surgical techniques cause substantial cervical stroma destruction with the risk of a possible incompetent cervix. Photodynamic therapy can preserve fertility due to selective tissue destruction. The aim of the present study was to compare the efficacy of cold-knife conization versus photodynamic therapy with topical 5-aminolevulinic acid in eradicating cervical intraepithelial neoplasia (CIN) II and associated HPV infection. Eleven HPV-positive non-pregnant women were selected for photodynamic therapy (PDT). To be eligible for this procedure superficial cervical PAP smears as well as colposcopic biopsies performed before therapy had to show CIN II with the lesion involving at least 15% of the cervix and being colposcopically visible. The deep endocervical PAP smear had to show normal endocervical epithelium. The next (following each PDT) 11 HPV-positive women with CIN II treated with cold-knife conization were used as a control group. The cervical sampling for HPV DNA was performed 3 months after conization and PDT. Patients were followed-up for 1 year with cytological smears and colposcopy at the outpatient department of the hospital. Follow-up at three months revealed that HPV was eradicated by both techniques in 73%. After 12 months follow-up, 100 vs. 91% (conization vs. PDT) of the patients were disease-free. No systemic side-effects and no local necrosis, sloughing or scarring occurred due to PDT. One patient treated with PDT presented with a relapsing suspicious PAP smear and an abnormal white colposcopic lesion after application of acetic acid 6 months post-PDT. A subsequent conization was performed and revealed a CIN I lesion. No statistically significant differences concerning HPV eradication (p > 0.05) and recurrence (p > 0.05) could be observed between the two methods. The results presented in this study indicate that topical PDT with 5-ALA is in most cases a successful

  18. ALAS2 acts as a modifier gene in patients with congenital erythropoietic porphyria.

    Science.gov (United States)

    To-Figueras, Jordi; Ducamp, Sarah; Clayton, Jerome; Badenas, Celia; Delaby, Constance; Ged, Cecile; Lyoumi, Said; Gouya, Laurent; de Verneuil, Hubert; Beaumont, Carole; Ferreira, Gloria C; Deybach, Jean-Charles; Herrero, Carmen; Puy, Herve

    2011-08-11

    Mutations in the uroporphyrinogen III synthase (UROS) gene cause congenital erythropoietic porphyria (CEP), an autosomal-recessive inborn error of erythroid heme biosynthesis. Clinical features of CEP include dermatologic and hematologic abnormalities of variable severity. The discovery of a new type of erythroid porphyria, X-linked dominant protoporphyria (XLDPP), which results from increased activity of 5-aminolevulinate synthase 2 (ALAS2), the rate-controlling enzyme of erythroid heme synthesis, led us to hypothesize that the CEP phenotype may be modulated by sequence variations in the ALAS2 gene. We genotyped ALAS2 in 4 unrelated CEP patients exhibiting the same C73R/P248Q UROS genotype. The most severe of the CEP patients, a young girl, proved to be heterozygous for a novel ALAS2 mutation: c.1757 A > T in exon 11. This mutation is predicted to affect the highly conserved and penultimate C-terminal amino acid of ALAS2 (Y586). The rate of 5-aminolevulinate release from Y586F was significantly increased over that of wild-type ALAS2. The contribution of the ALAS2 gain-of-function mutation to the CEP phenotype underscores the importance of modifier genes underlying CEP. We propose that ALAS2 gene mutations should be considered not only as causative of X-linked sideroblastic anemia (XLSA) and XLDPP but may also modulate gene function in other erythropoietic disorders.

  19. Combination therapies in adjuvant with topical ALA-mediated photodynamic therapy for DMBA-induced hamster buccal pouch premalignant lesions

    Science.gov (United States)

    Yang, Deng-Fu; Hsu, Yih-Chih

    2012-03-01

    In Taiwan, oral cancer has becomes the fastest growth male cancer disease due to the betel nut chewing habit combing with smoking and alcohol-drinking lifestyle of people. In order to eliminate the systemic phototoxic effect of 5-aminolevulinic acid (ALA), this study was designed to use a topical ALA-mediated PDT for treatment of DMBA-induced hamster buccal pouch precancerous lesions. DMBA was applied to one of the buccal pouches of hamsters thrice a week for 10 to 12 weeks. Cancerous lesions were induced and proven by histological examination. These DMBA-induced cancerous lesions were used for testing the efficacy of topical ALA-mediated PDT. Before PDT, fluorescence spectroscopy was used to determine when ALA reached its peak level in the lesional epithelial cells after topical application of ALA gel. We found that ALA reached its peak level in precancerous lesions about 2.5 hrs after topical application of ALA gel. The cancerous lesions in hamsters were then treated with topical ALA -mediated PDT with light exposure dose of 150 J/cm2 using LED 635 nm fiber-guided light device. Visual examination demonstrated that adjuvant topical ALA -mediated PDT group has shown better therapeutic results in compared to those of non-adjuvant topical ALA-mediated PDT group for DMBA-induced hamster buccal pouch precancerous lesions.

  20. Light Fractionation Significantly Increases the Efficacy of Photodynamic Therapy Using BF-200 ALA in Normal Mouse Skin.

    NARCIS (Netherlands)

    H.S. de Bruijn (Riette); S. Brooks (Sander); A. van der Ploeg-van den Heuvel (Angélique); T.L.M. ten Hagen (Timo); E.R.M. de Haas (Ellen); D.J. Robinson (Dominic)

    2016-01-01

    markdownabstractBACKGROUND: Light fractionation significantly increases the efficacy of 5-aminolevulinic acid (ALA) based photodynamic therapy (PDT) using the nano-emulsion based gel formulation BF-200. PDT using BF-200 ALA has recently been clinically approved and is under investigation in several

  1. A prevalent amino acid polymorphism at codon 98 (Ala98Val) of the hepatocyte nuclear factor-1alpha is associated with maturity-onset diabetes of the young and younger age at onset of type 2 diabetes in Asian Indians

    DEFF Research Database (Denmark)

    Anuradha, Shekher; Radha, Venkatesan; Deepa, Raj

    2005-01-01

    Among Europeans, mutations in the hepatocyte nuclear factor-1alpha (HNF1alpha) gene are associated with the most common form of maturity-onset diabetes of the young (MODY)3. In Asian Indians, type 2 diabetes occurs earlier and often overlaps with MODY, but the genetics of the latter are unknown. ....... The aim of this study was to estimate the prevalence of Ala98Val polymorphism of the HNF1alpha gene in different types of diabetes in Asian Indians....

  2. PPAR2Pro12Ala Polymorphism and Human Health

    Directory of Open Access Journals (Sweden)

    Weimin He

    2009-01-01

    Full Text Available The nuclear hormone receptor peroxisome proliferator activated receptor gamma (PPAR is an important transcription factor regulating adipocyte differentiation, lipid and glucose homeostasis, and insulin sensitivity. Numerous genetic mutations of PPAR have been identified and these mutations positively or negatively regulate insulin sensitivity. Among these, a relatively common polymorphism of PPAR, Pro12Ala of PPAR2, the isoform expressed only in adipose tissue has been shown to be associated with lower body mass index, enhanced insulin sensitivity, and resistance to the risk of type 2 diabetes in human subjects carrying this mutation. Subsequent studies in different ethnic populations, however, have revealed conflicting results, suggesting a complex interaction between the PPAR2 Pro12Ala polymorphism and environmental factors such as the ratio of dietary unsaturated fatty acids to saturated fatty acids and/or between the PPAR2 Pro12Ala polymorphism and genetic factors such as polymorphic mutations in other genes. In addition, this polymorphic mutation in PPAR2 is associated with other aspects of human diseases, including cancers, polycystic ovary syndrome, Alzheimer disease and aging. This review will highlight findings from recent studies.

  3. The role of DAMPS in ALA-PDT for skin squamous cell carcinoma (Conference Presentation)

    Science.gov (United States)

    Wang, Xiuli; Wang, Xiaojie; Ji, Jie; Zhang, Haiyan; Shi, Lei

    2016-03-01

    5-Aminolevulinic acid mediated photodynamic therapy (ALA-PDT) is an established local approach for skin squamous cell carcinoma. It is believed that dangerous signals damage-associated molecular patterns (DAMPs) play an important role in ALA-PDT. In this study, we evaluated in vitro and in vivo expressions of major DAMPs, calreticulin (CRT), heat shock proteins 70 (HSP70), and high mobility group box 1 (HMGB1), induced by ALA-PDT using immunohistochemistry, western blot, and ELISA in a squamous cell carcinoma (SCC) mouse model. The role of DAMPs in the maturation of DCs potentiated by ALA-PDT-treated tumor cells was detected by FACS and ELISA. Our results showed that ALA-PDT enhanced the expression of CRT, HSP70, and HMGB1. These induced DAMPs played an important role in activating DCs by PDT-treated tumor cells, including phenotypic maturation (upregulation of surface expression of MHC-II, CD80, and CD86) and functional maturation (enhanced capability to secrete IFN-γ and IL-12). Furthermore, injecting ALA-PDT-treated tumor cells into naïve mice resulted in complete protection against cancer cells of the same origin. Our findings indicate that ALA-PDT can upregulate DAMPs and enhance tumor immunogenicity, providing a promising strategy for inducing a systemic anticancer immune response.

  4. Molecular mechanisms associated with ALA-PDT of brain tumor cells

    Science.gov (United States)

    Alqawi, Omar; Espiritu, Myrna; Singh, Gurmit

    2009-06-01

    Previous studies have shown that low-dose PDT using 5-aminolevulinic acid (ALA)-induced photoporphyrin IX (PpIX) can induce apoptosis in tumor cells without causing necrosis. In this study we investigated the molecular mechanisms associated with apoptosis after ALA-PDT treatment in two brain glioma cell lines: human U87, and rat CNS-1cells. We used high energy light at a short time (acute PDT) and low energy light at a long time of exposure (metronomic PDT) to treat both cell lines. The cells were treated with 0.25 mM ALA at 5 joules for energy. We found that CNS-1 cells were more resistant to ALA-PDT than U87 cells when treated by both acute and metronomic PDT. To screen possible apoptosis mechanisms associated with acute and metronomic PDT, microarray analysis of gene expression was performed on RNA from glioblastoma cells treated with either acute or metronomic ALA-PDT. Within the set of genes that were negatively or positively regulated by both treatments are tumor necrosis factor receptors. The expression of TNF receptors was investigated further by RT-PCR and western blotting. The apoptosis mechanism of the cell death occurred through different pathways including BCL-2 and TNF receptors, and in part caused by cleaving caspase 3. Interestingly, metronomic ALA-PDT inhibited the expression of LTβR and the transcription factor NFκB. This inhibition was ALA concentration dependent at low concentrations.

  5. Balti jaama taha uus elurajoon / Askur Alas

    Index Scriptorium Estoniae

    Alas, Askur, 1973-

    2005-01-01

    Põhja-Tallinnas raudteeharude vahelisele maa-alale Balti jaama taha kavandatud elurajoonist. Detailplaneeringu eskiisi tegi Tõnu Laigu. Tallinna üldplaneeringu kohaselt jääb planeeritav ala kesklinna kontakttsooni arenguvööndisse

  6. ALA glossary of library and information science

    CERN Document Server

    Levine-Clark, Michael

    2013-01-01

    This fourth edition of ALA Glossary of Library and Information Science presents a thorough yet concise guide to the specific words that describe the materials, processes and systems relevant to the field of librarianship.

  7. Comparison of {sup 18}F-FET PET and 5-ALA fluorescence in cerebral gliomas

    Energy Technology Data Exchange (ETDEWEB)

    Floeth, Frank Willi; Sabel, Michael; Steiger, Hans Jakob [Heinrich Heine University, Department of Neurosurgery, Duesseldorf (Germany); Ewelt, Christian; Stummer, Walter [Westfaelische Wilhelms University, Department of Neurosurgery, Muenster (Germany); Felsberg, Joerg; Reifenberger, Guido [Heinrich Heine University, Department of Neuropathology, Duesseldorf (Germany); Stoffels, Gabriele; Langen, Karl-Josef [Medical Imaging Physics, Forschungszentrum Juelich, Institute of Neuroscience and Medicine 4, Juelich (Germany); Coenen, Heinz Hubert [Nuclear Chemistry, Forschungszentrum Juelich, Institute of Neuroscience and Medicine 5, Juelich (Germany)

    2011-04-15

    The aim of the study was to compare presurgical {sup 18}F-fluoroethyl-L-tyrosine ({sup 18}F-FET) uptake and Gd-diethylenetriaminepentaacetic acid (DTPA) enhancement on MRI (Gd) with intraoperative 5-aminolevulinic acid (5-ALA) fluorescence in cerebral gliomas. {sup 18}F-FET positron emission tomography (PET) was performed in 30 patients with brain lesions suggestive of diffuse WHO grade II or III gliomas on MRI. PET and MRI data were coregistered to guide neuronavigated biopsies before resection. After oral application of 5-ALA, 38 neuronavigated biopsies were taken from predefined tumour areas that were positive or negative for {sup 18}F-FET or Gd and checked for 5-ALA fluorescence. {sup 18}F-FET uptake with a mean tumour to brain ratio {>=}1.6 was rated as positive. Of 38 biopsies, 21 corresponded to high-grade glioma tissue (HGG) of WHO grade III (n = 19) or IV (n = 2) and 17 biopsies to low-grade glioma tissue (LGG) of WHO grade II. In biopsies corresponding to HGG, {sup 18}F-FET PET was positive in 86% (18/21), but 5-ALA and Gd in only 57% (12/21). A mismatch between Gd and 5-ALA was observed in 6 of 21 cases of HGG biopsy samples (3 Gd-positive/5-ALA-negative and 3 Gd-negative/5-ALA-positive). In biopsies corresponding to LGG, {sup 18}F-FET was positive in 41% (7/17), while 5-ALA and Gd were negative in all but one instance. All tumour areas with 5-ALA fluorescence were positive on {sup 18}F-FET PET. There are differences between {sup 18}F-FET and 5-ALA uptake in cerebral gliomas owing to a limited sensitivity of 5-ALA to detect tumour tissue especially in LGG. {sup 18}F-FET PET is more sensitive to detect glioma tissue than 5-ALA fluorescence and should be considered as an additional tool in resection planning. (orig.)

  8. Immobilization of ALA-Zn(II) Coordination Polymer Pro-photosensitizers on Magnetite Colloidal Supraparticles for Target Photodynamic Therapy of Bladder Cancer.

    Science.gov (United States)

    Tan, Jing; Sun, Chuanyu; Xu, Ke; Wang, Changchun; Guo, Jia

    2015-12-16

    5-Aminolevulinic acid (ALA) is a widely used photodynamic therapy (PDT) prodrug in the clinic. It can be metalized to the photosensitizer PpIX, which produces toxic singlet oxygen to kill cancer cells upon visible light irradiation. Herein, a core/shell-structured vehicle is designed to comprise magnetite colloidal supraparticles (MCSPs) as cores and ALA-Zn(II) coordination polymers as shells (Fe3O4@ALA-Zn(II) ) for target pro-photosensitizer delivery. The coordination polymers with 2D layered structures are locally deposited on the MCSPs by the complexation of the ALA and Zn(II) ions, and are readily controlled by varying the feed precursors and reaction temperatures. The maximum conjugated ALA amount is up to 17%. The Fe3O4@ALA-Zn(II) microspheres exhibit pH-sensitive release of ALA in acidic environment and rapid magnetic responsiveness. Cytotoxicity results demonstrate that Fe3O4@ALA-Zn(II) shows a significant inhibitory effect to T24 cells and is nontoxic to 293T normal cells as exposed to the 630 nm visible light for a very short time, which may due to the selective accumulation of ALA-induced PpIX in T24 cancer cells. Compared to the ALA used alone, the coordination polymer form is more efficient because of the bioactivity of incorporated Zn ions despite underlying the same apoptosis mechanism as ALA agent.

  9. Supplementation of milled chia seeds increases plasma ALA and EPA in postmenopausal women.

    Science.gov (United States)

    Jin, Fuxia; Nieman, David C; Sha, Wei; Xie, Guoxiang; Qiu, Yunping; Jia, Wei

    2012-06-01

    Ten postmenopausal women (age 55.6 ± 0.8 years, BMI 24.6 ± 1.1 kg/m²) ingested 25 g/day milled chia seed during a 7-week period, with six plasma samples collected for measurement of α-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA). Subjects operated as their own controls with overnight fasted blood samples taken at baseline (average of two samples), and then after 1, 2, 3, 5, and 7 weeks supplementation. Plasma ALA increased significantly after one week supplementation and was 138 % above baseline levels by the end of the study (overall time effect, P chia seeds for seven weeks by postmenopausal women resulted in significant increases in plasma ALA and EPA but not DPA and DHA.

  10. Towards understanding the tandem mass spectra of protonated oligopeptides. 2: The proline effect in collision-induced dissociation of protonated Ala-Ala-Xxx-Pro-Ala (Xxx = Ala, Ser, Leu, Val, Phe, and Trp).

    Science.gov (United States)

    Bleiholder, Christian; Suhai, Sándor; Harrison, Alex G; Paizs, Béla

    2011-06-01

    The product ion spectra of proline-containing peptides are commonly dominated by y(n) ions generated by cleavage at the N-terminal side of proline residues. This proline effect is investigated in the current work by collision-induced dissociation (CID) of protonated Ala-Ala-Xxx-Pro-Ala (Xxx includes Ala, Ser, Leu, Val, Phe, and Trp) in an electrospray/quadrupole/time-of-flight (QqTOF) mass spectrometer and by quantum chemical calculations on protonated Ala-Ala-Ala-Pro-Ala. The CID spectra of all investigated peptides show a dominant y(2) ion (Pro-Ala sequence). Our computational results show that the proline effect mainly arises from the particularly low threshold energy for the amide bond cleavage N-terminal to the proline residue, and from the high proton affinity of the proline-containing C-terminal fragment produced by this cleavage. These theoretical results are qualitatively supported by the experimentally observed y(2)/b(3) abundance ratios for protonated Ala-Ala-Xxx-Pro-Ala (Xxx = Ala, Ser, Leu, Val, Phe, and Trp). In the post-cleavage phase of fragmentation the N-terminal oxazolone fragment with the Ala-Ala-Xxx sequence and Pro-Ala compete for the ionizing proton for these peptides. As the proton affinity of the oxazolone fragment increases, the y(2)/b(3) abundance ratio decreases.

  11. Towards Understanding the Tandem Mass Spectra of Protonated Oligopeptides. 2: The Proline Effect in Collision-Induced Dissociation of Protonated Ala-Ala-Xxx-Pro-Ala (Xxx = Ala, Ser, Leu, Val, Phe, and Trp)

    Science.gov (United States)

    Bleiholder, Christian; Suhai, Sándor; Harrison, Alex G.; Paizs, Béla

    2011-06-01

    The product ion spectra of proline-containing peptides are commonly dominated by y n ions generated by cleavage at the N-terminal side of proline residues. This proline effect is investigated in the current work by collision-induced dissociation (CID) of protonated Ala-Ala-Xxx-Pro-Ala (Xxx includes Ala, Ser, Leu, Val, Phe, and Trp) in an electrospray/quadrupole/time-of-flight (QqTOF) mass spectrometer and by quantum chemical calculations on protonated Ala-Ala-Ala-Pro-Ala. The CID spectra of all investigated peptides show a dominant y 2 ion (Pro-Ala sequence). Our computational results show that the proline effect mainly arises from the particularly low threshold energy for the amide bond cleavage N-terminal to the proline residue, and from the high proton affinity of the proline-containing C-terminal fragment produced by this cleavage. These theoretical results are qualitatively supported by the experimentally observed y 2 / b 3 abundance ratios for protonated Ala-Ala-Xxx-Pro-Ala (Xxx = Ala, Ser, Leu, Val, Phe, and Trp). In the post-cleavage phase of fragmentation the N-terminal oxazolone fragment with the Ala-Ala-Xxx sequence and Pro-Ala compete for the ionizing proton for these peptides. As the proton affinity of the oxazolone fragment increases, the y 2 / b 3 abundance ratio decreases.

  12. Production of eicosapentaenoic acid by mortierella spp on barley spent grain

    CSIR Research Space (South Africa)

    Jacobs, A

    2006-02-01

    Full Text Available PUFAs convert α- linolenic acid (ALA) into EPA.In this study, the substrate was supplemented with linseed oil (containing approximately 60% ALA) to determine the effect of ALA on growth and PUFA production...

  13. Accumulation of porphyrins in Propionibacterium acnes by 5-aminolevulinic acid and its esters.

    Science.gov (United States)

    Ogata, Arisa; Hasunuma, Yuya; Kikuchi, Emii; Ishii, Takuya; Ishizuka, Masahiro; Tokuoka, Yoshikazu

    2017-09-01

    We have investigated the accumulation of porphyrins in Propionibacterium acnes (P.acnes) by 5-aminolevulinic acid hydrochloride (ALA) and its esters, ALA methyl ester hydrochloride (mALA), ALA octyl ester hydrochloride (oALA), and ALA benzyl ester hydrochloride (bALA). From the fluorescence spectra of porphyrins accumulated in P.acnes, the order of porphyrin accumulation is as follows: ALA≫mALA≈bALA>oALA (≈0). Moreover, the PDT efficacy is reduced in the order of ALA>mALA≈bALA>oALA (≈without additives). These results confirm that ALA is superior to ALA esters in accumulating porphyrins in P.acnes. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Pro-oxidant effect of ALA is implicated in mitochondrial dysfunction of HepG2 cells.

    Science.gov (United States)

    Laafi, Jihane; Homedan, Chadi; Jacques, Caroline; Gueguen, Naig; Schmitt, Caroline; Puy, Hervé; Reynier, Pascal; Carmen Martinez, Maria; Malthièry, Yves

    2014-11-01

    Heme biosynthesis begins in the mitochondrion with the formation of delta-aminolevulinic acid (ALA). In acute intermittent porphyria, hereditary tyrosinemia type I and lead poisoning patients, ALA is accumulated in plasma and in organs, especially the liver. These diseases are also associated with neuromuscular dysfunction and increased incidence of hepatocellular carcinoma. Many studies suggest that this damage may originate from ALA-induced oxidative stress following its accumulation. Using the MnSOD as an oxidative stress marker, we showed here that ALA treatment of cultured cells induced ROS production, increasing with ALA concentration. The mitochondrial energetic function of ALA-treated HepG2 cells was further explored. Mitochondrial respiration and ATP content were reduced compared to control cells. For the 300 μM treatment, ALA induced a mitochondrial mass decrease and a mitochondrial network imbalance although neither necrosis nor apoptosis were observed. The up regulation of PGC-1, Tfam and ND5 genes was also found; these genes encode mitochondrial proteins involved in mitochondrial biogenesis activation and OXPHOS function. We propose that ALA may constitute an internal bioenergetic signal, which initiates a coordinated upregulation of respiratory genes, which ultimately drives mitochondrial metabolic adaptation within cells. The addition of an antioxidant, Manganese(III) tetrakis(1-methyl-4-pyridyl)porphyrin (MnTMPyP), resulted in improvement of maximal respiratory chain capacity with 300 μM ALA. Our results suggest that mitochondria, an ALA-production site, are more sensitive to pro-oxidant effect of ALA, and may be directly involved in pathophysiology of patients with inherited or acquired porphyria. Copyright © 2014 Elsevier B.V. and Société française de biochimie et biologie Moléculaire (SFBBM). All rights reserved.

  15. Topical application of ALA PDT for the treatment of moderate to severe acne vulgaris

    Science.gov (United States)

    Wang, Xiu-Li; Wang, Hong-Wei; Zhang, Ling-Lin; Su, Lina; Guo, Ming-Xia; Huang, Zheng

    2009-06-01

    Objectives: To evaluate the effectiveness of topical 5-aminolevulinic acid (ALA)- medicated photodynamic therapy (ALA PDT) for the treatment of moderate to severe acne vulgaris. Methods: Sixteen Chinese patients with moderate to severe facial acne were treated with 1-3 courses of ALA PDT. ALA cream (3%) was freshly prepared and applied to acne lesions for 3-4 h. The lesions were irradiated by a 635 nm diode laser at dose levels of 60 - 80 J/cm2 at 100 mW/cm2. Clinical assessments were conducted before and after treatment up to 3 months. Results: All patents showed response to ALA PDT. Complete clearance was seen in 10 patients (62.5%) and partial clearance in 6 patients (37.5%). One case showed recurrence after complete clearance at 2 months and another two showed recurrence after complete clearance at 3 months. However, the number of new lesions were significantly reduced. Adverse effects were minimal. Conclusions: The results of this preliminary clinical study is encouraging. ALA PDT is a simple, safe and useful therapeutic option for the treatment of moderate to severe acne. Further studies to evaluate the treatment with a larger number of patients and for a longer period of follow-up are needed.

  16. ALA-PDT of glioma cell micro-clusters in BD-IX rat brain

    Science.gov (United States)

    Madsen, Steen J.; Angell-Petersen, Even; Spetalen, Signe; Carper, Stephen W.; Ziegler, Sarah A.; Hirschberg, Henry

    2006-02-01

    A significant contributory factor to the poor prognosis of patients with glioblastoma multiforme is the inability of conventional treatments to eradicate infiltrating glioma cells. A syngeneic rat brain tumor model is used to investigate the effects of aminolevulinic acid (ALA)-mediated photodynamic therapy (PDT) on small clusters of tumor cells sequestered in normal brain. The intrinsic sensitivity of rat glioma cells to PDT was investigated by exposing ALA-incubated cells to a range of radiant exposures and irradiances using 635 nm light. Biodistribution studies were undertaken on tumor-bearing animals in order to determine the tumor selectivity of the photosensitizer following systemic administration (i.p.) of ALA. Effects of ALA-PDT on normal brain and gross tumor were evaluated using histopathology. Effects of PDT on isolated glioma cells in normal brain were investigated by treating animals 48 h after tumor cell implantation: a time when the micro-clusters of cells are protected by an intact blood-brain-barrier (BBB). Rat glioma cells in monolayer are susceptible to ALA-PDT - lower irradiances are more effective than higher ones. Fluorescence microscopy of frozen tissue sections showed that photosensitizer is produced with better than 200:1 tumor-to-normal tissue selectivity following i.p. ALA administration. ALA-PDT resulted in significant damage to both gross tumor and normal brain, however, the treatment failed to prolong survival of animals with newly implanted glioma cells compared to non-treated controls if the drug was delivered either i.p. or directly into the brain. In contrast, animals inoculated with tumor cells pre-incubated in vitro with ALA showed a significant survival advantage in response to PDT.

  17. Photodynamic therapy with low-strength ALA, repeated applications and short contact periods (40-60 minutes) in acne, photoaging and vitiligo.

    Science.gov (United States)

    Serrano, Gabriel; Lorente, Matilde; Reyes, Madga; Millán, Fernando; Lloret, Adrián; Melendez, Joaquín; Navarro, Maria; Navarro, Miguel

    2009-06-01

    Topical aminolevulinic acid (ALA) photodynamic therapy (PDT) is currently being used for the treatment of actinic keratosis of the face and scalp. This study reports the results obtained after three to four treatments with ALA-PDT in patients with acne (n=12), photoaging (n=8) and vitiligo (n=6). ALA was applied on large areas (e.g., full face) and at very low strengths (1-2%). Side effects were minimal and self-limited.

  18. ALA 2010: Where to Eat in DC

    Science.gov (United States)

    Library Journal, 2010

    2010-01-01

    As host to visitors and transplants from around the world, Washington, DC, benefits from the constant infusion of different cultures. Although most neighborhoods lack a unified culinary flavor, make no mistake: DC is a city of distinctive areas, each with its own style, ensuring that hungry American Library Association (ALA) 2010 conference…

  19. The Mode of Action of Cyclo(l-Ala-l-Pro) in Inhibiting Aflatoxin Production of Aspergillus flavus.

    Science.gov (United States)

    Iimura, Kurin; Furukawa, Tomohiro; Yamamoto, Toshiyoshi; Negishi, Lumi; Suzuki, Michio; Sakuda, Shohei

    2017-07-12

    Cyclo(l-Ala-l-Pro) inhibits aflatoxin production in aflatoxigenic fungi without affecting fungal growth. The mode of action of cyclo(l-Ala-l-Pro) in inhibiting aflatoxin production of Aspergillus flavus was investigated. A glutathione S-transferase (GST) of the fungus, designated AfGST, was identified as a binding protein of cyclo(l-Ala-l-Pro) in an experiment performed using cyclo(l-Ala-l-Pro)-immobilized Sepharose beads. Cyclo(l-Ala-l-Pro) specifically bound to recombinant AfGST and inhibited its GST activity. Ethacrynic acid, a known GST inhibitor, inhibited the GST activity of recombinant AfGST and aflatoxin production of the fungus. Ethacrynic acid reduced the expression level of AflR, a key regulatory protein for aflatoxin production, similar to cyclo(l-Ala-l-Pro). These results suggest that cyclo(l-Ala-l-Pro) inhibits aflatoxin production by affecting GST function in A. flavus, and that AfGST inhibitors are possible candidates as selective aflatoxin production inhibitors.

  20. Monitoring blood flow and photobleaching during topical ALA PDT treatment

    Science.gov (United States)

    Sands, Theresa L.; Sunar, Ulas; Foster, Thomas H.; Oseroff, Allan R.

    2009-02-01

    Photodynamic therapy (PDT) using topical aminolevulinic acid (ALA) is currently used as a clinical treatment for nonmelanoma skin cancers. In order to optimize PDT treatment, vascular shutdown early in treatment must be identified and prevented. This is especially important for topical ALA PDT where vascular shutdown is only temporary and is not a primary method of cell death. Shutdown in vasculature would limit the delivery of oxygen which is necessary for effective PDT treatment. Diffuse correlation spectroscopy (DCS) was used to monitor relative blood flow changes in Balb/C mice undergoing PDT at fluence rates of 10mW/cm2 and 75mW/cm2 for colon-26 tumors implanted intradermally. DCS is a preferable method to monitor the blood flow during PDT of lesions due to its ability to be used noninvasively throughout treatment, returning data from differing depths of tissue. Photobleaching of the photosensitizer was also monitored during treatment as an indirect manner of monitoring singlet oxygen production. In this paper, we show the conditions that cause vascular shutdown in our tumor model and its effects on the photobleaching rate.

  1. 固相新方法合成肽醛Fmoc-Gly-Ala-Phe-Ile-Ala-H%A new method for solid-phase synthesis of peptide aldehyde Fmoc-Gly-Ala-Phe-Ile-Ala-H

    Institute of Scientific and Technical Information of China (English)

    康武; 王卫国; 智晓霞; 张波; 韦萍; 徐红岩

    2012-01-01

    采用新的链接剂二乙醇胺与氨基醛形成稳定的(噁)唑形式,将Fmoc-丙氨醛固定到二氯三苯甲基树脂上,经固相多肽合成后,用AcOH/DCM/H2O(8∶1∶1)将标题化合物从树脂上释放出来,纯化后纯度达98.2%,产品通过MS、1HNMR鉴定确证,且无消旋发生.%Protected amino acid aldehyde was immobilized on 2-Cl(trt) resin as stable oxazolidine formation via diethano-lamine. After classical Fmoc SPPS,treatment of the resin with Ac0H/DCM/H,0(8:1:1) afforded peptide aldehyde Fmoc-Gly-Ala-Phe-lle-Ala-H, which was confirmed by ESI-MS, 1HNMR and HPLC with 98. 2% purity and no racemization was detected.

  2. 5-ALA mediated photodynamic therapy induces autophagic cell death via AMP-activated protein kinase

    Directory of Open Access Journals (Sweden)

    Lin Yu-Hsin

    2010-04-01

    Full Text Available Abstract Photodynamic therapy (PDT has been developed as an anticancer treatment, which is based on the tumor-specific accumulation of a photosensitizer that induces cell death after irradiation of light with a specific wavelength. Depending on the subcellular localization of the photosensitizer, PDT could trigger various signal transduction cascades and induce cell death such as apoptosis, autophagy, and necrosis. In this study, we report that both AMP-activated protein kinase (AMPK and mitogen-activated protein kinase (MAPK signaling cascades are activated following 5-aminolevulinic acid (ALA-mediated PDT in both PC12 and CL1-0 cells. Although the activities of caspase-9 and -3 are elevated, the caspase inhibitor zVAD-fmk did not protect cells against ALA-PDT-induced cell death. Instead, autophagic cell death was found in PC12 and CL1-0 cells treated with ALA-PDT. Most importantly, we report here for the first time that it is the activation of AMPK, but not MAPKs that plays a crucial role in mediating autophagic cell death induced by ALA-PDT. This novel observation indicates that the AMPK pathway play an important role in ALA-PDT-induced autophagy.

  3. Controlled self-assembling structures of ferrocene-dipeptide conjugates composed of Ala-Pro-NHCH2CH2SH chain.

    Science.gov (United States)

    Moriuchi, Toshiyuki; Nishiyama, Taiki; Tayano, Yoshiki; Hirao, Toshikazu

    2017-05-18

    Bioorganometallic ferrocene-dipeptide conjugates with the Ala-Pro-cysteamine chain, Fc-L-Ala-L-Pro-NHCH2CH2SH (2) and Fc-L-Ala-D-Pro-NHCH2CH2SH (4) (Fc=ferrocenoyl), were prepared by the reduction of the ferrocene-dipeptide conjugates, Fc-L-Ala-L-Pro-cystamine-L-Pro-L-Ala-Fc (1) or Fc-L-Ala-D-Pro-cystamine-D-Pro-L-Ala-Fc (3), respectively. Control of the self-assembling structures of the ferrocene-dipeptide conjugates was demonstrated by changing the chirality of the amino acid. The molecular structure of 2 composed of the L-Ala-L-Pro-NHCH2CH2SH chain confirmed the formation of intramolecular hydrogen bond of N-H⋯N pattern between the NH of cysteamine moiety and the nitrogen of Pro moiety. Furthermore, intermolecular hydrogen bonds between NH (Ala) and CO (Pro of another molecule) and between NH (cysteamine) and CO (the ferrocenoyl moiety of another molecule) were formed, wherein each molecule is connected to four neighboring molecules by continuous intermolecular hydrogen bonds to form the hydrogen-bonded molecular assembling structure. On the contrary, the left-handed helical assembly through an intermolecular hydrogen-bonding network of 15-membered intermolecularly hydrogen-bonded ring between NH (Ala) and CO (the ferrocenoyl moiety of another molecule) and between NH (the cysteamine moiety of another molecule) and CO (Ala) was observed in the crystal packing of 4 composed of the L-Ala-D-Pro-NHCH2CH2SH chain. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Impact of Omega-3 Supplementation with Alpha-Linolenic Acid on Neuronal Cell Fatty Acid Status

    OpenAIRE

    Densel, Owen

    2016-01-01

    A method of treating retinoic acid differentiated SH-SY5Y neuroblastoma cells with alpha-linolenic acid (ALA) in the free acid form has been developed in order to examine impacts of such supplementation on fatty acid composition of cells and on functional outcomes. Through Bovine Serum Albumin: ALA conjugation, an ALA treatment media was created and compared to the stock media which contained no detectible amounts of ALA. Results from fatty acid analysis of the control cells (n=3) and ALA-sup...

  5. Predicting the "usefulness" of 5-ALA-derived tumor fluorescence for fluorescence-guided resections in pediatric brain tumors

    DEFF Research Database (Denmark)

    Stummer, Walter; Rodrigues, Floriano; Schucht, Philippe

    2014-01-01

    BACKGROUND: Five-aminolevulinic acid (Gliolan, medac, Wedel, Germany, 5-ALA) is approved for fluorescence-guided resections of adult malignant gliomas. Case reports indicate that 5-ALA can be used for children, yet no prospective study has been conducted as of yet. As a basis for a study, we cond......, 25 %) and pilocytic astrocytomas (two of 13; 15 %). RPA of pre-operative factors showed tumors with supratentorial location, strong contrast enhancement and first operation to have a likelihood of useful fluorescence of 64.3 %, as opposed to infratentorial tumors with first surgery (23.......1 %). CONCLUSIONS: Our survey demonstrates 5-ALA as being used in pediatric brain tumors. 5-ALA may be especially useful for contrast-enhancing supratentorial tumors. These data indicate controlled studies to be necessary and also provide a basis for planning such a study....

  6. The comparison between LAC and ALA

    Directory of Open Access Journals (Sweden)

    Tzu-heng Chiu

    2000-12-01

    Full Text Available A good library association serves its members, improves the librarianship, and helps library institutions achieving their missions. This article describes the history, missions and goals, organization structure, membership, financial sources, professional activities, publication, and website of the Library Association of China (LAC and American Library Association (ALA, respectively. Considering social / cultural / political differences between Taiwan and the United Sates, the author then compares these two library associations from the eight factors mentioned above. At the end, suggestions for the LAC are proposed.[Article content in Chinese

  7. Potentiation of ALA-PDT antitumor activity in mice using topical DMXAA

    Science.gov (United States)

    Marrero, Allison; Sunar, Ulas; Sands, Theresa; Oseroff, Allan; Bellnier, David

    2009-06-01

    Photodynamic treatment of subcutaneously implanted Colon 26 tumors in BALB/c mice using the aminolevulinic acid (ALA)-induced photosensitizer protoporphyrin IX (PpIX) was shown to be enhanced by the addition of the vascular disrupting agent 5,6-Dimethylxanthenone-4-acetic-acid (DMXAA; Novartis ASA404). DMXAA increases vascular permeability and decreases blood flow in both murine and human tumors. Sufficiently high parenteral DMXAA doses can lead to tumor collapse and necrosis. We have previously reported marked enhancement of antitumor activity when PDT, using either Photofrin or HPPH, is combined with low-dose intraperitoneal DMXAA. We now describe the first attempt to combine topically-applied DMXAA with PDT. For this, DMXAA was applied two hours before PpIX-activating light delivery. PDT with ALA-PDT alone (ALA 20%; 80 J/cm2 delivered at 75 mW/cm2) caused a 39% decrease in tumor volume compared to unirradiated controls. Addition of topical DMXAA to ALA-PDT resulted in a 74% reduction in tumor volume. Diffuse correlation spectroscopy (DCS), a non-invasive blood flow imaging method, is being used to understand the mechanism of this effect and to aid in the proper design of the therapy. For instance, our most recent DCS data suggests that the 2-hour interval between the DMXAA and light applications may not be optimum. This preliminary study suggests a potential role for topical DMXAA in combination with PDT for dermatologic tumors.

  8. Photodynamic damage study of HeLa cell line using ALA

    Science.gov (United States)

    AlSalhi, M. S.; Atif, M.; AlObiadi, A. A.; Aldwayyan, A. S.

    2011-04-01

    The present study evaluates the photodynamic damage with 5-aminolevulinic acid (5-ALA) using HeLa as experimental model. HeLa cell line was irradiated with red light (He-Ne laser, λ = 632.8 CW nm). The influence of different incubation times and concentrations of 5-ALA, different irradiation doses and various combinations of photosensitizer and light doses on the cellular viability of HeLa cells were studied. The optimal uptake of photosensitizer ALA in HeLa cells was investigated by means of PpIX fluorescence intensity by exciting the HeLa cell suspension at 450 nm and a detection wavelength set at 690 nm. Cells viability was determined by means of trypan blue solution. The spectrometric measurements showed that the maximal cellular uptake of 5-ALA occurred after 4 h in vitro incubation. We found that the combination with 5-ALA and laser irradiation leads to time/concentration-dependent increase of cells death and also energy doses-dependent enlarge the cells death. The fluorescence intensity after PDD of carcinoma cells reduce when compared with the control group. The fluorescence emission spectral profiles after PDD of carcinoma cells showed a dip around 425-525 nm when compared with the control group. This may be due to the damage of mitochondria component of cells. The percentage of HeLa cells after PDD shows that the percentage of cells survival rate as function of laser dose (power). Hence it is clear that at 200 μg/ml ALA and 20 mW laser irradiation, more than 70% of HeLa cells were dead after 15 min.

  9. Synthesis and Crystal Structure of a Novel Amino-acid-containing Polyoxometalate: K6[Cu(Ala)2(H2O)2]2[Cu4(H2O)2(AsW9O34)2]*16H2O%新型氨基酸-钨砷多金属氧酸盐K6[Cu(Ala)2*(H2O)2]2[Cu4(H2O)2(AsW9O34)2]*16H2O的合成与晶体结构

    Institute of Scientific and Technical Information of China (English)

    王永慧; 胡长文; 王恩波; 胡宁海; 贾恒庆; 邢彦

    2001-01-01

    The novel amino-acid-containing polyoxometalate K6[Cu(Ala)2(H2O)2]2[Cu4(H2O)2\\5(AsW9O34)2]*16H2O was synthesized from the rea ction of K10[Cu4(H2O)2(AsW9O34)2]*20H2O with β-alanine. Its structure has been determined by single crystal X-ray diffraction. It crystallizes in the triclinic space group P1, with a=1.196 3(2) nm, b=1.536 5(3) nm, c=1.591 4(3) nm, α=93.97(3)°, β=110.88(3)°, γ=101.07(3)°, V=2.651 8(9) nm3 and Z=1. Least-squares refinement of the structure leads to R and Rw factors of 0.067 3 and 0.162 8, respectively. An unusual structural feature of the compound is that the polyanion [Cu4(H2O)2(AsW9O34)2]10- is linked with the amino-acid complex of Cu2+ by a μ-oxygen atom.

  10. Allergic contact dermatitis to 5-aminolaevulinic acid methylester but not to 5-aminolaevulinic acid after photodynamic therapy.

    Science.gov (United States)

    Wulf, H C; Philipsen, P

    2004-01-01

    We report a patient with an allergy induced by photodynamic therapy (PDT) following simultaneous treatment with both 5-aminolaevulinic acid (ALA) and ALA methylester (ALA-ME). After several PDT treatments the patient presented with acute eczema of the treated areas and itch and hyper-reactivity of the untreated skin. Patch testing demonstrated a strong +++ reaction to ALA-ME only, indicating that derivatives common to ALA and ALA-ME were not involved. This is the first case of allergy to ALA-ME.

  11. Acides gras de la famille n-3 : alphalinolénique (ALA d’origine végétale et longues chaînes n-3 (LC-n-3

    Directory of Open Access Journals (Sweden)

    Delplanque Bernadette

    2004-03-01

    Full Text Available Les acides gras polyinsaturés (AGPI de la famille n-3 (oméga 3 sont des acides gras impliqués dans de multiples processus physiologiques qui ont un impact de prévention sur la santé et\\\\ou de traitement de maladies chroniques. Depuis 50 ans, le développement de toutes ces maladies explose dans le monde occidental, en même temps que la consommation d’oméga 6 a augmenté, alors que celle des oméga 3 a été oubliée, induisant un rapport n-6\\\

  12. Fluorescence photobleaching of ALA and ALA-heptyl ester induced protoporphyrin IX during photodynamic therapy of normal hairless mouse skin: a comparison of two light sources and different illumination schemes.

    Science.gov (United States)

    Pudroma, Xiao; Juzeniene, Asta; Ma, Li-Wei; Iani, Vladimir; Moan, Johan

    2011-01-01

    This study investigated photobleaching of protoporphyrin IX (PpIX) induced by 5-aminolevulinic acid (ALA) and ALA-heptyl ester during superficial photodynamic therapy (PDT) in normal skin of the female BALB/c-nu/nu athymic mouse. We examined the effects of two light sources (laser and broadband lamp) and two different illumination schemes (fractionated light and continuous irradiation) on the kinetics of photobleaching. Our results show that light exposure (0-30 minutes, 10 mW/cm2) of wavelengths of approximately 420 nm (blue light) and 635 nm (red light) induced time-dependent PpIX photobleaching for mouse skin of 2% ALA and ALA-heptyl ester. Blue light (10 mW/cm2) caused more rapid PpIX photobleaching than did red light (100 mW/cm2), which is attributed to stronger absorption at 407 nm than at 632 nm for PpIX. In the case of light fractionation, fractionated light induced faster photobleaching compared with continuous light exposure after topical application of 2% ALA and ALA-heptyl ester in vivo. These have been suggested to allow reoxygenation of the irradiated tissue, with a consequent enhancement of singlet oxygen production in the second and subsequent fractions.

  13. Maternal PPARG Pro12Ala polymorphism is associated with infant's neurodevelopmental outcomes at 18 months of age.

    Science.gov (United States)

    Torres-Espínola, Francisco J; Altmäe, Signe; Segura, Maria Teresa; Jerez, Antonio; Anjos, Tania; Chisaguano, Maribel; Carmen López-Sabater, M; Entrala, Carmen; Alvarez, Juan Carlos; Agil, Ahmad; Florido, Jesus; Catena, Andres; Pérez-García, Miguel; Campoy, Cristina

    2015-08-01

    Peroxisome proliferator activated receptors (PPARs) are ligand activated transcription factors with crucial functions in lipid homeostasis, glucose metabolism, anti-inflammatory processes, placental development, and are involved in cognitive functions and neurodegenerative diseases. Polymorphisms in PPAR genes are shown to influence the activity of these receptors. 1) To examine the association of PPARG Pro12Ala polymorphism in pregnant women and their offspring on infant's neurodevelopmental outcomes during the first 18 months of life; 2) to determine the influence of Pro12Ala polymorphism on fatty acid concentrations in plasma phospholipids and placental tissue. 138 mother-infant pairs from the PREOBE observational study were genotyped for PPARG Pro12Ala. Plasma phospholipids and placental fatty acid concentrations were measured at delivery. Infants' neuropsychological assessment at 6 and 18 months of age was performed using Bayley III. The effect of Pro12Ala on infant's neurodevelopmental outcomes was detected at 18 months, but not at 6 months of age. 18 months old infants born to mothers with wild-type Pro12 genotype had better cognitive (OR=5.11, 95% CI: 1.379-18.96, p=0.015), language (OR=3.41, 95% CI: 1.35-11.24, p=0.044), and motor development scores (OR=4.77, 95% CI: 1.243-18.33, p=0.023) than the Ala allele carriers. Pro12Ala variants did not seem to affect fatty acids concentrations in blood nor in placenta at delivery. Infants born to mothers with Pro12 genotype have better neurodevelopmental outcomes at 18 months of age than Ala allele carriers, indicating a long-term transplacental action of PPARγ variants on foetal brain development. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  14. A Study on the Photobleaching Effect of 5-ALA Conjugated Gold Nanoparticles in a CT26 Tumor Model During Photodynamic Therapy

    Directory of Open Access Journals (Sweden)

    Nafiseh Sobhani

    2012-09-01

    Full Text Available Introduction During the process photodynamic therapy (PDT, bleaching of photosensitizer induced by irradiation and generation of reactive oxygen species (ROS can provide some information concerning the efficiency of treatment. Since gold nanoparticles (GNPs have been highlighted as efficient drug delivery systems, in this study, by utilizing GNPs conjugated with 5 aminolevulinic acid (5-ALA-GNPs, the photobleaching of ALA-induced protoporphyrin IX (PpIX was estimated on a colon carcinoma tumor model. Materials and Methods CT26 tumor models were prepared by subcutaneous injection of 5×105 cells into the right flank of Balb/c inbred mice. To estimate the time required to reach maximum concentration of PpIX in the tumors, the fluorescence signal of PpIX was monitored and PDT was performed by intratumoral injection of 5-ALA-GNPs, GNPs, and 5-ALA in separated groups for 15 min with a cycle of 5 min irradiation and 1 min darkness. The photobleaching rate was calculated from recorded fluorescence signals at the darkness intervals. Results The maximum fluorescence of PpIX was recorded 3 and 5 hr after injection of 5-ALA and 5-ALA-GNPs, respectively. Despite the low PpIX accumulation in tumors receiving conjugate, the photobleaching rate of PpIX was determined to be higher than 5-ALA. The reduction of the fluorescence signal due to 5-ALA-GNPs clearance was higher than that of 5-ALA. Conclusion Administration of 5-ALA-GNPs, intensification of ROS generating and the subsequent elevation of photobleaching results in higher treatment efficiency. Also, more rapid clearance of PpIX has an important implication in clinical application of 5-ALA-GNPs that decreases the undesirable effects on healthy tissues.

  15. Toxicity to the normal hemocytes by ALA-PDT for the ex vivo purging of hematopoietic stem cell grafts

    Institute of Scientific and Technical Information of China (English)

    Zhang Baoqin; Zhang Zhenxi; Miao Lixia; Tan Lu; Xiao Mi; Xu Xia

    2008-01-01

    Objective To study the toxic effects of 5-amionlevulinic acid-based photodynamic therapy (ALA-PDT) on human peripheral blood mononuclear cells (PBMCs), cord blood mononuclear cells (CBMCs) and peripheral blood stem cells (PBSCs), and furthermore, to understand the possible causes of this response. Methods We used MTT assay to detect the survival rate of PBMCs, CBMCs and PBSCs after treated by ALA-PDT under the optimum experiment conditions with U937 as control;Annexin V-FITC/PI was used to detect the pattern of cell death induced by ALA-PDT. By using flow cytometry, we detected intracellular PpIX fluorescence intensity. Results After ALA-PDT treatment the survival rate of PBMCs had no significant change;however in PBSCs and CBMCs, the survival rate reduced to 70%, and the survival rate of leukemia cell U937 was the lowest, about 30%. After incubation with ALA,except for PBMCs, intraceUuiar PplX fluorescence intensity of the other two kinds of normal haemocytes and U937 increased obviously. These results combined with the flow cytometry suggested that the main pattern of cell death here was apoptosts. Conclusion Under the optimum experiment conditions, ALA-PDT has a slight effect on normal haemocytes but excellent depletions of leukemia cells. Therefore, it can effectively purify autologons bone marrow or stem cell grafts.

  16. Comparsion of light dose on topical ALA-mediated photodynamic therapy for DMBA-induced hamster buccal pouch premalignant lesions

    Science.gov (United States)

    Yang, Deng-Fu; Tseng, Meng-Ke; Liu, Chung-Ji; Hsu, Yih-Chih

    2012-03-01

    Oral cancer has becomes the most prominent male cancer disease due to the local betel nut chewing habit combing with smoking and alcohol-drinking lifestyle. In order to minimize the systemic phototoxic effect of 5-aminolevulinic acid (ALA), this study was designed to use a topical ALA-mediated PDT for treatment of DMBA-induced hamster buccal pouch cancerous lesions. DMBA was applied to one of the buccal pouches of hamsters thrice a week for 8 to 10 weeks. Precancerous lesions were induced and proven by histological examination. These DMBA-induced cancerous lesions were used for testing the efficacy of topical ALA -mediated PDT. We found that ALA reached its peak level in cancerous lesions about 2.5 hrs after topical application of ALA gel. The precancerous lesions in hamsters were then treated with topical ALA -mediated PDT with light exposure dose of 75 and 100 J/cm2 using LED 635 nm Wonderlight device. It is suggesting that optimization of the given light dose is critical to the success of PDT results.

  17. Kinetics and subcellular localization of 5-ALA-induced PpIX in DHL cells via two-photon excitation fluorescence microscopy.

    Science.gov (United States)

    Chen, Rong; Huang, Zufang; Chen, Guannan; Li, Yongzeng; Chen, Xianlian; Chen, Jianxin; Zeng, Haishan

    2008-04-01

    Two-photon excitation fluorescence (TPEF) microscopy was used to measure the 5-aminolevulinic acid (5-ALA)-induced PpIX fluorescence in follicular lymphoma DHL cells. Kinetics of 5-ALA-induced PpIX accumulation in DHL cells under various 5-ALA concentrations was studied. We found that during the course of continuous incubation with 5-ALA, the relationship between the DHL cell fluorescence signal and the incubation time showed a biphasic variation. Initially the PpIX signal increased with the incubation time and reached the maximal value at about 3 h, and then it decreased with time during the subsequent incubation period. By labeling the 5-ALA incubated DHL cells with different organelle-specific fluorescence probes: Rhodamine 123 (for mitochondria), DioC6(3) (for endoplasmic reticulum) and LysoTracker Green (for lysosomes) respectively, we found that 5-ALA-induced PpIX was primarily localized in endoplasmic reticulum and mitochondria; its concentration in the lysosome was much lower. The results suggested that 5-ALA could potentially be an effective photosensitizer in photodynamic purging of DHL cells. Two-photon excitation fluorescence microscope is a useful tool for studying 5-ALA-induced PpIX subcellular localization.

  18. Jüri Ratas: tasulise parkimise ala suurendamine probleeme ei tekita / Jüri Ratas ; interv. Askur Alas

    Index Scriptorium Estoniae

    Ratas, Jüri, 1978-

    2004-01-01

    Tallinna abilinnapea tasulise parkimise ala laiendamisest Tallinna kesklinnas ja sellega kaasnevatest võimalikest probleemidest. Kommenteerib Johannes Pirita. Kaart. Lisa: Rahvaalgatus sõdib tasulise parkimisega

  19. Jüri Ratas: tasulise parkimise ala suurendamine probleeme ei tekita / Jüri Ratas ; interv. Askur Alas

    Index Scriptorium Estoniae

    Ratas, Jüri, 1978-

    2004-01-01

    Tallinna abilinnapea tasulise parkimise ala laiendamisest Tallinna kesklinnas ja sellega kaasnevatest võimalikest probleemidest. Kommenteerib Johannes Pirita. Kaart. Lisa: Rahvaalgatus sõdib tasulise parkimisega

  20. Expression of the alaE gene is positively regulated by the global regulator Lrp in response to intracellular accumulation of l-alanine in Escherichia coli.

    Science.gov (United States)

    Ihara, Kohei; Sato, Kazuki; Hori, Hatsuhiro; Makino, Yumiko; Shigenobu, Shuji; Ando, Tasuke; Isogai, Emiko; Yoneyama, Hiroshi

    2017-04-01

    The alaE gene in Escherichia coli encodes an l-alanine exporter that catalyzes the active export of l-alanine using proton electrochemical potential. In our previous study, alaE expression was shown to increase in the presence of l-alanyl-l-alanine (Ala-Ala). In this study, the global regulator leucine-responsive regulatory protein (Lrp) was identified as an activator of the alaE gene. A promoter less β-galactosidase gene was fused to an alaE upstream region (240 nucleotides). Cells that were lacZ-deficient and harbored this reporter plasmid showed significant induction of β-galactosidase activity (approximately 17-fold) in the presence of 6 mM l-alanine, l-leucine, and Ala-Ala. However, a reporter plasmid possessing a smaller alaE upstream region (180 nucleotides) yielded transformants with strikingly low enzyme activity under the same conditions. In contrast, lrp-deficient cells showed almost no β-galactosidase induction, indicating that Lrp positively regulates alaE expression. We next performed an electrophoretic mobility shift assay (EMSA) and a DNase I footprinting assay using purified hexahistidine-tagged Lrp (Lrp-His). Consequently, we found that Lrp-His binds to the alaE upstream region spanning nucleotide -161 to -83 with a physiologically relevant affinity (apparent KD, 288.7 ± 83.8 nM). Furthermore, the binding affinity of Lrp-His toward its cis-element was increased by l-alanine and l-leucine, but not by Ala-Ala and d-alanine. Based on these results, we concluded that the gene expression of the alaE is regulated by Lrp in response to intracellular levels of l-alanine, which eventually leads to intracellular homeostasis of l-alanine concentrations.

  1. Comparative in vivo study of precursors of PpIX (ALA and MAL) used topically in photodynamic therapy

    Science.gov (United States)

    Rego, Raquel F.; Inada, Natalia M.; Ferreira, Juliana; Araújo-Moreira, Fernando M.; Bagnato, Vanderlei S.

    2009-06-01

    The efficacy of Photodynamic Therapy (PDT) combined with aminolevulinic acid (ALA) or methyl aminolevulinate (MAL) in treatment of cancer has been studied for over ten years. However, there is no established dose for the topical use of these drugs in PDT. The purpose of this study was the comparison of induced PDT response of ALAsense (5-aminolevulinic acid - ALA) and Metvix (methyl aminolevulinate - MAL). Depth of necrosis induced by PDT was analyzed in normal liver of male Wistar rats, using different light doses and topical application of both PpIX precursors - ALA and MAL. PDT was performed with a diode laser at 630 nm with different doses of light (20, 50, 100 and 200 J/cm2), and intensity of 250 mW/cm2. Depth of necrosis analysis was used to calculate the threshold dose for each drug. The results showed that MAL-PDT presented a better response than ALA-PDT, mainly due to formulation differences. Moreover, the ability of the ALA PpIX production was more efficient.

  2. Study of the efficacy of 5 ALA-mediated photodynamic therapy on human larynx squamous cell carcinoma (Hep2c) cell line

    Science.gov (United States)

    Khursid, A.; Atif, M.; Firdous, S.; Zaidi, S. S. Z.; Salman, R.; Ikram, M.

    2010-07-01

    5-aminolevulanic acid (ALA), a precursor of Protoporphyrin IX, was evaluated as an inducer of photodamage on Hep2c, human larynx squamous cell carcinoma, cell line. Porphyrins are used as active cytotoxic antitumor agents in photodynamic therapy (PDT). The present study evaluates the effects of photodynamic therapy (PDT) with 5-aminolevulinic acid (5-ALA) using human larynx cells as experimental model. Hep2c cell line was irradiated with red light (a diode laser, λ = 635 nm). The influence of different incubation times and concentrations of 5-ALA, different irradiation doses and various combinations of photosensitizer and light doses on the cellular viability of Hep2c cells were studied. The optimal uptake of photosensitizer ALA in Hep-2c cells was investigated by means of spectrometric measurement. Cells viability was determined by means of neutral red assay (NR). It was observed that sensitizer or light doses have no significant effect on cells viability when studied independently. The spectrometric measurements showed that the maximal cellular uptake of 5-ALA occurred after 7 h in vitro incubation. The photocytotoxic assay showed that light dose of 85 J/cm2 gives effective PDT outcome for Hep2c cell line incubated with 55 μg/ml of 5-ALA with a conclusion that Hep2c cell line is sensitive to ALA-mediated PDT.

  3. Proteomics and SSH Analyses of ALA-Promoted Fruit Coloration and Evidence for the Involvement of a MADS-Box Gene, MdMADS1.

    Science.gov (United States)

    Feng, Xinxin; An, Yuyan; Zheng, Jie; Sun, Miao; Wang, Liangju

    2016-01-01

    Skin color is a key quality attribute of fruits and how to improve fruit coloration has long been a major concern. 5-Aminolevulinic acid (ALA), a natural plant growth regulator, can significantly increase anthocyanin accumulation in fruit skin and therefore effectively improve coloration of many fruits, including apple. However, the molecular mechanism how ALA stimulates anthocyanin accumulation in fruit skin remains unknown. Here, we investigated the impact of ALA on apple skin at the protein and mRNA levels. A total of 85 differentially expressed proteins in apple skins between ALA and water treatment (control) were identified by complementary gel-based and gel-free separation techniques. Most of these differentially expressed proteins were up-regulated by ALA. Function analysis suggested that 87.06% of the ALA-responsive proteins were associated with fruit ripening. To further screen ALA-responsive regulators, we constructed a subtracted cDNA library (tester: ALA treatment; driver: control) and obtained 104 differentially expressed unigenes, of which 38 unigenes were indicators for the fruit ripening-related genes. The differentially changed proteins and transcripts did not correspond well at an individual level, but showed similar regulated direction in function at the pathway level. Among the identified fruit ripening-related genes, the expression of MdMADS1, a developmental transcription regulator of fruit ripening, was positively correlated with expression of anthocyanin biosynthetic genes (MdCHS, MdDFR, MdLDOX, and MdUFGT) in apple skin under ALA treatment. Moreover, overexpression of MdMADS1 enhanced anthocyanin content in transformed apple calli, which was further enhanced by ALA. The anthocyanin content in MdMADS1-silenced calli was less than that in the control with ALA treatment, but higher than that without ALA treatment. These results indicated that MdMADS1 is involved in ALA-induced anthocyanin accumulation. In addition, anthocyanin

  4. Proteomics and SSH Analyses of ALA-Promoted Fruit Coloration and Evidence for the Involvement of a MADS-Box Gene, MdMADS1

    Science.gov (United States)

    Feng, Xinxin; An, Yuyan; Zheng, Jie; Sun, Miao; Wang, Liangju

    2016-01-01

    Skin color is a key quality attribute of fruits and how to improve fruit coloration has long been a major concern. 5-Aminolevulinic acid (ALA), a natural plant growth regulator, can significantly increase anthocyanin accumulation in fruit skin and therefore effectively improve coloration of many fruits, including apple. However, the molecular mechanism how ALA stimulates anthocyanin accumulation in fruit skin remains unknown. Here, we investigated the impact of ALA on apple skin at the protein and mRNA levels. A total of 85 differentially expressed proteins in apple skins between ALA and water treatment (control) were identified by complementary gel-based and gel-free separation techniques. Most of these differentially expressed proteins were up-regulated by ALA. Function analysis suggested that 87.06% of the ALA-responsive proteins were associated with fruit ripening. To further screen ALA-responsive regulators, we constructed a subtracted cDNA library (tester: ALA treatment; driver: control) and obtained 104 differentially expressed unigenes, of which 38 unigenes were indicators for the fruit ripening-related genes. The differentially changed proteins and transcripts did not correspond well at an individual level, but showed similar regulated direction in function at the pathway level. Among the identified fruit ripening-related genes, the expression of MdMADS1, a developmental transcription regulator of fruit ripening, was positively correlated with expression of anthocyanin biosynthetic genes (MdCHS, MdDFR, MdLDOX, and MdUFGT) in apple skin under ALA treatment. Moreover, overexpression of MdMADS1 enhanced anthocyanin content in transformed apple calli, which was further enhanced by ALA. The anthocyanin content in MdMADS1-silenced calli was less than that in the control with ALA treatment, but higher than that without ALA treatment. These results indicated that MdMADS1 is involved in ALA-induced anthocyanin accumulation. In addition, anthocyanin

  5. Urinary delta-ALA: a potential biomarker of exposure and neurotoxic effect in rats co-treated with a mixture of lead, arsenic and manganese.

    Science.gov (United States)

    Andrade, Vanda; Mateus, M Luísa; Batoréu, M Camila; Aschner, Michael; dos Santos, A P Marreilha

    2013-09-01

    Lead (Pb), arsenic (As) and manganese (Mn) are neurotoxic elements that often occur in mixtures for which practically no information is available on biomarkers (BMs) for the evaluation of exposure/effects. Exposures to these metals may increase delta-aminolevulinic acid (delta-ALA), which in itself may potentiate neurotoxicity. The objective of this study was to investigate the utility of urinary delta-ALA (delta-ALA-U) levels as BM of exposure and/or neurotoxic effects induced by this mixture. Five groups of Wistar rats were treated for 8 days with Pb (5mg/kg), As (60mg/L), Mn (10mg/kg), the 3-metal mixture (same doses of the single metals), and control group. Motor activity was evaluated and 24-h urine collected before and after the treatment. 24-hours (h) after the last dose, the rats were sacrificed and the brains removed for analyses. Delta-ALA and metal levels were determined in brain and urine. Co-treated rats showed a significant (p<0.05) correlation between increased Pb, As, Mn and delta-ALA levels in the brain and decreased motor activity. Delta-ALA-U concentrations were higher in the mixture-treated group than the sum of the delta-ALA-U levels in each single-treated groups and discriminated (p<0.05) between the mixture and untreated rats. Moreover, delta-ALA-U was correlated (p<0.05) with brain delta-ALA levels. These results establish that treatments with this metal mixture exacerbate behavioral dysfunction, increasing most prominently brain Pb levels. This study is the first to establish that delta-ALA-U levels represent a sensitive BM of exposure/neurotoxic effect to this metal mixture.

  6. Toxicity to the normal hemocytes by ALA-PDT for the ex vivo purging of hematopoietic stem cell grafts

    Institute of Scientific and Technical Information of China (English)

    张宝琴; 张镇西; 苗丽霞; 谭璐; 肖谧; 徐霞

    2008-01-01

    Objective To study the toxic effects of 5-amionlevulinic acid-based photodynamic therapy (ALA-PDT) on human peripheral blood mononuclear cells (PBMCs), cord blood mononuclear cells (CBMCs) and peripheral blood stem cells (PBSCs), and furthermore, to understand the possible causes of this response. Methods We used MTT assay to detect the survival rate of PBMCs, CBMCs and PBSCs after treated by ALA-PDT under the optimum experiment conditions with U937 as control; Annexin V-FITC/PI was used to detect the patte...

  7. Impact of various emulsifiers on ALA bioavailability and chylomicron synthesis through changes in gastrointestinal lipolysis.

    Science.gov (United States)

    Couëdelo, L; Amara, S; Lecomte, M; Meugnier, E; Monteil, J; Fonseca, L; Pineau, G; Cansell, M; Carrière, F; Michalski, M C; Vaysse, C

    2015-05-01

    Formulating healthy food rich in omega 3 fatty acids requires prior knowledge of the parameters influencing their bioavailability and their metabolic fate. In this context, we studied the effects of various emulsifiers widely used in the food industry, on the gastrointestinal lipolysis of flaxseed oil emulsions in an in vitro model and on the intestinal absorption and lymphatic secretion of alpha-linolenic acid (ALA) in rats. In vitro data showed that the emulsification of flaxseed oil with soya lecithin improved the gastric lipolysis of the oil (+30%), while the presence of Tween 80 or of sodium caseinate decreased it (-80% and -40%, respectively). The in vivo data demonstrated that the intestinal absorption and the lymphatic secretion of ALA were improved with soya lecithin (Cmax = 24 mg mL(-1)) and reduced in the presence of sodium caseinate (Cmax = 7 mg mL(-1)) compared to unemulsified flaxseed oil (Cmax = 16 mg mL(-1)); Tween 80 had no effect. In addition, the synthesized chylomicrons were notably larger and more numerous with soya lecithin whereas they were smaller in the presence of sodium caseinate (p lecithin via an improved lipolysis, favouring the intestinal absorption of ALA and the secretion of many large chylomicrons in lymph.

  8. Photodynamic therapy (ALA-PDT) in the treatment of pathological states of the cornea

    Science.gov (United States)

    Switka-Wieclawska, Iwona; Kecik, Tadeusz; Kwasny, Miroslaw; Graczyk, Alfreda

    2003-10-01

    Each year an increasing amount of research is published on the use of photodynamic therapy in medicine. The most recent research has focused mostly on the use of photosensitizer called vertoporphyrin (Visudyne) is the treatment of subretinal neovascularization in age-related macular degeneration (AMD) or myopia, following a substantial amount of ophthalmology research mostly experimental on the application of the method in diagnosis and treatment of some eye tumors. In the Department of Ophthalmology of Polish Medical University in Warsaw, PDT was used as supplementary method in a selected group of patients with chronic virus ulcer of the cornea and keratopathies. During the treatment 5-aminolevulinic acid (5-ALA) was applied in ointment form as a photosensitizer activated with light wave of 633 nm. It appears, on the basis of the results obtained, that photodynamic therapy (ALA-PDT) may become in the future a valuable supplement to the methods being used at the present treating pathological states of the cornea.

  9. Optical scatter imaging as an apoptosis assay for cells undergoing ALA-mediated photodynamic therapy in vitro

    Science.gov (United States)

    Rossi, Vincent M.; Baugher, Paige J.; Jacques, Steven L.

    2013-02-01

    Aminolevulinic acid (ALA) is converted to protoporphyrin-IX (PpIX) within mitochondria, causing the assumption that ALA-mediated photodynamic therapy (PDT) results in mitochondrial damage and therefore an apoptotic response. Mitochondria within apoptosing cells swell, forming pores in their outer mitochondrial membranes which release cytochrome-c, triggering apoptosis. Optical scatter imaging (OSI) makes use of scattered fields in order to indicate the morphology of subcellular components, and is used here in order to measure changes in mitochondrial size as a response to ALA-mediated PDT. Two images of the same field of view are spatially filtered in the Fourier plane of a 4-F system. Both spatial filters block directly transmitted light, while accepting different angles of scattered light through an adjustable iris. The optical scatter image ratio (OSIR) of the local intensities of these two spatially filtered images is indicative of scattering particle size. Mie theory is used to calculate the predicted OSIR as a function of scattering particle size. In this fashion, the OSI system is calibrated using polystyrene microspheres of know sizes. Comparison of the measured OSIR from cellular images to theoretical values predicted for mitochondria then serves as an indication as to whether cells are apoptosing. Cells are treated at varying concentrations of ALA and varying exposures of 635 nm light and imaged at varying time points in order to develop a broader understanding of an apoptotic response of cells undergoing ALA mediated PDT.

  10. The use of 5-ALA to assist complete removal of residual non-enhancing part of childhood medulloblastoma

    DEFF Research Database (Denmark)

    Skjøth-Rasmussen, Jane; Bøgeskov, Lars; Sehested, Astrid

    2015-01-01

    PURPOSE: Medulloblastoma is the most common malignant brain tumor in childhood. Radical surgery in the non-metastatic stage is an important factor with respect to overall survival. In this case, 5-aminolevulinic acid (5-ALA) was used at second-look surgery in order to improve surgical results....... METHODS: The child was pretreated with 3 × 4 mg dexamethasone for 4 days prior to the second surgery. At 5 a.m. on the day of surgery, a freshly prepared solution of 5-ALA (20 mg/kg body weight; Medac, Germany) was given orally. RESULTS: At surgery, through the original opening, the vague red fluorescence...... changed from the high-risk medulloblastoma regimen to the standard-risk regimen. CONCLUSIONS: In this particular difficult case of non-contrast-enhancing tumor, 5-ALA was of vital importance to improve rate of resection and change the aggressiveness needed in postsurgery radiation therapy....

  11. Courtney Louise Young, Penn State Librarian, elected President of ALA

    Directory of Open Access Journals (Sweden)

    Linda Susan Neyer

    2013-10-01

    Full Text Available Courtney Louise Young, head librarian at the J. Clarence Kelly Library at Penn State Greater Allegheny, has been elected as 2014-15 president of the American Library Association (ALA.

  12. Conversion of alpha-linolenic acid in humans is influenced by the absolute amounts of alpha-linolenic acid and linoleic acid in the diet and not by their ratio

    NARCIS (Netherlands)

    Goyens, P.L.L.; Spilker, M.E.; Zock, P.L.; Katan, M.B.; Mensink, R.P.

    2006-01-01

    BACKGROUND: Human in vivo data on dietary determinants of alpha-linolenic acid (ALA; 18:3n-3) metabolism are scarce. OBJECTIVE: We examined whether intakes of ALA or linoleic acid (LA; 18:2n-6) or their ratio influences ALA metabolism. DESIGN: During 4 wk, 29 subjects received a control diet (7% of

  13. The role of sensitivity of ALA (PpIX)-based PDT on Human embryonic kidney cell line (HEK293T)

    Science.gov (United States)

    Fakhar-e-Alam, M.; Atif, M.; Rehman, T.; Sadia, H.; Firdous, S.

    2011-08-01

    Present study evaluates the effects of photodynamic therapy (PDT) with aminolevulinic acid (5-ALA) as photo sensitizer using Human embryonic kidney (HEK293T) cell line as an experimental model. Porphyrins derivatives are used as active cytotoxic antitumor agents in PDT. Above mentioned cell line were irradiated with red light (a diode laser, λ = 635 nm) at different doses (0-160 J/cm2) of light. The influence/effectiveness of incubation time, various concentrations of aminolevulinic acid (5-ALA) and light doses on the cellular viability was studied. HEK293T cells were deliberated by exposing the ALA-PpIX (0-1000 μg/ml) of concentrations. The optimal uptakes of photosensitizer (PS) in cell lines were investigated by means of spectro photo metric measurements. Cells viability was determined by means of neutral red assay (NRA). It was observed that alone, neither photosensitizer nor light dose have significant effect on cells viability, but optimal concentration of PS along with suitable dose of light exhibit effective impact on the viability of cell. Our results showed that light doses of 40 J/cm2 demonstrates effective PDT outcome for HEK293T cell line when incubated with 400 μg/ml, with wrapping up view that HEK293T cell line is very sensitive to ALA-mediated PDT as compared to cell line published in our data. At the end results has been verified by using reactive oxygen species (ROS) measure test.

  14. Protein engineering of insulin: Two novel fast-acting insulins [B16Ala]insulin and [B26Ala]insulin

    Institute of Scientific and Technical Information of China (English)

    ZHANG; Zhou; (张舟); TANG; Yuehua; (唐月华); YAO; Shiyin; (姚矢音); ZHU; Shangquan; (朱尚权); FENG; Youmin; (冯佑民)

    2003-01-01

    Blood glucose lowering assay proved that [B16Ala]insulin and [B26Ala]insulin exhibit potency of acute blood glucose lowering in normal pigs, which demonstrates that they are fast- acting insulin. Single-chain precursor of [B16Ala]insulin and [B26Ala]insulin is [B16Ala]PIP and [B26Ala]PIP, respectively, which are suitable for gene expression. Secretory expression level of the precursors in methylotrophic yeast Pichia pastoris was quite high, 650 mg/L and 130 mg/L, respectively. In vivo biological assay showed that the two fast-acting insulins have full or nearly full biological activity. So both [B16Ala]insulin and [B26Ala]insulin can be well developed as fast-acting insulin for clinic use.

  15. The peptide Z-Aib-Aib-Aib-L-Ala-OtBu.

    Science.gov (United States)

    Gessmann, Renate; Brückner, Hans; Petratos, Kyriacos

    2014-04-01

    The title peptide, N-benzyloxycarbonyl-α-aminoisobutyryl-α-aminoisobutyryl-α-aminoisobutyryl-L-alanine tert-butyl ester or Z-Aib-Aib-Aib-L-Ala-OtBu (Aib is α-aminoisobutyric acid, Z is benzyloxycarbonyl and OtBu indicates the tert-butyl ester), C27H42N4O7, is a left-handed helix with a right-handed conformation in the fourth residue, which is the only chiral residue. There are two 4→1 intramolecular hydrogen bonds in the structure. In the lattice, molecules are hydrogen bonded to form columns along the c axis.

  16. Ala/Ala Genotype of Pro12Ala Polymorphism in the Peroxisome Proliferator-Activated Receptor-γ2 Gene Is Associated with Obesity and Insulin Resistance in Asian Indians

    Science.gov (United States)

    Bhatt, Surya Prakash; Misra, Anoop; Sharma, Mukti; Luthra, Kalpana; Guleria, Randeep; Pandey, Ravindra Mohan

    2012-01-01

    Abstract Aim We determined the association of the Pro12Ala polymorphism of the peroxisome proliferator activated receptor (PPAR)-γ2 gene with obesity, insulin resistance (IR), and lipids in Asian Indians without diabetes in north India. Subjects and Methods In this cross-sectional study (n=495; 279 males and 216 females, 18–60 years of age), anthropometric (body mass index, waist and hip circumferences, and skinfold thickness) and biochemical (fasting glucose, lipid profile, fasting insulin, leptin, and adiponectin) parameters were assessed. Polymerase chain reaction–restriction fragment length polymorphism analysis was used for identification of individual genotypes. Results Frequencies of the Pro and Ala alleles were 0.89 and 0.11, respectively. The genotype frequencies (%) of Pro/Pro, Pro/Ala, and Ala/Ala were 82.6, 14.7, and 2.7, respectively, without any gender differences. The frequency of the Ala/Ala genotype was higher in obese than in nonobese subjects (4.9% vs. 1.5%, P=0.06). The Ala/Ala genotype was associated with higher values of hip circumference, subscapular skinfold thickness, and sum of four skinfold thickness than the Pro/Pro and Pro/Ala genotypes (P<0.05). Using a multivariate logistic regression model after adjusting for age, sex, and insulin, subjects with the Ala/Ala genotype showed a high risk of obesity (odds ratio [OR], 3.2, 95% confidence interval [CI] 1.2–12.9) and IR (OR, 3.6, 95% CI: 1.04–12.4). Conclusion The Ala/Ala genotype of the PPAR-γ2 gene is associated with obesity and IR in Asian Indians without diabetes living in north India. PMID:22694222

  17. The final story on the ALA3/ALIS1 complex

    DEFF Research Database (Denmark)

    Lopez Marques, Rosa Laura

    Research Foundation, Department of Plant Biology, University of Copenhagen, DK-1871 Frederiksberg C, Denmark; bBiochemistry Department MS200, University of Nevada Reno, NV 89557, USA; cHumboldt-University Berlin, Faculty of Mathematics and Natural Science I, Institute of Biology, 10115 Berlin, Germany.......         In Arabidopsis 12 P4-ATPase isoforms have been identified, named ALA1-12 for Aminophospholipid ATPase (Axelsen and Palmgren, 2001). So far, only one member of this family (ALA1) has been partially characterized and suggested to have a physiological relevance in chilling tolerance (Gomés et al., 2000...... of the growth medium. Electron micrographs show cellular defects in cells of the root cap of mutant plants related to the formation of vesicles in the trans side of the Golgi apparatus. We propose that the flippase activity of the ALA3/ALIS1 complex in the Golgi is required for important secretory processes...

  18. Effects of sub-lethal and chronic lead concentrations on blood and liver ALA-D activity and hematological parameters in Nile tilapia.

    Science.gov (United States)

    Dos Santos, Carlucio Rocha; Cavalcante, Ana Luiza Michel; Hauser-Davis, Rachel Ann; Lopes, Renato Matos; Mattos, Rita De Cássia Oliveira Da Costa

    2016-07-01

    Liver and blood δ-aminolevulinic acid dehydratase (ALA-D) inhibition by exposure to sub-lethal lead concentrations over time in Nile tilapia (Oreochromis niloticus) were investigated. All three lead concentrations (1mgkg(-1), 10mgkg(-1) and 100mgkg(-1)) significantly inhibited ALA-D activity in blood (319±29.2; 180±14.6 and 172±19µmols(-1)h(-1)L(-1) respectively) and liver (302±5.84; 201±41.4 and 93±22.1µmols(-1)h(-1)L(-1)) 24h after injection relative to controls (blood: 597±37.0µmols(-1)h(-1)L(-1); liver: 376±23.1µmols(-1)h(-1)L(-1)). Blood ALA-D was greatly inhibited in all but the highest lead dose. Fish were then exposed to 1mgkg(-1) lead for 9 days, and presented short-term hyperglycemia, decreased hemoglobin and hematocrit values and time-dependent blood ALA-D activity inhibition, corroborating blood ALA-D activity as being more suitable for investigating lead effects, showing dose and time-dependent ALA-D inhibition after lead exposure. The results of the present study also demonstrated that fish size affects blood ALA-D activity, as fish from the 24-h assay, which were slightly smaller (approximately 200g), showed higher ALA-D inhibition in response to lead exposure when compared to the fish from the 9-day assay (approximately 500g). Thus, fish size should always be taken into account both in the field and in laboratory settings, and efforts should be made to obtain uniform fish size samples for biomarker studies.

  19. Docosahexaenoic acid synthesis from alpha-linolenic acid is inhibited by diets high in polyunsaturated fatty acids.

    Science.gov (United States)

    Gibson, R A; Neumann, M A; Lien, E L; Boyd, K A; Tu, W C

    2013-01-01

    The conversion of the plant-derived omega-3 (n-3) α-linolenic acid (ALA, 18:3n-3) to the long-chain eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) can be increased by ALA sufficient diets compared to ALA deficient diets. Diets containing ALA above an optimal level result in no further increase in DHA levels in animals and humans. The present study evaluates means of maximizing plasma DHA accumulation by systematically varying both linoleic acid (LA, 18:2n-6) and ALA dietary level. Weanling rats were fed one of 54 diets for three weeks. The diets varied in the percentage of energy (en%) of LA (0.07-17.1 en%) and ALA (0.02-12.1 en%) by manipulating both the fat content and the balance of vegetable oils. The peak of plasma phospholipid DHA (>8% total fatty acids) was attained as a result of feeding a narrow dietary range of 1-3 en% ALA and 1-2 en% LA but was suppressed to basal levels (∼2% total fatty acids) at dietary intakes of total polyunsaturated fatty acids (PUFA) above 3 en%. We conclude it is possible to enhance the DHA status of rats fed diets containing ALA as the only source of n-3 fatty acids but only when the level of dietary PUFA is low (<3 en%).

  20. Identification and expression analyses of the alanine aminotransferase (AlaAT) gene family in poplar seedlings

    Science.gov (United States)

    Xu, Zhiru; Ma, Jing; Qu, Chunpu; Hu, Yanbo; Hao, Bingqing; Sun, Yan; Liu, Zhongye; Yang, Han; Yang, Chengjun; Wang, Hongwei; Li, Ying; Liu, Guanjun

    2017-01-01

    Alanine aminotransferase (AlaAT, E.C.2.6.1.2) catalyzes the reversible conversion of pyruvate and glutamate to alanine and α-oxoglutarate. The AlaAT gene family has been well studied in some herbaceous plants, but has not been well characterized in woody plants. In this study, we identified four alanine aminotransferase homologues in Populus trichocarpa, which could be classified into two subgroups, A and B. AlaAT3 and AlaAT4 in subgroup A encode AlaAT, while AlaAT1 and AlaAT2 in subgroup B encode glutamate:glyoxylate aminotransferase (GGAT), which catalyzes the reaction of glutamate and glyoxylate to α-oxoglutarate and glycine. Four AlaAT genes were cloned from P. simonii × P. nigra. PnAlaAT1 and PnAlaAT2 were expressed predominantly in leaves and induced by exogenous nitrogen and exhibited a diurnal fluctuation in leaves, but was inhibited in roots. PnAlaAT3 and PnAlaAT4 were mainly expressed in roots, stems and leaves, and was induced by exogenous nitrogen. The expression of PnAlaAT3 gene could be regulated by glutamine or its related metabolites in roots. Our results suggest that PnAlaAT3 gene may play an important role in nitrogen metabolism and is regulated by glutamine or its related metabolites in the roots of P. simonii × P. nigra. PMID:28378825

  1. Role of Superoxide Dismutase 2 Gene Ala16Val Polymorphism and Total Antioxidant Capacity in Diabetes and its Complications.

    Science.gov (United States)

    Pourvali, Katayoun; Abbasi, Mehrnaz; Mottaghi, Azadeh

    2016-01-01

    Diabetes Mellitus (DM) is a chronic heterogeneous disorder and oxidative stress is a key participant in the development and progression of it and its complications. Anti-oxidant status can affect vulnerability to oxidative damage, onset and progression of diabetes and diabetes complications. Superoxide dismutase 2 (SOD2) is one of the major antioxidant defense systems against free radicals. SOD2 is encoded by the nuclear SOD2 gene located on the human chromosome 6q25 and the Ala16Val polymorphism has been identified in exon 2 of the human SOD2 gene. Ala16Val (rs4880) is the most commonly studied SOD2 single nucleotide polymorphism (SNP) in SOD2 gene. This SNP changes the amino acid at position 16 from valine (Val) to alanine (Ala), which has been shown to cause a conformational change in the target sequence of manganese superoxide dismutase (MnSOD) and also affects MnSOD activity in mitochondria. Ala16Val SNP and changes in the activity of the SOD2 antioxidant enzyme have been associated with altered progression and risk of different diseases. Association of this SNP with diabetes and some of its complications have been studied in numerous studies. This review evaluated how rs4880, oxidative stress and antioxidant status are associated with diabetes and its complications although some aspects of this line still remain unclear.

  2. Stability, metabolism and transport of D-Asp(OBzl)-Ala--a model prodrug with affinity for the oligopeptide transporter

    DEFF Research Database (Denmark)

    Steffansen, B; Lepist, E I; Taub, M E

    1999-01-01

    The model prodrug D-Asp(OBzl)-Ala has previously been shown to have affinity and to be transported by the oligopeptide transporter PepT1 expressed in Caco-2 cells. The main objective of the present study was to investigate the aqueous stability of D-Asp(OBzl)-Ala and its in vitro metabolism...... in different gastrointestinal media arising from rats and humans, as well as in human plasma. The second major aim of the study was to evaluate our previous study in Caco-2 cell culture, by determining the effective intestinal permeability (Peff) of D-Asp(OBzl)-Ala in situ using the single-pass rat perfusion...... model. The aqueous stability studies show water, general buffer, as well as specific acid and base catalysis of D-Asp(OBzl)-Ala. The degradation of the model prodrug was independent of ionic strength. The half-lives in rat jejunal fluid and homogenate were >3 h. In human gastric and intestinal fluids...

  3. Analysis of the FABP2 Gene Ala54Thr Polymorphism in Non-obese and Obese Chinese%成都地区肥胖患者脂肪酸结合蛋白2基因Ala54Thr多态性研究

    Institute of Scientific and Technical Information of China (English)

    王晓苏; 白怀; 范平; 刘瑞; 刘宇; 刘秉文

    2011-01-01

    目的 研究脂肪酸结合蛋白2基因(fatty acid-binding protein 2,FABP2)Ala54Thr多态性是否与中国人肥胖有关联.为探讨肥胖的分子遗传基础提供依据.方法 应用聚合酶链反应一限制性片段长度多态性分析法(PCR-RFLP)对成都地区272例非肥胖者及121例肥胖患者FABP2基因Ala54Thr多态性位点进行分析.采用酶法和单向免疫扩散法对血脂和载脂蛋白水平进行测定.结果 FABP2基因Ala54Thr位点Ala、Thr等位基因的频率在肥胖组为71.5%、28.5%,在非肥胖组为71.1%、28.9%.两组间等位基因的频率差异无统计学意义(P>0.05).Ala54Thr位点在肥胖组AlaThr基因型携带者血清甘油三酯(TG)水平高于AlaAla基因型者(P0.05).结论 FABP2基因Ala54Thr多态性与成都地区中国汉族人肥胖无关联,但与血清TG和HDL-C水平有关,且具有性别差异.%Objective To investigate the fatty acid-binding protein 2 gene (FABP2) Ala54Thr polymorphism and its relationship to obesity in Chinese population. Methods Three hundred and ninety three subjects (272 nonobese and 121 obese individuals) from a population of Chinese Han nationality in Chengdu area were studied using PCR-restriction fragment length polymorphisms (PCR-RFLPs). Serum lipids were measured by enzymatic kits and apolipoproteins A Ⅰ , A Ⅱ , B100, C Ⅱ , CⅢ and E were measured by the RID kits. Results The frequencies of Ala and Thr allele at Ala54Thr site in obese and non-obese groups were 71. 5%、 28. 55%, and 71. 1%、 28. 9%, respectively. No significant difference in the allele frequencies between the two groups was observed (P>0. 05). In the obese group, subjects with Thr allele(AlaThr +ThrThr genotype carriers)had higher serum triglyceride (TG) concentrations than those with genotype AlaAla (P<0.05). Similar results were observed in obese male subgroup, when male and female subgroups were further separated. In addition, obese males with AlaThr had lower HDL-C levels than

  4. Leading by Example? ALA Division Publications, Open Access, and Sustainability

    Science.gov (United States)

    Hall, Nathan; Arnold-Garza, Sara; Gong, Regina; Shorish, Yasmeen

    2016-01-01

    This investigation explores scholarly communication business models in American Library Association (ALA) division peer-reviewed academic journals. Previous studies reveal the numerous issues organizations and publishers face in the academic publishing environment. Through an analysis of documented procedures, policies, and finances of five ALA…

  5. The Dipeptide Ala-Gly in the Gas Phase

    Science.gov (United States)

    Bermúdez, Celina; Varela, Marcelino; Cabezas, Carlos; Peña, Isabel; Alonso, José L.

    2014-06-01

    The dipeptide Ala-Gly has been examined in gas phase by laser ablation molecular beam Fourier transform microwave (LA-MB-FTMW) spectroscopy in the frequency region 3-12 GHz. Three rotamers have been detected in the supersonic expansion. The quadrupole hyperfine structure of two 14N (I=1) nuclei has been totally resolved allowing the conclusive identification of one conformer.

  6. ALA-induced PpIX fluorescence in epileptogenic tissue

    Science.gov (United States)

    Kleen, Jonathan K.; Valdes, Pablo A.; Harris, Brent T.; Holmes, Gregory L.; Paulsen, Keith D.; Roberts, David W.

    2011-03-01

    Astrogliotic tissue displays markedly increased levels of ALA-induced PpIX fluorescence, making it useful for fluorescence-guided resection in glioma surgery. In patients with temporal lobe epilepsy (TLE) and corresponding animal models, there are areas of astrogliosis that often co-localize with the epileptic focus, which can be resected to eliminate seizures in the majority of treated patients. If this epileptogenic tissue can exhibit PpIX fluorescence that is sufficiently localized, it could potentially help identify margins in epilepsy surgery. We tested the hypothesis that ALA-induced PpIX fluorescence could visually accentuate epileptogenic tissue, using an established animal model of chronic TLE. An acute dose of pilocarpine was used to induce chronic seizure activity in a rat. This rat and a normal control were given ALA, euthanized, and brains examined post-mortem for PpIX fluorescence and neuropathology. Preliminary evidence indicates increased PpIX fluorescence in areas associated with chronic epileptic changes and seizure generation in TLE, including the hippocampus and parahippocampal areas. In addition, strong PpIX fluorescence was clearly observed in layer II of the piriform cortex, a region known for epileptic reorganization and involvement in the generation of seizures in animal studies. We are further investigating whether ALA-induced PpIX fluorescence can consistently identify epileptogenic zones, which could warrant the extension of this technique to clinical studies for use as an adjuvant guidance technology in the resection of epileptic tissue.

  7. Leading by Example? ALA Division Publications, Open Access, and Sustainability

    Science.gov (United States)

    Hall, Nathan; Arnold-Garza, Sara; Gong, Regina; Shorish, Yasmeen

    2016-01-01

    This investigation explores scholarly communication business models in American Library Association (ALA) division peer-reviewed academic journals. Previous studies reveal the numerous issues organizations and publishers face in the academic publishing environment. Through an analysis of documented procedures, policies, and finances of five ALA…

  8. Tornide väljaku müüriäärse ala tulevik endiselt ebaselge / Askur Alas

    Index Scriptorium Estoniae

    Alas, Askur, 1973-

    2004-01-01

    Tallinna linna ja ehitusfirma Restor vaheline tüli linnamüüri äärse maa täisehitamise suhtes Suurtüki kvartalis pole lahendust leidnud. Linnaosavalitsus soovib müüri äärde parki ja tahab algatada ala detaiplaneeringut. Restoril on Plate ja Eppingi torni vahel ridaelamuboksid juba välja ehitatud

  9. Tornide väljaku müüriäärse ala tulevik endiselt ebaselge / Askur Alas

    Index Scriptorium Estoniae

    Alas, Askur, 1973-

    2004-01-01

    Tallinna linna ja ehitusfirma Restor vaheline tüli linnamüüri äärse maa täisehitamise suhtes Suurtüki kvartalis pole lahendust leidnud. Linnaosavalitsus soovib müüri äärde parki ja tahab algatada ala detaiplaneeringut. Restoril on Plate ja Eppingi torni vahel ridaelamuboksid juba välja ehitatud

  10. Photodynamic therapy with 5-aminolaevulinic acid or placebo for recalcitrant foot and hand warts

    DEFF Research Database (Denmark)

    Stender, I M; Na, R; Fogh, H

    2000-01-01

    Photodynamic therapy (PDT) with topical 5-aminolaevulinic acid (ALA) followed by irradiation with incoherent light (ALA-PDT) for recalcitrant warts have had beneficial results. Therefore, we undertook a randomised, parallel, double-blind clinical trial of ALA-PDT versus placeboPDT for recalcitrant...... foot and hand warts....

  11. Loss of the Arabidopsis thaliana P4-ATPases ALA6 and ALA7 Impairs Pollen Fitness and Alters the Pollen Tube Plasma Membrane

    Directory of Open Access Journals (Sweden)

    Stephen C McDowell

    2015-04-01

    Full Text Available Members of the P4 subfamily of P-type ATPases are thought to create and maintain lipid asymmetry in biological membranes by flipping specific lipids between membrane leaflets. In Arabidopsis, 7 of the 12 Aminophospholipid ATPase (ALA family members are expressed in pollen. Here we show that double knockout of ALA6 and ALA7 (ala6/7 results in siliques with a ~2-fold reduction in seed set with a high frequency of empty seed positions near the bottom. Seed set was reduced to near zero when plants were grown under a hot/cold temperature stress. Reciprocal crosses indicate that the ala6/7 reproductive deficiencies are due to a defect related to pollen transmission. In-vitro growth assays provide evidence that that ala6/7 pollen tubes are short and slow, with ~2-fold reductions in both maximal growth rate and overall length relative to wild-type. Outcrosses show that when ala6/7 pollen are in competition with wild-type pollen, they have a near 0% success rate in fertilizing ovules near the bottom of the pistil, consistent with ala6/7 pollen having short and slow growth defects. The ala6/7 phenotypes were rescued by the expression of either an ALA6-YFP or GFP-ALA6 fusion protein, which showed localization to both the plasma membrane and highly-mobile endomembrane structures. A mass spectrometry analysis of mature pollen grains revealed significant differences between ala6/7 and wild-type, both in the relative abundance of lipid classes and in the average number of double bonds present in acyl side chains. A change in the properties of the ala6/7 plasma membrane was also indicated by a ~10-fold reduction of labeling by lipophilic FM-dyes relative to wild-type. Together, these results indicate that ALA6 and ALA7 provide redundant activities that function to directly or indirectly change the distribution and abundance lipids in pollen, and support a model in which ALA6 and ALA7 are critical for pollen fitness under normal and temperature-stress conditions.

  12. ALA-PpIX variability quantitatively imaged in A431 epidermoid tumors using in vivo ultrasound fluorescence tomography and ex vivo assay

    Science.gov (United States)

    DSouza, Alisha V.; Flynn, Brendan P.; Gunn, Jason R.; Samkoe, Kimberley S.; Anand, Sanjay; Maytin, Edward V.; Hasan, Tayyaba; Pogue, Brian W.

    2014-03-01

    Treatment monitoring of Aminolevunilic-acid (ALA) - Photodynamic Therapy (PDT) of basal-cell carcinoma (BCC) calls for superficial and subsurface imaging techniques. While superficial imagers exist for this purpose, their ability to assess PpIX levels in thick lesions is poor; additionally few treatment centers have the capability to measure ALA-induced PpIX production. An area of active research is to improve treatments to deeper and nodular BCCs, because treatment is least effective in these. The goal of this work was to understand the logistics and technical capabilities to quantify PpIX at depths over 1mm, using a novel hybrid ultrasound-guided, fiber-based fluorescence molecular spectroscopictomography system. This system utilizes a 633nm excitation laser and detection using filtered spectrometers. Source and detection fibers are collinear so that their imaging plane matches that of ultrasound transducer. Validation with phantoms and tumor-simulating fluorescent inclusions in mice showed sensitivity to fluorophore concentrations as low as 0.025μg/ml at 4mm depth from surface, as presented in previous years. Image-guided quantification of ALA-induced PpIX production was completed in subcutaneous xenograft epidermoid cancer tumor model A431 in nude mice. A total of 32 animals were imaged in-vivo, using several time points, including pre-ALA, 4-hours post-ALA, and 24-hours post-ALA administration. On average, PpIX production in tumors increased by over 10-fold, 4-hours post-ALA. Statistical analysis of PpIX fluorescence showed significant difference among all groups; p<0.05. Results were validated by exvivo imaging of resected tumors. Details of imaging, analysis and results will be presented to illustrate variability and the potential for imaging these values at depth.

  13. Association between PRO12ALA polymorphism of the PPAR-γ2 gene and type 2 diabetes mellitus in Iranian patients

    Science.gov (United States)

    Motavallian, Azadeh; Andalib, Sasan; Vaseghi, Golnaz; Mirmohammad-Sadeghi, Hamid; Amini, Masoud

    2013-01-01

    BACKGROUND: Peroxisome proliferator-activated receptor (PPARs) have been identified as ligand-activated transcription factors that belong to the nuclear receptor superfamily. It has been shown that an association exists between Proline 12 alanine (Pro12Ala) polymorphism of PPAR-GAMMA2 (PPAR-γ2) gene and increased risk of type 2 diabetes mellitus (T2DM) in different populations. Therefore, the present study was designed to investigate the association between Pro12Ala polymorphism of PPAR-γ2 gene and T2DM in an Iranian population. MATERIALS AND METHODS: Two hundred unrelated people, including 100 healthy controls and 100 diabetic patients were recruited diagnosed based on American Diabetes Association criteria. Blood samples were used for isolation of genomic deoxyribonucleic acid (DNA). Having extracted the genomic DNA from human blood leukocytes by means of High Pure polymerase chain reaction (PCR) Template preparation kit, we carried out polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) on each blood sample. Then, Genomic DNA was digested by BstU-I restriction enzyme. Thereafter, restriction products were analyzed by means of Polyacrylamide gel electrophoresis and stained by Ethidium Bromide. RESULTS: We found that the frequency of Ala allele in healthy subjects was significantly higher than in diabetic subjects (P = 0003). Moreover, the genotype frequency of Ala/Ala in healthy subjects was significantly higher than in diabetic subjects (P < 0.001). However, the genotype frequency of Ala/Pro in diabetic subjects was significantly higher than in healthy subjects (P < 0.001). CONCLUSION: The present study suggests that polymorphism of PPAR-γ2 gene is associated with T2DM. Furthermore, Ala allele is significantly found in non-diabetic individual’s Iranian population. PMID:24019628

  14. Healthy reduced-fat Bologna sausages enriched in ALA and DHA and stabilized with Melissa officinalis extract.

    Science.gov (United States)

    Berasategi, Izaskun; Navarro-Blasco, Iñigo; Calvo, Maria Isabel; Cavero, Rita Yolanda; Astiasarán, Iciar; Ansorena, Diana

    2014-03-01

    Reduced-energy and reduced-fat Bologna products enriched with ω-3 polyunsaturated fatty acids were formulated by replacing the pork back-fat by an oil-in-water emulsion containing a mixture of linseed-algae oil stabilized with a lyophilized Melissa officinalis extract. Healthier composition and lipid profile was obtained: 85 kcal/100 g, 3.6% fat, 0.6 g ALA and 0.44 g DHA per 100 g of product and ω-6/ω-3 ratio of 0.4. Technological and sensory problems were not detected in the new formulations. Reformulation did not cause oxidation problems during 32 days of storage under refrigeration. The results suggest that it is possible to obtain reduced-fat Bologna-type sausages rich in ALA and DHA and stabilized with natural antioxidants, applying the appropriate technology without significant effects on the sensory quality, yielding interesting products from a nutritional point of view. © 2013.

  15. PPARγ2Pro12Ala Polymorphism and Human Health

    OpenAIRE

    Weimin He

    2009-01-01

    The nuclear hormone receptor peroxisome proliferator activated receptor gamma (PPAR) is an important transcription factor regulating adipocyte differentiation, lipid and glucose homeostasis, and insulin sensitivity. Numerous genetic mutations of PPAR have been identified and these mutations positively or negatively regulate insulin sensitivity. Among these, a relatively common polymorphism of PPAR, Pro12Ala of PPAR2, the isoform expressed only in adipose tissue has been shown to be associ...

  16. Alpha-linolenic acid and its conversion to longer chain n-3 fatty acids: benefits for human health and a role in maintaining tissue n-3 fatty acid levels.

    Science.gov (United States)

    Barceló-Coblijn, Gwendolyn; Murphy, Eric J

    2009-11-01

    There is little doubt regarding the essential nature of alpha-linolenic acid (ALA), yet the capacity of dietary ALA to maintain adequate tissue levels of long chain n-3 fatty acids remains quite controversial. This simple point remains highly debated despite evidence that removal of dietary ALA promotes n-3 fatty acid inadequacy, including that of docosahexaenoic acid (DHA), and that many experiments demonstrate that dietary inclusion of ALA raises n-3 tissue fatty acid content, including DHA. Herein we propose, based upon our previous work and that of others, that ALA is elongated and desaturated in a tissue-dependent manner. One important concept is to recognize that ALA, like many other fatty acids, rapidly undergoes beta-oxidation and that the carbons are conserved and reused for synthesis of other products including cholesterol and fatty acids. This process and the differences between utilization of dietary DHA or liver-derived DHA as compared to ALA have led to the dogma that ALA is not a useful fatty acid for maintaining tissue long chain n-3 fatty acids, including DHA. Herein, we propose that indeed dietary ALA is a crucial dietary source of n-3 fatty acids and its dietary inclusion is critical for maintaining tissue long chain n-3 levels.

  17. Pro12Ala polymorphism in PPARgamma2 associated with depression in Chinese nonagenarians/centenarians.

    Science.gov (United States)

    Ji-Rong, Yue; Bi-Rong, Dong; Chang-Quan, Huang; Zhen-Chan, Lu; Hong-Mei, Wu; Yan-Ling, Zhang; Mattis, Tod A

    2009-07-01

    The Pro12Ala polymorphism of peroxisome proliferator-activated receptor-gamma (PPARgamma) has been associated with decreased obesity, insulin resistance, type 2 diabetes and other age-associated diseases such as cognitive impairment, hypertension, cancer, osteoarthritis. Each one of these diseases had been linked to depression. Moreover, there is also an association between Pro12 Ala polymorphism in PPAR gamma2 and longevity. The aim of the study was to evaluate the association between Pro12 Ala polymorphism and depression in Chinese nonagenarians and centenarians. The sample included 697 unrelated Chinese nonagenarians/centenarians (aged between 90-108 years, mean age: 93.5+/-3.35 years; 67.2% women). The Pro12Ala variant was examined using polymerase chain reaction-restriction fragment length polymorphism. Depression was measured with brief 23-item Geriatrics Depression Scale Chinese-edition (GDS-CD). In this sample, the genotype frequencies of the Pro12Ala polymorphism were 0% Ala12Ala, 9.2% Pro12Ala, 90.8% Pro12Pro and the prevalence of depression was 25.3%. Subjects who were 12Ala carriers had significantly lower prevalence of depression than those who were not 12Ala carriers (14.06 vs. 26.38%, p=0.034). Subjects without depression also had a higher frequency of 12Ala gene than those with depression (5.28 vs. 2.56%, p=0.031). Adjusting for certain clinical factors that may be associated with depression or with 12Ala carriers, multiple logistic regressions showed the 12Ala gene was associated with decreased incidence of depression. In summary, we found that among Chinese nonagenarians and centenarians, the Pro12Ala polymorphism in PPARgamma2 was associated with depression and that the 12Ala gene may be a factor for decreased depression.

  18. The Pro12Ala Polymorphism of the Peroxisome Proliferator-Activated Receptor Gamma Gene Modifies the Association of Physical Activity and Body Mass Changes in Polish Women

    Directory of Open Access Journals (Sweden)

    Aleksandra Zarebska

    2014-01-01

    Full Text Available Peroxisome proliferator-activated receptor γ is a key regulator of adipogenesis, responsible for fatty acid storage and maintaining energy balance in the human body. Studies on the functional importance of the PPARG Pro12Ala polymorphic variants indicated that the observed alleles may influence body mass measurements; however, obtained results were inconsistent. We have decided to check if body mass changes observed in physically active participants will be modulated by the PPARG Pro12Ala genotype. The genotype distribution of the PPARG Pro12Ala allele was examined in a group of 201 Polish women measured for selected body mass variables before and after the completion of a 12-week training program. The results of our experiment suggest that PPARG genotype can modulate training-induced body mass measurements changes: after completion of the training program, Pro12/Pro12 homozygotes were characterised by a greater decrease of body fat mass measurements in comparison with 12Ala allele carriers. These results indicate that the PPARG 12Ala variant may impair the training-induced positive effects on body mass measurements; however, the detailed mechanism of such interaction remained unclear and observed correlation between PPARG genotype and body mass differential effects should be interpreted with caution.

  19. The Pro12Ala Polymorphism of the Peroxisome Proliferator-Activated Receptor Gamma Gene Modifies the Association of Physical Activity and Body Mass Changes in Polish Women.

    Science.gov (United States)

    Zarebska, Aleksandra; Jastrzebski, Zbigniew; Cieszczyk, Pawel; Leonska-Duniec, Agata; Kotarska, Katarzyna; Kaczmarczyk, Mariusz; Sawczuk, Marek; Maciejewska-Karlowska, Agnieszka

    2014-01-01

    Peroxisome proliferator-activated receptor γ is a key regulator of adipogenesis, responsible for fatty acid storage and maintaining energy balance in the human body. Studies on the functional importance of the PPARG Pro12Ala polymorphic variants indicated that the observed alleles may influence body mass measurements; however, obtained results were inconsistent. We have decided to check if body mass changes observed in physically active participants will be modulated by the PPARG Pro12Ala genotype. The genotype distribution of the PPARG Pro12Ala allele was examined in a group of 201 Polish women measured for selected body mass variables before and after the completion of a 12-week training program. The results of our experiment suggest that PPARG genotype can modulate training-induced body mass measurements changes: after completion of the training program, Pro12/Pro12 homozygotes were characterised by a greater decrease of body fat mass measurements in comparison with 12Ala allele carriers. These results indicate that the PPARG 12Ala variant may impair the training-induced positive effects on body mass measurements; however, the detailed mechanism of such interaction remained unclear and observed correlation between PPARG genotype and body mass differential effects should be interpreted with caution.

  20. Characterization of the l-alanine exporter AlaE of Escherichia coli and its potential role in protecting cells from a toxic-level accumulation of l-alanine and its derivatives.

    Science.gov (United States)

    Kim, Seryoung; Ihara, Kohei; Katsube, Satoshi; Hori, Hatsuhiro; Ando, Tasuke; Isogai, Emiko; Yoneyama, Hiroshi

    2015-08-01

    We previously reported that the alaE gene of Escherichia coli encodes the l-alanine exporter AlaE. The objective of this study was to elucidate the mechanism of the AlaE exporter. The minimum inhibitory concentration of l-alanine and l-alanyl-l-alanine in alaE-deficient l-alanine-nonmetabolizing cells MLA301ΔalaE was 4- and >4000-fold lower, respectively, than in the alaE-positive parent cells MLA301, suggesting that AlaE functions as an efflux pump to avoid a toxic-level accumulation of intracellular l-alanine and its derivatives. Furthermore, the growth of the alaE-deficient mutant derived from the l-alanine-metabolizing strain was strongly inhibited in the presence of a physiological level of l-alanyl-l-alanine. Intact MLA301ΔalaE and MLA301ΔalaE/pAlaE cells producing plasmid-borne AlaE, accumulated approximately 200% and 50%, respectively, of the [(3) H]l-alanine detected in MLA301 cells, suggesting that AlaE exports l-alanine. When 200 mmol/L l-alanine-loaded inverted membrane vesicles prepared from MLA301ΔalaE/pAlaE were placed in a solution containing 200 mmol/L or 0.34 μmol/L l-alanine, energy-dependent [(3) H]l-alanine accumulation occurred under either condition. This energy-dependent uphill accumulation of [(3) H]l-alanine was strongly inhibited in the presence of carbonyl cyanide m-chlorophenylhydrazone but not by dicyclohexylcarbodiimide, suggesting that the AlaE-mediated l-alanine extrusion was driven by proton motive force. Based on these results, physiological roles of the l-alanine exporter are discussed.

  1. δ-ALA-PDT治疗面部基底细胞癌、Bowen病及日光性角化病的临床研究%The clinical research on treating facial basal cell carcinoma,Bowen's disease and actinic keratosis with δ-Aminolaevulinic acid-photodynamic therapy

    Institute of Scientific and Technical Information of China (English)

    李洁思; 李森真; 李春香

    2009-01-01

    目的 探讨δ-氨基酮戊酸光动力学疗法(δ-ALA -PDT)治疗面部浅表基底细胞癌(BCC)、Bowen病(BD)及日光性角化病(AK)的近期效果.方法 24例患者中,16例皮肤BCC,3例BD病,5例AK,均经病理组织学确诊.局部外用新鲜配制的20%ALA乳膏,封包4 h后用中心波长630 nm的德国Waldmann PDT 1200不连续红光照射,病变部位照射强度为105~168 mW/cm2,剂量为150~200 J/cm2,照射时间20~30 min.结果 经过1次(12例)、2次(3例)和3次(1例)治疗后,BCC患者10例完全缓解,5例部分缓解,1例无反应;BD患者2例完全缓解,1例部分缓解;AK患者3例完全缓解,2例部分缓解.结论 δ-ALA-PDT治疗面部浅表BCC、BD病及AK有效,方法简单,患者耐受性好,无瘢痕形成,在保持患者面部美容方面有优势.

  2. The Pro12Ala variant at the peroxisome proliferator-activated receptor γ gene and change in obesity-related traits in the Diabetes Prevention Program

    Science.gov (United States)

    Franks, P. W.; Jablonski, K. A.; Delahanty, L.; Hanson, R. L.; Kahn, S. E.; Altshuler, D.; Knowler, W. C.; Florez, J. C.

    2008-01-01

    Aims/hypothesis Peroxisome proliferator-activated receptor γ (PPARγ), encoded by the PPARG gene, regulates insulin sensitivity and adipogenesis, and may bind polyunsaturated fatty acids (PUFA) and thiazolidinediones in a ligand-dependent manner. The PPARG proline for alanine substitution at position 12 (Pro12Ala polymorphism) has been related with obesity directly and via interaction with PUFA. Methods We tested the effect-modifying role of Pro12Ala on the 1 year change in obesity-related traits in a randomized clinical trial of treatment with metformin (n=989), troglita-zone (n=363) or lifestyle modification (n=1,004) vs placebo (n=1,000) for diabetes prevention in high-risk individuals. Results At baseline, Ala12 carriers had larger waists (p<0.001) and, in a subset, more subcutaneous adipose tissue (SAT; lumbar 2/3; p=0.04) than Pro12 homozygotes. There was a genotype-by-intervention interaction on 1-year weight change (p=0.01); in the placebo arm, Pro12 homozygotes gained weight and Ala12 carriers lost weight (p=0.001). In the metformin and lifestyle arms, weight loss occurred across genotypes, but was greatest in Ala12 carriers (p<0.05). Troglitazone treatment induced weight gain, which tended to be greater in Ala12 carriers (p=0.08). In the placebo group, SAT (lumbar 2/3, lumbar 4/5) decreased in Ala12 allele carriers, but was unchanged in Pro12 homozygotes (p≤0.005). With metformin treatment, SAT decreased independently of genotype. In the lifestyle arm, SAT (lumbar 2/3) reductions occurred across genotypes, but were greater in Ala12 carriers (p=0.03). A genotype-by-PUFA intake interaction on reduction in visceral fat (lumbar 4/5; p=0.04) was also observed, which was most evident with metformin treatment (p<0.001). Conclusions /interpretation Within the Diabetes Prevention Program, the Ala12 allele influences central obesity, an effect which may differ by treatment group and dietary PUFA intake (ClinicalTrials.gov ID no: NCT00004992). PMID:17898990

  3. Crystal structure of Boc-(S-ABOC-(S-Ala-(S-ABOC-(S-Phe-OBn chloroform monosolvate

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    Emmanuel Wenger

    2015-10-01

    Full Text Available In the title compound, phenyl (S-2-[(S-(1-{2-[(S-(1-{[(tert-butoxycarbonyl]amino}bicyclo[2.2.2]octan-2-ylformamido]propanamido}bicyclo[2.2.2]octan-2-ylformamido]-3-phenylpropanoate chloroform monosolvate, C42H56N4O7·CHCl3, the α,β-hybrid peptide contains two non-proteinogenic amino acid residues of (S-1-aminobicyclo[2.2.2]octane-2-carboxylic acid [(S-ABOC], two amino acid residues of (S-2-aminopropanoic acid [(S-Ala] and (S-2-amino-3-phenylpropanoic acid [(S-Phe], and protecting groups of tert-butoxycarbonyl (Boc and benzyl ester (OBn. The tetramer folds into a right-handed mixed 11/9 helix stabilized by intramolecular i,i + 3 and i,i − 1 C=O...H—N hydrogen bonds. In the crystal, the oligomers are linked by N—H...O=C hydrogen bonds into chains along the a-axis direction. The chloroform solvent molecules are intercalated between the folded chains via C—H...O=C interactions.

  4. The influence of the stereochemistry of alanine residue on the solid state conformation and crystal packing of opioid peptides containing D-Ala or L-Ala in message domain--XRD and NMR study.

    Science.gov (United States)

    Trzeciak-Karlikowska, Katarzyna; Bujacz, Anna; Ciesielski, Włodzimierz; Bujacz, Grzegorz D; Potrzebowski, Marek J

    2011-08-18

    In this work, an X-ray diffraction (XRD) and solid state NMR study of two tetrapeptides with different stereochemistry of alanine residue is presented using Tyr-(D-Ala)-Phe-Gly (1), an N-terminal sequence of opioid peptide dermorphin, and its biologically inactive analog Tyr-(L-Ala)-Phe-Gly (2). Single-crystal XRD proved that 1 crystallized under different conditions from exclusively one structure: a monoclinic crystal with P2(1) space group. In contrast, 2 very easily formed at least three crystallographic modifications, 2a (monoclinic P2(1)), 2b (orthorhombic P2(1)2(1)2) and 2c (tetragonal P4(1)2(1)2). Solid-state NMR spectroscopy was employed to investigate the structure and molecular dynamics of 1, 2a, and 2b. By employing different NMR experiments (dipolar dephasing and PILGRIM) and an analysis of the (13)C principal elements of the chemical shift tensor (CST), it was proven that the main skeleton of tetrapeptides is rigid, whereas significant differences in the molecular motion of the aromatic residues were observed. Comparing current data with those of previous studies (J. Phys. Chem. B2004, 108, 4535-4545 and Cryst. Growth Des. 2009, 9, 4050-4059), it can be assumed that an important preorganization mechanism anticipating the formation of peptide crystals containing D-Ala in sequence is the intramolecular CH-π interaction, which occurs for the amino acid with D stereochemistry. This effect may be responsible for the formation of only one crystallographic form of D-Ala peptides.

  5. In vitro skin permeation and retention of 5-aminolevulinic acid ester derivatives for photodynamic therapy.

    Science.gov (United States)

    De Rosa, Fernanda Scarmato; Tedesco, Antônio Cláudio; Lopez, Renata Fonseca Vianna; Pierre, Maria Bernadete Riemma; Lange, Norbert; Marchetti, Juliana Maldonado; Rotta, Jeane Cristina Gomes; Bentley, Maria Vitória Lopes Badra

    2003-04-29

    In photodynamic therapy (PDT), 5-aminiolevulinic acid (5-ALA) applied topically is converted, via the heme cycle, into protoporphyrin IX (PpIX), a photosensitizing agent, which upon excitation with light can induce tumor destruction. Due to its hydrophilic and zwitterionic characteristics, 5-ALA has limited penetration into the skin. More lipophilic 5-ALA ester derivatives are expected to cross stratum corneum more easily than 5-ALA. According to the determination of the partition coefficients of 5-ALA methyl, n-butyl, n-hexyl and n-octyl esters, these compounds showed an increased affinity to the SC, with 5-ALA hexyl ester and 5-ALA-octyl ester having the highest partition coefficients. Our in vitro skin permeation studies demonstrated an increased permeated amount for hexyl-ALA after 6 h of incubation, compared to other esters and 5-ALA. After 6 h, more 5-ALA-hexyl ester and -octyl ester were retained at viable epidermis and dermis than 5-ALA. According to these results, and considering that the conversion of 5-ALA into PpIX occurs preferentially in epidermis, it can be supposed that topical use of ester derivatives with longer chains (C(6) or C(8)) is an interesting proposal to optimize topical 5-ALA-PDT

  6. Hemoglobin Fontainebleau [a21(B2Ala>Pro]: The second report from India

    Directory of Open Access Journals (Sweden)

    Ranjeet Singh Mashon

    2013-01-01

    Full Text Available Structural hemoglobin (Hb variants are mainly due to point mutations in the globin genes resulting in single amino acid substitutions. Until date, about 200 alpha chain variants have been identified and they are usually detected during the hemoglobinopathy screening programs. Under a community control program for hemoglobinopathies, which involved screening of antenatal cases followed by prenatal diagnosis if indicated. Here, we report a rare alpha globin gene variant Hb Fontainebleau [a21(B2Ala>Pro] detected in the heterozygous condition in a 35-year-old pregnant lady screened during this program. This is the second report of this alpha globin variant from India. Unlike the earlier case from India where Hb Fontainebleau was reported in a neonate who was also a carrier of Hb Sickle and had no clinical problems, this case presented with a bad obstetric history associated with the secondary infertility. However, the presence of the variant and the obstetric complications may be unrelated.

  7. The MnSOD Ala16Val SNP: relevance to human diseases and interaction with environmental factors.

    Science.gov (United States)

    Bresciani, G; Cruz, I B M; de Paz, J A; Cuevas, M J; González-Gallego, J

    2013-10-01

    The relevance of reactive oxygen species (ROS) production relies on the dual role shown by these molecules in aerobes. ROS are known to modulate several physiological phenomena, such as immune response and cell growth and differentiation; on the other hand, uncontrolled ROS production may cause important tissue and cell damage, such as deoxyribonucleic acid oxidation, lipid peroxidation, and protein carbonylation. The manganese superoxide dismutase (MnSOD) antioxidant enzyme affords the major defense against ROS within the mitochondria, which is considered the main ROS production locus in aerobes. Structural and/or functional single nucleotide polymorphisms (SNP) within the MnSOD encoding gene may be relevant for ROS detoxification. Specifically, the MnSOD Ala16Val SNP has been shown to alter the enzyme localization and mitochondrial transportation, affecting the redox status balance. Oxidative stress may contribute to the development of type 2 diabetes, cardiovascular diseases, various inflammatory conditions, or cancer. The Ala16Val MnSOD SNP has been associated with these and other chronic diseases; however, inconsistent findings between studies have made difficult drawing definitive conclusions. Environmental factors, such as dietary antioxidant intake and exercise have been shown to affect ROS metabolism through antioxidant enzyme regulation and may contribute to explain inconsistencies in the literature. Nevertheless, whether environmental factors may be associated to the Ala16Val genotypes in human diseases still needs to be clarified.

  8. The Dietary {alpha}-Linolenic Acid to Linoleic Acid Ratio Does Not Affect the Serum Lipoprotein Profile in Humans

    NARCIS (Netherlands)

    Goyens, P.L.L.; Mensink, R.P.

    2005-01-01

    alpha-Linolenic acid [ALA, 18:3(n-3)] and linoleic acid [LA, 18:2(n-6)] have comparable effects on serum lipid and lipoprotein concentrations, but their effects on lipoprotein subclass distributions and particle sizes are unknown. It is also not known whether these effects are changed by the ALA:LA

  9. A high-fat, high-oleic diet, but not a high-fat, saturated diet, reduces hepatic alpha-linolenic acid and eicosapentaenoic acid content in mice

    Science.gov (United States)

    Considerable research centers upon the role of linoleic acid (LNA; 18:2n6) as a competitive inhibitor of a-linolenic (ALA; 18:3n3) metabolism; however, little data exist as to the impact of saturated fatty acids (SFA) and monounsaturated fatty acids (MUFA) on ALA metabolism. We tested the hypothesi...

  10. Vitamin D Combined with Aminolevulinate (ALA)-Mediated Photodynamic Therapy (PDT) for Human Psoriasis: A Proof-of-Principle Study.

    Science.gov (United States)

    Maytin, Edward V; Honari, Golara; Khachemoune, Amor; Taylor, Charles R; Ortel, Bernhard; Pogue, Brian W; Sznycer-Taub, Nathaniel; Hasan, Tayyaba

    2012-09-01

    We previously showed that select agents (methotrexate or Vitamin D), when administered as a preconditioning regimen, are capable of promoting cellular differentiation of epithelial cancer cells while simultaneously enhancing the efficacy of 5-aminolevulinic acid (ALA)-mediated photodynamic therapy (PDT). In solid tumors, pretreatment with Vitamin D simultaneously promotes cellular differentiation and leads to selective accumulation of target porphyrins (mainly protoporphyrin IX, PpIX) within diseased tissue. However, questions of whether or not the effects upon cellular differentiation are inexorably linked to PpIX accumulation, and whether these effects might occur in hyperproliferative noncancerous tissues, have remained unanswered. In this paper, we reasoned that psoriasis, a human skin disease in which abnormal cellular proliferation and differentiation plays a major role, could serve as a useful model to test the effects of pro-differentiating agents upon PpIX levels in a non-neoplastic setting. In particular, Vitamin D, a treatment for psoriasis that restores (increases) differentiation, might increase PpIX levels in psoriatic lesions and facilitate their responsiveness to ALA-PDT. This concept was tested in a pilot study of 7 patients with bilaterally-matched psoriatic plaques. A regimen in which calcipotriol 0.005% ointment was applied for 3 days prior to ALA-PDT with blue light, led to preferential increases in PpIX (~130%), and reductions in thickness, redness, scaling, and itching in the pretreated plaques. The results suggest that a larger clinical trial is warranted to confirm a role for combination treatments with Vitamin D and ALA-PDT for psoriasis.

  11. Relation between iron metabolism and antioxidants enzymes and δ-ALA-D activity in rats experimentally infected by Fasciola hepatica.

    Science.gov (United States)

    Bottari, Nathieli B; Mendes, Ricardo E; Baldissera, Matheus D; Bochi, Guilherme V; Moresco, Rafael N; Leal, Marta L R; Morsch, Vera M; Schetinger, Maria R C; Christ, Ricardo; Gheller, Larissa; Marques, Éder J; Da Silva, Aleksandro S

    2016-06-01

    The aim of this study was to evaluate the iron metabolism in serum, as well as antioxidant enzymes, in addition to the Delta-Aminolevulinic Acid Dehydratase (δ-ALA-D) activity in the liver of rats experimentally infected by Fasciola hepatica. Thirty male adult rats (Wistar) specific pathogen free were divided into four groups: two uninfected group (CTRL 1 and CTRL 2) with five animals each and two infected groups (INF 1 and INF 2) with 10 animals each. Infection was performed orally with 20 metacercariae at day 1. On day 15 (CTRL 1 and INF 1 groups) and 87 PI (CTRL 2 and INF 2 groups) blood and bone marrow were collected and the animals were subsequently euthanized for liver sampling. Blood was allocated in tubes without anticoagulant for serum acquisition to measure iron, transferrin and unsaturated iron binding capacity (UIBC). δ-ALA-D, superoxide dismutase (SOD), and catalase (CAT) activities were measured in the liver. A decrease in iron, transferrin and UIBC levels was observed in all infected animals compared to control groups (P iron accumulation was observed in bone marrow of infected mice. Infected animals showed an increase in δ-ALA-D activity at 87 post-infection (PI) (INF 2) as well as in SOD activity at days 15 (INF 1) and 87 PI (INF 2). On the other hand, CAT activity was reduced in rats infected by F. hepatica during acute and chronic phase of fasciolosis (INF 1 and INF 2 groups), when moderate (acute) and severe necrosis in the liver histopathology were observed. These results may suggest that oxidative damage to tissues along with antioxidant mechanisms might have taken part in fasciolosis pathogenesis and are also involved in iron deficiency associated to changes in δ-ALA-D activity during chronic phase of disease.

  12. Interaction of PPARG Pro12Ala with dietary fat influences plasma lipids in subjects at cardiometabolic risk[S

    Science.gov (United States)

    AlSaleh, Aseel; O'Dell, Sandra D.; Frost, Gary S.; Griffin, Bruce A.; Lovegrove, Julie A.; Jebb, Susan A.; Sanders, Thomas A. B.

    2011-01-01

    The PPARγ2 gene single nucleotide polymorphism (SNP) Pro12Ala has shown variable association with metabolic syndrome traits in healthy subjects. The RISCK Study investigated the effect of interaction between genotype and the ratio of polyunsaturated:saturated (P:S) fatty acid intake on plasma lipids in 367 white subjects (ages 30-70 years) at increased cardiometabolic risk. Interaction was determined after habitual diet at recruitment, at baseline after a 4-week high-SFA (HS) diet, and after a 24-week reference (HS), high-MUFA (HM), or low-fat (LF) diet. At recruitment, there were no significant associations between genotype and plasma lipids; however, P:S × genotype interaction influenced plasma total cholesterol (TC) (P = 0.02), LDL-cholesterol (LDL-C) (P = 0.002), and triglyceride (TG) (P = 0.02) concentrations. At P:S ratio ≤ 0.33, mean TC and LDL-C concentrations in Ala12 allele carriers were significantly higher than in noncarriers (respectively, P = 0.003; P = 0.0001). Significant trends in reduction of plasma TC (P = 0.02) and TG (P = 0.002) concentrations occurred with increasing P:S (respectively, ≤0.33 to >0.65; 0.34 to >0.65) in Ala12 allele carriers. There were no significant differences between carriers and noncarriers after the 4-week HS diet or 24-week interventions. Plasma TC and TG concentrations in PPARG Ala12 allele carriers decrease as P:S increases, but they are not dependent on a reduction in SFA intake. PMID:21949049

  13. Pro12Ala polymorphism in PPAR-gamma2 and dementia in Chinese nonagenarians/centenarians.

    Science.gov (United States)

    Yue, Ji-Rong; Dong, Bi-Rong; Huang, Chang-Quan; Lu, Zhen-Chan; Wu, Hong-Mei; Zhang, Yan-Ling

    2010-09-01

    We examined the existence of a relationship between polymorphism and dementia in subjects aged 90 years and above. The sample included 732 unrelated Chinese nonagenarians/centenarians (aged 90-108 years, mean age 93.68 years; 67.5% women). The Pro12Ala variant was examined using polymerase chain reaction restriction fragment length polymorphism. Cognitive function was measured with 30-item mini-mental state examination. The genotype frequencies of the Pro12Ala polymorphism were 0% Ala12Ala, 9.1% Pro12Ala, and 90.9% Pro12Pro. The prevalence rates of dementia were 64.9% in the whole sample (45.0% for men and 74.5% for women). In both men and women, between subjects with and without 12Ala carriers, there was no significant difference in cognitive function scores and also no significant difference in prevalence of dementia; there was no significant difference in frequency of 12Ala carriers between subjects with and without dementia. Multiple logistic regression was performed by adjusting clinical factors that are thought to be associated with cognitive function or with 12Ala carriers. We found that 12Ala is not a risk factor for dementia. We found that Pro12Ala polymorphism in PPAR-gamma2 was not directly correlated with dementia among Chinese nonagenarians and centenarians.

  14. Pro12Ala polymorphism in PPAR-γ2 and dementia in Chinese nonagenarians/centenarians

    Science.gov (United States)

    Ji-Rong, Yue; Chang-Quan, Huang; Zhen-Chan, Lu; Hong-Mei, Wu; Yan-Ling, Zhang

    2010-01-01

    We examined the existence of a relationship between polymorphism and dementia in subjects aged 90 years and above. The sample included 732 unrelated Chinese nonagenarians/centenarians (aged 90–108 years, mean age 93.68 years; 67.5% women). The Pro12Ala variant was examined using polymerase chain reaction restriction fragment length polymorphism. Cognitive function was measured with 30-item mini-mental state examination. The genotype frequencies of the Pro12Ala polymorphism were 0% Ala12Ala, 9.1% Pro12Ala, and 90.9% Pro12Pro. The prevalence rates of dementia were 64.9% in the whole sample (45.0% for men and 74.5% for women). In both men and women, between subjects with and without 12Ala carriers, there was no significant difference in cognitive function scores and also no significant difference in prevalence of dementia; there was no significant difference in frequency of 12Ala carriers between subjects with and without dementia. Multiple logistic regression was performed by adjusting clinical factors that are thought to be associated with cognitive function or with 12Ala carriers. We found that 12Ala is not a risk factor for dementia. We found that Pro12Ala polymorphism in PPAR-γ2 was not directly correlated with dementia among Chinese nonagenarians and centenarians. PMID:20640553

  15. Isomerization and epimerization of the aspartyl tetrapeptide Ala-Phe-Asp-GlyOH at pH 10-A CE study.

    Science.gov (United States)

    Brückner, Christin; Bunz, Svenja-Catharina; Imhof, Diana; Neusüss, Christian; Scriba, Gerhard K E

    2013-09-01

    Isomerization and enantiomerization of Asp in the tetrapeptide Ala-Phe-Asp-GlyOH are studied at pH 10 and 80°C as well as 25°C. CE-MS allowed the distinction between α-Asp and β-Asp linkages in degradation products based on the ratio of the b and y fragment ions. Besides isomerization and enantiomerization of Asp, enantiomerization of Ala and Phe was also observed at both temperatures by chiral amino acid HPLC analysis using Marfey's reagent for derivatization. The rate of enantiomerization of the amino acids proceeded in the order Asp > Ala > Phe. The CE assay was validated with respect to linearity, LOQ, LOD, and precision and employed to characterize the time course of the degradation of the tetrapeptide upon incubation in borate buffer, pH 10. Isomerization to β-Asp peptides was identified as the major degradation reaction. The configuration of Asp or Ala affected the half-life of the starting peptide to a minor extent but did not influence the distribution of the individual products under equilibrium conditions at 80°C. Degradation at 25°C proceeded very slowly so that the equilibrium was not reached after 245 days. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Light fractionation increases the efficacy of ALA-PDT but not of MAL-PDT: What is the role of (vascular) endothelial cells?

    Science.gov (United States)

    de Bruijn, H. S.; de Vijlder, H. C.; de Haas, E. R. M.; van der Ploeg-van den Heuvel, A.; Kruijt, B.; Poel-Dirks, D.; Sterenborg, H. J. C. M.; ten Hagen, T. L. M.; Robinson, D. J.

    2009-06-01

    Photodynamic therapy (PDT) using protoporpyrin IX (PpIX) precursors like 5-aminolevulinic acid (ALA) or methyl-aminolevulinate (MAL) has shown to be effective in the treatment of various skin diseases. Using ALA we have shown in numerous studies a significantly improved efficacy by applying light fractionation with a long dark interval. In contrast, in the hairless mouse model, the PDT efficacy using MAL is unaffected by adopting this approach. More acute edema is found after ALA-PDT suggesting a difference in response of endothelial cells to PDT. To investigate the role of endothelial cells, cryo-sections of hairless mouse skin after 4 hours of topical MAL or ALA application were stained with a fluorescent endothelial cell marker (CD31). Co-localization of this marker with the PpIX fluorescence was performed using the spectral imaging function of the confocal microscope. We have also used intra-vital confocal microscopy to image the PpIX fluorescence distribution in correlation with the vasculature of live mouse skin. Our results show PpIX fluorescence at depth in cryo-sections of mouse skin after 4 hours of topical application. Co-localization has shown to be difficult due to the changes in tissue organization caused by the staining procedure. As expected we found high PpIX fluorescence levels in the epidermis after both MAL and ALA application using intra-vital microscopy. After ALA application more PpIX fluorescence was found deep in the dermal layer of the skin than after MAL. Furthermore we detected localized fluorescence in unidentified structures that could not be correlated to blood vessels or nerves.

  17. Influence of ceramide 2 on in vitro skin permeation and retention of 5-ALA and its ester derivatives, for Photodynamic Therapy

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    Maria Bernadete Riemma Pierre

    2009-03-01

    Full Text Available Photodynamic therapy (PDT based on topical 5-aminolevulinic acid (5-ALA, an endogenous precursor of protoporphyrin, is an interesting approach for the treatment of skin cancer. However, 5-ALA is a hydrophilic molecule and such a characteristic limits its appropriate cutaneous penetration and retention. In this way, more lipophilic molecules, such as esterified 5-ALA derivatives, have been under investigation in order to improve the skin penetration of this molecule. Drug formulation can also alter 5-ALA skin penetration. Therefore, the aim of this work was to study the influence of ceramide 2 - the main lipid of the SC- on the cutaneous delivery of 5-ALA and its ester derivatives in vitro, using Franz diffusion cell. The skin permeation of all studied drugs was decreased in the presence of ceramide, representing a desirable characteristic in order to avoid the risk of systemic side effects. Nevertheless, the SC and [epidermis + dermis] retention after 16 h has also been decreased in the presence of ceramide, as compared to control. In conclusion, ceramide was not a good adjuvant, meaning that research of other vehicles could be useful to improve cutaneous delivery of 5-ALA.A Terapia Fotodinâmica (TFD tópica com um precursor das porfirinas endógenas, o ácido 5-aminolevulínico (5-ALA, constitui uma nova modalidade para o tratamento do câncer de pele. Entretanto, o 5-ALA é uma molécula hidrofílica, o que limita sua penetração e retenção cutânea apropriadas. Moléculas mais lipofílicas, tais como derivados esterificados do 5-ALA, estão sob intensa investigação para melhorar a penetração cutânea desta molécula. A formulação que contém o fármaco também pode alterar a penetração cutânea do 5-ALA. Desta forma, o objetivo deste trabalho foi estudar a influência da ceramida 2 - o principal lipídeo do EC- sobre a penetração cutânea de 5-ALA e seus derivados esterificados usando células de difusão de Franz. A permea

  18. MOLECULAR DYNAMICS STUDY OF INTERACTIONS OF POLYMYXIN B3 AND ITS ALA-MUTANTS WITH LIPOPOLYSACCHARIDE

    Directory of Open Access Journals (Sweden)

    Lisnyak Yu. V.

    2015-12-01

    LPS complexes with Ala-mutants of PmB3. The mutations disturbed the characteristic hydrogen-bond network of PmB3-LPS complex. Ala-mutations of Dab1, Dab8 and Dab9 amino acid residues of PmB3 destabilized PmB3- LPS complex to a greater extent: the values of binding energy for these mutants showed increase and largeamplitude irregular fluctuations. Conclusions. Hydrogen bonding of polymyxin B with the lipopolysaccharide is an important factor of the stability of PmB3-LPS complex. Detailed knowledge of the peculiarities of molecular interactions of polymyxins with its primary target on the outer membrane of Gramnegative bacteria is a prerequisite of a purposeful design of novel polymyxin-like lipopeptides.

  19. The Relationship between ALA16VAL Single Gene Polymorphism and Renal Cell Carcinoma.

    Science.gov (United States)

    Atilgan, Dogan; Parlaktas, Bekir S; Uluocak, Nihat; Kolukcu, Engin; Erdemir, Fikret; Ozyurt, Huseyin; Erkorkmaz, Unal

    2014-01-01

    Objectives. The aim of this study was to investigate the association of RCC and Ala16Val polymorphism in Turkish patients with RCC. Materials and Methods. A total of 41 patients with RCC who underwent radical or partial nephrectomy in our clinic and 50 healthy volunteers living in the same geographic area were included in this study. DNA samples from serum of RCC patients and controls were genotyped for MnSOD polymorphism analysis. Genotype ratios and allele frequencies were compared between two groups and odd ratios with 95% confidence intervals were calculated statistically. A P value of <0.05 was considered statistically significant. Results. There was a significant difference in the MnSOD genotype distributions between the RCC patients and the controls in terms of Ala/Ala+Ala/Val and Val/Val genotypes (P = 0.039). The Ala/Ala+Ala/Val genotypes were found significantly suspicious for RCC with an OR of 2.64 (95% CI = 1.06-6.69, P = 0.039). In addition, Ala allele was found significantly suspicious for RCC with an OR of 2.26 (95% CI = 1.24-4.12, P = 0.009). Conclusion. Our study indicated that MnSOD Ala16Val polymorphism may be one of the many genetic factors for renal cancer susceptibility in Turkish patients.

  20. The Relationship between ALA16VAL Single Gene Polymorphism and Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Dogan Atilgan

    2014-01-01

    Full Text Available Objectives. The aim of this study was to investigate the association of RCC and Ala16Val polymorphism in Turkish patients with RCC. Materials and Methods. A total of 41 patients with RCC who underwent radical or partial nephrectomy in our clinic and 50 healthy volunteers living in the same geographic area were included in this study. DNA samples from serum of RCC patients and controls were genotyped for MnSOD polymorphism analysis. Genotype ratios and allele frequencies were compared between two groups and odd ratios with 95% confidence intervals were calculated statistically. A P value of <0.05 was considered statistically significant. Results. There was a significant difference in the MnSOD genotype distributions between the RCC patients and the controls in terms of Ala/Ala+Ala/Val and Val/Val genotypes (P=0.039. The Ala/Ala+Ala/Val genotypes were found significantly suspicious for RCC with an OR of 2.64 (95% CI = 1.06–6.69, P= 0.039. In addition, Ala allele was found significantly suspicious for RCC with an OR of 2.26 (95% CI = 1.24–4.12, P= 0.009. Conclusion. Our study indicated that MnSOD Ala16Val polymorphism may be one of the many genetic factors for renal cancer susceptibility in Turkish patients.

  1. N-Protonated Isomers and Coulombic Barriers to Dissociation of Doubly Protonated Ala8Arg

    Science.gov (United States)

    Haeffner, Fredrik; Irikura, Karl K.

    2017-10-01

    Collision-induced dissociation (or tandem mass spectrometry, MS/MS) of a protonated peptide results in a spectrum of fragment ions that is useful for inferring amino acid sequence. This is now commonplace and a foundation of proteomics. The underlying chemical and physical processes are believed to be those familiar from physical organic chemistry and chemical kinetics. However, first-principles predictions remain intractable because of the conflicting necessities for high accuracy (to achieve qualitatively correct kinetics) and computational speed (to compensate for the high cost of reliable calculations on such large molecules). To make progress, shortcuts are needed. Inspired by the popular mobile proton model, we have previously proposed a simplified theoretical model in which the gas-phase fragmentation pattern of protonated peptides reflects the relative stabilities of N-protonated isomers, thus avoiding the need for transition-state information. For singly protonated Ala n ( n = 3-11), the resulting predictions were in qualitative agreement with the results from low-energy MS/MS experiments. Here, the comparison is extended to a model tryptic peptide, doubly protonated Ala8Arg. This is of interest because doubly protonated tryptic peptides are the most important in proteomics. In comparison with experimental results, our model seriously overpredicts the degree of backbone fragmentation at N9. We offer an improved model that corrects this deficiency. The principal change is to include Coulombic barriers, which hinder the separation of the product cations from each other. Coulombic barriers may be equally important in MS/MS of all multiply charged peptide ions. [Figure not available: see fulltext.

  2. Genotoxicity evaluation of alpha-linolenic acid-diacylglycerol oil

    Directory of Open Access Journals (Sweden)

    Hiroshi Honda

    2016-01-01

    Full Text Available The alpha-linolenic acid (ALA-diacylglycerol (DAG oil is an edible oil enriched with DAG (>80% and ALA (>50%. Although DAG oil, which mainly consists of oleic and linoleic acids has no genotoxic concerns, the fatty acid composition could affect the chemical property of DAG. Therefore, the purpose of this study was to evaluate the genotoxicity of ALA-DAG oil using standard genotoxicity tests in accordance with the OECD guidelines. ALA-DAG oil showed negative results in the bacterial reverse mutation test (Ames test and in vitro micronucleus test in cultured Chinese hamster lung cells with and without metabolic activation, and in the in vivo bone marrow micronucleus test in mice. Our results did not show any genotoxicity, suggesting that the fatty acid composition had no deleterious effects. We conclude that ALA-DAG oil had no genotoxicity concerns under the testing conditions.

  3. δ-Aminolevulinic acid cytotoxic effects on human hepatocarcinoma cell lines

    Directory of Open Access Journals (Sweden)

    del Batlle Alcira M

    2002-03-01

    Full Text Available Abstract Background Acute Intermittent Porphyria is a genetic disorder of heme metabolism, characterized by increased levels of porphyrin precursors, δ-aminolevulinic acid (ALA and porphobilinogen (PBG. ALA has been reported to generate reactive oxygen species and to cause oxidative damage to proteins, subcellular structures and DNA. It is known that oxidative stress can induce apoptosis. The aim of this work was to study the cytotoxic effect of ALA on two hepatocarcinoma cell lines. Results We have determined the impact of ALA on HEP G2 and HEP 3B hepatocarcinoma cell lines survival as measured by the MTT assay. ALA proved to be cytotoxic in both cell lines however; HEP G2 was more sensitive to ALA than HEP 3B. Addition of hemin or glucose diminished ALA cytotoxicity in HEP G2 cells; instead it was enhanced in HEP 3B cells. Because apoptosis is usually associated with DNA fragmentation, the DNA of ALA treated and untreated cells were analyzed. The characteristic pattern of DNA fragmentation ladders was observed in ALA treated cells. To elucidate the mechanisms of ALA induced apoptosis, we examined its effect on p53 expression. No changes in p53 mRNA levels were observed after exposure of both cell lines to ALA for 24 h. CDK2 and CDK4 protein levels were reduced after ALA treatment at physiological concentrations.

  4. Biological formation of 5-aminolevulinic acid by photosynthetic bacteria

    Institute of Scientific and Technical Information of China (English)

    LIU Xiu-yan; XU Xiang-yang; MA Qing-lan; WU Wei-hong

    2005-01-01

    In this study, 7 stains of Rhodopseudomonas sp. were selected from 36 photosynthetic bacteria stains storied in our laboratory.Rhodopseudomonas sp. strain 99-28 has the highest 5-aminolevulinic acid(ALA) production ability in these 7 strains. Rhodopseudomonas sp. 99-28 strain was mutated using ultraviolet radiation and a mutant strain L-1, which ALA production is higher than wild strain 99-28 about one times, was obtained. The elements affecting ALA formation of strain 99-28 and L-1 were studied. Under the optimal condition(pH 7.5,supplement of ALA dehydratase(ALAD) inhibitor, levulinic acid(LA) and precursors of ALA synthesis, glycine and succinat, 3000 Ix of light density), ALA formation of mutant L-1 was up to 22.15 mg/L. Strain L-1 was used to treat wastewater to remove CODCr and produce ALA. ALA production was 2.819 my/L, 1.531 rog/L, 2.166 mg/L, and 2.424 mg/L in monosodium glutamate wastewater(MGW),succotash wastewater(SW), brewage wastewater(BW), and citric acid wastewater(CAW) respectively. More than 90% of CODCr was removed in four kinds of wastewater. When LA, glycin and succinate were supplied, ALA production was dramatically increased,however, CODCr could hardly be removed.

  5. 5-ALA-PDT后鼻咽癌裸鼠荷瘤组织VEGF及HIF-1α表达改变的实验研究%Expressions of VEGF and HIF-1α in nasopharyngeal carcinoma tissues of nude mice after 5-ALA-PDT

    Institute of Scientific and Technical Information of China (English)

    谢莹; 韦正波; 张哲; 温文胜; 易翔; 黄光武

    2011-01-01

    OBJECTIVE: To investigate the different expressions of VEGF and HIF-1α in nude mice bearing nasopharyngeal carcinoma after 5-aminolevulinic acid-photodynamic therapy (5-ALA-PDT).METHODS: CNE-2 cells were implanted in the right flank of the BALB/c nude mice.When the size of tumor reached 0.1-0.15 cm3 ,the mice were administrated with 5-ALA intratumorally at a dose of 100 mg/kg and 3 - 3.5 h prior to laser irradiation (100 mW/cm2 ,100 J,630 nm), while the mice of the control group were under exposure to the same dose laser without 5-ALA used.VEGF and HIF-1α expressions in tumors in both 5-ALA-PDT and control groups were detected by real-time fluorescent quantitative PCR, immunohistochemistry, Western-blot 24 h and 14 d respectively after the exposure to laser.RESULTS: Both differences of HIF-1α mRNA and protein levels were not significant between the 5-ALA-PDT and control groups(P> 0.05).The expression of VEGF in the 5-ALA-PDT group prominently was down-regulated 14 d after PDT(80% positive rate) ,with slightly up-regulated 24 h after the exposure comparing to control group(40% positive rate).CONCLUSIONS: Down-regulation of VEGF in 14 d after 5-ALA-PDT can be the mechanism of inhibition of the development of NPC.This study shows no significant change of HIF-1α following 5-ALA-PDT.The further study will be clone to identify whether HIF-1α can regulate VEGF after PDT.%目的:探讨5-ALA光动力治疗后,裸鼠体内鼻咽癌组织中VEGF及HIF基因表达的改变.方法:鼻咽癌CNE2细胞接种到BALB/c裸鼠右腋下,当肿瘤长到0.1~0.15 cm3时,将动物随机分成3组,每组10只,局部给予5-ALA100 mg/kg,3~3.5h后激光照射(100 mW/cm2,100 J,630 nm),对照组相等激光剂量照射但不给药.分别用实时荧光定量PCR、免疫组化、蛋白质印迹法检测对照组、5-ALA-PDT后24 h及14 d裸鼠鼻咽癌负荷瘤中 VEGF及HIF-1α表达情况.结果:HIF-1α mRNA、蛋白水平在各组间表达差异无统计学意义,P>0.05,

  6. Effect of 5-aminolevulinic acid on erythropoiesis: A preclinical in vitro characterization for the treatment of congenital sideroblastic anemia

    Energy Technology Data Exchange (ETDEWEB)

    Fujiwara, Tohru [Department of Hematology and Rheumatology, Tohoku University Graduate School, Sendai (Japan); Department of Molecular Hematology/Oncology, Tohoku University Graduate School, Sendai (Japan); Okamoto, Koji; Niikuni, Ryoyu [Department of Hematology and Rheumatology, Tohoku University Graduate School, Sendai (Japan); Takahashi, Kiwamu [SBI Pharmaceuticals Co., Ltd., Tokyo (Japan); Okitsu, Yoko; Fukuhara, Noriko; Onishi, Yasushi [Department of Hematology and Rheumatology, Tohoku University Graduate School, Sendai (Japan); Ishizawa, Kenichi [Department of Hematology and Rheumatology, Tohoku University Graduate School, Sendai (Japan); Clinical Research, Innovation and Education Center, Tohoku University Hospital, Sendai (Japan); Ichinohasama, Ryo [Department of Hematopathology, Tohoku University Graduate School, Sendai (Japan); Nakamura, Yukio [Cell Engineering Division, RIKEN BioResource Center, Tsukuba, Ibaraki (Japan); Nakajima, Motowo; Tanaka, Tohru [SBI Pharmaceuticals Co., Ltd., Tokyo (Japan); Harigae, Hideo, E-mail: harigae@med.tohoku.ac.jp [Department of Hematology and Rheumatology, Tohoku University Graduate School, Sendai (Japan); Department of Molecular Hematology/Oncology, Tohoku University Graduate School, Sendai (Japan)

    2014-11-07

    Highlights: • Treatment with ALA induces erythroid differentiation of K562 cells. • Transportation of ALA into erythroid cells occurs predominantly via SLC36A1. • ALA restores defects in ALAS2 in human iPS cell-derived erythroblasts. • ALA may represent a novel therapeutic option for CSA caused by ALAS2 mutations. - Abstract: Congenital sideroblastic anemia (CSA) is a hereditary disorder characterized by microcytic anemia and bone marrow sideroblasts. The most common form of CSA is attributed to mutations in the X-linked gene 5-aminolevulinic acid synthase 2 (ALAS2). ALAS2 is a mitochondrial enzyme, which utilizes glycine and succinyl-CoA to form 5-aminolevulinic acid (ALA), a crucial precursor in heme synthesis. Therefore, ALA supplementation could be an effective therapeutic strategy to restore heme synthesis in CSA caused by ALAS2 defects. In a preclinical study, we examined the effects of ALA in human erythroid cells, including K562 cells and human induced pluripotent stem cell-derived erythroid progenitor (HiDEP) cells. ALA treatment resulted in significant dose-dependent accumulation of heme in the K562 cell line. Concomitantly, the treatment substantially induced erythroid differentiation as assessed using benzidine staining. Quantitative reverse transcription polymerase chain reaction (RT-PCR) analysis confirmed significant upregulation of heme-regulated genes, such as the globin genes [hemoglobin alpha (HBA) and hemoglobin gamma (HBG)] and the heme oxygenase 1 (HMOX1) gene, in K562 cells. Next, to investigate the mechanism by which ALA is transported into erythroid cells, quantitative RT-PCR analysis was performed on previously identified ALA transporters, including solute carrier family 15 (oligopeptide transporter), member (SLC15A) 1, SLC15A2, solute carrier family 36 (proton/amino acid symporter), member (SLC36A1), and solute carrier family 6 (neurotransmitter transporter), member 13 (SLC6A13). Our analysis revealed that SLC36A1 was abundantly

  7. [Production of 5-aminolevulinic acid from organic industrial wastewater by photosynthetic bacteria].

    Science.gov (United States)

    Xiuyan, Liu; Xiangyang, Xu; Min, Ye; Shuo, Xiang

    2008-09-01

    We used Rhodopseudomonas strains with high-yield of 5-aminolevulinic acid (ALA) to produce ALA from wastewater of producing monosodium glutamate, citric acid, beer, and soybean product. Cultivation was carried out under anaerobic light condition (3000 Lux) at 30 degrees C. For comparison, we tested the addition of levulinic acid (LA), glycin and succinate to the substrate to increase the production of ALA, effect of sterilization of the wastewater for both strains. Cell mass concentration (OD660) and the content of ALA were determined with spectrophotometer. Without adding levulinic acid (LA), glycin and succinate, the growth of strain 99-28 reached plateau after 72-96 h. The maxiam ALA production was obtained at 96 h. Both the yield of ALA and the Chemical Oxygen Demand (CODcr) removal rate of monosodium glutamate waster water were the highest in all tested wasterwaters. When LA, glycin and succinate were added, ALA production of strain 99-28 was significantly increased whereas the CODcr removal was adversely affected. Non-sterial wasterwater slightly reduced the growth and CODcr removal rate of strain 99-28, however the ALA production could be strongly reduced with the addition of LA, glycin and succinate. The growth and CODcr removal of mutant strain L-1 was similar with strain 99-28, but its ALA production was much higher than that of strain 99-28. The Rhodopseudomonas strains screened in our laboratory can use organic wasterwater as substrates to produce ALA and remove CODcr.

  8. Evidence for protective effect of lipoic acid and desvenlafaxine on oxidative stress in a model depression in mice.

    Science.gov (United States)

    Silva, Márcia Calheiros Chaves; de Sousa, Caren Nádia Soares; Gomes, Patrícia Xavier Lima; de Oliveira, Gersilene Valente; Araújo, Fernanda Yvelize Ramos; Ximenes, Naiara Coelho; da Silva, Jéssica Calheiros; Vasconcelos, Germana Silva; Leal, Luzia Kalyne Almeida Moreira; Macêdo, Danielle; Vasconcelos, Silvânia Maria Mendes

    2016-01-04

    Oxidative stress is implicated in the neurobiology of depression. Here we investigated oxidative alterations in brain areas of animals submitted to the model of depression induced by corticosterone (CORT) and the effects of the antioxidant compound alpha-lipoic acid (ALA) alone or associated with the antidepressant desvenlafaxine (DVS) in these alterations. Female mice received vehicle or CORT (20 mg/kg) during 14 days. From the 15th to 21st days different animals received further administrations of: vehicle, DVS (10 or 20 mg/kg), ALA (100 or 200 mg/kg), or the combinations of DVS10+ALA100, DVS20+ALA100, DVS10+ALA200, or DVS20+ALA200. Twenty-four hours after the last drug administration prefrontal cortex (PFC), hippocampus (HC) and striatum (ST) were dissected for the determination of the activity of superoxide dismutase (SOD), reduced glutathione (GSH) and lipid peroxidation (LP) levels. CORT significantly increased SOD activity in the PFC and HC, decreased GSH levels in the HC and increased LP in all brain areas studied when compared to saline-treated animals. Decrements of SOD activity were observed in all groups and brain areas studied when compared to controls and CORT. The hippocampal decrease in GSH was reversed by ALA100, DVS10+ALA100, DVS20+ALA100 and DVS20+ALA200. The same DVS+ALA combination groups presented increased levels of GSH in the PFC and ST. The greater GSH levels were observed in the PFC, HC and ST of DVS20+ALA200 mice. LP was reversed in the groups ALA200 (PFC), DVS10+ALA100, DVS20+ALA100 (PFC, HC and ST), and DVS20+ALA200 (PFC, HC). Our findings contribute to the previous preclinical evidences implicating ALA as a promising agent for augmentation therapy in depression. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Benchmark dose approach for low-level lead induced haematogenesis inhibition and associations of childhood intelligences with ALAD activity and ALA levels.

    Science.gov (United States)

    Wang, Q; Ye, L X; Zhao, H H; Chen, J W; Zhou, Y K

    2011-04-15

    Lead (Pb) levels, delta-aminolevulinic acid dehydratase (ALAD) activities, zinc protoporphyrin (ZPP) levels in blood, and urinary delta-aminolevulinic acid (ALA) and coproporphyrin (CP) concentrations were measured for 318 environmental Pb exposed children recruited from an area of southeast China. The mean of blood lead (PbB) levels was 75.0μg/L among all subjects. Benchmark dose (BMD) method was conducted to present a lower PbB BMD (lower bound of BMD) of 32.4μg/L (22.7) based on ALAD activity than those based on the other three haematological indices, corresponding to a benchmark response of 1%. Childhood intelligence degrees were not associated significantly with ALAD activities or ALA levels. It was concluded that blood ALAD activity is a sensitive indicator of early haematological damage due to low-level Pb exposures for children.

  10. The plant P4-ATPase ALA2 is involved in flipping of phosphatidylserine analogues

    DEFF Research Database (Denmark)

    Lopez Marques, Rosa Laura

    The plant P4-ATPase ALA2 is involved in flipping of phosphatidylserine analogues Rosa Laura López-Marqués1, Lisbeth Rosager Poulsen1, Katharina Meffert2, Thomas Pomorski2, Michael Gjedde Palmgren1 1Centre for Membrane Pumps in Cells and Disease - PUMPKIN, Danish National Research Foundation......, Department of Plant Biology and Biotechnology, University of Copenhagen, DK-1871 Frederiksberg C, Denmark 2Humboldt-University Berlin, Faculty of Mathematics and Natural Science I, Institute of Biology, 10115 Berlin, Germany In the model plant Arabidopsis thaliana 12 P4-ATPases are present, named ALA1 to 12...... (for Aminophospholipid ATPase). So far, two isoforms have been characterized (ALA1 and ALA3) and shown to be involved in translocation of phospholipid analogues (1, 2). At least ALA3, located to the Golgi, has been shown to be important for membrane trafficking within the secretory pathway (1...

  11. Studying the potential role of ALIS proteins on the functionality of ALA2

    DEFF Research Database (Denmark)

    Lopez Marques, Rosa Laura; Poulsen, Lisbeth Rosager; Meffert, Katharina

    The plant P4-ATPase ALA2 is involved in flipping of phosphatidylserine analogues Rosa Laura López-Marqués1, Lisbeth Rosager Poulsen1, Katharina Meffert2, Thomas Pomorski2, Michael Gjedde Palmgren1 1Centre for Membrane Pumps in Cells and Disease - PUMPKIN, Danish National Research Foundation......, Department of Plant Biology and Biotechnology, University of Copenhagen, DK-1871 Frederiksberg C, Denmark 2Humboldt-University Berlin, Faculty of Mathematics and Natural Science I, Institute of Biology, 10115 Berlin, Germany In the model plant Arabidopsis thaliana 12 P4-ATPases are present, named ALA1 to 12...... (for Aminophospholipid ATPase). So far, two isoforms have been characterized (ALA1 and ALA3) and shown to be involved in translocation of phospholipid analogues (1, 2). At least ALA3, located to the Golgi, has been shown to be important for membrane trafficking within the secretory pathway (1...

  12. The plant P4-ATPase ALA2 is involved in flipping of phosphatidylserine analogues

    DEFF Research Database (Denmark)

    Poulsen, Lisbeth Rosager

      The plant P4-ATPase ALA2 is involved in flipping of phosphatidylserine analogues Rosa Laura López-Marqués1, Lisbeth Rosager Poulsen1, Katharina Meffert2, Thomas Pomorski2, Michael Gjedde Palmgren1 1Centre for Membrane Pumps in Cells and Disease - PUMPKIN, Danish National Research Foundation......, Department of Plant Biology and Biotechnology, University of Copenhagen, DK-1871 Frederiksberg C, Denmark 2Humboldt-University Berlin, Faculty of Mathematics and Natural Science I, Institute of Biology, 10115 Berlin, Germany In the model plant Arabidopsis thaliana 12 P4-ATPases are present, named ALA1 to 12...... (for Aminophospholipid ATPase). So far, two isoforms have been characterized (ALA1 and ALA3) and shown to be involved in translocation of phospholipid analogues (1, 2). At least ALA3, located to the Golgi, has been shown to be important for membrane trafficking within the secretory pathway (1...

  13. The manganese superoxide dismutase Ala16Val dimorphism modulates iron accumulation in human hepatoma cells.

    Science.gov (United States)

    Nahon, Pierre; Charnaux, Nathalie; Friand, Véronique; Prost-Squarcioni, Catherine; Ziol, Marianne; Lièvre, Nicole; Trinchet, Jean-Claude; Beaugrand, Michel; Gattegno, Liliane; Pessayre, Dominique; Sutton, Angela

    2008-11-01

    The Ala/16Val dimorphism incorporates alanine (Ala) or valine (Val) in the mitochondrial targeting sequence of manganese superoxide dismutase (MnSOD), modifying MnSOD mitochondrial import and activity. In alcoholic cirrhotic patients, the Ala-MnSOD allele is associated with hepatic iron accumulation and an increased risk of hepatocellular carcinoma. The Ala-MnSOD variant could modulate the expression of proteins involved in iron storage (cytosolic ferritin), uptake (transferrin receptors, TfR-1 and-2), extrusion (hepcidin), and intracellular distribution (frataxin) to trigger hepatic iron accumulation. We therefore assessed the Ala/Val-MnSOD genotype and the hepatic iron score in 162 alcoholic cirrhotic patients. In our cohort, this hepatic iron score increased with the number of Ala-MnSOD alleles. We also transfected Huh7 cells with Ala-MnSOD-or Val-MnSOD-encoding plasmids and assessed cellular iron, MnSOD activity, and diverse mRNAs and proteins. In Huh7 cells, MnSOD activity was higher after Ala-MnSOD transfection than after Val-MnSOD transfection. Additionally, iron supplementation decreased transfected MnSOD proteins and activities. Ala-MnSOD transfection increased the mRNAs and proteins of ferritin, hepcidin, and TfR2, decreased the expression of frataxin, and caused cellular iron accumulation. In contrast, Val-MnSOD transfection had limited effects. In conclusion, the Ala-MnSOD variant favors hepatic iron accumulation by modulating the expression of proteins involved in iron homeostasis.

  14. Evaluation of ALA-induced PpIX as a photosensitizer for PDT in cats

    Science.gov (United States)

    Lucroy, Michael D.; Edwards, Benjamin F.; Peavy, George M.; Krasieva, Tatiana B.; Griffey, Stephen M.; Madewell, Bruce R.

    1998-07-01

    Given exogenously, ALA defeats intrinsic regulatory feedback mechanisms allowing intracellular accumulation of protoporphyrin IX (PpIX), a highly efficient photosensitizer. In vivo, PpIX synthesis in neoplastic mammary tissues averages 20-fold higher than in normal mammary tissues. PpIX is retained intracellularly, unlike perivascular localization of other photosensitizers, and it is then cleared quickly from the body. In vitro, ALA induced PpIX production in our laboratory in 6 cell lines tested, including an established feline kidney cell line and dermal fibroblasts from primary skin biopsy explant, resulting in photosensitization. Fluorescent microscopy confirmed PpIX production in skin adnexae following ALA administration in a normal cat. To evaluate toxicity, three cats were treated with a single i.v. dose of ALA (either 100, 200, of 400 mg/kg) and followed for 7 days. Cats receiving 100 or 200 mg/kg ALA i.v. had elevated liver enzymes and bilirubin within 24 hours. Histopathology revealed hydropic changes in the liver and renal fibrosis. The cat receiving 400 mg/kg ALA intravenously had cutaneous flush, bradycardia and apnea associated with ALA administration; within 24 hours the cat was lethargic, anorectic and icteric. ALT, AST and bilirubin concentrations had increased significantly. At necropsy the liver had a prominent lobular pattern; histopathology revealed severe periportal hepatitis and splenic necrosis. Systemically administered ALA induces PpIX production, but toxicity may preclude its clinical application in the cat. PpIX levels seem to be more time dependent than those dependent at these three ALA doses and they are well beyond the saturation point for adequate PpIX conversion. The literature is scant regarding toxicity associated with parenteral administration of ALA.

  15. N-3 fatty acids in the Mediterranean diet.

    Science.gov (United States)

    Galli, C; Marangoni, F

    2006-09-01

    Fats in the diet of countries in the Mediterranean basin are typically represented by olive oil, but the high consumptions of vegetables and to some extent also of fish result in appreciable intakes of n-3 fatty acids. In fact, various plant foods are relatively rich in the 18 carbon n-3 fatty acid, alpha linolenic acid, ALA, while the generally moderate consumption of fish, except for certain communities living close to the sea, contributes to the intake of the long-chain n-3. Although the amounts of fats in ALA-containing plant foods are low, the relatively high concentrations of this fatty acid and the large size of the portions consumed allow to reach appreciable doses of ALA, an n-3 fatty acid that has been shown to exert favourable effects on various relevant factors in cardiovascular protection. In addition, consumption of relatively small amounts of certain typical dry fruit components of the diet such as walnuts, provides a sizable supply of ALA that is also rather efficiently converted to the ALA derivative eicosapentaenoic acid (EPA). Additional rather typical wild food components of the diet in certain countries, i.e. snails and frogs, are also appreciable sources of ALA. It appears thus that the consumption of typical Mediterranean foods provides relevant intakes of n-3 fatty acids, especially ALA, that appears to be efficiently absorbed and also transformed at least to the long-chain derivative EPA.

  16. Agentes Locales Ambientales (ALAs: Hacia la ciudad sostenible

    Directory of Open Access Journals (Sweden)

    Marín-Herbert, S.

    2013-09-01

    Full Text Available Any action aimed at improving the quality of life in a city through more sustainable urban models, based on a reference framework such as the Local Agenda 21 or the, calls for changes to its inhabitants' behaviour. The ALAs project drives this change by making the city's youngest inhabitants Leaders of Change. They involve others (school friends, family members, neighbours in direct action in their neighbourhood, making the community participate independently in improving the city’s sustainability and quality of life. To the sequence “awareness- raising - action - monitoring - motivation tools such as our Geographical Information System have been added to support the neighbourhood action strategy by monitoring its efficiency and its effectiveness at meeting targets.Partiendo de un marco de referencia, como la Agenda Local 21 (1 o la Carta de Leipzig (2, cualquier acción encaminada a una mejora en la calidad de vida de una ciudad a través de modelos urbanos más sostenibles, requiere una modificación en las conductas de sus habitantes. El proyecto ALAs, motiva este cambio a través del paso directo a la acción liderada por los más jóvenes a través del Sistema Educativo quien mediante un efecto multiplicador (compañeros, familiares, vecinos y a través de la acción directa en sus barrios, consigue fomentar la participación autónoma de la población en la mejora de la sostenibilidad (3y la calidad de vida de su ciudad. A la secuencia “concienciación - acción - medición - motivación se han incorporado herramientas como el GIS que apoyan la estrategia de acción en los barrios controlando su e! cacia y e! ciencia en la consecución de los objetivos.

  17. Peroxisome proliferator activated receptor gamma polymorphism Pro12Ala in polycystic ovary syndrome (PCOS of South Indian Population

    Directory of Open Access Journals (Sweden)

    Raichel Jacob

    2016-05-01

    Conclusion: PPARγ2 gene Pro12Ala polymorphism was supposed to be susceptible genes in PCOS. The present study demonstrated that there is a statistical difference between the distributions of PPAR gamma Pro12Ala polymorphism in South Indian Population.

  18. Omega-3 fatty acids and antioxidants in edible wild plants.

    Science.gov (United States)

    Simopoulos, Artemis P

    2004-01-01

    Human beings evolved on a diet that was balanced in the omega-6 and omega-3 polyunsaturated fatty acids (PUFA), and was high in antioxidants. Edible wild plants provide alpha-linolenic acid (ALA) and higher amounts of vitamin E and vitamin C than cultivated plants. In addition to the antioxidant vitamins, edible wild plants are rich in phenols and other compounds that increase their antioxidant capacity. It is therefore important to systematically analyze the total antioxidant capacity of wild plants and promote their commercialization in both developed and developing countries. The diets of Western countries have contained increasingly larger amounts of linoleic acid (LA), which has been promoted for its cholesterol-lowering effect. It is now recognized that dietary LA favors oxidative modification of low density lipoprotein (LDL) cholesterol and increases platelet response to aggregation. In contrast, ALA intake is associated with inhibitory effects on the clotting activity of platelets, on their response to thrombin, and on the regulation of arachidonic acid (AA) metabolism. In clinical studies, ALA contributed to lowering of blood pressure, and a prospective epidemiological study showed that ALA is inversely related to the risk of coronary heart disease in men. Dietary amounts of LA as well as the ratio of LA to ALA appear to be important for the metabolism of ALA to longer-chain omega-3 PUFAs. Relatively large reserves of LA in body fat. as are found in vegans or in the diet of omnivores in Western societies, would tend to slow down the formation of long-chain omega-3 fatty acids from ALA. Therefore, the role of ALA in human nutrition becomes important in terms of long-term dietary intake. One advantage of the consumption of ALA over omega-3 fatty acids from fish is that the problem of insufficient vitamin E intake does not exist with high intake of ALA from plant sources.

  19. PPARg2 Ala¹² variant protects against Graves' orbitopathy and modulates the course of the disease.

    Science.gov (United States)

    Pawlak-Adamska, Edyta; Daroszewski, Jacek; Bolanowski, Marek; Oficjalska, Jolanta; Janusz, Przemyslaw; Szalinski, Marek; Frydecka, Irena

    2013-07-01

    Orbital fibroblast differentiation to adipocytes is a peroxisome proliferator-activated receptor g (PPARg)-dependent process essential for pathogenic tissue remodeling in Graves' orbitopathy (GO). PPARg2 Pro¹²Ala polymorphism modulates expression and/or function of the molecule encoded by this gene and is a promising locus of GO. Here, we analyzed associations of PPARg2 Pro¹²Ala with clinical manifestation of GO in 742 Polish Caucasians including 276 Graves' disease (GD) patients. In our study, the Ala¹² allele and Ala¹² variant (Ala¹²Ala and/or Pro¹²Ala genotype) decreased the risk of GO (p = 0.000012 and p = 0.00013). Moreover, Ala¹²Ala genotype was observed only in patients without GO (p = 0.002). GD patients with Ala¹² variant had less active and less severe eye symptoms. Female carriers of the Ala¹² allele rarely developed GO, but the marker was not related to symptoms of GO. The opposite finding was recorded in males, in whom the studied polymorphism was related to activity, but not to the development, of GO. In Ala¹² variant carriers without familial history of thyroid disease, risk of GO was lower than in persons with a familial background. The Ala¹² allele seemed to protect smokers from GO, but in nonsmokers, such a relation was not obvious. A multivariate analysis indicated the Pro¹²Ala marker as an independent risk factor of eye symptoms (p = 0.0001) and lack of Ala increases the risk of GO 3.24-fold. In conclusion, the gain-of-function Ala¹² variant protects against GO and modulates the course of the disease.

  20. 5-aminolevulinic acid-incorporated poly(vinyl alcohol nanofiber-coated metal stent for application in photodynamic therapy

    Directory of Open Access Journals (Sweden)

    Kang DH

    2012-05-01

    Full Text Available Jin Ju Yoo*, Chan Kim*, Chung-Wook Chung, Young-Il Jeong, Dae Hwan KangNational Research and Development Center for Hepatibiliary Disease, Pusan National University Yangsan Hospital, Gyeongnam 626-770, Korea *These authors contributed equally to this work.Background: The study investigated the use of combined photodynamic therapy (PDT and stent placement for the treatment of cholangiocarcinoma (CC. For this purpose, 5-aminolevulinic acid (ALA was incorporated into poly(vinyl alcohol (PVA nanofiber, and coated onto metal stents. Their efficacy was assessed in PDT towards HuCC-T1 CC cells.Methods: Fabrication of ALA-PVA nanofiber, and simultaneous coating onto metal stents, was performed through electrospinning. The dark-toxicity, generation of protoporphyrin IX (PpIX, and PDT effect of ALA and ALA-PVA nanofiber were studied in vitro, using HuCC-T1 CC cells.Results: The ALA-PVA nanofibers were coated onto metal stents less than 1000 nm in diameter. ALA-only displayed marginal cytotoxicity; ALA-PVA nanofiber showed less cytotoxicity. PpIX generation was not sigficantly different between ALA and ALA-PVA nanofiber treatments. PVA itself did not generate PpIX in tumor cells. ALA and ALA-PVA nanofiber displayed a similar PDT effect on tumor cells. Cell viability was decreased, dose-dependently, until ALA concentration reached 100 µg/mL. Necrosis and apoptosis of tumor cells occurred similarly for ALA and ALA- PVA nanofiber treatments.Conclusion: The ALA-PVA nanofiber-coated stent is a promising candidate for therapeutic use with cholangiocarcinoma.Keywords: nanofiber, photodynamic therapy, 5-aminolevulinic acid, poly(vinyl alcohol

  1. Quantitative evaluation of PPAR-γ2 Pro12Ala polymorphism with hypertension.

    Science.gov (United States)

    Yang, W; Wang, J; Ye, W; Li, X

    2017-09-18

    The peroxisome proliferator-activated receptor γ2 (PPARγ2)Pro12Ala polymorphism has been reported to be associated with hypertension. However, relevant studies have shown inconsistent results. To quantitatively evaluate the relationship between the PPARγ2Pro12Ala polymorphism and hypertension risk, we conducted a meta-analysis based on all available studies selected from Scopus, Web of Science, PubMed, Chinese National Knowledge Infrastructure, and Wanfang databases. In all, 13 studies were finally included in this meta-analysis. In the allelic model (Ala vs. Pro), the Ala allele of PPARγ2 Pro12Ala polymorphism was associated with hypertension (Odds Ratio [OR] = 0.723, 95% confidence interval [CI] = 0.607-0.861). Sensitivity analysis and exclusion of studies with poor quality scores or controls complicated by other diseases confirmed the validity of this association. Moreover, the PPARγ2Pro12Ala polymorphism was associated with hypertension in the codominant (OR = 0.710, 95% CI = 0.626-0.806), recessive (OR = 0.561, 95% CI = 0.418-0.754), and dominant (OR = 0.693, 95% CI = 0.577-0.833) models. The Ala allele appears to have a protective effect against hypertension and a dominant function.

  2. EKSISTENSI DAN MOTIVASI PRAMUWISATA LOKAL PEREMPUAN DI DAYA TARIK WISATA ALAS KEDATON

    Directory of Open Access Journals (Sweden)

    Gusti Ayu Putu Putri Indira Suari

    2017-01-01

    Full Text Available Keberadaan pramuwisata lokal yang seluruhnya berjenis kelamin perempuan menjadi keunikan tersendiri bagi Alas Kedaton sebagai suatu daya tarik wisata. Bertujuan untuk mengetahui eksistensi pramuwisata lokal perempuan di daya tarik wisata Alas Kedaton serta untuk mengetahui motivasi mereka bekerja sebagai pramuwisata lokal perempuan di daya tarik wisata Alas Kedaton. Jenis data yang digunakan adalah data kuantitatif dan kualitatif. Sedangkan sumber data yakni data primer dan sekunder. Data dikumpulkan melalui observasi, wawancara, kuesioner dan dokumentasi. Informan ditentukan secara purposive sampling. Terdapat 45 responden yang dipilih sebagai sampel dengan menggunakan metode simple random sampling. Dan teknik analisis data yang digunakan adalah analisis deskriptif kualitatif dan deskriptif kuantitatif. Hasil menunjukkan bahwa eksistensi pramuwisata lokal perempuan di daya tarik wisata Alas Kedaton dari awal terbentuknya sampai saat ini dapat dikatakan masih eksis. Meskipun jumlah pramuwisata lokal perempuan di daya tarik wisata Alas Kedaton berkurang dibandingkan ketika awal terbentuknya. Sedangkan motivasi mereka bekerja sebagai pramuwisata lokal di daya tarik wisata Alas Kedaton adalah untuk memenuhi beberapa kebutuhan seperti physiological needs, safety and security needs, affiliation or acceptance needs, esteem needs, dan self actualization. Dan rata-rata responden menjawab motivasi mereka bekerja sebagai pramuwisata lokal perempuan di daya tarik wisata Alas Kedaton adalah untuk memenuhi kebutuhan afiliasi atau affiliation or acceptance needs.

  3. Association between PPAR-γ2 Pro12Ala polymorphism and obesity: a meta-analysis.

    Science.gov (United States)

    Yao, Ying-Shui; Li, Jie; Jin, Yue-Long; Chen, Yan; He, Lian-Ping

    2015-06-01

    The peroxisome proliferator-activated receptor-γ2 (PPAR-γ2) gene has been reported in the pathogeny of obesity. However, the results have been inconsistent. The purpose of this meta-analysis was to acquire a more accurate assessment of the association between PPAR-γ2 Pro12Ala polymorphism and obesity. PubMed, Wan Fang (Chinese) databases, Chinese Biomedical Medical databases, and Chinese National Knowledge Infrastructure were searched to identify eligible studies. Finally, 25 studies (6491 cases and 8242 controls) were enrolled in this meta-analysis. The effect summary odds ratio (OR) with 95 % confidence interval (CI) was applied. Random-effects or fixed-effects model was performed based on the heterogeneity. STATA 12.0 was applied for this meta-analysis. The combined results showed that PPAR-γ Pro12Ala polymorphism was associated with the obesity risk (Ala vs. Pro: OR = 1.55, 95 % CI 1.34-1.80; Pro/Ala vs. Pro/Pro: OR = 1.54, 95 % CI 1.31-1.82; Ala/Ala + Pro/Ala vs. Pro/Pro: OR = 1.61, 95 % CI 1.36-1.90). Subgroup analysis by ethnicity showed that there were significant associations between PPAR-γ Pro12Ala polymorphism and obesity risk in Caucasians, Asians, and Mixed population. Subgroup analysis by obesity's cutoff points showed that the associations were found among the patients with the cutoff point of BMI ≥24 and BMI ≥30 but not among the patients with the cutoff point of BMI ≥95th percentile. These results suggested that PPAR-γ Pro12Ala polymorphism might be a risk factor for obesity susceptibility.

  4. Age-dependent dichotomous effect of superoxide dismutase Ala16Val polymorphism on oxidized LDL levels.

    Science.gov (United States)

    Dedoussis, George V; Kanoni, Stavroula; Panagiotakos, Demosthenes B; Louizou, Eirini; Grigoriou, Efi; Chrysohoou, Christina; Pitsavos, Christos; Stefanadis, Christodoulos

    2008-02-29

    We investigated the association between superoxide dismutase (SOD) Ala16Val polymorphism and the levels of oxidized LDL lipoprotein-C (ox-LDL-C) in two age-different Greek cohorts. Four hundred fifteen middle-aged (n=147 females: 43.2+/-13 years, n=268 males: 43.3+/-14 years) Caucasian Greek subjects consisted the middle aged cohort. One hundred seventy five elderly (n=88 females: 79.9+/-4 years; n=87 males: 80.6+/-4 years) were selected from the elderly cohort. Genotype data were obtained for all of them. Multiple linear regression analysis, stratified by gender and adjusted for age, smoking habits and body mass index as covariates, showed higher ox-LDL-C levels for the middle aged men with the Val/Val genotype, compared to the other allele (Ala/Ala and Ala/Val) carriers (65.9+/-25.7 vs. 55.7+/-20.5 mg/dl; standardized beta coefficient=0.192, P=0.012). On the contrary, elderly women with the Val/Val genotype occurred with lower ox-LDL-C levels compared to the Ala/Ala or Ala/Val genotype (74.2+/-22.1 vs. 86.5+/-26.6 mg/dl; standardized beta coefficient= -0.269, P=0.015). The same trend was also recorded in elderly men, however without reaching statistical significance (standardized beta coefficient= -0.187, P=0.077). Moreover, elderly men and women with the Ala/Ala or Ala/Val genotype presented higher triglycerides levels compared to Val/Val (women: 145.2+/-68.7 vs. 114.3+/- 34.3 mg/dl, P= 0.027; men: 147.8+/-72.4 vs. 103.7 +/-38.0 mg/dl, P=0.002). Additionally, middle aged men with the Val/Val genotype had higher HDL-C levels compared to the Ala allele carriers. The results suggest that SOD Ala16Val polymorphism is an age-dependent modulator of ox-LDL-C levels in middle-aged men and elderly women.

  5. A novel presenilin 1 mutation (Ala275Val) as cause of early-onset familial Alzheimer disease.

    Science.gov (United States)

    Luedecke, Daniel; Becktepe, Jos S; Lehmbeck, Jan T; Finckh, Ulrich; Yamamoto, Raina; Jahn, Holger; Boelmans, Kai

    2014-04-30

    Mutations in the presenilin 1 (PS1) gene (PSEN1) are associated with familial Alzheimer disease (FAD). Here, we report on a 50-year-old patient presenting with progressive deterioration of his short-term memory and a family history of early-onset dementia. Diagnostic workup included a neuropsychological examination, structural magnetic resonance (MR) imaging, cerebrospinal fluid (CSF) biomarkers including total tau, phosphorylated tau, and Aβ42 levels, as well as sequencing relevant fragments of the genes PSEN1, PSEN2, and APP. Additionally, we were able to obtain archival paraffin-embedded cerebellar tissue from the patient's father for cosegregation analysis. Clinical, neuropsychological and MR imaging data were indicative of early-onset Alzheimer disease. Furthermore, CSF biomarkers showed a typical pattern for Alzheimer disease. DNA sequencing revealed a heterozygous nucleotide transition (c.824C>T) in exon 8 of PSEN1, leading to an amino acid change from alanine to valine at codon 275 (Ala275Val). The same mutation was found in an archival brain specimen of the patient's demented father, but not in a blood sample of the non-demented mother. This mutation alters a conserved residue in the large hydrophilic loop of PS1, suggesting pathogenic relevance. Cosegregegation analysis and the structural as well as the presumed functional role of the mutated and highly conserved residue suggest FAD causing characteristics of the novel PSEN1 mutation Ala275Val.

  6. Effet de la dose d’acide alpha-linolénique alimentaire sur le métabolisme lipidique

    Directory of Open Access Journals (Sweden)

    Morise Anne

    2005-09-01

    Full Text Available The purpose of our study was to investigate the effects of high doses of ALA provided by linseed oil (containing 50% ALA on its own bioavailability and that of its derivatives as well as on lipid metabolism. We investigated in male hamsters the dose/response effects of ALA over a broad range of supply as linseed oil (1, 10, 20 and 41% of total fatty acids, FA, or 0.4, 3.6, 6.7 and 14.6% of total energy intake. ALA was substituted for oleic acid in order to keep constant linoleic acid (LA and saturated fatty acids which could interfere with the metabolism of n-3 PUFA and lipids, respectively. The capacity of ALA absorption, transport, storage and conversion into EPA had no limitation over the chosen range of dietary intake. However, dietary ALA failed to increase DHA content in plasma phospholipids. In parallel to the increase in EPA, arachidonic acid content decreased, resulting in an improved balance of 20 carbons FA. Moreover, in our atherogenic conditions, triglyceridemia decreased by 45% in response to 10% dietary ALA and was not affected by higher intakes. It was associated with lower hepatic activities of acetyl-CoA-carboxylase (up to – 29% and malic enzyme (up to – 42%, which were negatively correlated to ALA intake (r2 = 0.33 and r2 = 0.38, respectively. Substitution of 10% ALA for oleic acid increased cholesterolemia by 15% but, as in TG, higher ALA intakes did not amplify the response. The highest ALA intake (40% modified dramatically hepatobiliary metabolism of sterols. Thus, replacing 10% oleic acid by ALA is sufficient to improve its bioavailability and that of EPA, and to exert a beneficial hypotriglyceridemic effect, that may be counteracted by the slight increase in cholesterolemia. Higher intakes did not modify these parameters, but a very high dose resulted in adverse effects on sterol metabolism and does not seem appropriate for humans.

  7. Effect of zinc or S-adenosyl-l-methionine on long term administration of low doses of lead to rats.

    Science.gov (United States)

    Muñoz, J J; Roca, C; Santos, J L; Arroyo, M; de Salamanca, R E

    1993-10-01

    Two alternatives for the treatment of lead intoxication, administration of zinc or a thiol donor, S-adenosyl-L-methionine (SAM), were analysed. Rats were exposed to lead (Pb)-acetate (60 mg/l) in drinking water during 90 days; one group also received SO4Zn in water (40 mg/l), while another received both Pb and SAM (5 mg/24 hr intraperitoneally. Erythrocytic delta-aminolaevulinic dehydratase (ALA-D) activity was significantly reduced (P treatments. The high erythrocytic uroporphyrinogen synthetase (URO-S) activity noticed in Pb administered rats, was significantly (P treatment causes a surplus of thiols that allows the full expression of ALA-D catalytic activity.

  8. Bacteriocin protein BacL1 of Enterococcus faecalis targets cell division loci and specifically recognizes L-Ala2-cross-bridged peptidoglycan.

    Science.gov (United States)

    Kurushima, Jun; Nakane, Daisuke; Nishizaka, Takayuki; Tomita, Haruyoshi

    2015-01-01

    Bacteriocin 41 (Bac41) is produced from clinical isolates of Enterococcus faecalis and consists of two extracellular proteins, BacL1 and BacA. We previously reported that BacL1 protein (595 amino acids, 64.5 kDa) is a bacteriolytic peptidoglycan D-isoglutamyl-L-lysine endopeptidase that induces cell lysis of E. faecalis when an accessory factor, BacA, is copresent. However, the target of BacL1 remains unknown. In this study, we investigated the targeting specificity of BacL1. Fluorescence microscopy analysis using fluorescent dye-conjugated recombinant protein demonstrated that BacL1 specifically localized at the cell division-associated site, including the equatorial ring, division septum, and nascent cell wall, on the cell surface of target E. faecalis cells. This specific targeting was dependent on the triple repeat of the SH3 domain located in the region from amino acid 329 to 590 of BacL1. Repression of cell growth due to the stationary state of the growth phase or to treatment with bacteriostatic antibiotics rescued bacteria from the bacteriolytic activity of BacL1 and BacA. The static growth state also abolished the binding and targeting of BacL1 to the cell division-associated site. Furthermore, the targeting of BacL1 was detectable among Gram-positive bacteria with an L-Ala-L-Ala-cross-bridging peptidoglycan, including E. faecalis, Streptococcus pyogenes, or Streptococcus pneumoniae, but not among bacteria with alternate peptidoglycan structures, such as Enterococcus faecium, Enterococcus hirae, Staphylococcus aureus, or Listeria monocytogenes. These data suggest that BacL1 specifically targets the L-Ala-L-Ala-cross-bridged peptidoglycan and potentially lyses the E. faecalis cells during cell division.

  9. Influence of different CLA isomers on insulin resistance and adipocytokines in pre-diabetic, middle-aged men with PPARγ2 Pro12Ala polymorphism.

    Science.gov (United States)

    Rubin, Diana; Herrmann, Julia; Much, Daniela; Pfeuffer, Maria; Laue, C; Winkler, P; Helwig, Ulf; Bell, Doris; Auinger, Annegret; Darabaneanu, Stephanie; Ruether, Andreas; Schrezenmeir, Jürgen

    2012-10-01

    Conjugated linoleic acids (CLAs) are natural PPARγ ligands, which showed conflicting effects on metabolism in humans. We examined metabolic effects of different isomers of CLA in subjects with PPARγ2 Pro12Ala polymorphisms. A total of 35 men underwent four intervention periods in a crossover study design: subjects with either genotypes received c9, t11 CLA or t10, c12 CLA, a commercially available 1:1 mix of both isomers or reference oil (linoleic acid (LA)). Adipocytokines, insulin, glucose and triglycerides were assessed in the fasting state and after a standardized mixed meal. Across all genotypes, there was a significant (p = 0.025) CLA treatment effect upon postprandial (pp) HOMA-IR values, with c9, t11 CLA and CLA isomer mix improving, but t10, c12 CLA isomer worsening. In Ala12Ala subjects, the t10, c12 isomer caused weight gain (p = 0.03) and tended to increase postprandial insulin levels (p = 0.05). In Pro12Pro subjects, t10, c12 resulted in reduction in waist circumference (p = 0.03). The comparison of the different genotype groups revealed statistically different changes in fasting and postprandial insulin, HOMA-IR and leptin after intervention. c9, t11 CLA and the commercial CLA mix showed beneficial effects on insulin sensitivity compared with LA, while t10, c12 CLA adversely affects body weight and insulin sensitivity in different PPAR genotypes. CLA isomers have different effects on metabolism in Ala and Pro carriers.

  10. Conversion of the agent-oriented domain-specific language ALAS into JavaScript

    Science.gov (United States)

    Sredojević, Dejan; Vidaković, Milan; Okanović, Dušan; Mitrović, Dejan; Ivanović, Mirjana

    2016-06-01

    This paper shows generation of JavaScript code from code written in agent-oriented domain-specific language ALAS. ALAS is an agent-oriented domain-specific language for writing software agents that are executed within XJAF middleware. Since the agents can be executed on various platforms, they must be converted into a language of the target platform. We also try to utilize existing tools and technologies to make the whole conversion process as simple as possible, as well as faster and more efficient. We use the Xtext framework that is compatible with Java to implement ALAS infrastructure - editor and code generator. Since Xtext supports Java, generation of Java code from ALAS code is straightforward. To generate a JavaScript code that will be executed within the target JavaScript XJAF implementation, Google Web Toolkit (GWT) is used.

  11. Sadama ala planeering = Harbour area master plan / Ivan Sergejev, Helen Rebane, Karina Niinepuu

    Index Scriptorium Estoniae

    Sergejev, Ivan, 1987-

    2010-01-01

    EKA arhitektuuri ja linnaplaneerimise osakonna IV kursuse 2009-2010 õppeaastal erialase projekteerimise raames kavandatud planeeringu eesmärgiks on tihendada Tallinna sadama ala ning arendada sellest välja mitmekesine ja efektiivne linnaruum

  12. Sadama ala planeering = Harbour area master plan / Ivan Sergejev, Helen Rebane, Karina Niinepuu

    Index Scriptorium Estoniae

    Sergejev, Ivan, 1987-

    2010-01-01

    EKA arhitektuuri ja linnaplaneerimise osakonna IV kursuse 2009-2010 õppeaastal erialase projekteerimise raames kavandatud planeeringu eesmärgiks on tihendada Tallinna sadama ala ning arendada sellest välja mitmekesine ja efektiivne linnaruum

  13. Quantitation of alpha-linolenic acid elongation to eicosapentaenoic and docosahexaenoic acid as affected by the ratio of n6/n3 fatty acids

    Directory of Open Access Journals (Sweden)

    Somoza Veronika

    2009-02-01

    Full Text Available Abstract Background Conversion of linoleic acid (LA and alpha-linolenic acid (ALA to their higher chain homologues in humans depends on the ratio of ingested n6 and n3 fatty acids. Design and methods In order to determine the most effective ratio with regard to the conversion of ALA to eicosapentaenoic acid (EPA and docosahexaenoic acid (DHA, human hepatoma cells were incubated with varying ratios of [13C] labeled linoleic acid ([13C]LA- and alpha-linolenic acid ([13C]ALA-methylesters. Regulative cellular signal transduction pathways involved were studied by determinations of transcript levels of the genes encoding delta-5 desaturase (D5D and delta-6 desaturase (D6D, peroxisome proliferator-activated receptor alpha (PPARα and sterol regulatory element binding protein 1c (SREBP-1c. Mitogen-activated protein kinase kinase 1 (MEK1 and mitogen-activated protein kinase kinase kinase 1 (MEKK1 were also examined. Results Maximum conversion was observed in cells incubated with the mixture of [13C]LA/[13C]ALA at a ratio of 1:1, where 0.7% and 17% of the recovered [13C]ALA was converted to DHA and EPA, respectively. Furthermore, differential regulation of enzymes involved in the conversion at the transcript level, dependent on the ratio of administered n6 to n3 fatty acids in human hepatocytes was demonstrated. Conclusion Formation of EPA and DHA was highest at an administered LA/ALA ratio of 1:1, although gene expression of PPARα, SREBP-1c and D5D involved in ALA elongation were higher in the presence of ALA solely. Also, our findings suggest that a diet-induced enhancement of the cell membrane content of highly unsaturated fatty acids is only possible up to a certain level.

  14. Paired and LIM class homeodomain proteins coordinate differentiation of the C. elegans ALA neuron.

    Science.gov (United States)

    Van Buskirk, Cheryl; Sternberg, Paul W

    2010-06-01

    The ancient origin of sleep is evidenced by deeply conserved signaling pathways regulating sleep-like behavior, such as signaling through the Epidermal growth factor receptor (EGFR). In Caenorhabditis elegans, a sleep-like state can be induced at any time during development or adulthood through conditional expression of LIN-3/EGF. The behavioral response to EGF is mediated by EGFR activity within a single cell, the ALA neuron, and mutations that impair ALA differentiation are expected to confer EGF-resistance. Here we describe three such EGF-resistant mutants. One of these corresponds to the LIM class homeodomain (HD) protein CEH-14/Lhx3, and the other two correspond to Paired-like HD proteins CEH-10/Chx10 and CEH-17/Phox2. Whereas CEH-14 is required for ALA-specific gene expression throughout development, the Prd-like proteins display complementary temporal contributions to gene expression, with the requirement for CEH-10 decreasing as that of CEH-17 increases. We present evidence that CEH-17 participates in a positive autoregulatory loop with CEH-14 in ALA, and that CEH-10, in addition to its role in ALA differentiation, functions in the generation of the ALA neuron. Similarly to CEH-17, CEH-10 is required for the posterior migration of the ALA axons, but CEH-14 appears to regulate an aspect of ALA axon outgrowth that is distinct from that of the Prd-like proteins. Our findings reveal partial modularity among the features of a neuronal differentiation program and their coordination by Prd and LIM class HD proteins.

  15. Using a modified nasotracheal tube to prevent nasal ala pressure sore during prolonged nasotracheal intubation.

    Science.gov (United States)

    Cherng, Chen-Hwan; Chen, Yuan-Wu

    2010-12-01

    Nasotracheal tube induced nasal ala pressure sores or necrosis during prolonged nasotracheal intubation have been reported, and it is a serious but preventable complication. Here we introduce a modified nasotracheal tube to prevent this complication. This modified nasotracheal tube is composed of two parts, an oral endotracheal tube and a proximal part of a preformed nasotracheal tube, which are linked by a connector. The use of this modified nasotracheal tube can prevent nasal ala pressure sores during prolonged nasotracheal intubation.

  16. Cognitive decline and the PPAR-γ Pro12Ala genotype: variation by sex and ethnicity.

    Science.gov (United States)

    A West, Nancy; Baxter, Judith; L Bryant, Lucinda; L Nelson, Tracy

    2017-01-06

    We investigated the association between the peroxisome proliferator-activated receptor (PPAR)-gamma Pro12Ala polymorphism and cognitive decline in older adults. Participants from a population-based cohort of older Hispanic and non-Hispanic white adults (n = 492) were administered the Mini Mental State Examination (MMSE), a multi-domain cognitive screening tool, and the Behavioral Dyscontrol Scale (BDS), a measure of executive cognitive function, at baseline and at follow-up, an average of 22 months later. Multiple linear regression was used to investigate the association between the two cognitive test scores and the Pro12Ala polymorphism. At baseline, presence of the Ala12 allele was not significantly associated with MMSE score (P = 0.62) nor with BDS score (P = 0.85). Heterogeneity was present for cognitive decline as measured by the MMSE among ethnic, sex and Ala12 allele status (P = 0.04 for three-way interaction term). Stratification by the cross-classification of sex and ethnicity revealed significantly greater declines in MMSE score among male Hispanic carriers of the Ala12 allele compared to male Hispanic non-carriers (decline = 4.0 versus 1.6 points; P = 0.02). A significant difference in decline between Ala12 carriers and non-carriers was not present among the other sex/ethnic groups. Carriers of the PPAR-γ Ala12 allele showed greater cognitive decline compared to non-carriers as detected by the MMSE but the risk varied across sex and ethnic groups. Male Ala12 carriers of Hispanic origin may be a high-risk group for cognitive decline.

  17. Lack of association between serum adiponectin levels and the Pro12Ala polymorphism in Asian Indians.

    Science.gov (United States)

    Radha, V; Vimaleswaran, K S; Babu, S; Deepa, R; Anjana, M; Ghosh, S; Majumder, P P; Rao, M R S; Mohan, V

    2007-04-01

    The aim of the study was to investigate the association of serum adiponectin levels with the Pro12Ala polymorphism of the peroxisome proliferator activated receptor-gamma (PPARG) gene in Asian Indians. We selected 400 diabetic subjects, 200 with the Pro12Pro genotype (100 male and 100 female) and 200 with the Pro12Ala genotype (100 male and 100 female) and 400 age- and sex-matched normal glucose tolerance subjects with similar genotype profiles from the Chennai Urban Rural Epidemiology Study. Fasting serum adiponection levels were measured using radioimmunoassay. The Pro12Ala polymorphism was genotyped by PCR-restriction fragment length polymorphism using BstUI. All clinical and biochemical parameters were similar in the subjects with the Pro12Pro and Pro12Ala genotypes. There was no significant difference in serum adiponectin values between subjects with the Pro12Pro and Pro12Ala genotypes (males 5.4 vs. 5.8 microg/ml, P = 0.546; females 6.9 vs. 7.2 microg/ml, P = 0.748). Adiponectin values did not differ among these two genotypes even when categorized based on their diabetes status (normal glucose tolerance Pro12Pro 7.9 vs. Pro12Ala 7.7 microg/ml, P = 0.994; diabetes Pro12Pro 4.7 vs. Pro12Ala 5.4 microg/ml, P = 0.622). The Pro12Ala polymorphism of the PPARG gene is not associated with serum adiponectin levels in Asian Indians.

  18. α-linolenic acid and docosahexaenoic acid, alone and combined with trastuzumab, reduce HER2-overexpressing breast cancer cell growth but differentially regulate HER2 signaling pathways

    OpenAIRE

    2015-01-01

    Background Diets rich in the n-3 fatty acid alpha-linolenic acid (ALA) have been shown to reduce breast tumor growth, enhance the effectiveness of the HER2-targeted drug trastuzumab (TRAS) and reduce HER2 signaling in mouse models. It is unclear whether this is due to direct effects of ALA or due to its long-chain n-3 fatty acids metabolites including docosahexaenoic acid (DHA). Methods The ability of HER2-overexpressing BT-474 human breast cancer cells to convert ALA to long-chain n-3 fatty ...

  19. Basic research on interactions of heavy metals with pharmaceutical substances with relevance to the environment and residual toxicology

    Energy Technology Data Exchange (ETDEWEB)

    Gaede, W.; Kuehnert, M.

    1986-01-01

    Studies were conducted into interactions between long-time exposure of rats to subtoxic doses of lead and copper and humic acids orally applied to them in parallel. Tests were based on established activities of erythrocytic delta-aminolaevulinic acid dehydratase and on the length of hexobarbital-induced sleep. Also investigated were the effects of heavy metal on the blood level of a sulphonamide (sulphaclomide). Lead and copper interactions under the impact of pharmaceutical substances (humic acids and sulphaclomide) produced affirmative evidence to the well-known depression of activity of delta-aminolaevulinic acid dehydratase. There was also a high probability that cytochrome-P-450 had been induced by lead and copper and, perhaps, by humic acids, as well. Enteral absorption of sulphaclomide was clearly affected by protein-denaturing and permeability-reducing action of heavy metals on the gastro-intestinal mucosa. That locally delimited action of lead and copper was widely offset under the impact of humic acids, and sulphaclomide levels in the blood were renormalised. The above findings are likely to suggest that in the context of environmental toxicology long-time exposure of warm-blooded animals to heavy metals may impair the therapeutic effectiveness of pharmaceuticals (sulphaclomide in this case).

  20. PERANCANGAN KONSEP PRODUK ALAS KAKI DENGAN MENGGUNAKAN INTEGRASI METODE KANSEI ENGINEERING DAN MODEL KANO

    Directory of Open Access Journals (Sweden)

    Mei Haryono

    2014-06-01

    Full Text Available Penelitian dilakukan pada produk yang berupa alas kaki (sandal pria. Berdasarkan hasil observasi dapat diidentifikasi belum adanya upaya dari produsen/perajin alas kaki untuk melakukan penelusuran terhadap harapan dan keinginan konsumen akan produk alas kaki yang sesuai dengan perasaan psikologis konsumen. Di sisi lain kesadaran dan keinginan konsumen akan desain produk semakin meningkat. Penelitian ini berusaha untuk mengetahui citra atau harapan konsumen akan produk alas kaki yang berupa sandal pria melalui pendekatan emosional dan psikologis, sehingga dapat dilakukan perancangan dan pengembangan produk alas kaki yang sesuai dengan citra dan harapan mereka. Metode Kansei Engineering digunakan untuk memformulasikan rancangan produk alas kaki berdasarkan perasaan psikologis konsumen yang tercermin melalui kata kansei. Kuesioner yang digunakan pada metode Kansei Engineering ini adalah kuesioner elemen desain dan kuesioner semantic differential. Model Kano digunakan untuk memetakan atribut-atribut produk berdasarkan perfomansinya. Hasil akhir penelitian ini adalah dengan mengintegrasikan kedua metode tersebut sehingga diketahui bahwa desain yang sesuai dengan citra/image dan perasaan pskologis konsumen adalah desain dua kategori Kano, yaitu one- dimensional dan indifferent.

  1. PERANCANGAN KONSEP PRODUK ALAS KAKI DENGAN MENGGUNAKAN INTEGRASI METODE KANSEI ENGINEERING DAN MODEL KANO

    Directory of Open Access Journals (Sweden)

    Mei Haryono

    2014-06-01

    Full Text Available Penelitian dilakukan pada produk yang berupa alas kaki (sandal pria. Berdasarkan hasil observasi dapat diidentifikasi belum adanya upaya dari produsen/perajin alas kaki untuk melakukan penelusuran terhadap harapan dan keinginan konsumen akan produk alas kaki yang sesuai dengan perasaan psikologis konsumen. Di sisi lain kesadaran dan keinginan konsumen akan desain produk semakin meningkat. Penelitian ini berusaha untuk mengetahui citra atau harapan konsumen akan produk alas kaki yang berupa sandal pria melalui pendekatan emosional dan psikologis, sehingga dapat dilakukan perancangan dan pengembangan produk alas kaki yang sesuai dengan citra dan harapan mereka. Metode Kansei Engineering digunakan untuk memformulasikan rancangan produk alas kaki berdasarkan perasaan psikologis konsumen yang tercermin melalui kata kansei. Kuesioner yang digunakan pada metode Kansei Engineering ini adalah kuesioner elemen desain dan kuesioner semantic differential. Model Kano digunakan untuk memetakan atribut-atribut produk berdasarkan perfomansinya. Hasil akhir penelitian ini adalah dengan mengintegrasikan kedua metode tersebut sehingga diketahui bahwa desain yang sesuai dengan citra/image dan perasaan pskologis konsumen adalah desain dua kategori Kano, yaitu one-dimensional dan indifferent.

  2. [Association of PPARgamma2 Pro12Ala polymorphism and cognitive dysfunction in hypertension patients].

    Science.gov (United States)

    Peng, Yong; Luo, Xiao-jia; Chen, Xiao-ping; Li, Long-xin; Wan, Li-yan; He, Sen; Chen, Xiao-ni; Wu, Kai

    2010-11-01

    To study the relationship between PPARgamma2 Pro12Ala polymorphism and cognitive function in patients with primary hypertension. This study enrolled 502 hypertensive patients of Chinese Han population from Jan 2008 to Feb 2009 in West China Hospital of Sichuan University. We collected the general data and applied the mini mental state examination (MMSE) to test the cognitive function and computed score. Total cholesterol (TC), triglyeride (TG), fasting plasma glucose (FPG) and postprandial blood sugar (PPBS), fasting insulin (FINS) and postprandial plasma insulin (PINS) were measured. PCR-RELP method was used to analysis the PPARgamma2 Pro12Ala gene polymorphism. Pro12Pro genotype was present in 88.6% of the patients and Prol2Ala genotype was present in 11.4% of the population. Allele frequencies were 94.3% for Pro allele and 5.7% for Ala allele. In cognitive normal group, the frequencies of PP and PA genotype were 328 (87.2%) and 48 (12.8%), while the frequencies of PP and PA genotypes in the cognitive dysfunction group were 126 (92.9%), 9 (7.1%) respectively. Analyzed by chi2 test, both the genotype frequency and the allele frequency of PPARy2 Pro12Ala polymorphism did not display statistical variability between the cognitive normal group and the cognitive dysfunction group, even eliminating the influence of age and sexuality. Pro12Ala polymorphism in PPARgamma2 with primary hypertension may not associate with cognitive impairment.

  3. IFNA2 p.Ala120Thr impairs the inhibitory activity of Interferon-α2 against the hepatitis B virus through altering its binding to the receptor.

    Science.gov (United States)

    Chen, Chuming; Zhu, Xiang; Xu, Wenxiong; Yang, Fangji; Zhang, Genglin; Wu, Lina; Zheng, Yongyuan; Gao, Zhiliang; Xie, Chan; Peng, Liang

    2017-09-25

    Our previous study found that a rare genetic mutation IFNA2p.Ala120Thr affects the structure of IFN-α2 and contributes to increased host susceptibility to CHB. However, the way in which the single amino acid residue mutation affects IFN-α2 activity is unclear. The purpose of this research was to investigate the effects and mechanisms of IFNA2p.Ala120Thr on IFN-α2 activity. Plasmid transfection of BL-21 was used to construct both wild type IFNA2 (wt) and p.Ala120Thr IFNA2 (mut) proteins. The HepG2-NTCP model was established using a lentiviral vector (LV003). Anti-HBV activity of wt and mut were tested on HepG2-NTCP infected cells with HBV, through the detection of HBsAg and HBcAg using immunohistochemistry and by detecting HBV DNA with RT PCR. IF and Co-IP were performed in order to investigate the binding of the IFNA2 protein and its receptor. The changes in IFNAR density and signal molecule phosphorylation were measured with western blotting. We used qPCR to further explore anti-HBV protein expression including APOBEC3, MxA, OAS1, and PKR. Cell model experiments confirmed that IFNA2p.Ala120Thr impairs anti-HBV activity of IFN-α2. Co-IP tests indicated that the binding of mut-IFNα to IFNR was weaker in the mut-treated group. IFNR density on the cells surface increased after treatment with wt-IFN-α2. Obvious differences in the STAT phosphorylation profiles were seen between the mut-treated and wt-treated groups. The expression of four main kinds of anti-HBV proteins induced by mut was higher in the HepG2-NTCP cells. Thus, IFNA2p.Ala120Thr affects anti-HBV activity of IFN-α2. IFNA2p.Ala120Thr impairs the anti-HBV ability of IFN-a2, mainly by reducing its binding to the IFN receptor. Mut IFN-a2 has a very weak binding, barely inducing STAT phosphorylation, and induces the expression of only a low level of related anti-HBV ISG. This is quite different from the effects of wt IFN-a2, implying that modifying the key structural position of IFNa may lead to the

  4. Glacier area and mass changes since 1964 in the Ala Archa Valley, Kyrgyz Ala-Too, northern Tien Shan

    Directory of Open Access Journals (Sweden)

    T. Bolch

    2015-01-01

    Full Text Available Glaciers are an important source of fresh water for Central Asia as they release water during the summer months when precipitation is low and water demand highest. Many studies address glacier area changes but only changes in glacier mass can be directly linked to climate and runoff. Despite the importance, investigations of glacier mass changes have been restricted to only a few glaciers in the Tien Shan until now. Geodetic mass balance measurements are suitable to complement and extend existing in-situ measurements. In this study, both area and mass changes of the ~40 km² glacier ice in the Ala Archa Valley, Kyrgyz Tien Shan, were investigated using 1964 and 1971 stereo Corona, 2012 stereo ASTER, the SRTM digital terrain model and other optical data such as Landsat ETM+ or Rapid Eye. In addition, ice thickness was modeled taking the basal shear stress and the glacier surface topography into account. The results indicate an area loss of 18.3±5.0% from 1964 until 2010 with continuous shrinkage in all investigated periods. The glacier’s mass balance was −0.45±0.27 m w.e. a−1 for the period 1964–1999 and −0.42±0.66 m w.e. a−1 for 1999–2012. Golubin Glacier showed a possible slight mass gain for 1964– 1971 and a decelerated mass loss for the 1999–2012 period. This is in good agreement with existing in-situ measurements exiting from 1962 until 1994 and since 2010. The overall ice volume was estimated to be 1.56±0.47 km³ of ice in the year 2000. Hence, the entire ice would be lost by 2100 if the mass loss would continue at the same rate

  5. Theoretical study of fMet-tRNA and fAla-tRNA structures by using quantum calculation

    Directory of Open Access Journals (Sweden)

    M. Noei

    2016-11-01

    Full Text Available In the prokaryotes, protein synthesis always starts with N-formylmethionine amino acid. Comparison of this amino acid with other amino acids is attempted and that is why formylmethionine is always the first amino acid to begin protein synthesis, in this paper we added a formyl group to alanine amino acid and then studied it when attached to the tRNA molecule and compared this structure with formylmethionine-tRNA structure. The quantum chemical calculations have performed using Gaussian 03 suite of programs. The fAla-tRNA and fMet-tRNA structures have fully optimized at the HF and B3LYP levels with 3–21G∗ and 6–31G∗ basis sets as well as MP2/3–21G∗ level and theoretically solvent effects on the structures were investigated. Then we studied electronic structures of the compounds using Natural Bond Orbital (NBO analysis and calculated NMR parameters at the gas-phase. Frequency analysis was also calculated at the HF and B3LYP/3-21G∗ levels in the different solvents in 298.15 K, 310.15 K temperatures and 1.00 atmosphere pressure.

  6. Biosynthesis of 1-aminocyclopropane-1-carboxylic acid and ethylene from delta-aminolevulinic acid in ripening tomato fruits

    Energy Technology Data Exchange (ETDEWEB)

    El-Rayes, D.E.D.A.

    1987-01-01

    A new pathway for ethylene (C/sub 2/H/sub 4/) biosynthesis, which utilizes delta-aminolevulinic acid (ALA) as a precursor of 1-aminocyclopropane-1-carboxylic acid (ACC), the immediate precursor of C/sub 2/H/sub 4/, is presented. ALA enhanced ACC accumulation to 410% and C/sub 2/H/sub 4/ production to 232% of the control. The C/sub 2/H/sub 4/ production rate varied with the ALA concentration and the stage of tomato fruit development. As the ALA concentration increased from zero to 40 mM, the C/sub 2/H/sub 4/ production rate increased. Both treated and untreated pericarp discs from fruits at the pink stage of development yielded the largest C/sub 2/H/sub 4/ production rate. Radioactivity from (2,3-/sup 3/H)ALA was detected in both ACC and C/sub 2/H/sub 4/, and radioactivity from (4-/sup 14/C)ALA was detected in ACC and CO/sub 2/ but not in C/sub 2/H/sub 4/. However, radioactivity from (5-/sup 14/C)ALA was detected in CO/sub 2/, and its amount was greater than that obtained from (4-/sup 14/C)ALA. Neither ACC nor C/sub 2/H/sub 4/ showed any radioactivity when (5-/sup 14/C)ALA was supplied to the fruit discs. In addition, when (2,3-/sup 3/H)ALA or (4-/sup 14/C)ALA was supplied to the fruit discs, radioactivity was detected in other metabolites such as fumarate, succinate, malate, glutamate, glutamine, ..cap alpha..-ketoglutarate, and methionine, but the amount of radioactivity was insignificant as compared with the amount of radioactivity found in C/sub 2/H/sub 4/ and ACC.

  7. Optimized fluorescence diagnosis of tumors by comparing five-ALA-induced xenofluorescence and autofluorescence intensities of a murine tumor/nontumor tissue system cultivated on the CAM

    Science.gov (United States)

    Stroebele, Simone; Dressler, Cathrin; Ismail, M. Samy; Daskalaki, Anita; Philipp, Carsten M.; Berlien, Hans-Peter; Weitzel, H.; Liebsch, M.; Spielmann, H.

    1995-12-01

    The in vivo model of the chorioallantoic membrane of fertilized chicken embryos (CAM) was employed for studying the fluorescence characteristics of tumor tissue in comparison with non tumorous tissue. Tumors were grown from the murine fibrosarcoma cell line SSK II and murine 3T3 fibroblasts (clone A31) were used for cultivating non tumorous tissue. Autofluorescence and xenofluorescence intensities induced by 5-aminolaevulinic acid (5-ALA) were compared. Exogenous administration of 5-ALA, an early precursor in haem synthesis, induces accumulation of endogenous photoactive porphyrins, in particular protoporphyrin IX (PpIX). Fluorescence investigations were performed after 3-4d of incubation, when the tissues had reached macroscopically three dimensional stages of growth. Fluorescences were excited with a HBO-X 100 W lamp (Carl Zeiss) at a wavelength (lambda) equals 405 plus or minus 5 nm. Emissions were detected in the spectral range above 630 nm and visualized by real time digital image processing (Argus 10, HAMAMATSU) using an ICCD camera (HAMAMATSU). After administration of 0.4 mmolar 5-ALA solution to the CAM inoculated tissues the SSK II tumors exhibited higher fluorescence intensities than the 3T3 non tumorous tissues. Autofluorescence intensities of both types of tissues were not distinguishable. Furthermore, the effects of several biochemicals on the xenofluorescence intensities of the fibrosarcoma and fibroblast tissues were investigated.

  8. The enzymology of alanine aminotransferase (AlaAT) isoforms from Hordeum vulgare and other organisms, and the HvAlaAT crystal structure.

    Science.gov (United States)

    Duff, Stephen M G; Rydel, Timothy J; McClerren, Amanda L; Zhang, Wenlan; Li, Jimmy Y; Sturman, Eric J; Halls, Coralie; Chen, Songyang; Zeng, Jiamin; Peng, Jiexin; Kretzler, Crystal N; Evdokimov, Artem

    2012-12-01

    In this paper we describe the expression, purification, kinetics and biophysical characterization of alanine aminotransferase (AlaAT) from the barley plant (Hordeum vulgare). This dimeric PLP-dependent enzyme is a pivotal element of several key metabolic pathways from nitrogen assimilation to carbon metabolism, and its introduction into transgenic plants results in increased yield. The enzyme exhibits a bi-bi ping-pong reaction mechanism with a K(m) for alanine, 2-oxoglutarate, glutamate and pyruvate of 3.8, 0.3, 0.8 and 0.2 mM, respectively. Barley AlaAT catalyzes the forward (alanine-forming) reaction with a k(cat) of 25.6 s(-1), the reverse (glutamate-forming) reaction with k(cat) of 12.1 s(-1) and an equilibrium constant of ~0.5. The enzyme is also able to utilize aspartate and oxaloacetate with ~10% efficiency as compared to the native substrates, which makes it much more specific than related bacterial/archaeal enzymes (that also have lower K(m) values). We have crystallized barley AlaAT in complex with PLP and l-cycloserine and solved the structure of this complex at 2.7 Å resolution. This is the first example of a plant AlaAT structure, and it reveals a canonical aminotransferase fold similar to structures of the Thermotoga maritima, Pyrococcus furiosus, and human enzymes. This structure bridges our structural understanding of AlaAT mechanism between three kingdoms of life and allows us to shed some light on the specifics of the catalysis performed by these proteins.

  9. PPARγ2 Pro12Ala polymorphism is associated with improved lipoprotein lipase functioning in adipose tissue of insulin resistant obese women.

    Science.gov (United States)

    López-Alarcón, Mardia; Rodríguez-Cruz, Maricela; Vital-Reyes, Victor Saúl; Zavala-Ortega, María Isabel; Hinojosa-Cruz, Juan Carlos; Canizales-Quinteros, Samuel; Fernández, José

    2012-12-15

    Lipoprotein lipase (LPL) plays a pivotal role in lipid metabolism, contributes to metabolic disorders related to insulin action and body weight regulation, and is influenced by inflammation. The Pro12Ala polymorphism of the peroxisome proliferator-activated receptor (PPAR)γ2 gene seems to influence LPL functioning, but its role in obesity and insulin resistance status, which usually coexist in the clinical setting, has not been explored. Our aim was to analyze the association of obesity and insulin resistance with adipose LPL activity and expression, and the influence of the PPARγ2 Pro12Ala polymorphism. A cross-sectional study was conducted in 58 reproductive-age women who underwent elective abdominal surgery. Free-fatty acids, glucose, insulin, and selected adipokines were measured in fasting blood samples. DNA was isolated and the polymorphism genotyped. Biopsies of abdominal subcutaneous adipose tissue obtained during surgery were used to determine enzymatic LPL activity and expression; and expression of selected cytokines. Overweight/obese women presented lower LPL activity (P=0.022) and higher circulating TNF-α (P=0.020) than controls. Insulin resistant women also showed borderline lower LPL activity than non-resistant (P=0.052), but adiposity and inflammatory molecules were comparable. Nevertheless, LPL activity was higher in Pro12Ala carriers than in non-carriers after adjusting for obesity, insulin resistance and inflammation. Likewise, adipose LPL expression was increased in carriers while expression of cytokines was decreased. Our data suggest that insulin resistance is associated with low adipose LPL activity independently of obesity, but the PPARγ2 Pro12Ala polymorphism seems to protect the LPL functioning of obese insulin resistant women, likely through regulating inflammation in adipose tissue. Copyright © 2012 Elsevier B.V. All rights reserved.

  10. Study of the efficacy of 5-ALA mediated photodynamic therapy on human rhabdomyosarcoma cell line (RD)

    Science.gov (United States)

    Atif, M.; Fakhar-e-Alam, M.; Firdous, S.; Zaidi, S. S. Z.; Suleman, R.; Ikram, M.

    2010-10-01

    The aim of this study was to investigate the mechanism of cell death by photodynamic therapy (PDT) in the Rhabdomyosarcoma (RD) cell line. The present study evaluates the effects of photodynamic therapy (PDT) with 5-ALA as photosensitizer using human muscle cancer cells as experimental model. We study the photosensitizer uptake, cytotoxicity, phototoxicity, and cellular viability of the RD cells which was estimated by means of neutral-red spectrophotometric assay. The given experiment was consisted of two steps. For the first one, RD cells were exposed to 5-ALA at concentrations of 0 up to 1000 μg of ALA/ml in minimum essential medium (MEM). The optimal uptake of photosensitizer (5-ALA) in RD cells was investigated by means of spectrometric measurements. Cells viability was determined by means of neutral red assay (NRA). In the second step, 5-ALA exposed RD cells were irradiated with red light (a diode laser, λ = 635 nm) at total light dose of 80 J/cm2. The influence of different incubation times and concentrations of 5-ALA, different irradiation doses and various combinations of photosensitizer and light doses on the viability of RD cells were investigated. It was observed that sensitizer concentration or light doses have no significant effect on cells viability when studied independently. The maximal cellular uptake occurred after 47 hours in vitro incubation. The phototoxic assay showed that ALA-PDT induced killing of 76% of the cells at 250 μg/ml drug dose and 80 J/cm2 light dose.

  11. PPARgamma Pro12Ala polymorphism in HIV-1-infected patients with HAART-related lipodystrophy.

    Science.gov (United States)

    Saumoy, Maria; Veloso, Sergi; Alonso-Villaverde, Carlos; Domingo, Pere; Chacón, Matilde R; Miranda, Merce; Aragonès, Gerard; Gutiérrez, Maria Mar; Viladés, Consuelo; Peraire, Joaquim; Sirvent, Joan-Josep; López-Dupla, Miguel; Aguilar, Carmen; Richart, Cristóbal; Vidal, Francesc

    2009-09-01

    Peroxisome proliferator-activated receptor gamma (PPARgamma) is involved in obesity and in some components of the metabolic syndrome in unselected population. To determine whether PPARgamma genetic variants are associated with the risk of developing lipodystrophy and its associated metabolic disturbances in HIV-1-infected patients treated with HAART and to assess PPARgamma mRNA expression in subcutaneous adipose tissue (SAT). The study group comprised 278 patients infected with HIV-1 and treated with antiretroviral drugs (139 with lipodystrophy and 139 without) and 105 uninfected controls (UC). The PPARgamma Pro12Ala (C%>G) single nucleotide polymorphism (SNP) was assessed using PCR-RFLPs on white cell DNA. PPARgamma mRNA expression in SAT was assessed in 38 patients (25 with lipodystrophy and 13 without) and in 21 UC by real-time PCR. Statistical analysis was based on Student's T tests, Chi(2) tests, Spearman's correlations tests and logistic regression tests. PPARgamma Pro12Ala genotype distribution and allele frequencies were non-significantly different between both HIV-1-infected categories, lipodystrophy vs non-lipodystrophy (p=0.9 and p=0.87, respectively). Lipodystrophic patients harbouring the rare X/Ala genotype (Ala/Ala plus Pro/Ala) had significantly greater plasma total and LDL cholesterol levels compared with carriers of the common Pro/Pro genotype (p=0.029 and p=0.016, respectively) at univariate analyses. At multivariate analyses these associations were no longer significant. There was a near-significant decreased SAT PPARgamma mRNA expression in patients with lipodystrophy compared to UC (p=0.054). PPARgamma Pro12Ala SNP has no effect on the risk of developing lipodystrophy in HIV-1-infected patients treated with HAART. PPARgamma mRNA SAT expression appears decreased in lipodystrophy.

  12. Health risk assessment of lead for children in tinfoil manufacturing and e-waste recycling areas of Zhejiang Province, China

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Xiaofeng, E-mail: zjcdcwxf@gmail.com [Zhejiang Provincial Center for Disease Control and Prevention, 630 Xin Cheng Road, Binjiang District, Hangzhou 310051 (China); Centre for Environment and Population Health, Griffith School of Environment, Griffith University, 170 Kessels Road, Nathan, QLD 4111 (Australia); Miller, Greg [Centre for Environment and Population Health, Griffith School of Environment, Griffith University, 170 Kessels Road, Nathan, QLD 4111 (Australia); Ding, Gangqiang; Lou, Xiaoming; Cai, Delei; Chen, Zhijian; Meng, Jia; Tang, Jun [Zhejiang Provincial Center for Disease Control and Prevention, 630 Xin Cheng Road, Binjiang District, Hangzhou 310051 (China); Chu, Cordia [Centre for Environment and Population Health, Griffith School of Environment, Griffith University, 170 Kessels Road, Nathan, QLD 4111 (Australia); Mo, Zhe; Han, Jianlong [Zhejiang Provincial Center for Disease Control and Prevention, 630 Xin Cheng Road, Binjiang District, Hangzhou 310051 (China)

    2012-06-01

    Tinfoil manufacturing and electronic waste (e-waste) recycling remain rudimentary processes in Zhejing Province, China, which could account for elevated blood lead levels (BLLs) and health impacts on children. We assessed the potential health risks of lead in tinfoil manufacturing and e-waste recycling areas. 329 children in total aged 11-12 who lived in a tinfoil manufacturing area (Lanxi), an e-waste recycling area (Luqiao) and a reference area (Chun'an) were studied. Lead levels in children's blood were determined by inductively coupled plasma mass spectrometer (ICP-MS). Blood urea nitrogen (BUN), serum creatinine, serum calcium, {delta}-Aminolaevulinic acid ({delta}-ALA) and intelligence quotient (IQ) were also measured. Geometric mean of BLLs in Lanxi, Luqiao and Chun'an were 8.11 {mu}g/dL, 6.97 {mu}g/dL, and 2.78 {mu}g/dL respectively, with 35.1%, 38.9% and 0% of children who had BLLs above 10 {mu}g/dL. The BLLs in exposed areas were much higher than those in the control area. Lanxi children had higher creatinine and calcium than Chun'an children, and Luqiao children had higher {delta}-ALA and lower calcium than Chun'an children. No significant differences of IQ were observed between Lanxi, Luqiao and Chun'an, however a negative relationship between BLLs and IQ was shown for the study children. The results indicated that lead pollution from e-waste recycling and tinfoil processing appears to be a potential serious threat to children's health. - Highlights: Black-Right-Pointing-Pointer No report on tinfoil processing impact on children's health before. Black-Right-Pointing-Pointer Few studies reported health impacts of lead from e-waste processing. Black-Right-Pointing-Pointer Children with blood lead levels < 10 {mu}g/dL are associated with a decrease in IQ. Black-Right-Pointing-Pointer Threshold appears to exist at blood lead level of about 20 {mu}g/dL for urinary {delta}-ALA.

  13. Applications of 5-aminolevulinic acid on the physiological and biochemical characteristics of strawberry fruit during postharvest cold storage

    Directory of Open Access Journals (Sweden)

    Yi Li

    Full Text Available ABSTRACT: The compound 5-aminolevulinic acid (ALA is a key precursor in the biosynthesis of porphyrins, such as chlorophyll, heme and phytochromobilin, and has multiple physiological effects on plants. Varying concentrations of ALA (50mg L-1, 100mg L-1, and 150mg L-1 and water (control were applied to white stage 'Sweet Charlie' strawberry fruit. All ALA treatments delayed senescence and improved the qualities of strawberries fruit during storage. Among the treatments, 150mg L-1 ALA was the most effective dosage concentration. Exogenously applied ALA significantly reduced the decay index, respiration rate, O2 - production rate (O2 -, H2O2 and malondialdehyde (MDA content, increased superoxide dismutase (SOD, ascorbate peroxidase activities (APX, total soluble solids (TSS content, titratable acidity (TA and anthocyanin content during the initial stage of storage. These results supported the pre harvest application of ALA as a beneficial strategy for the prevention of postharvest decay of strawberry fruit.

  14. Peroxisome proliferator-activated receptor mRNA levels are modified by dietary n-3 fatty acid restriction and energy restriction in the brain and liver of growing rats

    Science.gov (United States)

    Without dietary sources of long chain (LC) n-3 fatty acids, alpha-linolenic acid (ALA;18:3n-3) is the precursor for docosahexaenoic acid (DHA; 22:6n-3). It is not known how energy restriction (ER) impacts ALA conversion to DHA. We tested the hypothesis that ER reduces LCn-3 content in growing rats ...

  15. gamma-linolenic acid does not augment long-chain polyunsaturated fatty acid omega-3 status

    NARCIS (Netherlands)

    Brouwer, DAJ; Hettema, Y; van Doormaal, JJ; Muskiet, FAJ

    1998-01-01

    Augmentation of long chain polyunsaturated omega 3 fatty acid (LCPUFA omega 3) status can be reached by consumption of fish oil or by improvement of the conversion of a-linolenic acid (ALA) to LCPUFA omega 3. Since gamma-linolenic acid (GLA) might activate the rate-limiting Delta-6 desaturation, we

  16. gamma-linolenic acid does not augment long-chain polyunsaturated fatty acid omega-3 status

    NARCIS (Netherlands)

    Brouwer, DAJ; Hettema, Y; van Doormaal, JJ; Muskiet, FAJ

    1998-01-01

    Augmentation of long chain polyunsaturated omega 3 fatty acid (LCPUFA omega 3) status can be reached by consumption of fish oil or by improvement of the conversion of a-linolenic acid (ALA) to LCPUFA omega 3. Since gamma-linolenic acid (GLA) might activate the rate-limiting Delta-6 desaturation, we

  17. Does Pro12Ala Polymorphism Enhance the Physiological Role of PPARγ2?

    Directory of Open Access Journals (Sweden)

    A. C. Pereira

    2013-01-01

    Full Text Available Obesity and type 2 diabetes mellitus (T2D are two major public health problems that have motivated the scientific community to investigate the high contribution of genetic factors to these disorders. The peroxisome proliferator activated by gamma 2 (PPARγ2 plays an important role in the lipid metabolism. Since PPARγ2 is expressed mainly in adipose tissue, a moderate reduction of its activity influences the sensitivity to insulin, diabetes, and other metabolic parameters. The present study aims to contribute to the elucidation of the impact of the Pro12Ala polymorphism associated with T2D and obesity through a meta-analysis study of the literature that included approximately 11500 individuals, from which 3870 were obese and 7625 were diabetic. Statistical evidence supports protective effect in T2D of polymorphism Pro12Ala of PPARγ2 (OR = 0.702 with 95% CI: 0.622; 0.791, P<0.01. Conversely the same polymorphism Pro12Ala of PPARγ2 seems to favor obesity since 1.196 more chance than nonobese was found (OR = 1.196 with 95% CI: 1.009; 1.417, P<0.004. Our results suggest that Pro12Ala polymorphism enhances both adipogenic and antidiabetogenic physiological role of PPARγ. Does Pro12Ala polymorphism represent an evolutionary step towards the stabilization of the molecular function of PPARγ transcription factor signaling pathway?

  18. D2-Thr92Ala, thyroid hormone levels and biochemical hypothyroidism in preeclampsia.

    Science.gov (United States)

    Procopciuc, Lucia Maria; Caracostea, Gabriela; Hazi, Georgeta; Nemeti, Georgiana; Stamatian, Florin

    2017-02-01

    To identify if there is a relationship between the deiodinase D2-Thr92Ala genetic variant, thyroid hormone levels and biochemical hypothyroidism in preeclampsia. We genotyped 125 women with preeclampsia and 131 normal pregnant women using PCR-RFLP. Serum thyroid hormone levels were determined using ELISA. Our study showed higher TSH and FT4 levels and lower FT3 levels in women with preeclampsia compared to normal pregnant women, with statistical significance for women with mild and severe preeclampsia. The risk to develop pregnancy-induced hypertension (PIH), mild or severe preeclampsia was increased in carriers of at least one D2-Ala92 allele. TSH and FT4 levels were significantly higher and FT3 levels were significantly lower in preeclamptic women with severe preeclampsia if they carried the D2-Ala92 allele compared to non-carriers. Pregnant women with PIH and mild preeclampsia, carriers of at least one D2-Ala92 allele, delivered at lower gestational age neonates with a lower birth weight compared to non-carriers, but the results were statistically significant only in severe preeclampsia. The D2-Thr92Ala genetic variant is associated with the severity and the obstetric outcome of preeclampsia, and it also influences thyroid hormone levels. The study demonstrates non-thyroidal biochemical hypothyroidism - as a result of deiodination effects due to D2 genotypes.

  19. Does Pro12Ala Polymorphism Enhance the Physiological Role of PPARγ2?

    Science.gov (United States)

    Pereira, A. C.; Oliveira, R.; Castro, A. C.; Fernandes, R.

    2013-01-01

    Obesity and type 2 diabetes mellitus (T2D) are two major public health problems that have motivated the scientific community to investigate the high contribution of genetic factors to these disorders. The peroxisome proliferator activated by gamma 2 (PPARγ2) plays an important role in the lipid metabolism. Since PPARγ2 is expressed mainly in adipose tissue, a moderate reduction of its activity influences the sensitivity to insulin, diabetes, and other metabolic parameters. The present study aims to contribute to the elucidation of the impact of the Pro12Ala polymorphism associated with T2D and obesity through a meta-analysis study of the literature that included approximately 11500 individuals, from which 3870 were obese and 7625 were diabetic. Statistical evidence supports protective effect in T2D of polymorphism Pro12Ala of PPARγ2 (OR = 0.702 with 95% CI: 0.622; 0.791, P Pro12Ala of PPARγ2 seems to favor obesity since 1.196 more chance than nonobese was found (OR = 1.196 with 95% CI: 1.009; 1.417, P Pro12Ala polymorphism enhances both adipogenic and antidiabetogenic physiological role of PPARγ. Does Pro12Ala polymorphism represent an evolutionary step towards the stabilization of the molecular function of PPARγ transcription factor signaling pathway? PMID:23983677

  20. Pro12Ala PPAR gamma2 gene polymorphism in women with polycystic ovary syndrome.

    Science.gov (United States)

    Bidzińska-Speichert, Bozena; Lenarcik, Agnieszka; Tworowska-Bardzińska, Urszula; Slezak, Ryszard; Bednarek-Tupikowska, Grazyna; Milewicz, Andrzej; Krepuła, Katarzyna

    2011-06-01

    The pathogenesis of PCOS has not been definitively determined and includes a number of genes linked with steroidogenesis, regulation of gonadotropin secretion, actions of insulin, obesity as well as chronic inflammatory processes. Some authors indicate that PPARgamma play a role in insulin sensitivity and are probably involved in hyperandrogenism in PCOS. The aim of the study was to assess the frequency of the Pro12Ala and Pro115Gln PPARgamma2 gene polymorphisms in women with PCOS. 54 PCOS women and 51 healthy women were recruited. Genetic studies to detect Pro12Ala and Pro115Gln PPARgamma2 gene polymorphism were performed. In the whole studied group the Pro115Gln polymorphism of the PPARgamma2 gene was not found. The frequency of the Pro12Ala polymorphism was estimated at 26.47% in the controls and at 23.15% in the PCOS patients. Women from the control and PCOS groups with BMI > or = 30 had statistically higher occurrence of the Ala allele than women with BMI Pro12Ala polymorphism observed in the sample of women from the Lower Silesian population was significantly higher than in the majority of European populations.

  1. Association between the intake of α-linolenic acid and the risk of CHD

    DEFF Research Database (Denmark)

    Vedtofte, Mia Sadowa; Jakobsen, Marianne Uhre; Lauritzen, Lotte;

    2014-01-01

    The intake of the mainly plant-derived n-3 PUFA α-linolenic acid (ALA) has been reported to be associated with a lower risk of CHD. However, the results have been inconsistent. Therefore, the objective of the present study was to examine the association between the intake of ALA and the risk of CHD...

  2. Effect of Alpha-lipoic Acid Supplementation on Serum Lipid Profile in Women with Rheumatoid Arthritis

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    Elham Mirtaheri

    2014-09-01

    Conclusions: In the present study, serum lipid profile was not significantly affected by ALA intervention. However, ALA supplementation aiming at prevention or treatment of dyslipidemia in RA patients should be further investigated. Keywords: Lipoic acid, Supplementation, Rheumatoid arthritis, Women, Lipid profile

  3. Long-chain polyunsaturated fatty acids in chronic childhood disorders: panacea, promising, or placebo

    Science.gov (United States)

    Long-chain polyunsaturated fatty acids (LCPUFA, or LCP) include the essential fatty acids alpha-linolenic acid (ALA, 18:3 n-3) and linoleic acid (LA, 18:2 n-6) as well as a number of metabolites of both, including eicosapentaenoic acid (EPA, 20:5n-3), docosahexaenoic acid (DHA, 22:6n-3), and arachid...

  4. 5-Aminolevulinic acid protects against cisplatin-induced nephrotoxicity without compromising the anticancer efficiency of cisplatin in rats in vitro and in vivo.

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    Yoshio Terada

    Full Text Available BACKGROUND/AIMS: Nephrotoxicity is a frequent and major limitation in cisplatin (CDDP-based chemotherapy. 5-Aminolevulinic acid (ALA is widely distributed in animal cells, and it is a precursor of tetrapyrole compounds such as heme that is fundamentally important in aerobic energy metabolism. The aim of this study is to evaluate the protective role of ALA in CDDP-induced acute kidney injury (AKI. METHOD: We used CDDP-induced AKI rat model and cultured renal tubular cells (NRK-52E. We divided four groups of rats: control, CDDP only, CDDP + ALA(post;(ALA 10 mg/kg + Fe in drinking water after CDDP, CDDP + ALA(pre & post. RESULT: CDDP increased Cr up to 6.5 mg/dl, BUN up to 230 mg/dl, and ALA significantly reduced these changes. ALA ameliorates CDDP-induced morphological renal damages, and reduced tubular apoptosis evaluated by TUNEL staining and cleaved caspase 3. Protein and mRNA levels of ATP5α, complex(COX IV, UCP2, PGC-1α in renal tissue were significantly decreased by CDDP, and ALA ameliorates reduction of these enzymes. In contrast, Heme Oxigenase (HO-1 level is induced by CDDP treatment, and ALA treatment further up-regulates HO-1 levels. In NRK-52E cells, the CDDP-induced reduction of protein and mRNA levels of mitochondrial enzymes was significantly recovered by ALA + Fe. CDDP-induced apoptosis were ameliorated by ALA + Fe treatment. Furthermore, we evaluated the size of transplantated bladder carcinoma to the rat skin, and ALA did not change the anti cancer effects of CDDP. CONCLUSION: These data suggested that the protective role of ALA in cisplatin-induced AKI is via protection of mitochondrial viability and prevents tubular apoptosis. Also there are no significant effects of ALA on anticancer efficiency of CDDP in rats. Thus, ALA has the potential to prevent CDDP nephrotoxicity without compromising its anticancer efficacy.

  5. 5-Aminolevulinic acid protects against cisplatin-induced nephrotoxicity without compromising the anticancer efficiency of cisplatin in rats in vitro and in vivo.

    Science.gov (United States)

    Terada, Yoshio; Inoue, Keiji; Matsumoto, Tatsuki; Ishihara, Masayuki; Hamada, Kazu; Shimamura, Yoshiko; Ogata, Koji; Inoue, Kosuke; Taniguchi, Yoshinori; Horino, Taro; Karashima, Takashi; Tamura, Kenji; Fukuhara, Hideo; Fujimoto, Shimpei; Tsuda, Masayuki; Shuin, Taro

    2013-01-01

    Nephrotoxicity is a frequent and major limitation in cisplatin (CDDP)-based chemotherapy. 5-Aminolevulinic acid (ALA) is widely distributed in animal cells, and it is a precursor of tetrapyrole compounds such as heme that is fundamentally important in aerobic energy metabolism. The aim of this study is to evaluate the protective role of ALA in CDDP-induced acute kidney injury (AKI). We used CDDP-induced AKI rat model and cultured renal tubular cells (NRK-52E). We divided four groups of rats: control, CDDP only, CDDP + ALA(post);(ALA 10 mg/kg + Fe in drinking water) after CDDP, CDDP + ALA(pre & post). CDDP increased Cr up to 6.5 mg/dl, BUN up to 230 mg/dl, and ALA significantly reduced these changes. ALA ameliorates CDDP-induced morphological renal damages, and reduced tubular apoptosis evaluated by TUNEL staining and cleaved caspase 3. Protein and mRNA levels of ATP5α, complex(COX) IV, UCP2, PGC-1α in renal tissue were significantly decreased by CDDP, and ALA ameliorates reduction of these enzymes. In contrast, Heme Oxigenase (HO)-1 level is induced by CDDP treatment, and ALA treatment further up-regulates HO-1 levels. In NRK-52E cells, the CDDP-induced reduction of protein and mRNA levels of mitochondrial enzymes was significantly recovered by ALA + Fe. CDDP-induced apoptosis were ameliorated by ALA + Fe treatment. Furthermore, we evaluated the size of transplantated bladder carcinoma to the rat skin, and ALA did not change the anti cancer effects of CDDP. These data suggested that the protective role of ALA in cisplatin-induced AKI is via protection of mitochondrial viability and prevents tubular apoptosis. Also there are no significant effects of ALA on anticancer efficiency of CDDP in rats. Thus, ALA has the potential to prevent CDDP nephrotoxicity without compromising its anticancer efficacy.

  6. SLC6A3 coding variant Ala559Val found in two autism probands alters dopamine transporter function and trafficking.

    Science.gov (United States)

    Bowton, E; Saunders, C; Reddy, I A; Campbell, N G; Hamilton, P J; Henry, L K; Coon, H; Sakrikar, D; Veenstra-VanderWeele, J M; Blakely, R D; Sutcliffe, J; Matthies, H J G; Erreger, K; Galli, A

    2014-10-14

    Emerging evidence associates dysfunction in the dopamine (DA) transporter (DAT) with the pathophysiology of autism spectrum disorder (ASD). The human DAT (hDAT; SLC6A3) rare variant with an Ala to Val substitution at amino acid 559 (hDAT A559V) was previously reported in individuals with bipolar disorder or attention-deficit hyperactivity disorder (ADHD). We have demonstrated that this variant is hyper-phosphorylated at the amino (N)-terminal serine (Ser) residues and promotes an anomalous DA efflux phenotype. Here, we report the novel identification of hDAT A559V in two unrelated ASD subjects and provide the first mechanistic description of its impaired trafficking phenotype. DAT surface expression is dynamically regulated by DAT substrates including the psychostimulant amphetamine (AMPH), which causes hDAT trafficking away from the plasma membrane. The integrity of DAT trafficking directly impacts DA transport capacity and therefore dopaminergic neurotransmission. Here, we show that hDAT A559V is resistant to AMPH-induced cell surface redistribution. This unique trafficking phenotype is conferred by altered protein kinase C β (PKCβ) activity. Cells expressing hDAT A559V exhibit constitutively elevated PKCβ activity, inhibition of which restores the AMPH-induced hDAT A559V membrane redistribution. Mechanistically, we link the inability of hDAT A559V to traffic in response to AMPH to the phosphorylation of the five most distal DAT N-terminal Ser. Mutation of these N-terminal Ser to Ala restores AMPH-induced trafficking. Furthermore, hDAT A559V has a diminished ability to transport AMPH, and therefore lacks AMPH-induced DA efflux. Pharmacological inhibition of PKCβ or Ser to Ala substitution in the hDAT A559V background restores AMPH-induced DA efflux while promoting intracellular AMPH accumulation. Although hDAT A559V is a rare variant, it has been found in multiple probands with neuropsychiatric disorders associated with imbalances in DA neurotransmission

  7. Pro12Ala polymorphism in PPAR gamma 2 associated with essential hypertension in Chinese nonagenarians/centenarians.

    Science.gov (United States)

    Lu, Zhenchan; Dong, Birong; Mo, Xianming; Chen, Tie; Wu, Hongmei; Zhang, Yanling; Xiao, Hengyi

    2008-12-01

    The Pro12Ala polymorphism of PPAR gamma 2 has been shown to influence hypertension and the benefit of longevity in previous studies. We examined whether the polymorphism was related to essential hypertension among long-lived subjects (is greater than 90 years). The Pro12Ala variant was examined using polymerase chain reaction restriction fragment length polymorphism in a population-based sample of 839 long-lived subjects (mean 94 years SD 4 years, aged 90-108 years). The genotype frequencies of the Pro12Ala polymorphism were 0.2% Ala12Ala, 9.4% Pro12Ala and 90.4% Pro12Pro in all participants. The frequency of the Ala12 allele was 3.45% in the hypertension group and 6.92% among the normotension group (P=0.001). Moreover, in the total study population, Ala12 allele carriers had lower levels of triglycerides (1.03+/-0.5 mmol/L (means+/-SD) vs. 1.25+/-0.61 mmol/L; PPro12Ala polymorphism of the PPAR gamma 2 gene is associated with hypertension and triglycerides levels in Chinese nonagenarians/centenarians.

  8. Pleiotropic effects of 5-aminolevulinic acid in mouse brain.

    Science.gov (United States)

    Lavandera, Jimena; Rodríguez, Jorge; Ruspini, Silvina; Meiss, Roberto; Zuccoli, Johanna Romina; Martínez, María Del Carmen; Gerez, Esther; Batlle, Alcira; Buzaleh, Ana María

    2016-08-01

    5-Aminolevulinic acid (ALA) seems to be responsible for the neuropsychiatric manifestations of acute intermittent porphyria (AIP). Our aim was to study the effect of ALA on the different metabolic pathways in the mouse brain to enhance our knowledge about the action of this heme precursor on the central nervous system. Heme metabolism, the cholinergic system, the defense enzyme system, and nitric oxide metabolism were evaluated in the encephalon of CF-1 mice receiving a single (40 mg/kg body mass) or multiple doses of ALA (40 mg/kg, every 48 h for 14 days). We subsequently found ALA accumulation in the encephalon of the mice. ALA also altered the brain cholinergic system. After one dose of ALA, a decrease in superoxide dismutase activity and a reduction in glutathione levels were detected, whereas malondialdehyde levels and catalase activity were increased. Heme oxygenase was also increased as an antioxidant response to protect the encephalon against injury. All nitric oxide synthase isoforms were induced by ALA, these changes were more significant for the inducible isoform in glial cells. In conclusion, ALA affected several metabolic pathways in mouse encephalon. Data indicate that a rapid response to oxidative stress was developed; however, with long-term intoxication, the redox balance was probably restored, thereby minimizing oxidative damage.

  9. Investigation of Microstructures of AlAs Oxides Before and After Oxidation

    Institute of Scientific and Technical Information of China (English)

    WANG Yong; JIA Hai-Qiang; MAI Zhen-Hong; JIA Quan-Jie; JIANG Xiao-Ming

    2004-01-01

    @@ The effect of lateral oxidation on microstructures of the GaAs/AlAs/GaAs heterostructure was studied by x-ray specular reflectivity, nonspecular scattering and diffraction. The GaAs/Al2Oa/GaAs multilayer was obtained after oxidation of the GaAs/AlAs/GaAs sample. The results show that, before oxidation, there are two 40-Athick intermixing layers, one located between the AlAs sublayer and the GaAs substrate, and the other between the AlAs sublayer and the upper GaAs sublayer. After oxidation, these two intermixing sublayers disappear. The AlAs was oxidized into amorphous Al2O3 totally. The surface and interface roughnesses of the sample also decrease after oxidation.

  10. Pressure dependence of backbone chemical shifts in the model peptides Ac-Gly-Gly-Xxx-Ala-NH2.

    Science.gov (United States)

    Erlach, Markus Beck; Koehler, Joerg; Crusca, Edson; Kremer, Werner; Munte, Claudia E; Kalbitzer, Hans Robert

    2016-06-01

    For a better understanding of nuclear magnetic resonance (NMR) detected pressure responses of folded as well as unstructured proteins the availability of data from well-defined model systems are indispensable. In this work we report the pressure dependence of chemical shifts of the backbone atoms (1)H(α), (13)C(α) and (13)C' in the protected tetrapeptides Ac-Gly-Gly-Xxx-Ala-NH2 (Xxx one of the 20 canonical amino acids). Contrary to expectation the chemical shifts of these nuclei have a nonlinear dependence on pressure in the range from 0.1 to 200 MPa. The polynomial pressure coefficients B 1 and B 2 are dependent on the type of amino acid studied. The coefficients of a given nucleus show significant linear correlations suggesting that the NMR observable pressure effects in the different amino acids have at least partly the same physical cause. In line with this observation the magnitude of the second order coefficients of nuclei being direct neighbors in the chemical structure are also weakly correlated.

  11. Association of the PPARγ2 Pro12Ala polymorphism with increased risk of cardiovascular diseases.

    Science.gov (United States)

    Li, Y; Zhu, J; Ding, J Q

    2015-12-29

    This meta-analysis investigated the correlation between the PPARγ2 Pro12Ala polymorphism and cardiovascular disease (CVD). Electronic database and manual searches were conducted to retrieve studies published relevant to the PPARγ2 Pro12Ala polymorphism and CVD. Rigorous inclusion and exclusion criteria were employed for selection of high-quality patients-control studies. Statistical data analyses on allelic, dominant, homozygous, heterozygous, and recessive inheritance models were performed using the R 3.1.0 and Stata 12.0 software. We enrolled 12 case-control studies consisting of 10,189 patients with CVD [1070 with myocardial infarction (MI), 7849 with coronary artery disease (CAD), and 1270 with acute coronary syndromes (ACS)] and 17,899 controls. The results of meta-analyses revealed that the PPARγ2 Pro12Ala (rs1801282) polymorphism was correlated with a higher risk of CVD under both allelic and dominant models, while no statistical significance was found under homozygous, heterozygous, or recessive models. Subgroup analysis based on disease showed that the PPARγ2 Pro12Ala (rs1801282) polymorphism was correlated with a higher risk of MI under both allelic and dominant models, while no statistical significance was found for association with CAD or ACS under allele or dominant models. Furthermore, under homozygous, heterozygous, and recessive models, the PPARγ2 Pro12Ala (rs1801282) polymorphism had no statistically significant association with MI, CAD, or ACS. The results of this meta-analysis suggest that the PPARγ2 Pro12Ala (rs1801282) polymorphism might be correlated with a higher risk of CVD, particularly MI, and could serve as an important early indicator for CVD.

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

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    Hector Garcia-Alcala

    2015-01-01

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

  13. Vegetable oils rich in alpha linolenic acid increment hepatic n-3 LCPUFA, modulating the fatty acid metabolism and antioxidant response in rats.

    Science.gov (United States)

    Rincón-Cervera, Miguel Ángel; Valenzuela, Rodrigo; Hernandez-Rodas, María Catalina; Barrera, Cynthia; Espinosa, Alejandra; Marambio, Macarena; Valenzuela, Alfonso

    2016-08-01

    Alpha-linolenic acid (C18:3 n-3, ALA) is an essential fatty acid and the metabolic precursor of long-chain polyunsaturated fatty acids (LCPUFA) from the n-3 family with relevant physiological and metabolic roles: eicosapentaenoic acid (C20:5 n-3, EPA) and docosahexaenoic acid (C22:6 n-3, DHA). Western diet lacks of suitable intake of n-3 LCPUFA and there are recommendations to increase the dietary supply of such nutrients. Seed oils rich in ALA such as those from rosa mosqueta (Rosa rubiginosa), sacha inchi (Plukenetia volubis) and chia (Salvia hispanica) may constitute an alternative that merits research. This study evaluated hepatic and epididymal accretion and biosynthesis of n-3 LCPUFA, the activity and expression of Δ-5 and Δ-6 desaturase enzymes, the expression and DNA-binding activity of PPAR-α and SREBP-1c, oxidative stress parameters and the activity of antioxidative enzymes in rats fed sunflower oil (SFO, 1% ALA) as control group, canola oil (CO, 10% ALA), rosa mosqueta oil (RMO, 33% ALA), sacha inchi oil (SIO, 49% ALA) and chia oil (ChO, 64% ALA) as single lipid source. A larger supply of ALA increased the accretion of n-3 LCPUFA, the activity and expression of desaturases, the antioxidative status, the expression and DNA-binding of PPAR-α, the oxidation of fatty acids and the activity of antioxidant enzymes, whereas the expression and DNA-binding activity of SREBP-1c transcription factor and the biosynthetic activity of fatty acids declined. Results showed that oils rich in ALA such as SIO and ChO may trigger metabolic responses in rats such as those produced by n-3 PUFA.

  14. Ala from Zeljin: Results of the recent research of folk mythology in Zupa

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    Todorović Ivica

    2011-01-01

    Full Text Available The paper presents the results of the recent ethnological research, conduced in Aleksandrovacka Zupa and other areas. In this paper, the emphasis has been placed on notions on mythical beings, i.e. alas and dragons, which in the context of the materials collected take up one of most prominent positions, indicating the specific nature of the micro-regional unit, but also a symbol of the local identity. Namely, there are recordings of numerous and extremely interesting variations of the myth and ideas on the ala from Zeljin which, as the definitely most exposed mythical entity, is certainly a Zupa-specific property.

  15. The revised Appreciation of the Liberal Arts Scale (ALAS-R: Development, reliability and validity

    Directory of Open Access Journals (Sweden)

    Howard Malcolm Reid

    2013-11-01

    Full Text Available Three studies were conducted to develop and evaluate an Appreciation of the Liberal Arts Scale. The final 24-item revision (ALAS-R was reliable (α = .86. Students who had a greater appreciation of the liberal arts were less materialistic, had greater life satisfaction, had greater ability to defer gratification, and reported greater openness to experiences, leadership, wisdom, and judgment. In addition, ALAS-R scores were predictably related to students’ choice of academic major, with Arts and Humanities majors scoring higher. This scale has the potential to contribute to prediction of student retention and major, as well as the assessment of a dimension of college student development.

  16. Effect of domoic acid on brain amino acid levels.

    Science.gov (United States)

    Durán, R; Arufe, M C; Arias, B; Alfonso, M

    1995-03-01

    The administration of Domoic Acid (Dom) in a 0.2 mg/kg i.p. dose induces changes in the levels of amino acids of neurochemical interest (Asp, Glu, Gly, Tau, Ala, GABA) in different rat brain regions (hypothalamus, hippocampus, amygdala, striatum, cortex and midbrain). The most affected amino acid is the GABA, the main inhibitory amino acid neurotransmitter, whereas glutamate, the main excitatory amino acid, is not affected. The rat brain regions that seem to be the main target of the Dom action belong to the limbic system (hippocampus, amygdala). The possible implication of the amino acids in the actions of Dom is also discussed.

  17. Glacier lake outburst floods caused by glacier shrinkage: case study of Ala-Archa valley, Kyrgyz Ala Too, northern Tian Shan, Kyrgyzstan

    Science.gov (United States)

    Petrakov, D.; Erochin, S. A.; Harbor, J.; Ivanov, M.; Rogozhina, I.; Stroeven, A. P.; Usubaliev, R.

    2012-12-01

    Changes in glacier extent and runoff in Central Asia increase socio-economic stress and may result in political conflict between donors of freshwater (Kyrgyzstan, Tajikistan) and recipients of freshwater (Uzbekistan, China). Glaciers in the Pamir and Tian Shan regions have experienced an unprecedented downwasting due to regional climate changes over the past decades. This is because air temperature increases are in some areas accompanied by a decrease in precipitation. Such conditions have already resulted in a reduction of glacier runoff, especially in the northern and western Tian Shan, and an increase of the number and area of glacial lakes in Kyrgyzstan. Even though glacial lakes in the mountains are in general relatively small and located far from densely populated areas, their outbursts often produce destructive debris flows. Such debris flows are especially common in Kyrgyzstan because of its steep river channels and abundance of Holocene and Quaternary glacier deposits that can be remobilized. The glacial lake outburst flood (GLOF) in the Shakhimardan river catchment in 1999, for example, resulted in 100 fatalities in Uzbekistan, and the GLOF from the Zyndan glacial lake led to substantial economic losses in 2009. According to the latest inventory, there are more than 350 glacial lakes in Kyrgyzstan of which about 70 occur in the Kyrgyz Ala Too. The Ala-Archa valley is among the most important glacierized catchments in Kyrgyzstan. Despite the presence of a relatively small glacier-covered area of 36 km2, the Ala-Archa river is of critical importance to the Bishkek area, its agriculture, and its population which currently exceeds one million. GLOFs are therefore a threat to both numerous settlements of touristic value in the Ala-Archa headwaters and to Bishkek. The Teztor lake in the Adygene catchment of the Ala-Archa river system experienced an outburst during 1988 and 2005. On the early morning of July 31, 2012, this lake began draining through a dam

  18. Association of thrombomodulin Ala455Val dimorphism and inflammatory cytokines with carotid atherosclerosis in the Chinese Han population

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    Qian G

    2012-11-01

    Full Text Available Gaochao Qian,1 Zhixiang Ding,1 Binxia Zhang,2 Qihua Li,2 Wentao Jin,1 Qi Zhang21Clinical Laboratory Department, 2Department of Cardiology, Changzhou TCM Hospital Affiliated to Nanjing TCM University, Changzhou, ChinaBackground and methods: It has been reported that C/T dimorphism at position 1418 of the thrombomodulin gene causes a cytosine (C transition to thymidine (T, resulting in an alanine (A to valine (V substitution at amino acid position 455 (TM455. TM455 had been found not only in African American and American whites, but also in whites in The Netherlands and Sweden. Among these populations, the C/C genotype is predominant, although the distribution of this dimorphism is different. Thrombomodulin is an important anticoagulant protein that is downregulated in endothelial cells overlying atherosclerotic plaques and is also an anti-inflammatory molecule. TM455 is located in the last epidermal growth factor-like repeat of thrombomodulin, which is functionally important for protein C activation and thrombin binding. The distribution of thrombomodulin polymorphism and association between TM455, inflammatory cytokines, and carotid atherosclerosis in the Chinese Han population is unclear.Methods: This thrombomodulin dimorphism was analyzed by allele-specific amplification in 144 patients with carotid atherosclerosis and in 384 healthy controls. TM455 was found in the Chinese Han population, but the genotype frequency and distribution of each genotype in this population differed substantially from that in other ethnic subgroups. The C/T and T/T genotypes were predominant in the Chinese Han population, and the frequency of the T allele in this population (63.8% was much higher than that in whites in The Netherlands (18%, Sweden (26.1%, and the US (18.4%, and in blacks in the US (7.6%. The frequencies of these single nucleotide polymorphisms complied well with the Hardy-Weinberg equilibrium in healthy individuals. The C allele was significantly

  19. Association between the Pro12Ala Polymorphism of the Peroxisome Proliferator-Activated Receptor Gamma Gene and Strength Athlete Status

    Science.gov (United States)

    Maciejewska-Karlowska, Agnieszka; Sawczuk, Marek; Cieszczyk, Pawel; Zarebska, Aleksandra; Sawczyn, Stanislaw

    2013-01-01

    Background The 12Ala allele of the Peroxisome Proliferator-Activated Receptor gamma gene (PPARG) Pro12Ala polymorphism produces a decreased binding affinity of the PPARγ2 protein, resulting in low activation of the target genes. The 12Ala allele carriers display a significantly improved insulin sensitivity that may result in better glucose utilisation in working skeletal muscles. We hypothesise that the PPARG 12Ala allele could be associated with strength athlete status in Polish athletes. Methodology The genotype distribution of PPARG Pro12Ala was examined in 660 Polish athletes. The athletes were stratified into four subgroups: endurance, strength-endurance, sprint-strength and strength. Control samples were prepared from 684 unrelated sedentary volunteers. A χ2 test was used to compare the PPARG Pro12Ala allele and genotype frequencies between the different groups of athletes and control subjects. Bonferroni’s correction for multiple testing was applied. Results A statistically significant higher frequency of PPARG 12Ala alleles was observed in the subgroup of strength athletes performing short-term and very intense exertion characterised by predominant anaerobic energy production (13.2% vs. 7.5% in controls; P = 0.0007). Conclusion The PPARG 12Ala allele may be a relevant genetic factor favouring strength abilities in professional athletes, especially in terms of insulin-dependent metabolism, a shift of the energy balance towards glucose utilisation and the development of a favourable weight-to-strength ratio. PMID:23799144

  20. Association between the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor gamma gene and strength athlete status.

    Science.gov (United States)

    Maciejewska-Karlowska, Agnieszka; Sawczuk, Marek; Cieszczyk, Pawel; Zarebska, Aleksandra; Sawczyn, Stanislaw

    2013-01-01

    The 12Ala allele of the Peroxisome Proliferator-Activated Receptor gamma gene (PPARG) Pro12Ala polymorphism produces a decreased binding affinity of the PPARγ2 protein, resulting in low activation of the target genes. The 12Ala allele carriers display a significantly improved insulin sensitivity that may result in better glucose utilisation in working skeletal muscles. We hypothesise that the PPARG 12Ala allele could be associated with strength athlete status in Polish athletes. The genotype distribution of PPARG Pro12Ala was examined in 660 Polish athletes. The athletes were stratified into four subgroups: endurance, strength-endurance, sprint-strength and strength. Control samples were prepared from 684 unrelated sedentary volunteers. A χ(2) test was used to compare the PPARG Pro12Ala allele and genotype frequencies between the different groups of athletes and control subjects. Bonferroni's correction for multiple testing was applied. A statistically significant higher frequency of PPARG 12Ala alleles was observed in the subgroup of strength athletes performing short-term and very intense exertion characterised by predominant anaerobic energy production (13.2% vs. 7.5% in controls; P = 0.0007). The PPARG 12Ala allele may be a relevant genetic factor favouring strength abilities in professional athletes, especially in terms of insulin-dependent metabolism, a shift of the energy balance towards glucose utilisation and the development of a favourable weight-to-strength ratio.

  1. Association between the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor gamma gene and strength athlete status.

    Directory of Open Access Journals (Sweden)

    Agnieszka Maciejewska-Karlowska

    Full Text Available BACKGROUND: The 12Ala allele of the Peroxisome Proliferator-Activated Receptor gamma gene (PPARG Pro12Ala polymorphism produces a decreased binding affinity of the PPARγ2 protein, resulting in low activation of the target genes. The 12Ala allele carriers display a significantly improved insulin sensitivity that may result in better glucose utilisation in working skeletal muscles. We hypothesise that the PPARG 12Ala allele could be associated with strength athlete status in Polish athletes. METHODOLOGY: The genotype distribution of PPARG Pro12Ala was examined in 660 Polish athletes. The athletes were stratified into four subgroups: endurance, strength-endurance, sprint-strength and strength. Control samples were prepared from 684 unrelated sedentary volunteers. A χ(2 test was used to compare the PPARG Pro12Ala allele and genotype frequencies between the different groups of athletes and control subjects. Bonferroni's correction for multiple testing was applied. RESULTS: A statistically significant higher frequency of PPARG 12Ala alleles was observed in the subgroup of strength athletes performing short-term and very intense exertion characterised by predominant anaerobic energy production (13.2% vs. 7.5% in controls; P = 0.0007. CONCLUSION: The PPARG 12Ala allele may be a relevant genetic factor favouring strength abilities in professional athletes, especially in terms of insulin-dependent metabolism, a shift of the energy balance towards glucose utilisation and the development of a favourable weight-to-strength ratio.

  2. Polymorphism of Pro12Ala and C1431T PPARγin the pathogenesis of Graves' orbitopathy

    Directory of Open Access Journals (Sweden)

    D M Serkin

    2013-09-01

    Full Text Available AIM: to examine the association of polymorphisms Pro12Ala and C1431T PPARγwith the development of thyroid eye disease (TEO. Materials and methods. A total of 88 people: 52 patients with TEO, 36 – healthy individuals. Identified polymorphisms Pro12Ala and C1431T PPARγby PCR. Results. In more common TEO homozygous genotypes Pro/Pro and Ala/Ala (χ 2 = 6,035, p = 0.049 and allele Ala (χ 2 = 15,062, p <0,001 polymorphism Pro12Ala; geno types C/C and T/T (χ 2 = 28,34, p <0,001, the allele C (χ 2 = 15,06, p <0,001 polymorphism C1431T PPARγ, than in the control. The relative risk of TEO in the Ala/Ala genotype of 1.73 (95% CI, 1.45–2.08, with C/T genotype of 0.61 (95% CI, 0.39–0.96. The odds ratio for C/T genotype in patients with TEO 0.33 (95% CI, 0.13–0.82.

  3. Substitution of the Lys linker with the β-Ala linker dramatically decreased the renal uptake of 99mTc-labeled Arg-X-Asp-conjugated and X-Ala-Asp-conjugated α-melanocyte stimulating hormone peptides.

    Science.gov (United States)

    Flook, Adam M; Yang, Jianquan; Miao, Yubin

    2014-11-13

    The purpose of this study was to examine whether the substitution of the Lys linker with the β-Ala could reduce the renal uptake of (99m)Tc-labeled Arg-X-Asp-conjugated and X-Ala-Asp-conjugated α-melanocyte stimulating hormone (α-MSH) peptides. RSD-β-Ala-(Arg(11))CCMSH (1) {c[Arg-Ser-Asp-dTyr-Asp]-β-Ala-Cys-Cys-Glu-His-dPhe-Arg-Trp-Cys-Arg-Pro-Val-NH2}, RTD-β-Ala-(Arg(11))CCMSH (2), RVD-β-Ala-(Arg(11))CCMSH (3), RAD-β-Ala-(Arg(11))CCMSH (4), NAD-β-Ala-(Arg(11))CCMSH (5), and EAD-β-Ala-(Arg(11))CCMSH (6) peptides were synthesized and evaluated for their melanocortin 1 (MC1) receptor binding affinities in B16/F1 melanoma cells. The biodistribution of their (99m)Tc-conjugates were determined in B16/F1 melanoma-bearing C57 mice. The substitution of the Lys linker with β-Ala linker dramatically reduced the renal uptake of all six (99m)Tc-peptides. (99m)Tc-4 exhibited the highest melanoma uptake (15.66 ± 6.19% ID/g) and the lowest kidney uptake (20.18 ± 3.86% ID/g) among these (99m)Tc-peptides at 2 h postinjection. The B16/F1 melanoma lesions could be clearly visualized by single photon emission computed tomography (SPECT)/CT using (99m)Tc-4 as an imaging probe.

  4. Patarei ja Lennusadama ala planeering = Plan for the Patarei Fort and Lennusadam Port Area

    Index Scriptorium Estoniae

    2007-01-01

    Patarei ja Lennusadama ala mahulise planeerimise rahvusvaheline ideevõistlus 2007. aastal. Võistlustööd "Kolm õuna" (I preemia - Sverre Laanjärv, Ivar Lubjak), "Põhi" (II preemia - Tõnu Laanemäe, Jaak-Adam Looveer, Toomas Paaver, kaasautorid Indrek Järve ja Lauri Saar) ja "Kompass" (III preemia - Ott Kadarik ja Villem Tomiste, AB Kosmos)

  5. Pathogenic mitochondrial mt-tRNA(Ala) variants are uniquely associated with isolated myopathy.

    Science.gov (United States)

    Lehmann, Diana; Schubert, Kathrin; Joshi, Pushpa R; Hardy, Steven A; Tuppen, Helen A L; Baty, Karen; Blakely, Emma L; Bamberg, Christian; Zierz, Stephan; Deschauer, Marcus; Taylor, Robert W

    2015-12-01

    Pathogenic mitochondrial DNA (mtDNA) point mutations are associated with a wide range of clinical phenotypes, often involving multiple organ systems. We report two patients with isolated myopathy owing to novel mt-tRNA(Ala) variants. Muscle biopsy revealed extensive histopathological findings including cytochrome c oxidase (COX)-deficient fibres. Pyrosequencing confirmed mtDNA heteroplasmy for both mutations (m.5631G>A and m.5610G>A) whilst single-muscle fibre segregation studies (revealing statistically significant higher mutation loads in COX-deficient fibres than in COX-positive fibres), hierarchical mutation segregation within patient tissues and decreased steady-state mt-tRNA(Ala) levels all provide compelling evidence of pathogenicity. Interestingly, both patients showed very high-mutation levels in all tissues, inferring that the threshold for impairment of oxidative phosphorylation, as evidenced by COX deficiency, appears to be extremely high for these mt-tRNA(Ala) variants. Previously described mt-tRNA(Ala) mutations are also associated with a pure myopathic phenotype and demonstrate very high mtDNA heteroplasmy thresholds, inferring at least some genotype:phenotype correlation for mutations within this particular mt-tRNA gene.

  6. 5-ALA Fluorescence Image Guided Resection of Glioblastoma Multiforme: A Meta-Analysis of the Literature

    Directory of Open Access Journals (Sweden)

    Samy Eljamel

    2015-05-01

    Full Text Available Background: Glioblastoma multiforme (GBM is one of the most deadly cancers in humans. Despite recent advances in anti-cancer therapies, most patients with GBM die from local disease progression. Fluorescence image guided surgical resection (FIGR was recently advocated to enhance local control of GBM. This is meta-analyses of 5-aminolevulinic (5-ALA induced FIGR. Materials: Review of the literature produced 503 potential publications; only 20 of these fulfilled the inclusion criteria of this analysis, including a total of 565 patients treated with 5-ALA-FIGR reporting on its outcomes and 800 histological samples reporting 5-ALA-FIGR sensitivity and specificity. Results: The mean gross total resection (GTR rate was 75.4% (95% CI: 67.4–83.5, p < 0.001. The mean time to tumor progression (TTP was 8.1 months (95% CI: 4.7–12, p < 0.001. The mean overall survival gain reported was 6.2 months (95% CI: −1–13, p < 0.001. The specificity was 88.9% (95% CI: 83.9–93.9, p < 0.001 and the sensitivity was 82.6% (95% CI: 73.9–91.9, p < 0.001. Conclusion: 5-ALA-FIGR in GBM is highly sensitive and specific, and imparts significant benefits to patients in terms of improved GTR and TTP.

  7. "LJ" Report "Anaheim, ALA 2008": Amid the Fantasy, Doses of Reality

    Science.gov (United States)

    Blumenstein, Lynn; Berry, John; Fialkoff, Francine; Fox, Bette-Lee; Hadro, Josh; Horrocks, Norman; Oder, Norman; Roncevic, Mirela

    2008-01-01

    If the resort city of Anaheim, California, home of Disneyland and its "imagineers," marked a departure from the urban reality of the typical American Library Association (ALA) annual conference, it was impossible, at this 2008 meeting, to avoid urgent library issues. How do libraries maintain their value and cultural presence as users…

  8. Shifting with the Paradigm: LJ's Picks & Pans for ALA in Disneyland

    Science.gov (United States)

    Berry, John N., III

    2008-01-01

    The feelings of librarians planning for the American Library Association (ALA) conference at Disneyland (aka Anaheim, California, June 26-July 2) range from moderate pleasure to dread. Some remember the joys and difficulties of Orlando, especially the exorbitant cab fares and mediocre restaurants. Others quail at screaming kids and tourists in…

  9. Mida suudab muusikateraapia? / Melanie Voigt, Esa Ala-Ruona ; inetrvjueerinud Kristel Kossar

    Index Scriptorium Estoniae

    Voigt, Melanie

    2012-01-01

    Eesti Muusika- ja Teatriakadeemias toimunud Euroopa Muusikateraapia Konföderatsiooni peaassambleel ja sümpoosionil ettekannetega esinenud muusikaterapeudid Malanie Voigt Saksamaalt ja Esa Ala-Ruona Soomest räägivad tööst puuetega lastega ja tööstressist ning heliilmast

  10. Analisa Kadar Assm Lemak Minyak Goreng Yang Dipakai Penjual Ayam Ala Kentucky Di Jalan Binjai Medan

    OpenAIRE

    Yulina

    2012-01-01

    Konsumsi minyak goreng di Indonesia makin meningkat setiap tahunnya karena hampir seluruh masakan sehari-hari orang Indonesia menggunakan minyak goreng dalam jumlah yang cukup bermakna. Minyak goreng dibutuhkan dalam industri makanan terutama Penjual Ayam Ala Kentucky dalam jumlah banyak dan dipergunakan kembali sampai habis untuk menghemat biaya pmduksi. Pemakaian minyak goreng berulang diduga mengakibatkan perubahan komposisi asam lemaknya. 981000107

  11. X-linked macrocytic dyserythropoietic anemia in females with an ALAS2 mutation.

    Science.gov (United States)

    Sankaran, Vijay G; Ulirsch, Jacob C; Tchaikovskii, Vassili; Ludwig, Leif S; Wakabayashi, Aoi; Kadirvel, Senkottuvelan; Lindsley, R Coleman; Bejar, Rafael; Shi, Jiahai; Lovitch, Scott B; Bishop, David F; Steensma, David P

    2015-04-01

    Macrocytic anemia with abnormal erythropoiesis is a common feature of megaloblastic anemias, congenital dyserythropoietic anemias, and myelodysplastic syndromes. Here, we characterized a family with multiple female individuals who have macrocytic anemia. The proband was noted to have dyserythropoiesis and iron overload. After an extensive diagnostic evaluation that did not provide insight into the cause of the disease, whole-exome sequencing of multiple family members revealed the presence of a mutation in the X chromosomal gene ALAS2, which encodes 5'-aminolevulinate synthase 2, in the affected females. We determined that this mutation (Y365C) impairs binding of the essential cofactor pyridoxal 5'-phosphate to ALAS2, resulting in destabilization of the enzyme and consequent loss of function. X inactivation was not highly skewed in wbc from the affected individuals. In contrast, and consistent with the severity of the ALAS2 mutation, there was a complete skewing toward expression of the WT allele in mRNA from reticulocytes that could be recapitulated in primary erythroid cultures. Together, the results of the X inactivation and mRNA studies illustrate how this X-linked dominant mutation in ALAS2 can perturb normal erythropoiesis through cell-nonautonomous effects. Moreover, our findings highlight the value of whole-exome sequencing in diagnostically challenging cases for the identification of disease etiology and extension of the known phenotypic spectrum of disease.

  12. Patarei ja Lennusadama ala planeering = Plan for the Patarei Fort and Lennusadam Port Area

    Index Scriptorium Estoniae

    2007-01-01

    Patarei ja Lennusadama ala mahulise planeerimise rahvusvaheline ideevõistlus 2007. aastal. Võistlustööd "Kolm õuna" (I preemia - Sverre Laanjärv, Ivar Lubjak), "Põhi" (II preemia - Tõnu Laanemäe, Jaak-Adam Looveer, Toomas Paaver, kaasautorid Indrek Järve ja Lauri Saar) ja "Kompass" (III preemia - Ott Kadarik ja Villem Tomiste, AB Kosmos)

  13. Mida suudab muusikateraapia? / Melanie Voigt, Esa Ala-Ruona ; inetrvjueerinud Kristel Kossar

    Index Scriptorium Estoniae

    Voigt, Melanie

    2012-01-01

    Eesti Muusika- ja Teatriakadeemias toimunud Euroopa Muusikateraapia Konföderatsiooni peaassambleel ja sümpoosionil ettekannetega esinenud muusikaterapeudid Malanie Voigt Saksamaalt ja Esa Ala-Ruona Soomest räägivad tööst puuetega lastega ja tööstressist ning heliilmast

  14. Absence of GABRA1 Ala322Asp mutation in juvenile myoclonic epilepsy families from India

    Indian Academy of Sciences (India)

    A. Kapoor; J. Vijai; H. M. Ravishankar; P. Satishchandra; K. Radhakrishnan; A. Anand

    2003-04-01

    An Ala322Asp mutation in the GABRA1 gene was recently reported to be responsible for causing the autosomal dominant (AD) form of juvenile myoclonic epilepsy (JME) in a French-Canadian family. To study if JME families from India exhibiting the AD mode of inheritance carry the Ala322Asp mutation, we examined 35 unrelated JME-affected individuals from such families for the Ala322Asp mutation in GABRA1. Ala322Asp mutation was not observed in any of these JME-affected individuals, suggesting that this mutation is unlikely to be a predominant mutation involved in causation of epilepsy. To evaluate the possibility of other mutation(s) in and around GABRA1 that may predispose to JME, we compared the allele frequencies at two marker loci, D5S2118 and D5S422, flanking GABRA1, in probands and 100 matched population controls. One of the allele frequencies at D5S422 shows a significant difference between the cases and controls (2 = 11.44, d.f. = 1, $P = 0.0007$), suggesting genetic association between JME and genes located in the proximity of the DNA marker.

  15. Preservice Legal Education for Academic Librarians within ALA-Accredited Degree Programs

    Science.gov (United States)

    Cross, William M.; Edwards, Phillip M.

    2011-01-01

    In order to explore the current state of legal education for graduates of LIS programs, we present the results of an examination of the curricula and faculty composition at all 57 institutions that offer ALA-accredited graduate degrees. Concluding that, even under the best circumstances, many students graduate with a limited understanding of legal…

  16. Hey, Small Spender: An Insider's Guide to Navigating ALA's Chicago Conference on the Cheap

    Science.gov (United States)

    School Library Journal, 2009

    2009-01-01

    This article presents an insider's guide to navigating the American Library Association's (ALA) annual conference in Chicago on July 9-15. As for the extracurricular activities, Chicago has a lot to offer. This article provides tips from the arts and entertainment bible "Time Out Chicago" on where to go and what to do (on a limited…

  17. [Two-photon excitation fluorescence of 5-ALA induced PpIX in DHL cells].

    Science.gov (United States)

    Huang, Zu-Fang; Chen, Rong; Li, Yong-Zeng; Chen, Guan-Nan; Chen, Xian-Ling; Feng, Shang-Yuan; Jia, Pei-Min

    2008-11-01

    Two-photon fluorescence microscopy is a novel imaging technique, which is primarily sensitive to a specimen's response coming from an in-focus plane, thus has low photo-bleaching and photo-damage to biological samples. 5-ALA induced production of PpIX in DHL cells was excited by 820 nm femtosecond laser; two-photon excitation fluorescence of single cell was obtained in Lambda mode of laser scanning confocal microscope. The specific fluorescence intensity of PpIX which accumulated in DHL cells was measured at 2, 4 and 10 mmol x L(-1) concentration of 5-ALA with different incubation time, which reflected the kinetics of 5-ALA accumulated in DHL cells. Accumulation of PpIX in DHL cells was a dynamic change process. Biphasic alterations of PpIX accumulation were noted: PpIX content enhanced with the increasing time and reached the maximal value around 3 h, however PpIX content decreased in the subsequent incubation time. Results indicate that two-photon fluorescence based on laser scanning microscope can be a useful technology for studying the kinetics of 5-ALA induced PpIX production in DHL cells and other leukemia cells.

  18. ALA Office for Intellectual Freedom: Who We Are and How We Help Librarians

    Science.gov (United States)

    Pekoll, Kristin

    2015-01-01

    The American Library Association's (ALA's) Office for Intellectual Freedom (OIF) strives to educate librarians and the public about the nature and importance of intellectual freedom in libraries, and it will celebrate its fiftieth anniversary in 2017. Libraries are a forum for information and ideas (under the First Amendment), and librarians are…

  19. Isolated cleft of the ala nasi: A report of seven cases

    Directory of Open Access Journals (Sweden)

    J Rajesh Jinka

    2012-01-01

    Full Text Available Craniofacial clefts other than cleft lip & palate are reported to be 1.4 to 4.9 per 100,000 live births. Of these, clefts of nose are usually associated with other clefts. Isolated cleft of Ala is rare, 0.7% of all clefts reported by Monasterio. In an analysis of photographic records of 3,500 consecutive patients with craniofacial clefts including cleft lip & palate registered with us between 1985- 2012 which were accessed through our data base, 13 patients with nasal clefts were identified, seven out of which had Isolated cleft of the Ala. All were treated by a rotation flap of the Ala with good results with the longest follow up of 14Yrs. The authors have emphasised the rarity of the condition and presented a simple surgical procedure for correction. In the opinion of the authors this very simple procedure which can be performed by the junior surgeon gives a good long term result in the management of cleft Ala.

  20. Association of Pro12Ala polymorphism in peroxisome proliferator activated receptor gamma with proliferative diabetic retinopathy

    Science.gov (United States)

    Tariq, Khadija; Malik, Saira Bano; Ali, Syeda Hafiza Benish; Maqsood, Sundas Ejaz; Azam, Aisha; Muslim, Irfan; Khan, Muhammad Shakil; Azam, Maleeha; Waheed, Nadia Khalida

    2013-01-01

    Purpose The association of non-synonymous substitution polymorphism rs1801282 (c.34C>G, p.Pro12Ala) in exon 4 of the peroxisome proliferator activated receptor gamma gene with diabetic retinopathy (DR) has been reported inconsistently. Therefore, the purpose of the present study was to understand the population-specific role of the Pro12Ala polymorphism in DR susceptibility in Pakistani subjects. Methods A total of 180 subjects with DR, 193 subjects with type 2 diabetes mellitus (T2DM) with no diabetic retinopathy, and 200 healthy normoglycemic non-retinopathic Pakistani individuals were genotyped for the rs1801282 (c.34C>G) polymorphism using polymerase chain reaction-restriction fragment length polymorphism. Results We found the individuals with T2DM carrying 12Ala were at a reduced risk of developing DR (odds ratio [OR]=0.53; 95% confidence interval [CI]=0.33–0.87). Upon stratified analysis regarding disease severity, we observed this protective effect was confined to proliferative DR (OR=0.4; 95% CI=0.2–0.8) with non-significant effects on the susceptibility of non-proliferative DR (OR=0.67; 95% CI=0.37–1.19). Conclusions We report a protective role of the 12Ala polymorphism against proliferative DR in individuals with T2DM in Pakistan. PMID:23559865

  1. Association of Pro12Ala polymorphism in peroxisome proliferator activated receptor gamma with proliferative diabetic retinopathy

    NARCIS (Netherlands)

    Tariq, K.; Malik, S.B.; Ali, S.H.; Maqsood, S.E.; Azam, A.; Muslim, I.; Khan, M.S.; Azam, M.; Waheed, N.K.; Qamar, R.

    2013-01-01

    PURPOSE: The association of non-synonymous substitution polymorphism rs1801282 (c.34C>G, p.Pro12Ala) in exon 4 of the peroxisome proliferator activated receptor gamma gene with diabetic retinopathy (DR) has been reported inconsistently. Therefore, the purpose of the present study was to

  2. The association between the Pro12Ala polymorphism in the PPARg gene and

    DEFF Research Database (Denmark)

    Schow, Trine

    2006-01-01

    The interaction between the Pro12Ala polymorphism in peroxisome-proliferator-activator receptor gamma PPARg -2 and physical activity in the association with obesity (BMI ≥30 kg m-2) was explored in 901 women and 903 men between 30 and 75 years participating in a population survey of cardiovascular....... The proportion carrying the Pro12Ala variant allele was 24% in both sexes. In women ≥50 years Ala carriage was associated with obesity (OR: 1.79, CI: 1.05-3.07). This association was stronger in women with a low LTPA (OR: 2.01, CI: 1.10-3.67), but was not present in those with a high level of LTPA (OR: 1.06, CI......: 0.19-5.91). This association was not seen in men or in women Pro12Ala polymorphism was associated with obesity in women above 50 years, but this risk was prevented already by a moderate level of LTPA. These findings support the emphasis...

  3. Peroxisome proliferator-activated receptor alpha controls hepatic heme biosynthesis through ALAS1.

    Science.gov (United States)

    Degenhardt, Tatjana; Väisänen, Sami; Rakhshandehroo, Maryam; Kersten, Sander; Carlberg, Carsten

    2009-05-01

    Heme is an essential prosthetic group of proteins involved in oxygen transport, energy metabolism and nitric oxide production. ALAS1 (5-aminolevulinate synthase) is the rate-limiting enzyme in heme synthesis in the liver and is highly regulated to adapt to the metabolic demand of the hepatocyte. In the present study, we describe human hepatic ALAS1 as a new direct target for the nuclear receptor peroxisome proliferator-activated receptor alpha (PPARalpha). In primary human hepatocytes and in HepG2 cells, PPARalpha agonists induced an increase in ALAS1 mRNA levels, which was abolished by PPARalpha silencing. These effects are mediated by two functional PPAR binding sites at positions -9 and -2.3 kb relative to the ALAS1 transcription start site. PPARalpha ligand treatment also up-regulated the mRNA levels of the genes ALAD (5-aminolevulinate dehydratase), UROS (uroporphyrinogen III synthase), UROD (uroporphyrinogen decarboxylase), CPOX (coproporphyrinogen oxidase) and PPOX (protoporphyrinogen oxidase) encoding for enzymes controlling further steps in heme biosynthesis. In HepG2 cells treated with PPARalpha agonists and in mouse liver upon fasting, the association of PPARalpha, its partner retinoid X receptor, PPARgamma co-activator 1alpha and activated RNA polymerase II with the transcription start site region of all six genes was increased, leading to higher levels of the metabolite heme. In conclusion, these data strongly support a role of PPARalpha in the regulation of human ALAS1 and of five additional genes of the pathway, consequently leading to increased heme synthesis.

  4. Omega 6 to omega 3 fatty acid imbalance early in life leads to persistent reductions in DHA levels in glycerophospholipids in rat hypothalamus even after long-term omega 3 fatty acid repletion.

    Science.gov (United States)

    Li, Duo; Weisinger, Harrison S; Weisinger, Richard S; Mathai, Michael; Armitage, James A; Vingrys, Algis J; Sinclair, Andrew J

    2006-06-01

    Failure to provide omega 3 fatty acids in the perinatal period results in alterations in nerve growth factor levels, dopamine production and permanent elevations in blood pressure. The present study investigated whether changes in brain (i.e., hypothalamus) glycerophospholipid fatty acid profiles induced by a diet rich in omega 6 fatty acids and very low in alpha-linolenic acid (ALA) during pregnancy and the perinatal period could be reversed by subsequent feeding of a diet containing ALA. Female rats (6 per group) were mated and fed either a low ALA diet or a control diet containing ALA throughout pregnancy and until weaning of the pups at 3 weeks. At weaning, the pups (20 per group) remained on the diet of their mothers until 9 weeks, when half the pups were switched onto the other diet, thus generating four groups of animals. At 33 weeks, pups were killed, the hypothalamus dissected from the male rats and analysed for glycerophospholipid fatty acids. In the animals fed the diet with very little ALA and then re-fed the control diet containing high levels of ALA for 24 weeks, the DHA levels were still significantly less than the control values in PE, PS and PI fractions, by 9%, 18% and 34%, respectively. In this group, but not in the other dietary groups, ALA was detected in all glycerophospholipid classes at 0.2-1.7% of the total fatty acids. The results suggest that omega 6-3 PUFA imbalance early in life leads to irreversible changes in hypothalamic composition. The increased ALA and reduced DHA proportions in the animals re-fed ALA in later life are consistent with a dysfunction or down-regulation of the conversion of ALA to 18:4n-3 by the delta-6 desaturase.

  5. OPTIMIZATIONS FOR 5-AMINOLEVULINIC ACID BASED PHOTODYNAMIC THERAPY IN PURGING LEUKEMIA CELL HL60

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Objective To optimize experimental parameters for the photosensitization of 5-aminolevulinic acid (ALA) in promyelocytic leukemia cell HL60 and compare them with normal human peripheral blood mononuclear cell (PBMC). Methods ALA incubation time, wavelength applied to irradiate, concentration of ALA incubated, irradiation fluence may modulate the effect of 5-aminolevulinic acid based Photodynamic Therapy (ALA-PDT).The high-pressure mercury lamps of 400W served as light source, the interference filter of 410nm, 432nm, 545nm, 577nm were used to select the specific wavelength. Fluorescence microscope was used to detect the fluorescence intensity and location of protoporphyrin IX (PpIX) endogenously produced by ALA. MTT assay was used to measure the survival of cell. Flow cytometry with ANNEXIN V FITC kit (contains annexin V FITC, binding buffer and PI) was used to detect the mode of cell death. Results ① 1mmol/L ALA incubated 1×105/mL HL60 cell line for 4 hours, the maximum fluorescence of ALA induced PpIX was detected in cytomembrane. ② Irradiated with 410nm for 14.4J/cm2 can result in the minimum survivability of HL60 cell. ③ The main mode of HL60 cell death caused by ALA-PDT is necrosis. Conclusion ALA for 1mmol/L, 4 hours for dark incubation time, 410nm for irradiation wavelength, 14.4J/cm2 for irradiation fluence were the optimal parameters to selectively eliminate promyelocytic leukemia cell HL60 by ALA based PDT. The photosensitization of ALA based PDT caused the necrosis of HL60 cell, so it could be used for inactivation of certain leukemia cells.

  6. Dietary supplementation with 5-aminolevulinic acid modulates growth performance and inflammatory responses in broiler chickens.

    Science.gov (United States)

    Sato, K; Matsushita, K; Takahashi, K; Aoki, M; Fuziwara, J; Miyanari, S; Kamada, T

    2012-07-01

    The objective of this study was to investigate the effect of dietary supplementation with 5-aminolevulinic acid (5-ALA) on the immune system, inflammatory response, and growth performance of broiler chickens. The levels of cluster of differentiation 3 (CD3) mRNA in the spleens of chickens gradually increased with dietary 5-ALA concentration, while the expression levels of interleukin (IL)-2 decreased. Mitogen-induced proliferation of splenic mononuclear cells and blood mononuclear cell phagocytosis in chickens fed 0.001 and 0.01% 5-ALA-supplemented diets were significantly greater than in chickens fed a basal diet (control). Plasma thiobarbituric acid reactive substance (TBARS) concentration gradually increased along with 5-ALA supplement concentration. These results provide the first evidence that the use of dietary 0.001 and 0.01% 5-ALA supplementation induces the T-cell immune system via mild oxidative stress in chickens. Three hours after Escherichia coli lipopolysaccharide-induced immune stimulation, the levels of mRNA encoding pro-inflammatory cytokines, such as IL-6 and tumor necrosis factor-like ligand 1A (TL1A), in chickens fed a 0.001% 5-ALA-supplemented diet were significantly lower than those in chickens exposed to other treatments. The plasma caeruloplasmin concentration in chickens fed a 0.001% 5-ALA-supplemented diet was significantly lower than in controls or in chickens fed diets supplemented with other concentrations of 5-ALA 24 h after injection of LPS. In addition, BW at 21 and 50 d of age was significantly higher in chickens fed a 0.001% 5-ALA-supplemented diet than in control chickens. The findings suggest that supplementation of diets with 0.001% 5-ALA could prevent the catabolic changes induced by immunological stimulation. These results show that 5-ALA might be useful as an immunomodulator to stimulate T-cells via mild oxidative stress in growing broiler chickens, thereby improving the growth performance.

  7. Pressure dependence of side chain (13)C chemical shifts in model peptides Ac-Gly-Gly-Xxx-Ala-NH2.

    Science.gov (United States)

    Beck Erlach, Markus; Koehler, Joerg; Crusca, Edson; Munte, Claudia E; Kainosho, Masatsune; Kremer, Werner; Kalbitzer, Hans Robert

    2017-09-14

    For evaluating the pressure responses of folded as well as intrinsically unfolded proteins detectable by NMR spectroscopy the availability of data from well-defined model systems is indispensable. In this work we report the pressure dependence of (13)C chemical shifts of the side chain atoms in the protected tetrapeptides Ac-Gly-Gly-Xxx-Ala-NH2 (Xxx, one of the 20 canonical amino acids). Contrary to expectation the chemical shifts of a number of nuclei have a nonlinear dependence on pressure in the range from 0.1 to 200 MPa. The size of the polynomial pressure coefficients B 1 and B 2 is dependent on the type of atom and amino acid studied. For H(N), N and C(α) the first order pressure coefficient B 1 is also correlated to the chemical shift at atmospheric pressure. The first and second order pressure coefficients of a given type of carbon atom show significant linear correlations suggesting that the NMR observable pressure effects in the different amino acids have at least partly the same physical cause. In line with this observation the magnitude of the second order coefficients of nuclei being direct neighbors in the chemical structure also are weakly correlated. The downfield shifts of the methyl resonances suggest that gauche conformers of the side chains are not preferred with pressure. The valine and leucine methyl groups in the model peptides were assigned using stereospecifically (13)C enriched amino acids with the pro-R carbons downfield shifted relative to the pro-S carbons.

  8. Alpha-Linolenic Acid: Is It Essential to Cardiovascular Health?

    NARCIS (Netherlands)

    Geleijnse, J.M.; Goede, de J.; Brouwer, I.A.

    2010-01-01

    There is a large body of scientific evidence that has been confirmed in randomized controlled trials indicating a cardioprotective effect for omega-3 fatty acids from fish. For alpha-linolenic acid (ALA), which is the omega-3 fatty acid from plants, the relation to cardiovascular health is less clea

  9. Enhanced 5-aminolevulinic acid-gold nanoparticle conjugate-based photodynamic therapy using pulse laser

    Science.gov (United States)

    Xu, Hao; Yao, Cuiping; Wang, Jing; Chang, Zhennan; Zhang, Zhenxi

    2016-02-01

    The low bioavailability is a crucial limitation for the application of 5-aminolevulinic acid (ALA) in theranostics. In this research, 5-aminolevulinic acid and gold nanoparticle conjugates (ALA-GNPs) were synthesized to improve the bioavailability of ALA and to investigate the impact of ALA photodynamic therapy (ALA-PDT) in Hela cells. A 532 nm pulse laser and light-emitting diode (central wavelengths 502 nm) were jointly used as light sources in PDT research. The results show a 532 nm pulse laser can control ALA release from ALA-GNPs by adjusting the pulse laser dose. This laser control release may be attributed to the heat generation from GNPs under pulse laser irradiation, which indicates accurately adjusting the pulse laser dose to control the drug release in the cell interior can be considered as a new cellular surgery modality. Furthermore, the PDT results in Hela cells indicate the enhancement of ALA release by pulse laser before PDT can promote the efficacy of cell eradication in the light-emitting diode PDT (LED-PDT). This laser mediated drug release system can provide a new online therapy approach in PDT and it can be utilized in the optical monitor technologies based individual theranostics.

  10. Characterization of the Ala62Pro polymorphic variant of human cytochrome P450 1A1 using recombinant protein expression

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Seung Heon; Kang, Sukmo [College of Veterinary Medicine, BK21plus Program for Creative Veterinary Science Research, and Research Institute for Veterinary Science, Seoul National University, Seoul (Korea, Republic of); Dong, Mi Sook [School of Life Sciences and Biotechnology, Korea University, Seoul (Korea, Republic of); Park, Jung-Duck [College of Medicine, Chung-Ang University, Seoul (Korea, Republic of); Park, Jinseo; Rhee, Sangkee [College of Agriculture of Life Science, Seoul National University, Seoul (Korea, Republic of); Ryu, Doug-Young, E-mail: dyryu@snu.ac.kr [College of Veterinary Medicine, BK21plus Program for Creative Veterinary Science Research, and Research Institute for Veterinary Science, Seoul National University, Seoul (Korea, Republic of)

    2015-06-15

    Cytochrome P450 (CYP) 1A1 is a heme-containing enzyme involved in detoxification of hydrophobic pollutants. Its Ala62Pro variant has been identified previously. Ala62 is located in α-helix A of CYP1A1. Residues such as Pro and Gly are α-helix breakers. In this study, the Ala62Pro variant was characterized using heterologous expression. E. coli expressing the Ala62Pro variant, and the purified variant protein, had lower CYP (i.e. holoenzyme) contents than their wild-type (WT) equivalents. The CYP variant from E. coli and mammalian cells exhibited lower 7-ethoxyresorufin O-dealkylation (EROD) and benzo[a]pyrene hydroxylation activities than the WT. Enhanced supplementation of a heme precursor during E. coli culture did not increase CYP content in E. coli expressing the variant, but did for the WT. As for Ala62Pro, E. coli expressing an Ala62Gly variant had a lower CYP content than the WT counterpart, but substitution of Ala62 with α-helix-compatible residues such as Ser and Val partially recovered the level of CYP produced. Microsomes from mammalian cells expressing Ala62Pro and Ala62Gly variants exhibited lower EROD activities than those expressing the WT or Ala62Val variant. A region harboring α-helix A has interactions with another region containing heme-interacting residues. Site-directed mutagenesis analyses suggest the importance of interactions between the two regions on holoenzyme expression. Together, these findings suggest that the Ala62Pro substitution leads to changes in protein characteristics and function of CYP1A1 via structural disturbance of the region where the residue is located. - Highlights: • Ala62 is located in α-helix A of the carcinogen-metabolizing enzyme CYP1A1. • Pro acts as an α-helix breaker. • A variant protein of CYP1A1, Ala62Pro, had lower heme content than the wild-type. • The variant of CYP1A1 had lower enzyme activities than the wild-type.

  11. In-vivo kinetics of ALA-induced fluorescence in the canine oral cavity: influence of drug dose and tissue type

    Science.gov (United States)

    Vaidyanathan, Vijay; Rastegar, Sohi; Fossum, Theresa W.; Flores, P.; van der Breggen, E. W. J.; Egger, N. G.; Jacques, Steven L.; Motamedi, Massoud

    1997-06-01

    Fluorescence spectroscopic detection and photodynamic therapy may provide an effective approach for early detection and treatment of oral cancer. Thus the development of a safe photosensitizer that could enhance the spectroscopic contrast between normal and neoplastic tissue, while allowing for selective photosensitization and treatment of pre-malignant and malignant lesions in the oral cavity, is highly desired. In this study, the pharmacokinetics and a safety of 5-aminolevulinic acid (ALA) that could induce an endogenous precursor of protoporphyrin IX and heme in the biosynthetic pathway was investigated. Two doses of ALA:25 and 75 mg/kg were administered intravenously to 4 and 3 dogs, respectively. A 'wash-out' period of 1 week between administration of each does was allowed to ensure against PpIX build-up. Using an optical multichannel analyzer, the fluorescence from the oral cavity was recorded at 3 sites: buccal mucosa, gums, and the tongue, and also from a remote site, the skin. A fiber optic probe was used to deliver excitation and collect the emitted fluorescence. Results showed that the ALA-induced fluorescence reached a peak at 2-4 hours, and returned to baseline in 24-31 hours. The dogs were stable during the course of the study, minimal vomiting was noted. In conclusion, the study showed that higher doses result in a higher peak at a later time.It was observed that different tissues have different pharmacokinetic response, the tongue and the gums have the highest peak fluorescence values, followed by the buccal mucosa and skin.

  12. Effect of alpha lipoic acid on retinal ganglion cell survival in an optic nerve crush model

    Science.gov (United States)

    Liu, Ruixing; Wang, Yanling; Pu, Mingliang

    2016-01-01

    Purpose This study was conducted to determine whether alpha lipoic acid (ALA) promotes the survival of retinal ganglion cells (RGCs) in a rat model of optic nerve crush (ONC) injury and to investigate the neuroprotective mechanisms of ALA in the retina in this ONC injury model. Methods Adult male Sprague-Dawley rats (180–220 g) were subjected to ONC injury surgery. ALA (63 mg/kg) was injected intravenously 1 day before or after the ONC injury. Animals were euthanized after 10 days, and the number of ganglion cells positive for RNA-binding protein with multiple splicing (Rbpms), which is an RGC marker, were counted on the whole mount retinas. In addition, immunofluorescence and immunoblotting were performed to examine the localization and levels of erythropoietin receptor (EPOR) and neurotrophin-4/5 (NT4/5) in the retinas in all experimental groups. To determine whether the EPO/EPOR signaling pathway was involved in the ALA antioxidant pathway, the rats were subjected to ruxolitinib (INCB018424, 0.25 mg/kg, bid, intraperitoneal, i.p.) treatment after the animals were injected intravenously with ALA 1 day before ONC injury. Results The average number of Rbpms-positive cells/mm2 in the control group (sham-operated group), the ONC group, the ALA-ONC group, and the ONC-ALA group retinas was 2219±28, 418±8, 848±22, and 613±18/mm2, respectively. The ALA-ONC and ONC-ALA groups showed a statistically significantly increased RGC survival rate compared to the ONC group. There were statistical differences in the RGC survival rates between the ALA-ONC (39%) and ONC-ALA groups (28%; p<0.05). Immunofluorescent labeling showed that EPOR and NT4/5 expression was significant in the retinal ganglion cell layer (GCL). At the same time, western blot analysis revealed that ALA induced upregulation of EPOR protein and NT4/5 protein expression in the retina after ONC injury. However, INCB018424 reversed the protective effects of ALA on the ONC retinas. Conclusions ALA has

  13. Polymorphism of Gly482Ser PPARGC 1A and Ala203Pro PPARGC 1B in the pathogenesis of Graves’ orbitopathy

    Directory of Open Access Journals (Sweden)

    D M Serkin

    2015-06-01

    Full Text Available Aim. To examine the association of polymorphisms Gly482Ser PPARGC 1A and Ala203Pro PPARGC 1B with the development of thyroid eye disease (TEO. Materials and methods. A total of 88 people: 52 patients with TEO, 36 - healthy individuals. Identified polymorphisms Gly482Ser PPARGC 1A and Ala203Pro PPARGC 1B by PCR. Results. When TEO detected differences in the frequency of allele and genotype SNPs investigated compared with the control. The prevalence of genotypes and alleles in patients with TEO (Gly/Gly - 38.5%, Gly/Ser - 34.6%, Ser/Ser - 26.9%, Gly-allele - 55.8%, Ser-allele - 44.2% gene PPARGC 1A; Ala/Ala - 19.2%, Ala/Pro - 55.8%, Pro/Pro - 25%, Ala-allele - 47.1%, Pro-allele - 52.9% gene PPARGC 1B. The prevalence of genotypes and alleles in the control group (Gly/Gly - 38.9%, Gly/Ser - 44.4%, Ser/Ser - 16.7%, Gly-allele - 61.1%, Ser-allele - 38.9% of the gene PPARGC 1A; Ala/Ala - 25%, Ala/Pro - 58.3%, Pro/Pro - 16.7%, Ala-allele - 54.2%, Pro-allele - 45.8% of the gene PPARGC 1B. Conclusion. At TEO more common genotypes Ser482Ser PPARGC 1A, Pro203Pro PPARGC 1B and Ser allele polymorphism Gly482Ser PPARGC 1A, Pro polymorphism Ala203Pro PPARGC 1B, as well as less common genotypes Gly482Ser PPARGC 1A, Ala203Ala PPARGC 1B and Gly allele polymorphism Gly482Ser PPARGC 1A, Ala polymorphism Ala203Pro PPARGC 1B. Polymorphisms and allele Gly482Ser PPARGC 1A gene and gene Ala203Pro PPARGC 1B do not modify the risk of TEO.

  14. Effect of 5-aminolevulinic acid on erythropoiesis: a preclinical in vitro characterization for the treatment of congenital sideroblastic anemia.

    Science.gov (United States)

    Fujiwara, Tohru; Okamoto, Koji; Niikuni, Ryoyu; Takahashi, Kiwamu; Okitsu, Yoko; Fukuhara, Noriko; Onishi, Yasushi; Ishizawa, Kenichi; Ichinohasama, Ryo; Nakamura, Yukio; Nakajima, Motowo; Tanaka, Tohru; Harigae, Hideo

    2014-11-07

    Congenital sideroblastic anemia (CSA) is a hereditary disorder characterized by microcytic anemia and bone marrow sideroblasts. The most common form of CSA is attributed to mutations in the X-linked gene 5-aminolevulinic acid synthase 2 (ALAS2). ALAS2 is a mitochondrial enzyme, which utilizes glycine and succinyl-CoA to form 5-aminolevulinic acid (ALA), a crucial precursor in heme synthesis. Therefore, ALA supplementation could be an effective therapeutic strategy to restore heme synthesis in CSA caused by ALAS2 defects. In a preclinical study, we examined the effects of ALA in human erythroid cells, including K562 cells and human induced pluripotent stem cell-derived erythroid progenitor (HiDEP) cells. ALA treatment resulted in significant dose-dependent accumulation of heme in the K562 cell line. Concomitantly, the treatment substantially induced erythroid differentiation as assessed using benzidine staining. Quantitative reverse transcription polymerase chain reaction (RT-PCR) analysis confirmed significant upregulation of heme-regulated genes, such as the globin genes [hemoglobin alpha (HBA) and hemoglobin gamma (HBG)] and the heme oxygenase 1 (HMOX1) gene, in K562 cells. Next, to investigate the mechanism by which ALA is transported into erythroid cells, quantitative RT-PCR analysis was performed on previously identified ALA transporters, including solute carrier family 15 (oligopeptide transporter), member (SLC15A) 1, SLC15A2, solute carrier family 36 (proton/amino acid symporter), member (SLC36A1), and solute carrier family 6 (neurotransmitter transporter), member 13 (SLC6A13). Our analysis revealed that SLC36A1 was abundantly expressed in erythroid cells. Thus, gamma-aminobutyric acid (GABA) was added to K562 cells to competitively inhibit SLC36A1-mediated transport. GABA treatment significantly impeded the ALA-mediated increase in the number of hemoglobinized cells as well as the induction of HBG, HBA, and HMOX1. Finally, small-interfering RNA

  15. Comment: studies of the Pro12Ala polymorphism of the PPAR-gamma gene in the Danish MONICA cohort: homozygosity of the Ala allele confers a decreased risk of the insulin resistance syndrome

    DEFF Research Database (Denmark)

    Frederiksen, Laura; Brødbaek, Kasper; Fenger, Mogens

    2002-01-01

    The Pro12Ala polymorphism of PPAR-gamma 2 has been shown to influence insulin sensitivity and the risk of type 2 diabetes in various ethnic populations. We examined whether the polymorphism was related to the insulin resistance syndrome (IRS) among nondiabetic Danish subjects. The Pro12Ala variant...... Resistance criteria enabling a classification of the study population in an IRS group and a non-IRS group. The allelic frequency of the Pro12Ala polymorphism in the total study sample was 14% (95% confidence interval, 13-15%). Two hundred ninety-four subjects fulfilled the European Group for the Study...

  16. Reversal of corticosterone-induced BDNF alterations by the natural antioxidant alpha-lipoic acid alone and combined with desvenlafaxine: Emphasis on the neurotrophic hypothesis of depression.

    Science.gov (United States)

    de Sousa, Caren Nádia Soares; Meneses, Lucas Nascimento; Vasconcelos, Germana Silva; Silva, Márcia Calheiros Chaves; da Silva, Jéssica Calheiros; Macêdo, Danielle; de Lucena, David Freitas; Vasconcelos, Silvânia Maria Mendes

    2015-12-15

    Brain derived neurotrophic factor (BDNF) is linked to the pathophysiology of depression. We hypothesized that BDNF is one of the neurobiological pathways related to the augmentation effect of alpha-lipoic acid (ALA) when associated with antidepressants. Female mice were administered vehicle or CORT 20mg/kg during 14 days. From the 15th to 21st days the animals were divided in groups that were further administered: vehicle, desvenlafaxine (DVS) 10 or 20mg/kg, ALA 100 or 200mg/kg or the combinations of DVS10+ALA100, DVS20+ALA100, DVS10+ALA200 or DVS20+ALA200. ALA or DVS alone or in combination reversed CORT-induced increase in immobility time in the forced swimming test and decrease in sucrose preference, presenting, thus, an antidepressant-like effect. DVS10 alone reversed CORT-induced decrease in BDNF in the prefrontal cortex (PFC), hippocampus (HC) and striatum (ST). The same was observed in the HC and ST of ALA200 treated animals. The combination of DVS and ALA200 reversed CORT-induced alterations in BDNF and even, in some cases, increased the levels of this neurotrophin when compared to vehicle-treated animals in HC and ST. Taken together, these results suggest that the combination of the DVS+ALA may be valuable for treating conditions in which BDNF levels are decreased, such as depression. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  17. Prevalence of the Pro12Ala missense mutation in the PPARG2 gene in Kuwaiti patients with primary knee osteoarthritis.

    Science.gov (United States)

    Al-Jarallah, Khaled F; Shehab, Diaa K; Haider, Mohammad Z

    2011-01-01

    Peroxisome proliferator-activated receptors (PPARs) play an important role in a number of cellular and metabolic functions. This study was carried out to determine the prevalence of a missense mutation (Pro12Ala) in the PPARG2 gene in Kuwaiti Arab patients with primary knee osteoarthritis (OA) and healthy controls with the aim of identifying a possible association. A prospective cross-sectional study carried out at three major teaching hospitals (referral centers) in the country over a one-year period. The prevalence of PPARG2 gene Pro12Ala missense mutation was determined in 104 Kuwaiti Arab patients with primary knee OA and 111 ethnically matched healthy controls. The prevalence of this Pro12Ala missense mutation was also determined in clinical subgroups of OA patients divided on the basis of age at onset, function and radiologic grading. The Pro-Pro genotype of the PPARG2 gene Pro12Ala missense mutation was detected in 95/104 (91.3%) cases compared to 111/111 (100%) in the control subjects. The heterozygous Pro-Ala genotype was detected in 9/104 (8.7%) of the OA patients, while it was not detected in any of the controls. The Ala-Ala genotype was not detected in any of the OA patients or the controls. No significant differences were detected in the PPARG2 gene Pro12Ala genotypes in the subgroups of patients classified on the basis of age at onset, functional assessment using Lequesne's functional index, and radiological grading using Kellgren-Lawrence (K-L) grading. This study found no significant association between the PPARG2 gene Pro12Ala missense mutation and knee OA. However, the presence of the Pro-Pro genotype of the PPARG2 gene mutation has a protective effect against development of OA.

  18. Photodynamic inactivation of Klebsiella pneumoniae biofilms and planktonic cells by 5-aminolevulinic acid and 5-aminolevulinic acid methyl ester.

    Science.gov (United States)

    Liu, Chengcheng; Zhou, Yingli; Wang, Li; Han, Lei; Lei, Jin'e; Ishaq, Hafiz Muhammad; Nair, Sean P; Xu, Jiru

    2016-04-01

    The treatment of Klebsiella pneumoniae, particularly extended-spectrum β-lactamase (ESBL)-producing K. pneumoniae, is currently a great challenge. Photodynamic antimicrobial chemotherapy is a promising approach for killing antibiotic-resistant bacteria. The aim of this study was to evaluate the capacity of 5-aminolevulinic acid (5-ALA) and its derivative 5-ALA methyl ester (MAL) in the presence of white light to cause photodynamic inactivation (PDI) of K. pneumoniae planktonic and biofilm cells. In the presence of white light, 5-ALA and MAL inactivated planktonic cells in a concentration-dependent manner. Biofilms were also sensitive to 5-ALA and MAL-mediated PDI. The mechanisms by which 5-ALA and MAL caused PDI of ESBL-producing K. pneumonia were also investigated. Exposure of K. pneumonia to light in the presence of either 5-ALA or MAL induced cleavage of genomic DNA and the rapid release of intracellular biopolymers. Intensely denatured cytoplasmic contents and aggregated ribosomes were also detected by transmission electron microscopy. Scanning electron microscopy showed that PDI of biofilms caused aggregated bacteria to detach and that the bacterial cell envelope was damaged. This study provides insights into 5-ALA and MAL-mediated PDI of ESBL-producing K. pneumoniae.

  19. A first-principles study of functionalized clusters and carbon nanotubes or fullerenes with 5-Aminolevulinic acid as vehicles for drug delivery

    Science.gov (United States)

    Kia, Majid; Golzar, Maryam; Mahjoub, Kosar; Soltani, Alireza

    2013-10-01

    At present work, we explore the adsorption properties of the 5-Aminolevulinic acid (5ALA) interacting with SWCNTs, C60, and C24 by density functional ab initio (DFT) calculations. It was found that the electronic structure of C60 is more sensitive to the presence of 5ALA in comparison with C24, (5, 5), and (9, 0) SWCNT. Our results demonstrate that the interactions between 5ALA and the nanostructures are chemisorption. The natural bond orbital (NBO) and density of states (DOSs) analyses represent that the nature of 5ALA adsorption on the applied nanostructures is permanently electrostatic rather than covalent.

  20. HOMEOSIS EN LA EVOLUCION DEL ALA DE LAS AVES: UN ACERCAMIENTO COMPARATIVO Y EXPERIMENTAL

    OpenAIRE

    SALINAS SAAVEDRA, MIGUEL ANDRES H.

    2012-01-01

    La identidad de los tres dígitos del ala de las aves ha sido un tema de gran discusión entre biólogos del desarrollo y paleontólogos durante más de 140 años. Por una parte, basándose en el patrón de desarrollo de los dígitos, se sostiene que los dedos del ala de las aves son de identidad II, III y IV. En cambio, la comparación de la morfología digital en el linaje hacia las aves, sugiere que sus identidades son I, II y III. Una hipótesis propuesta para explicar dicha situación, es la ocurrenc...

  1. [Clinical characterization of allergic patients sensitized to Chamaecyparis obtusa--using AlaSTAT system].

    Science.gov (United States)

    Okano, M; Nishioka, K; Nagano, T; Ohta, N; Masuda, Y

    1994-09-01

    Clinical characterization of patients with allergy to Chamaecyparis obtusa (Cypress) pollen and their specific IgE antibody was investigated by using AlaSTAT assay, a new method for measurement of antigen-specific IgE antibody. Positive rate of antigen-specific antibody in patients with allergic pollinosis was 83.5% for Japanese cedar pollen and 80.0% for Chamaecyparis obtusa pollen. 76.4% of patients were sensitized both to Japanese cedar and Chamaecyparis obtusa pollen, however, 7.9% were sensitized only to the latter. As for clinical symptoms, duration of attack was short and severity was mild or moderate in the patients sensitized only to Chamaecyparis obtusa pollen. Patients who visited hospital in April, in that Chamaecyparis obtusa pollen disseminated in the air predominantly, showed significant elevation in AlaSTAT scores compared with patients who visited in February and March (p < 0.05).

  2. The miniband spectrum in (AlAs) sub M (GaAs) sub N (111)

    CERN Document Server

    Karavaev, G F; Egunov, R M

    2002-01-01

    The electron states for energies in the conduction band of (AlAs) sub M (GaAs) sub N (111) superlattices with M >= N (N < 10) are considered. The properties of such superlattices are mainly determined by electrons of X-valley in AlAs and L-valley in GaAs. The calculations are carried out on the basis of the envelope-function model of interface band mixing. Miniband spectra, symmetry and localization of wave functions, and also probabilities of the interminiband infrared absorption are defined and analyzed. It is shown that the latter have a significant magnitude not only at light polarization along the superlattice growth axis, but also at normal incidence of a light wave to the surface. The analysis has been normal incidence of a light wave to the surface. The analysis has shown the importance of consideration of X sub 5 -states belonging to the valence band for infrared absorption

  3. Lipid metabolic dose response to dietary alpha-linolenic acid in monk parrot (Myiopsitta monachus).

    Science.gov (United States)

    Petzinger, Christina; Heatley, J J; Bailey, Christopher A; Bauer, John E

    2014-03-01

    Monk parrots (Myiopsitta monachus) are susceptible to atherosclerosis, a progressive disease characterized by the formation of plaques in the arteries accompanied by underlying chronic inflammation. The family of n-3 fatty acids, especially eicosapentaenoic acid (20:5n-3, EPA) and docosahexaenoic acid (22:6n-3, DHA), have consistently been shown to reduce atherosclerotic risk factors in humans and other mammals. Some avian species have been observed to convert α-linolenic acid (18:3n-3, ALA) to EPA and DHA (Htin et al. in Arch Geflugelk 71:258-266, 2007; Petzinger et al. in J Anim Physiol Anim Nutr, 2013). Therefore, the metabolic effects of including flaxseed oil, as a source of ALA, in the diet at three different levels (low, medium, and high) on the lipid metabolism of Monk parrots was evaluated through measuring plasma total cholesterol (TC), free cholesterol (FC), triacylglycerols (TAG), and phospholipid fatty acids. Feed intake, body weight, and body condition score were also assessed. Thus the dose and possible saturation response of increasing dietary ALA at constant linoleic acid (18:2n-6, LNA) concentration on lipid metabolism in Monk parrots (M. monachus) was evaluated. Calculated esterified cholesterol in addition to plasma TC, FC, and TAG were unaltered by increasing dietary ALA. The high ALA group had elevated levels of plasma phospholipid ALA, EPA, and docosapentaenoic acid (DPAn-3, 22:5n-3). The medium and high ALA groups had suppressed plasma phospholipid 20:2n-6 and adrenic acid (22:4n-6, ADA) compared to the low ALA group. When the present data were combined with data from a previous study (Petzinger et al. in J Anim Physiol Anim Nutr, 2013) a dose response to dietary ALA was observed when LNA was constant. Plasma phospholipid ALA, EPA, DPAn-3, DHA, and total n-3 were positively correlated while 20:2n-6, di-homo-gamma-linoleic acid (20:3n-6Δ7), arachidonic acid (20:4n-6), ADA, and total n-6 were inversely correlated with dietary en% ALA.

  4. First principles predictions of intrinsic defects in aluminum arsenide, AlAs : numerical supplement.

    Energy Technology Data Exchange (ETDEWEB)

    Schultz, Peter Andrew

    2012-04-01

    This Report presents numerical tables summarizing properties of intrinsic defects in aluminum arsenide, AlAs, as computed by density functional theory. This Report serves as a numerical supplement to the results published in: P.A. Schultz, 'First principles predictions of intrinsic defects in Aluminum Arsenide, AlAs', Materials Research Society Symposia Proceedings 1370 (2011; SAND2011-2436C), and intended for use as reference tables for a defect physics package in device models.

  5. The Library of Congress View on Its Relation to the ALA MARC Advisory Committee

    Directory of Open Access Journals (Sweden)

    Henriette D. Avram

    1974-06-01

    Full Text Available This paper is a statement of the Library of Congress' recommendation that a MARC advisory committee be appointed within the present structure of the RTSD/ISAD/RASD Committee on Representation in Machine-Readable Form of Bibliographic Information (MARBI and describes the Library's proposed relation to such a committee. The proposals and recommendations suggested were adopted by the MARBI Committee during its deliberations at ALA Midwinter, January 1974, and are now in effect.

  6. Politsei otsib salapärast ameeriklannat / Askur Alas, Janar Filippov

    Index Scriptorium Estoniae

    Alas, Askur, 1973-

    2007-01-01

    Ilmunud ka: Infopress 1. juuni nr. 22. lk. 160-161. Politsei otsib taga ameeriklannat, kes võis filmida Dmitri Ganini tapmist. 26.-27. aprillil Tallinnas Woodstocki baari vandaalide eest kaitsnud isikud kirjeldavad toonaseid sündmusi ning D. Ganini ja tema sõbra Olegi osa neis. Vt. samas: Askur Alas, Krister Kivi. Ganin sai nuga pärast esimese kiirabi lahkumist. Tallinna kiirabi tegevus kriisiperioodil

  7. Relationship between impaired glycation and the N-terminal structure of the Hb Görwihl [beta5(A2)Pro-->Ala] variant.

    Science.gov (United States)

    Ito, Shigenori; Nakahari, Takashi; Yamamoto, Daisuke

    2010-01-01

    We studied the structural environment surrounding the beta-N-terminal glycation site of a hemoglobin (Hb) molecule in which the proline residue at beta5(A2) was substituted by alanine in silico. By computer analysis that used Protein Data Bank data (PDB ID: 1BZ0), we tried to clarify the reason for impaired glycation of Hb Görwihl [beta5(A2)Pro-->Ala]. On the basis of the results, we predicted that the glycation site would have the following characteristics: 1) glycation of the beta-N-terminus of Hb is probably accelerated by the neighboring histidine residue at beta2(NA2), which acts as an acid-base catalyst via a phosphate-mediated proton transfer; and 2) the mutation beta5(A2)Pro-->Ala would bring about impaired glycation of the N-terminal residue by forming an electrostatic bond between the alpha amino group of beta1(NA1)Val and beta carboxyl group of beta79(EF3)Asp.

  8. Down-regulation of malignant potential by alpha linolenic acid in human and mouse colon cancer cells.

    Science.gov (United States)

    Chamberland, John P; Moon, Hyun-Seuk

    2015-03-01

    Omega-3 fatty acids (also called ω-3 fatty acis or n-3 fatty acid) are polyunsaturated fatty acids (PUFAs) with a double bond (C=C) at the third carbon atom from the end of the carbon chain. Numerous test tube and animal studies have shown that omega-3 fatty acids may prevent or inhibit the growth of cancers, suggesting that omega-3 fatty acids are important in cancer physiology. Alpha-linolenic acid (ALA) is one of an essential omega-3 fatty acid and organic compound found in seeds (chia and flaxseed), nuts (notably walnuts), and many common vegetable oils. ALA has also been shown to down-regulate cell proliferation of prostate, breast, and bladder cancer cells. However, direct evidence that ALA suppresses to the development of colon cancer has not been studied. Also, no previous studies have evaluated whether ALA may regulate malignant potential (adhesion, invasion and colony formation) in colon cancer cells. In order to address the questions above, we conducted in vitro studies and evaluated whether ALA may down-regulate malignant potential in human (HT29 and HCT116) and mouse (MCA38) colon cancer cell lines. We observed that treatment with 1-5 mM of ALA inhibits cell proliferation, adhesion and invasion in both human and mouse colon cancer cell lines. Interestingly, we observed that ALA did not decrease total colony numbers when compared to control. By contrast, we found that size of colony was significantly changed by ALA treatment when compared to control in all colon cancer cell lines. We suggest that our data enhance our current knowledge of ALA's mechanism and provide crucial information to further the development of new therapies for the management or chemoprevention of colon cancer.

  9. In vivo wide-field multispectral dosimeter for use in ALA-PpIX based photodynamic therapy of skin

    Science.gov (United States)

    LaRochelle, Ethan P. M.; Davis, Scott C.; de Souza, Ana Luiza Ribeiro; Pogue, Brian W.

    2017-02-01

    Photodynamic therapy (PDT) for Actinic Kertoses (AK) using aminoluvelinic acid (ALA) is an FDA-approved treatment, which is generally effective, yet response rates vary. The origin of the variability is not well characterized, but may be related to inter-patient variability in the production of protoporphyrin IX (PpIX). While fiber-based point probe systems provide a method for measuring PpIX production, these measurements have demonstrated large spatial and inter-operator variability. Thus, in an effort to improve patient-specific dosimetry and treatment it is important to develop a robust system that accounts for spatial variability and reduces the chance of operator errors. To address this need, a wide-field multispectral imaging system was developed that is capable of quantifying maps of PpIX in both liquid phantoms and in vivo experiments, focusing on high sensitivity light signals. The system uses both red and blue excitation to elicit a fluorescent response at varying skin depths. A ten-position filter wheel with bandpass filters ranging from 635nm to 710nm are used to capture images along the emission band. A linear least-square spectral fitting algorithm provides the ability to decouple background autofluorescence from PpIX fluorescence, which has improved the system sensitivity by an order of magnitude, detecting nanomolar PpIX concentrations in liquid phantoms in the presence of 2% whole blood and 2% intralipid.

  10. Ab-initio study of structural and electronic properties of AlAs

    Science.gov (United States)

    Munjal, N.; Sharma, G.; Vyas, V.; Joshi, K. B.; Sharma, B. K.

    2012-08-01

    The structural properties, i.e. equilibrium lattice constant, transition pressure, bulk modulus and its pressure derivatives, together with electronic properties, i.e. energy bands, Compton profile and autocorrelation function, of AlAs are presented in this work. The linear combination of atomic orbitals (LCAO) method of the CRYSTAL code was applied considering the Perdew-Burke-Ernzerhof correlation energy functional and Becke's ansatz for the exchange. The total energy of AlAs as a function of primitive cell volume has also been calculated for the zincblende (B3), nickel arsenide (B8), sodium chloride (B1) and cesium chloride (B2) phases. Structural parameters of the B3, B8, B1 and B2 phases are determined. The calculated structural parameters are found to be in good agreement with the results of previous investigations. The spherically averaged theoretical values of Compton profile are in good agreement with an earlier measurement. The LCAO calculation shows an indirect band gap of 1.85 eV, in reasonable agreement with earlier data. On the basis of the equal-valence-electron-density Compton profile, it is found that AlAs is more ionic compared to AlSb.

  11. Characterization of a TK6-Bcl-xL gly-159-ala Human Lymphoblast Clone

    Energy Technology Data Exchange (ETDEWEB)

    Chyall, L.: Gauny, S.; Kronenberg, A.

    2006-01-01

    TK6 cells are a well-characterized human B-lymphoblast cell line derived from WIL-2 cells. A derivative of the TK6 cell line that was stably transfected to express a mutated form of the anti-apoptotic protein Bcl-xL (TK6-Bcl-xL gly-159- ala clone #38) is compared with the parent cell line. Four parameters were evaluated for each cell line: growth under normal conditions, plating efficiency, and frequency of spontaneous mutation to 6‑thioguanine resistance (hypoxanthine phosphoribosyl transferase locus) or trifluorothymidine resistance (thymidine kinase locus). We conclude that the mutated Bcl-xL protein did not affect growth under normal conditions, plating efficiency or spontaneous mutation frequencies at the thymidine kinase (TK) locus. Results at the hypoxanthine phosphoribosyl transferase (HPRT) locus were inconclusive. A mutant fraction for TK6‑Bcl-xL gly-159-ala clone #38 cells exposed to 150cGy of 160kVp x-rays was also calculated. Exposure to x-irradiation increased the mutant fraction of TK6‑Bcl-xL gly-159-ala clone #38 cells.

  12. Challenges for Community-Based Forest Management in the KoloAla Site Manompana

    Science.gov (United States)

    Urech, Zora Lea; Sorg, Jean-Pierre; Felber, Hans Rudolph

    2013-03-01

    Following the IUCN 5th World Congress on Protected Areas in 2003, the then-President of Madagascar decided to increase the area of Madagascar's protected areas from 1.7 to 6 million ha. To combine the aims of protection and timber production, a new concept was developed through the establishment of community-based forest management (CBFM) sites, called KoloAla. However, experience shows that similar management transfers to communities in Madagascar have only been successful in a very few cases. We aimed to explore the success to be expected of this new approach in the particular case of the Manompana corridor at Madagascar's eastern coast. In a first step, the readiness of the corridor's resource users for CBFM has been analysed according to the seven resource users' attributes developed by Ostrom that predict an effective self-organized resource management. In a second step, we explored how KoloAla addresses known challenges of Madagascar's CBFM. Analyses lead in a rather sober conclusion. Although KoloAla attempts to address the goals of poverty alleviation, biodiversity conservation and timber production under a single umbrella, it does so in a rather non-innovative way. Challenges with regard to the state's environmental governance, agricultural inefficiency and thus deforestation remain unsolved.

  13. No effects of n)3 fatty acid supplementation on serum total testosterone levels in older men: the Alpha Omega Trial

    NARCIS (Netherlands)

    Giltay, E.J.; Geleijnse, J.M.; Heijboer, A.C.; Goede, de J.; Oude Griep, L.M.; Blankenstein, M.A.; Kromhout, D.

    2012-01-01

    The intake of the n-3 fatty acids alpha-linolenic acid (ALA), acid (EPA) and docosahexaenoic acid (DHA) has been related to testosterone levels in epidemiological analyses. The aim of this study was to assess whether the n-3 fatty acids affects testosterone levels in post-myocardial infarction (MI)

  14. Comment: studies of the Pro12Ala polymorphism of the PPAR-gamma gene in the Danish MONICA cohort: homozygosity of the Ala allele confers a decreased risk of the insulin resistance syndrome

    DEFF Research Database (Denmark)

    Frederiksen, Laura; Brødbaek, Kasper; Fenger, Mogens

    2002-01-01

    The Pro12Ala polymorphism of PPAR-gamma 2 has been shown to influence insulin sensitivity and the risk of type 2 diabetes in various ethnic populations. We examined whether the polymorphism was related to the insulin resistance syndrome (IRS) among nondiabetic Danish subjects. The Pro12Ala varian...... of body composition (BMI and waist circumference). In conclusion, homozygosity of the codon 12 variant of PPAR-gamma 2 confers a reduced risk of the IRS among Danish Caucasian subjects....

  15. Alpha linolenic acid in maternal diet halts the lipid disarray due to saturated fatty acids in the liver of mice offspring at weaning

    OpenAIRE

    2015-01-01

    Background Alpha linolenic acid (ALA, 18:3) in maternal diets has been shown to attenuate obesity associated insulin resistance (IR) in adult offspring in mice. The objective in the present study was to detect the early effects of maternal dietary saturated fatty acids (SFA) and their partial substitution with ω-3 ALA, docosa hexenoic acid (DHA,22:6) and eicosapentenoic acid 20:5 (EPA,20:5) on the HOMA index, liver lipids and fatty acid desaturases in the offspring at weaning. Methods 3 month...

  16. Homology modeling of human γ-butyric acid transporters and the binding of pro-drugs 5-aminolevulinic acid and methyl aminolevulinic acid used in photodynamic therapy.

    Directory of Open Access Journals (Sweden)

    Yan Baglo

    Full Text Available Photodynamic therapy (PDT is a safe and effective method currently used in the treatment of skin cancer. In ALA-based PDT, 5-aminolevulinic acid (ALA, or ALA esters, are used as pro-drugs to induce the formation of the potent photosensitizer protoporphyrin IX (PpIX. Activation of PpIX by light causes the formation of reactive oxygen species (ROS and toxic responses. Studies have indicated that ALA and its methyl ester (MAL are taken up into the cells via γ-butyric acid (GABA transporters (GATs. Uptake via GATs into peripheral sensory nerve endings may also account for one of the few adverse side effects of ALA-based PDT, namely pain. In the present study, homology models of the four human GAT subtypes were constructed using three x-ray crystal structures of the homologous leucine transporter (LeuT as templates. Binding of the native substrate GABA and the possible substrates ALA and MAL was investigated by molecular docking of the ligands into the central putative substrate binding sites in the outward-occluded GAT models. Electrostatic potentials (ESPs of the putative substrate translocation pathway of each subtype were calculated using the outward-open and inward-open homology models. Our results suggested that ALA is a substrate of all four GATs and that MAL is a substrate of GAT-2, GAT-3 and BGT-1. The ESP calculations indicated that differences likely exist in the entry pathway of the transporters (i.e. in outward-open conformations. Such differences may be exploited for development of inhibitors that selectively target specific GAT subtypes and the homology models may hence provide tools for design of therapeutic inhibitors that can be used to reduce ALA-induced pain.

  17. Exogenous 5-aminolevulenic acid promotes seed germination in Elymus nutans against oxidative damage induced by cold stress.

    Directory of Open Access Journals (Sweden)

    Juanjuan Fu

    Full Text Available The protective effects of 5-aminolevulenic acid (ALA on germination of Elymus nutans Griseb. seeds under cold stress were investigated. Seeds of E. nutans (Damxung, DX and Zhengdao, ZD were pre-soaked with various concentrations (0, 0.1, 0.5, 1, 5, 10 and 25 mg l(-1 of ALA for 24 h before germination under cold stress (5°C. Seeds of ZD were more susceptible to cold stress than DX seeds. Both seeds treated with ALA at low concentrations (0.1-1 mg l(-1 had higher final germination percentage (FGP and dry weight at 5°C than non-ALA-treated seeds, whereas exposure to higher ALA concentrations (5-25 mg l(-1 brought about a dose dependent decrease. The highest FGP and dry weight of germinating seeds were obtained from seeds pre-soaked with 1 mg l(-1 ALA. After 5 d of cold stress, pretreatment with ALA provided significant protection against cold stress in the germinating seeds, significantly enhancing seed respiration rate and ATP synthesis. ALA pre-treatment also increased reduced glutathione (GSH, ascorbic acid (AsA, total glutathione, and total ascorbate concentrations, and the activities of superoxide dismutase (SOD, catalase (CAT, ascorbate peroxidase (APX and glutathione reductase (GR, whereas decreased the contents of malondialdehyde (MDA and hydrogen peroxide (H2O2, and superoxide radical (O2•- release in both germinating seeds under cold stress. In addition, application of ALA increased H+-ATPase activity and endogenous ALA concentration compared with cold stress alone. Results indicate that ALA considered as an endogenous plant growth regulator could effectively protect E. nutans seeds from cold-induced oxidative damage during germination without any adverse effect.

  18. 外源 ALA 对干旱胁迫下辣椒幼苗的缓解效应研究%Mitigative Effects of Exogenous ALA on Pepper Seedlings under Drought Stress

    Institute of Scientific and Technical Information of China (English)

    张春梅; 闫芳; 王勤礼

    2013-01-01

    Using the major pepper cultivar Longjiao No.2 for heliogreenhouse planting in Hexi corridor of Gansu, we studied the effects of spraying exogenous ALA on improving drought stress of pepper seedlings in pots by controlling water usage. The results showed that, compared with the control treatment (spaying clear water), spraying exogenous ALA could significantly improve the soluble sugar content, chlorophyll content, SOD activity and POD activity, and lowered MDA content, which indicated that spraying exogenous ALA could improve the drought resistance of pepper seedlings.%以甘肃河西走廊日光温室主栽辣椒品种(陇椒2号)为试材,采用盆栽控水的方法,研究了干旱胁迫下喷施外源 ALA 提高辣椒幼苗抗旱性的效应。研究结果表明,与喷清水对照相比,外源 ALA 提高了干旱胁迫下辣椒幼苗叶片可溶性糖、叶绿素含量,超氧化物歧化酶(SOD)和过氧化物酶(POD)活性,而丙二醛(MDA)含量则相反,表明喷施外源 ALA 能提高辣椒幼苗的抗旱性。

  19. Growth optimization and characterization of high mobility two-dimensional electron systems in AlAs quantum wells

    Energy Technology Data Exchange (ETDEWEB)

    Dasgupta, Shivaji

    2009-02-15

    In this work two-dimensional electron systems (2DESs) based on AlAs/AlGaAs heterostructures doped with Si are investigated. The electrons are confined in AlAs quantum wells (QWs) sandwiched between AlGaAs buffers. Analytical calculations and simulations for AlAs QWs are presented in the first chapter. The results show a cross-over width, above which the wide (001)-oriented QWs show double valley occupancy and wide (110)-oriented QWs show single valley occupancy. We solve the Schroedinger equation analytically for anisotropic masses. The solution shows the orientation dependence of the elliptical cyclotron orbit due to the anisotropic mass. We also present an introduction to the Landau level crossings based on g{sup *}m{sup *} product. In the next chapter, we present experimental results for the double-valley (001)-oriented AlAs QWs. We present the different structures of the deep AlAs QWs along with the low temperature magnetotransport data for these QWs. Thereafter, we present the results on shallow AlAs QWs. We achieved a mobility of 4.2 x 10{sup 5} cm{sup 2}/Vs at 330 mK for the deep backside doped AlAs QW. For the shallow QWs, we achieved a mobility of2.3 x 10{sup 5} cm{sup 2}/Vs at 330 mK, for a density of 2.9 x 10{sup 11} cm{sup -2}. From the magneto-transport data, we see evidence of the double-valley occupation for the (001)-oriented AlAs wide QWs. In the next chapter, we present experimental results for the single-valley (110)-oriented AlAs QWs. We deduced the donor binding energy and the doping efficiency for this facet from a doping series of double-sided doped QWs. Thereafter, we designed different structures for the (110)-oriented AlAs QWs, which we present along with their respective low temperature magneto-transport data. We measured one of the double-sided doped AlAs QWs at very high magnetic fields and low temperatures, down to 60 mK. At the end of the chapter, we present a spike feature observed in the magneto-transport data of these QWs. This

  20. Association of the Pro12Ala Polymorphism with the Metabolic Parameters in Women with Polycystic Ovary Syndrome

    Directory of Open Access Journals (Sweden)

    Moushira Zaki

    2017-06-01

    CONCLUSION: The PPARG Pro12Ala polymorphism might contribute to the risk of PCOS and abnormal metabolic parameters and could be considered as a biomarker for early diagnosis and clinic prediction of metabolic complications.

  1. Association of peroxisome proliferator-activated receptor γ Pro12Ala gene polymorphism with type 2 diabetic nephropathy risk in Caucasian population.

    Science.gov (United States)

    Zhou, Tian-Biao; Guo, Xue-Feng; Yin, Sheng-Sheng

    2014-06-01

    Association of peroxisome proliferator-activated receptor gamma (PPARγ) Pro12Ala gene polymorphism with type 2 diabetic nephropathy (T2DN) risk in Caucasians is still not clear. This investigation was conducted to assess if there was an association between the PPARγ Pro12Ala gene polymorphism and T2DN risk in Caucasians using meta-analysis. The relevant literatures were identified from PubMed, and Cochrane Library on 10 October 2013, and eligible studies were included and synthesized. Six reports including eight studies were recruited into this meta-analysis for the association of the PPARγ Pro12Ala gene polymorphism with T2DN risk in Caucasians. The Pro/Pro genotype was shown to be associated with T2DN risk in Caucasians. However, the Ala/Ala genotype and Ala allele were not associated with T2DN risk in Caucasians. In the sensitivity analysis, according to the control source from hospital, the control source from population, the genotyping methods using PCR-RFLP, Taqman, sample size of case Pro12Ala gene polymorphism with T2DN risk was similar to those in non-sensitivity analysis. In conclusion, the PPARγ Pro/Pro genotype was associated with T2DN risk in Caucasians, but the Ala/Ala genotype and Ala allele not. However, additional studies are required to firmly establish a correlation between the PPARγ Pro12Ala gene polymorphism and T2DN risk in Caucasians.

  2. Is there A Role for Alpha-Linolenic Acid in the Fetal Programming of Health?

    Science.gov (United States)

    Leikin-Frenkel, Alicia I.

    2016-01-01

    The role of ω3 alpha linolenic acid (ALA) in the maternal diet during pregnancy and lactation, and its effect on the prevention of disease and programming of health in offspring, is largely unknown. Compared to ALA, ω3 docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids have been more widely researched due to their direct implication in fetal neural development. In this literature search we found that ALA, the essential ω3 fatty acid and metabolic precursor of DHA and EPA has been, paradoxically, almost unexplored. In light of new and evolving findings, this review proposes that ALA may have an intrinsic role, beyond the role as metabolic parent of DHA and EPA, during fetal development as a regulator of gene programming for the prevention of metabolic disease and promotion of health in offspring. PMID:27023621

  3. Is there A Role for Alpha-Linolenic Acid in the Fetal Programming of Health?

    Science.gov (United States)

    Leikin-Frenkel, Alicia I

    2016-03-23

    The role of ω3 alpha linolenic acid (ALA) in the maternal diet during pregnancy and lactation, and its effect on the prevention of disease and programming of health in offspring, is largely unknown. Compared to ALA, ω3 docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids have been more widely researched due to their direct implication in fetal neural development. In this literature search we found that ALA, the essential ω3 fatty acid and metabolic precursor of DHA and EPA has been, paradoxically, almost unexplored. In light of new and evolving findings, this review proposes that ALA may have an intrinsic role, beyond the role as metabolic parent of DHA and EPA, during fetal development as a regulator of gene programming for the prevention of metabolic disease and promotion of health in offspring.

  4. Is there A Role for Alpha-Linolenic Acid in the Fetal Programming of Health?

    Directory of Open Access Journals (Sweden)

    Alicia I. Leikin-Frenkel

    2016-03-01

    Full Text Available The role of ω3 alpha linolenic acid (ALA in the maternal diet during pregnancy and lactation, and its effect on the prevention of disease and programming of health in offspring, is largely unknown. Compared to ALA, ω3 docosahexaenoic (DHA and eicosapentaenoic (EPA acids have been more widely researched due to their direct implication in fetal neural development. In this literature search we found that ALA, the essential ω3 fatty acid and metabolic precursor of DHA and EPA has been, paradoxically, almost unexplored. In light of new and evolving findings, this review proposes that ALA may have an intrinsic role, beyond the role as metabolic parent of DHA and EPA, during fetal development as a regulator of gene programming for the prevention of metabolic disease and promotion of health in offspring.

  5. 5-Aminolevulinic Acid-Based Sonodynamic Therapy Induces the Apoptosis of Osteosarcoma in Mice.

    Science.gov (United States)

    Li, Yongning; Zhou, Qi; Hu, Zheng; Yang, Bin; Li, Qingsong; Wang, Jianhua; Zheng, Jinhua; Cao, Wenwu

    2015-01-01

    Sonodynamic therapy (SDT) is promising for treatment of cancer, but its effect on osteosarcoma is unclear. This study examined the effect of 5-Aminolevulinic Acid (5-ALA)-based SDT on the growth of implanted osteosarcoma and their potential mechanisms in vivo and in vitro. The dose and metabolism of 5-ALA and ultrasound periods were optimized in a mouse model of induced osteosarcoma and in UMR-106 cells. The effects of ALA-SDT on the proliferation and apoptosis of UMR-106 cells and the growth of implanted osteosarcoma were examined. The levels of mitochondrial membrane potential (ΔψM), ROS production, BcL-2, Bax, p53 and caspase 3 expression in UMR-106 cells were determined. Treatment with 5-ALA for eight hours was optimal for ALA-SDT in the mouse tumor model and treatment with 2 mM 5-ALA for 6 hours and ultrasound (1.0 MHz 2.0 W/cm2) for 7 min were optimal for UMR-106 cells. SDT, but not 5-ALA, alone inhibited the growth of implanted osteosarcoma in mice (Ptreatment with 5-ALA significantly enhanced the SDT-mediated apoptosis (posteosarcoma cells and BcL-2 expression, but increased levels of Bax, p53 and caspase 3 expression in the implanted osteosarcoma tissues (posteosarcoma growth in vivo and reduced UMR-106 cell survival by inducing osteosarcoma cell apoptosis through the ROS-related mitochondrial pathway.

  6. Degradation mechanism and stability of 5-aminolevulinic acid.

    Science.gov (United States)

    Bunke, A; Zerbe, O; Schmid, H; Burmeister, G; Merkle, H P; Gander, B

    2000-10-01

    The physiological substance and precursor of the heme synthesis 5-aminolevulinic acid (ALA) is a promising prodrug for photodiagnosis and photodynamic therapy of epithelial tumors, particularly in urological and gynecological tissues. For the clinical use of this substance, a chemically stable and sterile drug formulation is required. In the present study, degradation mechanism of ALA in aqueous solution and possibilities to improve its stability were examined. A capillary electrophoretic method was developed that was suitable for the quantification of ALA and of two degradation products. The intermediate degradation product was 2, 5-dicarboxyethyl-3,6-dihydropyrazine, which was further oxidized to 2,5-dicarboxyethylpyrazine. The structures of the degradation products were proven by (1)H and (13)C nuclear magnetic resonance spectroscopy. ALA degradation was very efficiently inhibited by adjusting the pH of the aqueous solution to a value market introduction.

  7. Photodynamic therapy with 5-aminolevulinic acid: basic principles and applications

    Science.gov (United States)

    Pottier, Roy H.; Kennedy, James C.

    1996-01-01

    Numerous photosensitizing pigments that absorb visible light and are selectively retained in neoplastic tissue are being investigated as potential photochemotherapeutic agents. While much emphasis is being placed on the synthesis of new, far-red absorbing photosensitizers, an alternative approach has been to stimulate the human body to produce its own natural photosensitizer, namely protoporphyrin IX (PpIX). Exogenous 5-aminolevulinic acid (ALA) is rapidly bioconverted into PP by mitochondria, the process being particularly efficient in tumor cells. Since PpIX has a natural and rapid clearing mechanism (via the capture of iron in the process of being converted into heme), ALA-PDT does not suffer from lingering skin phototoxicity. ALA may be introduced orally, intravenously, or topically, and ALA-PDT has been shown to be effective in the treatment of both malignant and non-malignant lesions.

  8. Valor educativo y generalización del grupo "Alas por la vida" Educational value and generalization of "Alas por la Vida"

    Directory of Open Access Journals (Sweden)

    Alexis Hugo Cantero Ronquillo

    2012-03-01

    Full Text Available En el tratamiento del cáncer de mama, además de la agresión quirúrgica, en ocasiones mutilante, seguida o precedida por las molestias inherentes a los tratamientos oncoespecíficos, a veces persisten "heridas", que aunque invisibles, no siempre cierran totalmente, y afectan durante mucho tiempo, o toda la vida, a un grupo importante de pacientes y familiares cercanos. El proyecto "Alas por la vida" propone nuevas alternativas en el tratamiento de la mujer con cáncer de mama, que puedan prepararla para una nueva etapa, y vivir con el estatus de enferma crónica, que no refleje invalidez en el desempeño de sus funciones, que alcance la recuperación de su equilibrio biopsicosocial, y, consecuentemente, el disfrute de una adecuada calidad de vida. Mediante intercambios entre sobrevivientes de la enfermedad, familiares y profesionales, charlas científicas, sesiones de preguntas y respuestas, reflexiones de operadas en su lucha contra el cáncer de mama y también de sus esposos, así como con actividades socioculturales, etc., se han logrado resultados muy positivos por este grupo, lo que se refleja en encuestas realizadas a tal efecto. El Grupo de Apoyo a Pacientes Mastectomizadas "Alas por la vida", ha resultado ser un instrumento muy útil para elevar la autoestima y mejorar la calidad de vida de las sobrevivientes, que a la vez ha fortalecido y humanizado nuestra lucha contra el cáncer de mama, y se han aglutinando crecientemente más seguidores en esta noble causa, por lo que recomendamos se organicen proyectos similares en todas las provincias del país.In the treatment of beast cancer besides the surgical aggression occasionally mutilating followed or precedes by the molecules inherent to specific oncologic treatments, sometimes the "wounds" persist that although invisibles, not always are totally closed involving for much time or for life to a significant group of patients and close relatives.The project "Alas por la Vida" proposes

  9. Assay for identification of heterozygous single-nucleotide polymorphism (Ala67Thr in human poliovirus receptor gene

    Directory of Open Access Journals (Sweden)

    Shyam Sundar Nandi

    2016-01-01

    Results: A new SNP assay for detection of heterozygous Ala67Thr genotype was developed and validated by testing 150 DNA samples. Heterozygous CD155 was detected in 27.33 per cent (41/150 of DNA samples tested by both SNP detection assay and sequencing. Interpretation & conclusions: The SNP detection assay was successfully developed for identification of Ala67Thr polymorphism in human PVR/CD155 gene. The SNP assay will be useful for large scale screening of DNA samples.

  10. The manganese superoxide dismutase Ala16Val dimorphism modulates both mitochondrial import and mRNA stability.

    Science.gov (United States)

    Sutton, Angela; Imbert, Audrey; Igoudjil, Anissa; Descatoire, Véronique; Cazanave, Sophie; Pessayre, Dominique; Degoul, Françoise

    2005-05-01

    A genetic dimorphism incorporates either alanine (Ala) or valine (Val) in the mitochondrial targeting sequence (MTS) of manganese superoxide dismutase (MnSOD). The Ala-MTS confers a 40% higher MnSOD activity than the Val-MTS after import into isolated mitochondria in vitro. The present study aimed to characterize functional consequences in whole cells. HuH7 human hepatoma cells were transfected with vectors encoding for the human Ala- or Val-MnSOD variants fused to a Myc-His-tag. The Ala-variant resulted in four-fold higher levels of the mature exogenous protein and MnSOD activity than the Val-variant. Studies with a proteasome inhibitor indicated that precursor proteins are either imported into the mitochondria or degraded by the proteasome. Despite identical levels 8 h after transfection, mRNA levels at 36 h were two-fold higher for the Ala-encoding mRNA than the Val-mRNA. Decreasing the mitochondrial membrane potential decreased both MnSOD mitochondrial import and its mRNA levels. Much larger differences in the activity of the human Val- and Ala-MnSOD variants are observed in whole cells rather than after import experiments performed in vitro. First, the slowly imported Val-MnSOD is degraded by the proteasome in cells. Second, the slower mitochondrial import of the Val-variant may be associated with decreased mRNA stability, possibly due to impaired cotranslational import.

  11. Pro12Ala polymorphism of the peroxisome proliferator-activated receptor γ2 in patients with fatty liver diseases

    Science.gov (United States)

    Rey, Johannes W; Noetel, Andrea; Hardt, Aline; Canbay, Ali; Alakus, Hakan; zur Hausen, Axel; Dienes, Hans Peter; Drebber, Uta; Odenthal, Margarete

    2010-01-01

    AIM: To test the occurrence of the Pro12Ala mutation of the peroxisome proliferator-activated receptor-γ (PPARγ)2-gene in patients with non-alcoholic fatty liver disease (NAFLD) or alcoholic fatty liver disease (AFLD). METHODS: DNA from a total of 622 specimens including 259 blood samples of healthy blood donors and 363 histologically categorized liver biopsies of patients with NAFLD (n = 263) and AFLD (n = 100) were analyzed by Real-time polymerase chain reaction using allele-specific probes. RESULTS: In the NAFLD and the AFLD collective, 3% of the patients showed homozygous occurrence of the Ala12 PPARγ2-allele, differing from only 1.5% cases in the healthy population. In NAFLD patients, a high incidence of the Ala12 mutant was not associated with the progression of fatty liver disease. However, we observed a significantly higher risk (odds ratio = 2.50, CI: 1.05-5.90, P = 0.028) in AFLD patients carrying the mutated Ala12 allele to develop inflammatory alterations. The linkage of the malfunctioning Ala12-positive PPARγ2 isoform to an increased risk in patients with AFLD to develop severe steatohepatitis and fibrosis indicates a more prominent anti-inflammatory impact of PPARγ2 in progression of AFLD than of NAFLD. CONCLUSION: In AFLD patients, the Pro12Ala single nuclear polymorphism should be studied more extensively in order to serve as a novel candidate in biomarker screening for improved prognosis. PMID:21155004

  12. Pro12Ala PPAR γ2 gene polymorphism in PCOS women: the role of compounds regulating satiety.

    Science.gov (United States)

    Bidzińska-Speichert, Bożena; Lenarcik, Agnieszka; Tworowska-Bardzińska, Urszula; Slęzak, Ryszard; Bednarek-Tupikowska, Grażyna; Milewicz, Andrzej

    2012-03-01

    Five to ten percent of women of reproductive age suffer from polycystic ovary syndrome (PCOS). Leptin, NPY, galanin, cholecystokinin (CCK) are involved in the regulation of eating behavior. PPARγ are receptors that are probably involved in hyperandrogenism. This study was designed to assess associations between the Pro12Ala PPARγ2 gene polymorphism and satiety factors in PCOS. Fifty-four PCOS women and 51 healthy women were studied. Leptin, NPY, galanin, CCK levels, and genetic studies to detect Pro12Ala PPARγ2 gene polymorphism were assessed. The leptin levels in the PCOS women carrying Pro12Ala genotype were higher than in those with Pro12Pro and Ala12Ala. The PCOS women had higher leptin and NPY levels and lower galanin levels. Obese PCOS patients had lower CCK levels. In the PCOS women, a single Ala allele may have a protective role as far as hyperleptinemia is concerned. The PCOS women may reveal a disrupted central leptin/NPY feedback loop with some shifts in food intake.

  13. Association of peroxisome proliferator-activated receptor-gamma 2 Pro12Ala polymorphism with advanced-stage endometriosis.

    Science.gov (United States)

    Hwang, Kyu Ri; Choi, Young Min; Kim, Jong Mee; Lee, Gyoung Hoon; Kim, Jin Ju; Chae, Soo Jin; Moon, Shin Yong

    2010-11-01

    To investigate whether the peroxisome proliferator-activated receptor (PPAR)-γ2 Pro12Ala polymorphism is associated with a risk of advanced-stage endometriosis in a Korean population.   Case-control study in a collective of 446 patients and 427 controls. The Pro12Ala polymorphism of PPAR-γ2 gene was genotyped using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis. The distribution of the PPAR-γ2 Pro12Ala polymorphism was different between the advanced-stage endometriosis group and the control group (non-CC rates were 5.2% for patients with advanced endometriosis and 10.1% for the control group, respectively, P = 0.006). The frequency for the Ala-12 allele variant was significantly lower in patients with advanced stage of endometriosis (2.7%) than in the control group (5.3%) (P = 0.006). These findings suggest that the PPAR-γ2 Pro12Ala polymorphism is associated with advanced-stage endometriosis in the Korean population. Unlike results from other studies reported so far, the Ala-12 allele may have protective effects against advanced-stage endometriosis in the Korean population. © 2010 John Wiley & Sons A/S.

  14. Association of the Pro12Ala Polymorphism with the Metabolic Parameters in Women with Polycystic Ovary Syndrome.

    Science.gov (United States)

    Zaki, Moushira; Hassan, Naglaa; El-Bassyouni, Hala T; Kamal, Sanaa; Basha, Walaa; Azmy, Osama; Amr, Khalda

    2017-06-15

    To investigate the association of peroxisome proliferator-activated receptor gamma (PPARG) Pro12Ala polymorphism with polycystic ovary syndrome (PCOS) and its effect on the metabolic parameters in PCOS women. The study used PCR to identify the presence of the PPARG Pro12Ala polymorphism in 100 PCOS women and 120 age-matched healthy women. All participants were subjected to anthropometry, biochemical and metabolic evaluation. Significant difference in the genotypes distributions of PPARG Pro12Ala polymorphism was observed among PCOS women and controls (p = 0.03). The frequency of the polymorphic allele Ala was significantly higher in PCOS cases than that in the controls (OR = 2.01, p = 0.01). The carries of the variant allele Ala in PCOS women showed significant higher values in body mass index (BMI), systolic and diastolic blood pressure, waist circumference, waist to hip ratio, sum of skin folds, fasting blood glucose, fasting blood insulin, HOMA-IR, fasting triglycerides, total cholesterol and low-density lipoprotein than non-carriers. The PPARG Pro12Ala polymorphism might contribute to the risk of PCOS and abnormal metabolic parameters and could be considered as a biomarker for early diagnosis and clinic prediction of metabolic complications.

  15. Effect of Ala-Gln and BCAA on traumatized rat%Ala-Gln和BCAA对创伤大鼠静脉营养支持作用的实验研究

    Institute of Scientific and Technical Information of China (English)

    靳继德; 徐琪寿; 韦京豫; 郭长江; 郑子新

    2000-01-01

    目的观察富含丙氨酰谷氨酰胺(Ala-Gln)和支链氨基酸(BCAA)的氨基酸注射液对创伤大鼠的静脉营养支持效果.方法Wistar大鼠40只,行创伤和中心静脉插管后,随机分为无氮组、正常饲料组、对照组和实验组.测定饲料摄入量、体重、氮平衡、血浆蛋白和氨基酸含量、外周血淋巴细胞转化率、伤口埋植海绵中羟脯氨酸含量、皮肤抗张力强度和小肠粘膜蛋白质及核酸.结果无氮组动物营养状况欠佳,各项指标均较差.实验组动物的血浆谷氨酰胺(Gln)、BCAA含量,外周血淋巴细胞转化率,伤口皮肤抗张力强度和羟脯氨酸含量都显著高于对照组和正常饲料组(P<0.05);实验组和正常饲料组动物第8天氮平衡,小肠粘膜核酸和蛋白质明显高于对照组(P<0.05).结论Gln和BCAA有助于改善创伤后机体的营养及代谢状况,增强免疫功能,促进小肠粘膜细胞增殖.%Purpose To observe the effects of amino acids solution supplimenteel with alanylglutamine (Ala-Gln) and branched-chain amino acids (BCAA) on traumatized rats. Methods After the injuny, and centeral vena catheter placed, 40 male, Wistar rats were randomly divided into nitrogen-free, normal diet, control and experimental groups. Dietary intake was weighed everyday, and body weight was checked every other day. On days 4 and 8, nitrogen balance was measured. On days 14, serum proteins and amino acids concentration and peripheral lymphocyte blastogenesis were determined. At the end of the study, the animals were sacrificed, hydroxyproline and tensile strength of wound, and intestinal mucosal DNA, RNA and protein content were examined. Results Nitrogenfree group was worse in all variance than other groups. The nitrogen balance on days 8 was remarkably improved in experimental and normal diet groups compared with control group. There were highter serum glutamine (Gln) and BCAA concentration, hydroxyproline content and tensile strength of wound

  16. The effect of Ala-Gln and BCAA on traumatized rat%Ala-Gln和BCAA对创伤大鼠营养支持作用的实验研究

    Institute of Scientific and Technical Information of China (English)

    靳继德; 王钢乐; 徐琪寿; 郑子新; 韦京豫; 杨继军; 郭长江

    2001-01-01

    目的观察富含丙氨酰谷氨酰胺(Ala-Gln)和支链氨基酸(BCAA)的氨基酸注射液,对创伤大鼠的营养支持效果。方法 Wistar大鼠40只,行创伤和中心静脉插管后,随机分为无氮组、正常饲料组、对照组和实验组。测定饲料摄入量、体重、氮平衡、血浆蛋白和氨基酸含量、外周血淋巴细胞转化率、伤口埋植海绵中羟脯氨酸含量、皮肤抗张力强度和小肠粘膜蛋白质及核酸。结果无氮组动物营养状况欠佳,各项指标均较差。实验组动物的血浆谷氨酰胺(Gln)、BCAA含量、外周血淋巴细胞转化率、伤口皮肤抗张力强度和羟脯氨酸含量均显著高于对照组和正常饲料组(P<0.05)实验组和正常饲料组动物第8天氮平衡,小肠粘膜核酸和蛋白质明显高于对照组(P<0.05)。结论 Gln和BCAA有助于改善创伤后机体的营养及代谢状况,增强免疫功能,促进小肠粘膜细胞增殖。%Objective To observe the effects of amino acids solution rich with alanylglutamine(Ala-Gln)and branched-chain amino acids(BCAA)on traumatized rats. Methods After injured and centeral vena catheter placed,40Wistar male rats were divided into nitrogen-free,normal diet,control and experimental groups randomly.Dietary intake was weighed everday and body weight every other day. On days 4 and 8,nitrogen balance was measured.On days 14,serum proteins and amino acids concentration and peripheral lymphocyte blastogenesis were determined.At last,the animals were killed,the hydroxyproline and tensile strength of wound,and intestinal mucosal DNA,RNA and prontein content were examined. Results Nitrogen-free group in all variance was worser than other groups.The nitrogen balance on days 8 was remarkably improved in experimental and normal diet groups compared with control group.There were higher serum glutamine(Gln) and BCAA concentration,hydroxyproline content and tensile strength of wound,and better lymphocyte

  17. An increase in dietary n-3 fatty acids decreases a marker of bone resorption in humans

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    Hilpert Kirsten F

    2007-01-01

    Full Text Available Abstract Human, animal, and in vitro research indicates a beneficial effect of appropriate amounts of omega-3 (n-3 polyunsaturated fatty acids (PUFA on bone health. This is the first controlled feeding study in humans to evaluate the effect of dietary plant-derived n-3 PUFA on bone turnover, assessed by serum concentrations of N-telopeptides (NTx and bone-specific alkaline phosphatase (BSAP. Subjects (n = 23 consumed each diet for 6 weeks in a randomized, 3-period crossover design: 1 Average American Diet (AAD; [34% total fat, 13% saturated fatty acids (SFA, 13% monounsaturated fatty acids (MUFA, 9% PUFA (7.7% LA, 0.8% ALA], 2 Linoleic Acid Diet (LA; [37% total fat, 9% SFA, 12% MUFA, 16% PUFA (12.6% LA, 3.6% ALA], and 3 α-Linolenic Acid Diet (ALA; [38% total fat, 8% SFA, 12% MUFA, 17% PUFA (10.5% LA, 6.5% ALA]. Walnuts and flaxseed oil were the predominant sources of ALA. NTx levels were significantly lower following the ALA diet (13.20 ± 1.21 nM BCE, relative to the AAD (15.59 ± 1.21 nM BCE (p

  18. Modification of Docosahexaenoic Acid Composition of Milk from Nursing Women Who Received Alpha Linolenic Acid from Chia Oil during Gestation and Nursing.

    Science.gov (United States)

    Valenzuela, Rodrigo; Bascuñán, Karla; Chamorro, Rodrigo; Barrera, Cynthia; Sandoval, Jorge; Puigrredon, Claudia; Parraguez, Gloria; Orellana, Paula; Gonzalez, Valeria; Valenzuela, Alfonso

    2015-08-04

    α-Linolenic acid (ALA) is the precursor of docosahexaenoic acid (DHA) in humans, which is fundamental for brain and visual function. Western diet provides low ALA and DHA, which is reflected in low DHA in maternal milk. Chia oil extracted from chia (Salvia hispanica L.), a plant native to some Latin American countries, is high in ALA (up to 60%) and thereby is an alternative to provide ALA with the aim to reduce DHA deficits. We evaluated the modification of the fatty acid profile of milk obtained from Chilean mothers who received chia oil during gestation and nursing. Forty healthy pregnant women (22-35 years old) tabulated for food consumption, were randomly separated into two groups: a control group with normal feeding (n = 21) and a chia group (n = 19), which received 16 mL chia oil daily from the third trimester of pregnancy until the first six months of nursing. The fatty acid profile of erythrocyte phospholipids, measured at six months of pregnancy, at time of delivery and at six months of nursing, and the fatty acid profile of the milk collected during the first six months of nursing were assessed by gas-chromatography. The chia group, compared to the control group, showed (i) a significant increase in ALA ingestion and a significant reduction of linoleic acid (LA) ingestion, no showing modification of arachidonic acid (AA), eicosapentaenoic acid (EPA) and DHA; (ii) a significant increase of erythrocyte ALA and EPA and a reduction of LA. AA and DHA were not modified; (iii) a increased milk content of ALA during the six months of nursing, whereas LA showed a decrease. AA and EPA were not modified, however DHA increased only during the first three months of nursing. Consumption of chia oil during the last trimester of pregnancy and the first three months of nursing transiently increases the milk content of DHA.

  19. Modification of Docosahexaenoic Acid Composition of Milk from Nursing Women Who Received Alpha Linolenic Acid from Chia Oil during Gestation and Nursing

    Directory of Open Access Journals (Sweden)

    Rodrigo Valenzuela

    2015-08-01

    Full Text Available α-Linolenic acid (ALA is the precursor of docosahexaenoic acid (DHA in humans, which is fundamental for brain and visual function. Western diet provides low ALA and DHA, which is reflected in low DHA in maternal milk. Chia oil extracted from chia (Salvia hispanica L., a plant native to some Latin American countries, is high in ALA (up to 60% and thereby is an alternative to provide ALA with the aim to reduce DHA deficits. We evaluated the modification of the fatty acid profile of milk obtained from Chilean mothers who received chia oil during gestation and nursing. Forty healthy pregnant women (22–35 years old tabulated for food consumption, were randomly separated into two groups: a control group with normal feeding (n = 21 and a chia group (n = 19, which received 16 mL chia oil daily from the third trimester of pregnancy until the first six months of nursing. The fatty acid profile of erythrocyte phospholipids, measured at six months of pregnancy, at time of delivery and at six months of nursing, and the fatty acid profile of the milk collected during the first six months of nursing were assessed by gas-chromatography. The chia group, compared to the control group, showed (i a significant increase in ALA ingestion and a significant reduction of linoleic acid (LA ingestion, no showing modification of arachidonic acid (AA, eicosapentaenoic acid (EPA and DHA; (ii a significant increase of erythrocyte ALA and EPA and a reduction of LA. AA and DHA were not modified; (iii a increased milk content of ALA during the six months of nursing, whereas LA showed a decrease. AA and EPA were not modified, however DHA increased only during the first three months of nursing. Consumption of chia oil during the last trimester of pregnancy and the first three months of nursing transiently increases the milk content of DHA.

  20. Alternative origins for omega-3 fatty acids in the diet

    NARCIS (Netherlands)

    Lenihan-Geels, Georgia; Bishop, Karen S.

    2016-01-01

    Fish and seafood are important sources for LC PUFAs, EPA and DHA. These fatty acids may be synthesised in the body from short-chain fatty acids, including ALA; however, the enzymes involved in this pathway are considered inefficient. This means direct EPA and DHA sources are an important part of

  1. UK Food Standards Agency alpha-linolenic acid workshop report

    NARCIS (Netherlands)

    Sanderson, P; Finnegan, YE; Williams, CM; Calder, PC; Burdge, GC; Wootton, SA; Griffin, BA; Millward, DJ; Pegge, NC; Bemelmans, WJE

    2002-01-01

    The UK Food Standards Agency convened a group of expert scientists to review current research investigating whether n-3 polyunsaturated fatty acids (PUFA) from plant oils (alpha-linolenic acid; ALA) were as beneficial to cardiovascular health as the n-3 PUFA from the marine oils, eicosapentaenoic ac

  2. Moss Chloroplasts Are Surrounded by a Peptidoglycan Wall Containing D-Amino Acids[OPEN

    Science.gov (United States)

    Hirano, Takayuki; Tanidokoro, Koji; Shimizu, Yasuhiro; Kawarabayasi, Yutaka; Ohshima, Toshihisa; Sato, Momo; Tadano, Shinji; Ishikawa, Hayato; Takio, Susumu; Takechi, Katsuaki; Takano, Hiroyoshi

    2016-01-01

    It is believed that the plastids in green plants lost peptidoglycan (i.e., a bacterial cell wall-containing d-amino acids) during their evolution from an endosymbiotic cyanobacterium. Although wall-like structures could not be detected in the plastids of green plants, the moss Physcomitrella patens has the genes required to generate peptidoglycan (Mur genes), and knocking out these genes causes defects in chloroplast division. Here, we generated P. patens knockout lines (∆Pp-ddl) for a homolog of the bacterial peptidoglycan-synthetic gene encoding d-Ala:d-Ala ligase. ∆Pp-ddl had a macrochloroplast phenotype, similar to other Mur knockout lines. The addition of d-Ala-d-Ala (DA-DA) to the medium suppressed the appearance of giant chloroplasts in ∆Pp-ddl, but the addition of l-Ala-l-Ala (LA-LA), DA-LA, LA-DA, or d-Ala did not. Recently, a metabolic method for labeling bacterial peptidoglycan was established using ethynyl-DA-DA (EDA-DA) and click chemistry to attach an azide-modified fluorophore to the ethynyl group. The ∆Pp-ddl line complemented with EDA-DA showed that moss chloroplasts are completely surrounded by peptidoglycan. Our findings strongly suggest that the moss plastids have a peptidoglycan wall containing d-amino acids. By contrast, no plastid phenotypes were observed in the T-DNA tagged ddl mutant lines of Arabidopsis thaliana. PMID:27325639

  3. Clinical applications of 5-aminolevulinic acid-mediated fluorescence for gastric cancer.

    Science.gov (United States)

    Namikawa, Tsutomu; Yatabe, Tomoaki; Inoue, Keiji; Shuin, Taro; Hanazaki, Kazuhiro

    2015-08-07

    5-aminolevulinic acid (ALA) is a naturally occurring amino acid that is a protoporphyrin IX (PpIX) precursor and a next-generation photosensitive substance. After exogenous administration of ALA, PpIX specifically accumulates in cancer cells owing to the impaired metabolism of ALA to PpIX in mitochondria, which results in a red fluorescence following irradiation with blue light and the formation of singlet oxygen. Fluorescence navigation by photodynamic diagnosis (PDD) using ALA provides good visualization and detection of gastric cancer lesions and is a potentially valuable diagnostic tool for gastric cancer for evaluating both the surgical resection margins and extension of the lesion. Furthermore, PDD using ALA might be used to detect peritoneal metastases during preoperative staging laparoscopy, where it could provide useful information for the selection of a therapeutic approach. Another promising application for this modality is in the evaluation of lymph node metastases. Photodynamic therapy (PDT) using ALA to cause selective damage based on the accumulation of a photosensitizer in malignant tissue is expected to be a non-invasive endoscopic treatment for superficial early gastric cancer. ALA has the potential to be used not only as a diagnostic agent but also as a therapeutic drug, resulting in a new strategy for cancer diagnosis and therapy. Here, we review the current use of PDD and PDT in gastric cancer and evaluate its future potential beyond conventional modalities combined with a light energy upconverter, a light-emitting diode and near-infrared rays as light sources.

  4. Dietary omega-3 fatty acids for women.

    Science.gov (United States)

    Bourre, Jean-Marie

    2007-01-01

    This review details the specific needs of women for omega-3 fatty acids, including alpha linoleic acid (ALA) and the very long chain fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Omega-3 fatty acid (dietary or in capsules) ensures that a woman's adipose tissue contains a reserve of these fatty acids for the developing fetus and the breast-fed newborn infant. This ensures the optimal cerebral and cognitive development of the infant. The presence of large quantities of EPA and DHA in the diet slightly lengthens pregnancy, and improves its quality. Human milk contains both ALA and DHA, unlike that of other mammals. Conditions such as diabetes can alter the fatty acid profile of mother's milk, while certain diets, like those of vegetarians, vegans, or even macrobiotic diets, can have the same effect, if they do not include seafood. ALA, DHA and EPA, are important for preventing ischemic cardiovascular disease in women of all ages. Omega-3 fatty acids can help to prevent the development of certain cancers, particularly those of the breast and colon, and possibly of the uterus and the skin, and are likely to reduce the risk of postpartum depression, manic-depressive psychosis, dementias (Alzheimer's disease and others), hypertension, toxemia, diabetes and, to a certain extend, age-related macular degeneration. Omega-3 fatty acids could play a positive role in the prevention of menstrual syndrome and postmenopausal hot flushes. The normal western diet contains little ALA (less than 50% of the RDA). The only adequate sources are rapeseed oil (canola), walnuts and so-called "omega-3" eggs (similar to wild-type or Cretan eggs). The amounts of EPA and DHA in the diet vary greatly from person to person. The only good sources are fish and seafood, together with "omega-3" eggs.

  5. HYDROLOGIC MODELLING OF KATSINA-ALA RIVER BASIN: AN EMERGING SCENARIO FROM LAKE NYOS THREAT

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    J. O. Akinyede

    2012-07-01

    Full Text Available Understanding the hydrologic system surrounding crater lakes is of great importance for prevention of flooding damages, conservation of ecological environment, and assessment of socio-economic impact of dam failure on the civilians in the downstream regions. Lake Nyos is a crater lake formed by volcanic activities at the Oku volcanic field on the Cameroon Volcanic Line. It is a freshwater lake with a maximum depth of 200 meter. In 1986, a limnic eruption at the lake emitted 1.6 million tonnes of carbon dioxide from the bottom of saturated water into the air and suffocated up to 1,800 people and 3,500 livestock at nearby villages. The lake waters are held in place by a natural dam composed of loosely consolidated volcanic rock, which is now at the verge of collapse due to accelerated erosion. This study was carried out to determine the flood risks and vulnerability of population and infrastructure along Katsina-Ala drainage basins. The project integrated both satellite images and field datasets into a hydrologic model for Katsina-Ala River Basin and its vicinity including the Lake Nyos. ArcHydro was used to construct a hydrologic database as 'data models' and MIKE SHE was employed to conduct hydrologic simulations. Vulnerable infrastructures, population and socio-economic activities were identified to assist the Federal and State governments in disaster mitigation and management plans. The result of the project provides comprehensive knowledge of hydrologic system of Katsina-Ala drainage basin to mitigate potential future disasters from a potential dam failure and manage water resources against such disasters.

  6. Disruption of the blood brain barrier following ALA mediated photodynamic therapy

    Science.gov (United States)

    Hirschberg, Henry; Peng, Qian; Uzal, Francisco A.; Chighvinadze, David; Zhang, Michelle J.; Madsen, Steen J.

    2008-02-01

    Introduction: Failure of treatment for high grade gliomas is usually due to local recurrence at the site of surgical resection indicating that a more aggressive form of local therapy, such as PDT, could be of benefit. PDT causes damage to tumor cells as well as degradation of the blood brain barrier (BBB). We have evaluated the ability of ALA mediated PDT to open the BBB in rats. This will permit access of chemotherapeutic agents to brain tumor cells remaining in the resection cavity wall, but limit their penetration into normal brain remote from the site of illumination. Materials and Methods: ALA-PDT was performed on non tumor bearing inbred Fisher rats at increasing fluence levels. T2 weighted MRI scans were used to evaluate edema formation and post-contrast T I MRI scans were used to monitor the degree BBB disruption which could be inferred from the intensity and volume of the contrast agent visualized. Results. PDT at increasing fluence levels between 9J and 26J demonstrated an increasing contrast flow rate. No effect on the BBB was observed if 26J of light were given in the absence of ALA. A similar increased contrast volume was observed with increasing fluence rates. The BBB was found to be disrupted 2hrs. following PDT and 80-100% restored 72hrs later. Conclusion: PDT was highly effective in opening the BBB in a limited region of the brain. The degradation of the BBB was temporary in nature, opening rapidly following treatment and significantly restored during the next 72 hrs.

  7. Reduction of the invasiveness of human glioma cells by ALA-mediated photodynamic therapy

    Science.gov (United States)

    Hirschberg, Henry; Sun, Chung-Ho; Madsen, Steen

    2006-02-01

    Introduction: High grade gliomas are characterised by rapid and invasive growth, that cause massive tissue destruction at both the tumour- brain boarder as well as in regions remote from the tumor core. Eradication or inhibition of infiltrating glioma cells poses a significant clinical challenge that is unlikely to be solved using conventional treatment regimens consisting of ionizing radiation and chemotherapeutic agents. In this study we evaluated the effects of ALA mediated photodynamic therapy (PDT) on the invesivness of human glioma cells migrating from implanted multicell tumor spheroids. Materials and method 3-400nm diameter tumor spheroids, derived from the human glioma cell line ACBT, were implanted into a gel matrix of collagen type I. 24 hours following implantation there was a significant invasion of the surrounding gel by individual tumor cells to an average distance of 400nm. The cultures were incubated in increasing concentrations of ALA (10-1000 ug/ml) for four hours and then exposed to 635nm laser light in a titration of both fluence level and fluence rate. Results Fluences of 25J/cm2 were clearly cytotoxic for both the infiltrating cells as well as the spheroids at all ALA concentrations. Fluence levels of 6J did not stop the spheroid growth or prove cytotoxic to the glioma cells that had previously migrated into the gel, in a majority of cultures but inhibited further migration of the cells by 80-90% compared to control. Conclusion: Measurement of cell survival and cell proliferation indices seemed to indicate a direct migratory inhibition effect on the invading cells and not cytotoxicity as the most likely mechanism for this observation.

  8. Peroxisome Proliferator–Activated Receptor γ Polymorphism Pro12Ala Is Associated With Nephropathy in Type 2 Diabetes

    Science.gov (United States)

    Zhang, Hui; Zhu, Shimiao; Chen, Jing; Tang, Yang; Hu, Hailong; Mohan, Viswanathan; Venkatesan, Radha; Wang, Jianmin; Chen, Haiping

    2012-01-01

    OBJECTIVE Insulin resistance plays a part in diabetic nephropathy (DN). The association between the peroxisome proliferator–activated receptor γ Pro to Ala alteration at codon 12 (Pro12Ala) polymorphism and the risk of insulin resistance has been confirmed. The association between the polymorphism and DN risk has also been widely studied recently, but no consensus was available up to now. RESEARCH DESIGN AND METHODS A systematic search of electronic databases (MEDLINE, Embase, and China National Knowledge Infrastructure) and reference lists of relevant articles was carried out, and then 18 case-control studies involving 3,361 DN cases and 5,825 control subjects were identified. RESULTS In the overall analysis, the Ala12 variant was observed to be significantly associated with decreased DN risk (odds ratio 0.76 [95% CI 0.61–0.93]). Some evidence of heterogeneity among the included studies was detected, which could be explained by the difference of ethnicity and stage of DN. Subgroup analyses stratified by ethnicity and stage of DN were performed, and results indicated the Pro12Ala polymorphism was associated with the risk of DN in Caucasians but no similar association was observed in Asians. Additionally, we observed that Ala12 was associated with decreased risk of albuminuria. With only a few of subjects were available, we failed to detect statistically significant association between the polymorphism and end-stage renal disease (ESRD). CONCLUSIONS Our results indicated that the Ala12 variant is a significantly protective factor for DN. Future research should focus on the effect of Pro12Ala polymorphism on ESRD and gathering data of Africans. PMID:22619290

  9. PPARγ Pro12Ala and ACE ID polymorphisms are associated with BMI and fat distribution, but not metabolic syndrome.

    Science.gov (United States)

    Passaro, Angela; Dalla Nora, Edoardo; Marcello, Caterina; Di Vece, Francesca; Morieri, Mario Luca; Sanz, Juana M; Bosi, Cristina; Fellin, Renato; Zuliani, Giovanni

    2011-12-14

    Metabolic Syndrome (MetS) results from the combined effect of environmental and genetic factors. We investigated the possible association of peroxisome proliferator-activated receptor-γ2 (PPARγ2) Pro12Ala and Angiotensin Converting Enzyme (ACE) I/D polymorphisms with MetS and interaction between these genetic variants. Three hundred sixty four unrelated Caucasian subjects were enrolled. Waist circumference, blood pressure, and body mass index (BMI) were recorded. Body composition was estimated by impedance analysis; MetS was diagnosed by the NCEP-ATPIII criteria. A fasting blood sample was obtained for glucose, insulin, lipid profile determination, and DNA isolation for genotyping. The prevalence of MetS did not differ across PPARγ2 or ACE polymorphisms. Carriers of PPARγ2 Ala allele had higher BMI and fat-mass but lower systolic blood pressure compared with Pro/Pro homozygotes. A significant PPARγ2 gene-gender interaction was observed in the modulation of BMI, fat mass, and blood pressure, with significant associations found in women only. A PPARγ2-ACE risk genotype combination for BMI and fat mass was found, with ACE DD/PPARγ2 Ala subjects having a higher BMI (p = 0.002) and Fat Mass (p = 0.002). Pro12Ala was independently associated with waist circumference independent of BMI and gender. Carriers of PPARγ2 Ala allele had higher BMI and fat-mass but not a worse metabolic profile, possibly because of a more favorable adipose tissue distribution. A gene interaction exists between Pro12Ala and ACE I/D on BMI and fat mass. Further studies are needed to assess the contribution of Pro12Ala polymorphism in adiposity distribution.

  10. PPARγ Pro12Ala and ACE ID polymorphisms are associated with BMI and fat distribution, but not metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Passaro Angela

    2011-12-01

    Full Text Available Abstract Background Metabolic Syndrome (MetS results from the combined effect of environmental and genetic factors. We investigated the possible association of peroxisome proliferator-activated receptor-γ2 (PPARγ2 Pro12Ala and Angiotensin Converting Enzyme (ACE I/D polymorphisms with MetS and interaction between these genetic variants. Methods Three hundred sixty four unrelated Caucasian subjects were enrolled. Waist circumference, blood pressure, and body mass index (BMI were recorded. Body composition was estimated by impedance analysis; MetS was diagnosed by the NCEP-ATPIII criteria. A fasting blood sample was obtained for glucose, insulin, lipid profile determination, and DNA isolation for genotyping. Results The prevalence of MetS did not differ across PPARγ2 or ACE polymorphisms. Carriers of PPARγ2 Ala allele had higher BMI and fat-mass but lower systolic blood pressure compared with Pro/Pro homozygotes. A significant PPARγ2 gene-gender interaction was observed in the modulation of BMI, fat mass, and blood pressure, with significant associations found in women only. A PPARγ2-ACE risk genotype combination for BMI and fat mass was found, with ACE DD/PPARγ2 Ala subjects having a higher BMI (p = 0.002 and Fat Mass (p = 0.002. Pro12Ala was independently associated with waist circumference independent of BMI and gender. Conclusions Carriers of PPARγ2 Ala allele had higher BMI and fat-mass but not a worse metabolic profile, possibly because of a more favorable adipose tissue distribution. A gene interaction exists between Pro12Ala and ACE I/D on BMI and fat mass. Further studies are needed to assess the contribution of Pro12Ala polymorphism in adiposity distribution.

  11. An α-linolenic acid-rich formula reduces oxidative stress and inflammation by regulating NF-κB in rats with TNBS-induced colitis.

    Science.gov (United States)

    Hassan, Aktham; Ibrahim, Ayman; Mbodji, Khaly; Coëffier, Moïse; Ziegler, Frédéric; Bounoure, Frédéric; Chardigny, Jean-Michel; Skiba, Mohamed; Savoye, Guillaume; Déchelotte, Pierre; Marion-Letellier, Rachel

    2010-10-01

    We have previously shown that α-linolenic acid (ALA), a (n-3) PUFA exerts in vitro antiinflammatory effects in the intestine. In this study, we aimed to evaluate its effect on inflammatory and oxidative stress in a colitis model. Colitis was induced in 2 groups at d 0 by intrarectal injection of 2-4-6-trinitrobenzen sulfonic acid (TNBS), whereas the control group received the vehicle. Rats we fed 450 mg . kg(-1) . d(-1) of ALA (TNBS+ALA) while the other colitic group (TNBS) and the control group were fed an isocaloric corn oil formula for 14 d (from d -7 to d 7). RBC fatty acid composition was assessed. Oxidative stress was studied by measuring urinary 8-isoprostanes (8-IP) and colon glutathione (GSH) concentration and inducible nitric oxide synthase (iNOS) expression. Colitis was assessed histologically, by production of proinflammatory mediators, including cytokines, leukotrienes B(4) (LTB(4)), and cyclooxygenase-2 (COX-2) and by nuclear factor-κB (NF-κB) activation. The ALA-rich diet significantly increased the RBC levels of ALA, eicosapentaenoic acid, and docosapentaenoic acid (n-3) compared with the TNBS group (P TNBS group. ALA also protected against colon inflammation as assessed by lower tumor necrosis factor-α secretion and mRNA level (P TNBS group. These findings show that an ALA-rich formula is beneficial to TNBS-induced colitic rats via inhibition of oxidative and inflammatory stress.

  12. 5-Aminolevulinic acid-mediated photodynamic therapy for oral cancers and precancers

    Directory of Open Access Journals (Sweden)

    Hsin-Ming Chen

    2012-12-01

    Full Text Available Previous studies have used both systemic and topical 5-aminolevulinic acid (ALA-mediated photodynamic therapy (PDT to treat oral precancers including oral leukoplakia (OL, oral erythroleukoplakia (OEL, and oral verrucous hyperplasia (OVH as well as oral cancers including oral verrucous carcinoma (OVC and oral squamous cell carcinoma (OSCC. Systemic ALA-PDT has been used to treat oral dysplastic lesions and oral cancers with promising clinical outcomes. The efficacy of a regular topical ALA-PDT (fluence rate, 100 mW/cm2; light dose, 100 J/cm2 was tested on an extensive buccal OVC and an enhanced topical ALA-PDT (fluence rate, 200 mW/cm2; light dose, 200 J/cm2 on an early-invasive OSCC; complete regression of the carcinomas was demonstrated after 28 and 18 PDT treatments, respectively. Several previous studies showed relatively good outcomes for OL lesions treated with topical ALA-PDT. However, it was found that the regular topical ALA-PDT is very effective for OVH and OEL lesions but less so for OL lesions. Better PDT outcomes are significantly associated with OVH and OEL lesions with smaller size, pink to red color, epithelial dysplasia, or thinner surface keratin layer. Moreover, the thicker surface keratin layer on the OL lesions is responsible for the relatively poorer PDT outcomes for OL lesions. In addition, both light emitting diode light- and laser light-mediated topical ALA-PDTs are comparative treatment modalities for OVH and OEL lesions. Methotrexate- or vitamin D3-preconditioned prostate or skin carcinoma cells can accumulate more intracellular protoporphyrin IX, resulting in an increased killing of these preconditioned cells by subsequent ALA-PDT. Because chemotherapy can help destroy carcinoma cells and tumor-associated vasculatures and cryotherapy pretreatment may help the diffusion of ALA into lesional epithelial cells, the chemotherapy or cryotherapy-combined topical ALA-PDT may be a new effective PDT alternative for

  13. 5-Aminolevulinic acid and the hepatic oxidative stress in the early phase of experimental hexachlorobenzene intoxication Ácido delta-aminolevulinico e estresse oxidativo hepático na fase inicial da intoxicação experimental por hexaclorobenzeno

    OpenAIRE

    Tânia Cristina Higashi Sawada; Vanessa Vitoriano da Silva; Sonia Barros; Cristina Dislich Röpke; Silvia Berlanga de Moraes Barros

    2004-01-01

    This work evaluated the levels of 5-aminolevulinic acid (ALA) in the liver of rats exposed to different doses of HCB (25,50, and 100 mg/kg b.w. for 4 weeks) and correlated them with lipid peroxidation parameters. Levels of ALA were determined by high-pressure liquid chromatography after derivatization with acetylacetone and formaldehyde, followed by fluorescence detection. The methodology was carefully validated, nonetheless hepatic levels of ALA in all animals treated or not were below the d...

  14. Aminolevulinic Acid-Mediated Photodynamic Therapy Causes Cell Death in MG-63 Human Osteosarcoma Cells.

    Science.gov (United States)

    White, Bradley; Rossi, Vince; Baugher, Paige J

    2016-09-01

    The aim of this study was to test the efficacy of aminolevulinic acid-mediated photodynamic therapy (PDT) against the human osteosarcoma cell line MG-63. Osteosarcoma is the most common type of primary malignant bone tumor diagnosed in the United States among adolescents and children. Treatments for osteosarcoma often result in diminished limb use or amputation. Because ALA-mediated PDT exhibits dual specificity in the context of tumor killing, this therapy could represent a less invasive, but effective, treatment for this disease. To assess ALA dark toxicity in MG-63 cells, cells were incubated with varying concentrations of ALA, and cell viability was determined by crystal violet assay. Protoporphyrin IX (PpIX) accumulation was assessed subsequent to ALA incubation at various concentrations using spectrofluorometry. Cell death subsequent to ALA-PDT was determined by illuminating cells at a wavelength of 635 nm at various light intensities subsequent to ALA incubation. Cell viability was assessed using the MTT assay. ALA dark toxicity was observed only at the highest concentrations of 2, 5, and 10 mM. Maximal PpIX concentration was observed at 0.5 and 1 mM ALA, subsequent to a 24-h incubation. Maximal cell death with minimal light toxicity was observed at 0.5 and 1 mM ALA after illumination with 0.6 and 3 J/cm(2) light. Collectively, our data indicate that ALA-PDT can result in the death of MG-64 human osteosarcoma cells in vitro.

  15. Interference with the Jaffé Method for Creatinine Following 5-Aminolevulinic Acid Administration

    Science.gov (United States)

    Quon, Harry; Grossman, Craig E.; King, Rebecca L.; Putt, Mary; Donaldson, Keri; Kricka, Larry; Finlay, Jarod; Malloy, Kelly; Cengel, Keith A.; Busch, Theresa M.

    2013-01-01

    Background The photosensitizer pro-drug 5-aminolevulinic acid (5-ALA) has been administered systemically for photodynamic therapy. Although several toxicities have been reported, nephrotoxicity has never been observed. Materials and Methods Patients with head and neck mucosal dysplasia have been treated on a phase 1 study of escalating light doses in combination with 60 mg/kg of oral 5-ALA. Serum creatinine was measured with the modified Jaffe method or an enzymatic method in the first 24 hours after 5-ALA. Interference by 5-ALA, as well as by its photosensitizing product protoporphyrin IX, was assessed. Results Among 11 subjects enrolled to date, 9 of 11 had blood chemistries collected within the first 5 hours with 7 demonstrating significant grade 3 creatinine elevations (p=0.030). There was no additional evidence of compromised renal function or increased PDT-induced mucositis. Creatinine levels measured by the Jaffe assay increased linearly as a function of the ex-vivo addition of ALA (p<.0001). The exogenous addition of PpIX did not alter creatinine levels. ALA did not interfere with creatinine levels as measured by an enzymatic assay. A total of 4 of the 11 subjects had creatinine levels prospectively measured by both the Jaffe and the enzymatic assays. Only the Jaffe method demonstrated significant elevations as a function of time after ALA administration. Conclusions The transient increase in creatinine after systematic ALA can be attributed, in part, if not entirely, to interference of ALA in the Jaffe reaction. Alternative assays should be employed in situations calling for monitoring of kidney function after systemic ALA. PMID:21112550

  16. Effect of an increased intake of alpha-linolenic acid and group nutritional education on cardiovascular risk factors : the Mediterranean Alpha-linolenic Enriched Groningen Dietary Intervention (MARGARIN) study

    NARCIS (Netherlands)

    Bemelmans, W.J.; Broer, J.; Feskens, E.J.; Smit, A.J.; Muskiet, F.A.; Lefrandt, J.D.; Bom, V.J.; May, J.F.; Meyboom-de Jong, B.

    2002-01-01

    Background: The effect of long-term increased intakes of alpha-linolenic acid (ALA; 18:3n-3) on cardiovascular risk factors is unknown. Objectives: Our objectives were to assess the effect of increased ALA intakes on cardiovascular risk factors and the estimated risk of ischemic heart disease (IHD)

  17. Preservation of homochirality of aspartic acid films irradiated with 8.5 eV vacuum ultraviolet light

    Science.gov (United States)

    Izumi, Yudai; Matsui, Takahiro; Koketsu, Toshiyuki; Nakagawa, Kazumichi

    2008-10-01

    Enantiomeric excess was reported for amino acids detected from some meteorites. These results imply that these amino acids might escape from racemization processes in space. Here, in an attempt to examine whether non-polarized vacuum ultraviolet (VUV) light was one of racemization factors, we irradiated solid films of homochiral L- or D-aspartic acid ( L- or D-Asp) with a 146 nm excimer lamp in vacuum at 290 K. After irradiation for L-Asp films, L-alanine ( L-Ala) and β-Ala were observed, but D-Asp or D-Ala was not observed. On the contrast, for irradiation to D-Asp films, D-Ala and β-Ala were observed, but L-Asp or L-Ala was not observed. Therefore, we concluded that the chirality was preserved through the photolysis of Asp to Ala. It is of interest to carry out the similar experiments using high-energy particles and/or γ-ray irradiation.

  18. Preservation of homochirality of aspartic acid films irradiated with 8.5 eV vacuum ultraviolet light

    Energy Technology Data Exchange (ETDEWEB)

    Izumi, Yudai [Graduate School of Human Development and Environment, Kobe University, Nada-ku, Kobe 657-8501 (Japan)], E-mail: izumi@radix.h.kobe-u.ac.jp; Matsui, Takahiro; Koketsu, Toshiyuki [Graduate School of Cultural Studies and Human Science, Kobe University, Nada-ku, Kobe 657-8501 (Japan); Nakagawa, Kazumichi [Graduate School of Human Development and Environment, Kobe University, Nada-ku, Kobe 657-8501 (Japan); Graduate School of Cultural Studies and Human Science, Kobe University, Nada-ku, Kobe 657-8501 (Japan)], E-mail: nakagawa@kobe-u.ac.jp

    2008-10-15

    Enantiomeric excess was reported for amino acids detected from some meteorites. These results imply that these amino acids might escape from racemization processes in space. Here, in an attempt to examine whether non-polarized vacuum ultraviolet (VUV) light was one of racemization factors, we irradiated solid films of homochiral L- or D-aspartic acid (L- or D-Asp) with a 146 nm excimer lamp in vacuum at 290 K. After irradiation for L-Asp films, L-alanine (L-Ala) and {beta}-Ala were observed, but D-Asp or D-Ala was not observed. On the contrast, for irradiation to D-Asp films, D-Ala and {beta}-Ala were observed, but L-Asp or L-Ala was not observed. Therefore, we concluded that the chirality was preserved through the photolysis of Asp to Ala. It is of interest to carry out the similar experiments using high-energy particles and/or {gamma}-ray irradiation.

  19. Delta-ALA-mediated fluorescence spectroscopy of gastrointestinal tumors: comparison of in vivo and in vitro results

    Science.gov (United States)

    Vladimirov, B.; Borisova, E.; Avramov, L.

    2007-06-01

    The limitations of standard endoscopy for detection of dysplastic changes of mucosa are significant challenge and initiate development of new photodiagnostic techniques, additional to diagnostic possibilities of standard endoscopic equipment. One of the most widely examined optical modalities is the laser- or light-induced fluorescence spectroscopy (LIFS), because of its rapid and highly sensitive response to early biochemical and morphological changes in biological tissues. In the recent study delta-aminolevulinic acid/protoporphyrin IX is used as fluorescent marker for dysplasia and tumor detection in esophagus and stomach. The δ -ALA is administered per os six hours before measurements at dose 20mg/kg weight. High-power light-emitting diode at 405 nm is used as an excitation source. Special opto-mechanical device is built to use the light guide of standard video-endoscopic system. Through endoscopic instrumental channel a fiber is applied to return information about fluorescence to microspectrometer. The fluorescence detected from in vivo tumor sites has very complex spectral origins. It consists of autofluorescence, fluorescence from exogenous fluorophores and re-absorption from the chromophores accumulated in the tissue investigated. Mucosa autofluorescence lies at 450-600 nm region. The fluorescence of PpIX is clearly pronounced at the 630-710 nm region. Deep minima in the tumor fluorescence signals are observed in the region 540-575 nm, related to hemoglobin re-absorption. Such high hemoglobin content is an indication of the tumors vascularization and it is clearly pronounced in all dysplastic and tumor sites investigated. After formalin conservation for in vitro samples hemoglobin absorption is strongly reduced that increases mucous fluorescence signal in green-yellow spectral region. Simultaneously the maxima at 635 nm and 720 nm are reduced.

  20. Aminolevulinic Acid-Mediated Photodynamic Therapy of Human Meningioma: An in Vitro Study on Primary Cell Lines

    Directory of Open Access Journals (Sweden)

    Mustafa El-Khatib

    2015-04-01

    Full Text Available Objective: Five-aminolevulinic acid (5-ALA-induced porphyrins in malignant gliomas are potent photosensitizers. Promising results of ALA-PDT (photodynamic therapy in recurrent glioblastomas have been published. Recently, 5-ALA-induced fluorescence was studied in meningioma surgery. Here, we present an experimental study of ALA-PDT in an in vitro model of primary meningioma cell lines. Methods: We processed native tumor material obtained intra-operatively within 24 h for cell culture. Epithelial membrane antigen (EMA immunohistochemistry was performed after the first passage to confirm that cells were meningioma cells. For 5-ALA-PDT treatment, about 5000 cells per well were seeded in 20 wells of a blank 96-well plate. Each block of 4 wells was inoculated with 150 µL of 0, 25, 50 and 100 µg/mL 5-ALA solutions; one block was used as negative control without 5-ALA and without PDT. Following incubation for 3 h PDT was performed using a laser (635 nm, 18.75 J/cm2. The therapeutic response was analyzed by the water soluble tetrazolium salt (WST-1 cell viability assay 90 min after PDT. Results: 5-ALA-PDT was performed in 14 primary meningioma cell lines. EMA expression was verified in 10 primary cell cultures. The remaining 4 were EMA negative and PDT was without any effect in these cultures. All 10 EMA-positive cell lines showed a significant and dose-dependent decrease in viability rate (p < 0.001. Cell survival at 5-ALA concentrations of 12.5, 25, 50 and 100 μg/mL was 96.5% ± 7.6%, 67.9% ± 29.9%, 24.0% ± 16.7% and 13.8% ± 7.5%, respectively. For the negative controls (no 5-ALA/PDT and ALA/no PDT, the viability rates were 101.72% ± 3.5% and 100.17% ± 3.6%, respectively. The LD50 for 5-ALA was estimated between 25 and 50 µg/mL. Conclusion: This study reveals dose-dependent cytotoxic effects of 5-ALA-PDT on primary cell lines of meningiomas. Either 5-ALA or PDT alone did not affect cell survival. Further efforts are necessary to study the

  1. Evidence for depletion of CASP5 Ala90Thr heterozygous genotype in aged subjects.

    Science.gov (United States)

    Ulybina, Yulia M; Kuligina, Ekatherina Sh; Mitiushkina, Nathalia V; Sherina, Nathalia Yu; Yanus, Grigoriy A; Gorodnova, Tatiana V; Katanugina, Anna S; Koloskov, Andrey V; Togo, Alexandr V; Imyanitov, Evgeny N

    2010-09-01

    Our previous studies, which included genotyping of multiple coding apoptotic gene polymorphisms, unexpectedly demonstrated a depletion of heterozygous CASP5 Ala90Thr (rs507879, c.268 G>A) genotypes in elderly subjects. Present investigation was aimed to validate this trend. An analysis of 510 subjects aged 75-103years revealed 205 (40%) CASP5 Ala90Thr heterozygotes as compared to 254 (50%) expected from the minor allele frequency 0.470 (p=0.000014). This deviation was not observed in 549 middle-aged (18-50years) controls (270 (49%) heterozygotes observed vs. 274 (50%) expected; minor allele frequency 0.475; p=0.743). Unfavorable significance of CASP5 heterozygous genotype may be explained by the role of the caspase-5 in inflammation-related processes. Almost all prior gene-longevity association studies focused on discrimination between "good" and "bad" gene variants. Here we present a distinct situation, where the combination of alternative alleles (i.e., heterozygosity) appears to be unfavorable as compared to the homozygous carriership of either gene variant.

  2. Fold deformations of the paleozoic basement roof in the Chunkurchak Trough, Kyrgyz Ala-Too Range

    Science.gov (United States)

    Przhiyalgovskii, E. S.; Lavrushina, E. V.

    2017-07-01

    A structural-geological study has been performed on the northern slope of the Kyrgyz Ala-Too Range. Deformations of the peneplaned Paleozoic basement surface, structures of granite disintegration, and morphostructural manifestation of Late Cenozoic tectonic movements have been investigated. Based on the location of pre-Paleocene peneplain remnants with the retained weathering mantle partly overlapped by Paleocene-Miocene sedimentary complexes, we have reconstructed the morphology of the folded surface of the Chunkurchak Trough separated from the Chu Basin at the early Miocene. The dome-fold forms, the morphology and arrangement of which are controlled by disintegration of the basement, have been described for the basement surface. It has been established that granites are broken by systems of steeply dipping, fanshaped, and gently dipping faults and fractures. Variously oriented insignificant offsets along slickensides, as well as displacements deduced from the geometry of fracture intersections, are a result of volumetric cataclastic flow of rocks. The tectonic mobility of disintegrated granites, which are abundant in the Paleozoic-Precambrian basement, explains the complexity and scale of tectonic processes initiated by Cenozoic activation. In paleotectonic reconstructions, which take into consideration tectonic flow and the redistribution of basement masses, the estimates of Cenozoic relative rapprochement of the Chu Basin and the Kyrgyz Ala-Too Range decrease substantially to 4-6 km.

  3. The Ala16Val genetic dimorphism modulates the import of human manganese superoxide dismutase into rat liver mitochondria.

    Science.gov (United States)

    Sutton, Angela; Khoury, Hania; Prip-Buus, Carina; Cepanec, Claude; Pessayre, Dominique; Degoul, Françoise

    2003-03-01

    A genetic dimorphism encodes for either alanine (Ala) or valine (Val) in the mitochondrial targeting sequence (MTS) of human manganese superoxide dismutase (MnSOD) and has been reported to modulate the risk of some cancers, neurodegenerative diseases and severe alcoholic liver disease. Although functional consequences of this dimorphism on MnSOD activity have not been assessed, computer models predict a partial alpha-helix structure for the Ala-MnSOD/MTS, but a beta-sheet structure for the Val-variant, which could hamper mitochondrial import. To investigate this hypothesis, we studied the in-vitro import of chimaeric proteins composed of either one of the MnSOD/MTS fused to the mouse dihydrofolate reductase (DHFR) protein, and the import of the two human MnSOD precursor variants into rat liver mitochondria. Compared to Ala-proteins, the Val-MnSOD/MTS-DHFR precursor and Val-MnSOD precursor were both partly arrested within the inner mitochondrial membrane. The Ala-MnSOD precursor generated 30-40% more of the active, matricial, processed MnSOD homotetramer than the Val-MnSOD precursor. These results show that the Ala-MnSOD/MTS allows efficient MnSOD import into the mitochondrial matrix, while the Val-variant causes partial arrest of the precursor within the inner membrane and decreased formation of the active MnSOD tetramer in the mitochondrial matrix.

  4. The Pro12Ala polymorphism of the PPAR-gamma gene is not associated with the polycystic ovary syndrome.

    Science.gov (United States)

    Xita, Nectaria; Lazaros, Leandros; Georgiou, Ioannis; Tsatsoulis, Agathocles

    2009-01-01

    Insulin resistance is a key factor in the pathogenesis of polycystic ovary syndrome (PCOS). Peroxisome proliferator-activated- receptor-gamma (PPAR-gamma) has been implicated in insulin resistance and adiposity. The aim of the study was to investigate the possible involvement of the Pro12Ala polymorphism of the PPAR-gamma gene in the pathogenesis of PCOS. We studied 180 women with PCOS and 140 healthy controls. Body mass index (BMI) was recorded. Blood samples were drawn after overnight fasting and serum glucose, insulin, lipid and hormonal profiles were determined. The fasting glucose/insulin ratio and HOMA index were calculated. Moreover, 100 women with PCOS underwent a 75g oral glucose tolerance test and the area under the curve for insulin and glucose was estimated. DNA was extracted from peripheral blood leucocytes and the Pro12Ala polymorphism was genotyped. The PPAR-gamma genotypes were found to be in the Hardy-Weinberg equilibrium in both study groups. No difference was found in the distribution of the Pro12Ala polymorphism between PCOS and controls. Insulin resistance indices and lipid and hormonal profile were not different among the various genotypes of the Pro12Ala polymorphism. The Pro12Ala polymorphism of the PPAR-gamma gene is not involved in the pathogenesis or the phenotypic expression of PCOS.

  5. Association analysis of PPARγ (p.Pro12Ala) polymorphism with type 2 diabetic retinopathy in patients from north India.

    Science.gov (United States)

    Kaur, Navdeep; Vanita, Vanita

    2017-01-01

    The present study aimed to examine the association of PPARγ (p.Pro12Ala) polymorphism with type 2 diabetic retinopathy (DR) in patients from north India. In this case-control association study a total of 1325 subjects (717 DR patients and 608 individuals with confirmed type 2 diabetes mellitus (T2DM) without retinopathy taken as controls (CDR)), were recruited. Genotyping for PPARγ (p.Pro12Ala) polymorphism was performed by Taqman SNP Genotyping Assays using Real time PCR. Statistically significant differences were observed between the two analyzed groups in the duration of diabetes and random blood glucose levels (p = 0.000 and p = 0.011, respectively). However, genotype and allele frequency distribution of PPARγ (p.Pro12Ala) polymorphism did not differ significantly between DR and CDR groups (p = 0.507 and 0.625, respectively). These findings suggest no significant association of p.Pro12Ala polymorphism with retinopathy in tested type 2 diabetic retinopathy patients as compared to T2DM individuals take as controls. To our knowledge, this is the first report of association analysis of p.Pro12Ala polymorphism in PPARγ in DR patients from India.

  6. A meta-analysis on the association between PPAR-γ Pro12Ala polymorphism and polycystic ovary syndrome.

    Science.gov (United States)

    He, Junli; Wang, Li; Liu, Junhong; Liu, Feng; Li, Xuliang

    2012-07-01

    To investigate the influence of the peroxisome proliferator activated receptor gamma (PPAR-γ) Pro12Ala polymorphism on the susceptibility of polycystic ovary syndrome (PCOS) and body mass index (BMI), fast insulin levels, homeostasis model assessment of insulin resistance (HOMA-IR) in PCOS patients. PubMed, EMBASE, MEDLINE and CENTRAL databases were searched to identify eligible studies. We then conducted a meta-analysis to examine the association between Pro12Ala polymorphism and PCOS. Seventeen eligible studies, including 2,149 patients and 2,124 controls were enrolled in this meta-analysis. Pro12Ala polymorphism was significantly associated with the susceptibility of PCOS (odds ratio [OR] 0.74, 95 % confidence interval [CI] [0.61, 0.90] for allele; OR 0.70, 95 % CI [0.57, 0.86] for genotype). In the European subgroup of PCOS, the X/Ala genotype was associated with lower BMI (mean difference [MD] -1.08, 95 % CI [-2.08, -0.09]) and fast insulin levels (MD -19.82, 95 % CI [-34.07, -5.58]). However, this polymorphism did not display an impact on HOMA-IR in PCOS patients. Ala variant would decrease the risk of PCOS and result in lower BMI and fast insulin levels in a European population, but had no impact on HOMA-IR in PCOS patients. Further studies are required to elucidate these associations more clear.

  7. Comparative analysis of the effects of CO2 fractional laser and sonophoresis on human skin penetration with 5-aminolevulinic acid.

    Science.gov (United States)

    Choi, J H; Shin, E J; Jeong, K H; Shin, M K

    2017-08-19

    Successful delivery of a photosensitizer into the skin is an important factor for effective photodynamic therapy (PDT). The effective method to increase drug penetration within short incubation time overcoming skin barrier have been investigated. This study was performed to analyze and compare the effectiveness of ablative fractional laser (FXL) pretreatment and/or sonophoresis for enhancing the penetration of 5-aminolevulinic acid (ALA) into human skin in vivo. Twenty-four identical 1 × 1 cm(2) treatment areas were mapped on the backs of ten healthy male subjects. Each area received FXL pretreatment and/or sonophoresis with different energy settings and ALA incubation times. After treatments, porphyrin fluorescence reflecting the ALA penetration were measured. Application of ablative CO2 FXL pretreatment resulted to higher fluorescence intensities than the non-treatment group. Incubation times were positively correlated with the increments of ALA penetration. However, increasing pulse energy or combining with sonophoresis did not show additional positive effects on ALA penetration. Ablative CO2 FXL pretreatment effectively facilitated ALA penetration in human skin in vivo. Ablative CO2 FXL alone without sonophoresis setting pulse energy of 10 and 20 mJ with more than 60 min of ALA incubation time could be an ideal setting for ALA penetration.

  8. Evaluation of Hydrogel Suppositories for Delivery of 5-Aminolevulinic Acid and Hematoporphyrin Monomethyl Ether to Rectal Tumors

    Directory of Open Access Journals (Sweden)

    Xuying Ye

    2016-10-01

    Full Text Available We evaluated the potential utility of hydrogels for delivery of the photosensitizing agents 5-aminolevulinic acid (ALA and hematoporphyrin monomethyl ether (HMME to rectal tumors. Hydrogel suppositories containing ALA or HMME were administered to the rectal cavity of BALB/c mice bearing subcutaneous tumors of SW837 rectal carcinoma cells. For comparison, ALA and HMME were also administered by three common photosensitizer delivery routes; local administration to the skin and intratumoral or intravenous injection. The concentration of ALA-induced protoporphyrin IX or HMME in the rectal wall, skin, and subcutaneous tumor was measured by fluorescence spectrophotometry, and their distribution in vertical sections of the tumor was measured using a fluorescence spectroscopy system. The concentration of ALA-induced protoporphyrin IX in the rectal wall after local administration of suppositories to the rectal cavity was 9.76-fold (1 h and 5.8-fold (3 h higher than in the skin after cutaneous administration. The maximal depth of ALA penetration in the tumor was ~3–6 mm at 2 h after cutaneous administration. Much lower levels of HMME were observed in the rectal wall after administration as a hydrogel suppository, and the maximal depth of tumor penetration was <2 mm after cutaneous administration. These data show that ALA more readily penetrates the mucosal barrier than the skin. Administration of ALA as an intrarectal hydrogel suppository is thus a potential delivery route for photodynamic therapy of rectal cancer.

  9. Effect of Increasing Doses of Linoleic and α-Linolenic Acids on High-Fructose and High-Fat Diet Induced Metabolic Syndrome in Rats.

    Science.gov (United States)

    Zhang, Jianan; Wang, Ou; Guo, Yingjian; Wang, Tuo; Wang, Siyi; Li, Guopeng; Ji, Baoping; Deng, Qianchun

    2016-02-01

    Doses and ratio of linoleic acid (LA) and α-linolenic acid (ALA) preventing metabolic syndrome (MS) were investigated. SD rats were fed (i) basal diet, (ii) high-fructose and high-fat diet (HFFD), (iii) HFFD with increasing-dose LA (0.75 energy-% ALA + 3, 6, 9, 12, 15, and 30 energy-% LA), and (iv) HFFD with increasing-dose ALA (6 energy-% LA + 0.3, 0.5, 0.75, 1.5, 2.25, and 3.75 energy-% ALA) for 18 weeks. Results showed 6, 12, 15, and 30 energy-% LA significantly ameliorated central obesity, hyperlipidemia, glucose homeostasis, and leptin status; 0.5 and 0.75 energy-% ALA significantly improved insulin sensitivity, adiponectin, and anti-inflammatory status. Moreover, high intakes of ALA (1.5, 2.25, and 3.75 energy-%) presented a pro-oxidant activity. In conclusion, dose instead of ratio determines the prevention of MS. The optimal doses are 6 energy-% LA and 0.75 energy-% ALA; high intakes of ALA may have side effects.

  10. Promotion by 5-Aminolevulinic Acid of Germination of Pakchoi (Brassica campestris ssp. chinensis var. communis Tsen et Lee) Seeds Under Salt Stress

    Institute of Scientific and Technical Information of China (English)

    Liang-Ju WANG; Wei-Bing JIANG; Hui LIU; Wei-Qin LIU; Lang KANG; Xi-Lin HOU

    2005-01-01

    The seed germination and seedling growth of pakchoi (Brassica campestris ssp. chinensis var.communis Tsen et Lee cv. Hanxiao) were not significantly inhibited until the concentration of NaCl was increased to150 mmol/L. Treatment of pakchoi seeds with exogenous 5-aminolevulinic acid (ALA), at concentrations ranging from 0.01 to 10.00 mg/L, promoted seed germination when seeds were stressed by salinity, whereas levulinic acid (LA), an inhibitor of ALA dehydrase, significantly inhibited seed germination and seedling growth, suggesting that metabolism of ALA into porphyrin compounds was necessary for seed germination and seedling growth. Determination of respiratory rate during seed germination showed that ALA increased seed respiration under both normal conditions and salt stress. Furthermore, salt stress decreased levels of endogenous ALA, as well as heme, in etiolated seedlings. More salt-tolerant cultivars of pakchoi contained higher relative levels of endogenous ALA and heme under conditions of salt stress.These results indicate that salt stress may inhibit the biosynthesis of endogenous ALA and then heme,which is necessary for seed germination, and treatment of seeds with exogenous ALA prior to germination may be associated with the biosynthesis of heme.

  11. Evaluation of single nucleotide polymorphisms of Pro12Ala in peroxisome proliferator-activated receptor-γ and Gly308Ala in tumor necrosis factor-α genes in obese Asian Indians: a population-based study.

    Science.gov (United States)

    Bhagat, Namita; Agrawal, Mukta; Luthra, Kalpana; Vikram, Naval K; Misra, Anoop; Gupta, Rajeev

    2010-10-11

    A population-based case control study was performed to determine the associations of Pro12Ala polymorphism in peroxisome proliferator-activated receptor-γ (PPARG) and Gly308Ala polymorphism in tumor necrosis factor-α (TNFA) genes in obese subjects. Of 1,400 eligible subjects, ≧20 years, we recruited only 1,127. For extreme phenotype case-control design, we evaluated 201 subjects with body mass index (BMI) ≧30 kg/m(2) (Group 1) and 143 with BMI Pro12Ala polymorphism in PPARG was found in 15 (7.5%) subjects in Group 1 and 3 (2.1%) subjects in Group 2 (P = 0.028), and heterozygous Gly308Ala polymorphism in TNFA was found in 19 (9.5%) in Group 1 and 7 (4.9%) in Group 2 (P = 0.115). Presence of heterozygous polymorphism in PPARG and TNFA-predicted obesity with univariate odds ratio ([OR], 95% confidence intervals) of 2.25 (1.32-3.84, P = 0.003) and 1.48 (1.10-1.99, P = 0.009) and with multivariate OR 1.74 (1.03-2.93, P = 0.038) and 1.46 (1.05-2.03, P = 0.024), respectively. The addition of dietary and physical activity variables did not result in significant change. Obese Asian Indians have greater prevalence of heterozygous polymorphisms of Pro12Ala in PPARG and Gly308Ala in TNFA genes.

  12. Enzymatic modification of phosphatidylcholine with n-3 PUFA from silkworm oil fatty acids

    Directory of Open Access Journals (Sweden)

    Shanker Kaki, Shiva

    2014-06-01

    Full Text Available α-Linolenic acid (ALA containing phosphatidylcholine (PC was prepared by an enzymatic method employing natural substrates comprising of egg and eri silkworm oil. Eri silkworm oil extracted from eri pupae was saponified to obtain the fatty acid mixture which was further subjected to urea complexation to obtain an ALA rich fraction with a purity of about 93%. Transesterification of PC with the ALA rich fraction with three immobilized lipases namely Lipozyme TL IM, Lipozyme RM IM and lipase from Candida Antarcticaz showed that only the lipase from Candida antarctica was successful for the incorporation of ALA into egg yolk PC. It was found that ALA was incorporated by up to 27% in the sn-1 position of egg PC and the positional distribution analysis of fatty acids in the modified PC showed that the sn-1 position was found to contain about 59% ALA.El ácido α-linolénico (ALA contenido en fosfatidilcolina (PC se preparó mediante un método enzimático empleando sustratos naturales que comprenden huevo y aceite de gusanos de seda. El aceite extraído de las crisálidas de gusanos de seda se saponificó para obtener la mezcla de ácidos grasos que se sometió a complejación con urea para obtener la fracción rica en ALA, con una pureza aproximadamente del 93%. La transesterificación de PC con fracción rica en ALA con tres lipasas inmovilizadas, Lipozyme TL IM, Lipozyme RM IM y lipasa de Candida antárctica, mostró que sólo la lipasa de Candida antarctica tuvo éxito en la incorporación de ALA en PC de yema de huevo. Se encontró que el ALA fue incorporado hasta 27% en la posición sn-1 de PC de huevo y el análisis de la distribución de los ácidos grasos en PC modificado mostró que la posición sn-1 que contenía aproximadamente 59% de ALA.

  13. Dietary α-linolenic acid, linoleic acid, and n-3 long-chain PUFA and risk of ischemic heart disease

    DEFF Research Database (Denmark)

    Vedtofte, Mia Sadowa; Jakobsen, Marianne Uhre; Lauritzen, Lotte

    2011-01-01

    n-3 (omega-3) PUFA has been proposed as having health-promoting effects, primarily in relation to ischemic heart disease (IHD). Whether these benefits can be achieved by both α-linolenic acid (ALA, 18:3n-3) and n-3 long-chain PUFA (LC-PUFA) is debatable.......n-3 (omega-3) PUFA has been proposed as having health-promoting effects, primarily in relation to ischemic heart disease (IHD). Whether these benefits can be achieved by both α-linolenic acid (ALA, 18:3n-3) and n-3 long-chain PUFA (LC-PUFA) is debatable....

  14. Association between the Pro12Ala polymorphism of peroxisome proliferator-activated receptor gamma 2 and inflammatory bowel disease: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Zhi-Feng Zhang

    Full Text Available BACKGROUND: Peroxisome proliferator-activated receptor gamma (PPARγ, a nuclear receptor, has been implicated playing a role in the development of inflammatory bowel disease (IBD. However, previous studies evaluating the association between the PPARγ2 Pro12Ala polymorphism and IBD are inconsistent. We performed a meta-analysis to determine whether the PPARγ2 Pro12Ala mutation was associated with the presence of IBD. METHODS AND FINDINGS: Electronic databases were searched for case-control studies evaluating the association between the Pro12Ala mutation and the presence of IBD. Effects were summarized with the methods recommended by the Cochrane Collaboration. A total of 7 studies including 1002 ulcerative colitis (UC cases, 1090 Crohǹs disease (CD cases and 1983 controls were involved in this meta-analysis. In the overall analysis, no significant association of this polymorphism with UC or CD was found. In the subgroup analyses in different populations, AlaAla genotype seemed to protect the European Caucasian population against the development of CD (Pro vs Ala: OR = 1.135, 95%CI = 0.951-1.354, P = 0.162, Bon = 1.000; ProPro vs ProAla: OR = 1.042, 95%CI = 0.852-1.273, P = 0.690, Bon = 1.000; ProPro vs AlaAla: OR = 2.379, 95%CI = 1.110-5.100, P = 0.026, Bon = 0.156; ProAla vs AlaAla: OR = 2.315, 95%CI = 1.064-5.037, P = 0.034, Bon = 0.204; Pro homozygotes vs Ala positives: OR = 1.094, 95%CI = 0.899-1.330, P = 0.371, Bon = 1.000; Pro positives vs Ala homozygotes: OR = 2.360, 95%CI = 1.103-5.053, P = 0.027, Bon = 0.162; heterozygotes vs all homozygotes: OR = 0.976, 95%CI = 0.799-1.192, P = 0.809, Bon = 1.000. There was no significant association of this polymorphism with UC or CD in the East Asian population and the Turkish population. CONCLUSION: AlaAla genotype may be a protective factor in the European Caucasian population against

  15. Association between the Pro12Ala polymorphism of peroxisome proliferator-activated receptor gamma 2 and inflammatory bowel disease: a meta-analysis.

    Science.gov (United States)

    Zhang, Zhi-Feng; Yang, Ning; Zhao, Gang; Zhu, Lei; Wang, Li-Xia

    2012-01-01

    Peroxisome proliferator-activated receptor gamma (PPARγ), a nuclear receptor, has been implicated playing a role in the development of inflammatory bowel disease (IBD). However, previous studies evaluating the association between the PPARγ2 Pro12Ala polymorphism and IBD are inconsistent. We performed a meta-analysis to determine whether the PPARγ2 Pro12Ala mutation was associated with the presence of IBD. Electronic databases were searched for case-control studies evaluating the association between the Pro12Ala mutation and the presence of IBD. Effects were summarized with the methods recommended by the Cochrane Collaboration. A total of 7 studies including 1002 ulcerative colitis (UC) cases, 1090 Crohǹs disease (CD) cases and 1983 controls were involved in this meta-analysis. In the overall analysis, no significant association of this polymorphism with UC or CD was found. In the subgroup analyses in different populations, AlaAla genotype seemed to protect the European Caucasian population against the development of CD (Pro vs Ala: OR = 1.135, 95%CI = 0.951-1.354, P = 0.162, Bon = 1.000; ProPro vs ProAla: OR = 1.042, 95%CI = 0.852-1.273, P = 0.690, Bon = 1.000; ProPro vs AlaAla: OR = 2.379, 95%CI = 1.110-5.100, P = 0.026, Bon = 0.156; ProAla vs AlaAla: OR = 2.315, 95%CI = 1.064-5.037, P = 0.034, Bon = 0.204; Pro homozygotes vs Ala positives: OR = 1.094, 95%CI = 0.899-1.330, P = 0.371, Bon = 1.000; Pro positives vs Ala homozygotes: OR = 2.360, 95%CI = 1.103-5.053, P = 0.027, Bon = 0.162; heterozygotes vs all homozygotes: OR = 0.976, 95%CI = 0.799-1.192, P = 0.809, Bon = 1.000). There was no significant association of this polymorphism with UC or CD in the East Asian population and the Turkish population. AlaAla genotype may be a protective factor in the European Caucasian population against the development of CD in a recessive way.

  16. [Association of the Pro12Ala and C1431T polymorphism of the PPAR gamma2 gene and their haplotypes with obesity and type 2 diabetes].

    Science.gov (United States)

    Dong, Chun-ping; He, Lan; Li, Jian-ning; Ye, Feng; He, Ming; Wang, Yi

    2008-08-01

    To study the association of the Pro12Ala and C1431T polymorphism of the PPAR gamma2 gene and their haplotypes with obesity and type 2 diabetes in Chinese population. PCR-restriction fragment length polymorphism was used to determine the Pro12Ala and C1431T polymorphisms in 207 patients with type 2 diabetes and 101 non-diabetic control subjects. (1) In non-diabetic control population, the Ala allele frequency was 0.064, the T1431 allele frequency was 0.252. Haplotype analysis showed that the Pro12Ala and C1431T polymorphisms were in linkage disequilibrium (Do=0.63, r(2)=0.074), which constituted three major haplotypes Pro-C, Pro-T and Ala-T. (2) There were no significant differences of the distribution frequencies of the Pro12Ala and C1431T polymorphism and their haplotypes between the type 2 diabetes mellitus group and non-diabetic control group (P > 0.05). (3) The Pro12Ala polymorphism was associated with blood pressure and lipidemia in diabetic patients. The Ala allele significantly decreased the diastolic blood pressure of non-obese diabetic patients (P or = 25 layer was significantly higher than that in the body mass index Pro12Ala and C1431T polymorphisms of the PPAR gamma2 gene might not be a major etiological factor for type 2 diabetes; the C1431T polymorphism was associated with overweight or obesity in diabetic patients.

  17. Double blind randomized clinical trial controlled by placebo with an alpha linoleic acid and prebiotic enriched cookie on risk cardiovascular factor in obese patients Ensayo clínico aletorizado doble ciego controlado con placebo con una galleta enriquecida en ácido alfa linoleico y prebióticos en el patrón de riesgo cardiovascular de pacientes obesos

    OpenAIRE

    D. A. De Luis; B. de la  Fuente; O. Izaola; Conde, R.; Gutiérrez, S.; M.ª Morillo; C. Teba Torres

    2011-01-01

    Introduction: Inulin and FOS are prebiotics with potential benefit in cardiovascular risk factors. Alpha linolenic acid (ALA) is the metabolic precursor of the long chain n-3 fatty acid eicosapentaenoic acid (20: 5n-3), this fatty acid has anti-inflammatory properties. The aim of our study was to evaluate the response of the cardiovascular risk profile in obese patients after inclusion in the diet of an ALA, FOS and inulin enriched-cookie. Material and methods: 36 patients were randomized in ...

  18. Energetics of island formation of AlAs, GaAs, and InAs on Si(100)

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Geunjung; Efimov, Oleg; Yoon, Younggui [Chung-Ang University, Seoul (Korea, Republic of)

    2012-03-15

    We study the energetics of island formation of AlAs, GaAs, and InAs on Si(100)2x1 substrates from first-principles. Si(100)2x1:As is stable under As-rich conditions in all cases. Si(100)2x1:(AlAs) and Si(100)2x1:(GaAs) are stable under Al-rich and Ga-rich conditions, respectively. However, the surface energy of Si(100)2x1:InAs is higher than that of Si(100)2x1:As under In-rich conditions. The energies of thicker epitaxial overlayer films of AlAs, GaAs, and InAs are predicted to be higher than the corresponding energies of these monolayer films.

  19. Alzheimer hastalığında ve depresyonda PPARΓ2-PRO12ALA polimorfizminin rolü

    OpenAIRE

    Özdaş, Şule Beyhan; Akın, Demet; CANKURTARAN, MUSTAFA; Çurgunlu, Aslı

    2012-01-01

    Amaç: Peroksizom proliferatör-aktive reseptör gama (PPAR-γ) adipoz dokunun gelişiminde ve fonksiyonunda önemli bir transkripsiyon faktörüdür. PPARγ genindeki Pro- 12Ala polimorfizmi insülin sensitivitesinde artış ve diabet riskinde azalma ile ilişkili bulunmuştur. Yine PPARγ2-Pro12Ala polimorfizmine sahip yaşlılarda depresyon riskinin azaldığı saptanmıştır. Ayrıca son yıllarda yapılan sınırlı sayıdaki çalışmada PPARγ2-Pro12Ala polimorfizminin Azheimer hastalığı riskinde artışa neden olduğu ve...

  20. Omega-3 polyunsaturated fatty acids and vegetarian diets.

    Science.gov (United States)

    Saunders, Angela V; Davis, Brenda C; Garg, Manohar L

    2013-08-19

    While intakes of the omega-3 fatty acid α-linolenic acid (ALA) are similar in vegetarians and non-vegetarians, intakes of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are low in vegetarians and virtually absent in vegans. Plasma, blood and tissue levels of EPA and DHA are lower in vegetarians than in non-vegetarians, although the clinical significance of this is unknown. Vegetarians do not exhibit clinical signs of DHA deficiency, but further research is required to ascertain whether levels observed in vegetarians are sufficient to support optimal health. ALA is endogenously converted to EPA and DHA, but the process is slow and inefficient and is affected by genetics, sex, age and dietary composition. Vegetarians can take practical steps to optimise conversion of ALA to EPA and DHA, including reducing intake of linoleic acid. There are no official separate recommendations for intake of fatty acids by vegetarians. However, we suggest that vegetarians double the current adequate intake of ALA if no direct sources of EPA and DHA are consumed. Vegetarians with increased needs or reduced conversion ability may receive some advantage from DHA and EPA supplements derived from microalgae. A supplement of 200-300 mg/day of DHA and EPA is suggested for those with increased needs, such as pregnant and lactating women, and those with reduced conversion ability, such as older people or those who have chronic disease (eg, diabetes).

  1. Effect of Proliferator-Activated Receptor-γ Pro12Ala Polymorphism on Colorectal Cancer Risk: A Meta-Analysis.

    Science.gov (United States)

    Wei, Zhijiang; Han, Guoda; Bai, Xiyong

    2015-06-02

    The association between peroxisome proliferators-activated receptor γ (PPARγ) Pro12Ala polymorphism and colorectal cancer (CRC) risk is still controversial. A meta-analysis was performed. We conducted a literature search using PubMed, EMBASE, and Cochran databases. The pooled odds ratio (OR) with 95% confidence intervals (CIs) were calculated. Fixed-effects and random-effects models were used. Dominant model, recessive model, and additive model were used in this meta-analysis. Fifteen studies including 13575 cases and 17085 controls were included in our meta-analysis. Result of this meta-analysis found that PPARγ Pro12Ala polymorphism was significantly associated with a reduced risk of CRC (OR=0.90; 95% CI 0.83-0.98; P=0.01). No significant association was found between PPARγ Pro12Ala polymorphism and CRC risk in Asians (OR=0.80; 95% CI 0.60-1.09; P=0.15). However, PPARγ Pro12Ala polymorphism was significantly associated with a reduced risk of CRC in Caucasians (OR=0.91; 95% CI 0.83-0.99; P=0.03). When stratified analysis was performed by CRC site, no positive association was found between PPARγ Pro12Ala polymorphism and rectal cancer (OR=0.95; 95% CI 0.74-1.22; P=0.71). However, a reduced risk of colon cancer was observed (OR=0.85; 95% CI 0.76-0.94; P=0.002). In summary, this study suggests that PPARγ Pro12Ala polymorphism was a protective factor of CRC.

  2. No association of Pro12Ala polymorphism of PPAR-gamma gene with coronary artery disease in Korean subjects.

    Science.gov (United States)

    Rhee, Eun Jung; Kwon, Chang Hee; Lee, Won Young; Kim, Se Yeon; Jung, Chan Hee; Kim, Byung Jin; Sung, Ki Chul; Kim, Bum Soo; Oh, Ki Won; Kang, Jin Ho; Park, Sung Woo; Kim, Sun Woo; Lee, Man Ho; Park, Jung Roe

    2007-03-01

    Peroxisome proliferator-activated receptor (PPAR)-gamma, a member of the nuclear hormone receptor family, which is involved in the differentiation of adipose tissue, is reported to be associated with the pathogenesis of type 2 diabetes mellitus, insulin resistance and atherosclerosis. Whether the prevalence of coronary artery disease (CAD) is associated with Pro12Ala polymorphism in exon B of PPAR-gamma was investigated in Korean adults. The study was conducted in 267 subjects (158 males, 109 females, mean age 58 years) who underwent coronary angiography because of chest pain. Cardiovascular risk factors, such as blood pressure, body mass index (BMI), fasting blood sugar and serum lipid profiles, were assessed in all subjects, who were divided into 4 groups according to the number of stenosed coronary arteries: normal, 1-vessel, 2-vessel and 3-vessel disease. Genotyping of Pro12Ala polymorphism was done with real-time polymerase chain reaction. Allelic frequency for proline was 0.955 and 0.045 for alanine, which was in Hardy-Weinberg equilibrium (p=0.74). One hundred and seventeen subjects (43.8%) had normal coronary arteries, 88 (33%) had 1-vessel disease, 39 (14.6%) had 2-vessel disease and 23 (8.6%) had 3-vessel disease. When the cardiovascular risk factors were compared among the 4 groups, there were no meaningful differences except for age and FBG levels, which were significant even after adjustment for age and BMI. There were no significant differences in the prevalence or severity of CAD according to the different genotypes of Pro12Ala, and in logistic regression analysis Pro12Ala polymorphism was not a predictor for CAD. There was no significant association between Pro12Ala polymorphism in exon B of PPAR-gamma and prevalence or severity of CAD in Korean adults. Further studies on the correlation between Pro12Ala polymorphism and CAD should be carried out in a larger Korean population in the future.

  3. The PPARγ2 Pro12Ala variant is protective against progression of nephropathy in people with type 2 diabetes.

    Science.gov (United States)

    Lapice, Emanuela; Monticelli, Antonella; Cocozza, Sergio; Pinelli, Michele; Cocozza, Sara; Bruzzese, Dario; Riccardi, Gabriele; Vaccaro, Olga

    2015-03-12

    Cross-sectional studies suggest the association between diabetic nephropathy and the PPARγ2 Pro12Ala polymorphism of the peroxisome proliferator-activated receptor γ2 (PPARγ2). Prospective data are limited to microalbuminuria and no information on renal function is available to date. The present study evaluates the association between the Pro12Ala polymorphism of PPARγ2 and the progression of albuminuria and decay in glomerular filtration rate (GFR) in type 2 diabetes. We studied 256 patients with an average 5-year follow-up. Among others, urinary albumin excretion rate (UAER) was measured on spot sample, GFR was estimated with the CKD-EPI Equation. Baseline UAER and GFR were similar for carriers or non-carriers of the polymorphism. At follow-up no significant changes from baseline were observed for UAER or eGFR in carriers of the Pro12Ala polymorphism whereas a significant increase in UAER [17 (11.3-37.9) versus 24.5 (13.8-49.9) μg/mg, p Pro12Ala polymorphism. Progression of nephropathy - defined according to a combined end point of UAER and eGFR- i.e. doubling of baseline UAER to at least 100 μg/mg, or new onset microalbuminuria, or progression from micro to macroalbuminuria, or 25% reduction of eGFR, or annualized eGFR decline >3 ml/min/year - was significantly less frequent in Ala carriers than non carriers (11.4% vs 35.8%; p Pro12Ala polymorphism is protective against progression of nephropathy and decay of renal function independent of major confounders.

  4. Association of Pro12Ala (rs1801282) variant of PPAR gamma with rheumatoid arthritis in a Pakistani population.

    Science.gov (United States)

    Jalil, Syed Fazal; Ahmed, Iltaf; Gauhar, Zeeshan; Ahmed, Mushtaq; Malik, Javaid M; John, Peter; Bhatti, Attya

    2014-05-01

    Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) belongs to a receptor superfamily of ligand-activated transcription factors, encoded by PPARG gene. Role of PPARγ has been well established in variety of metabolic disorders and in regulation of inflammation. In the present study, we aimed to investigate the association of PPARG (Pro12Ala; rs1801282) in clinically definite Pakistani Rheumatoid Arthritis (RA) patients and matching controls. The genotypes of the Pro12Ala variant in the PPARG were determined in a sample of 300 Pakistanis, including 150 RA cases and 150 controls. The genotyping was performed using Amplification Refractory Mutation System-Polymerase Chain Reaction (ARMS-PCR) method, and the data was analyzed through Graphpad Prism 5 V software. Allele-specific primer set (two forward: PPARG-F1, PPARG-F2 and a common reverse primer: PPARG-R) was used for amplification, and the product was resolved on 2 % agarose gel. The CC (ProPro) genotype has higher frequency in controls than RA cases [75 (50.0 %) vs. 51 (34.0 %)], whereas the CG (ProAla) genotype has relatively same frequencies in both cases and controls [72 (48.0 %) vs. 70 (46.6 %)]. However, significantly higher frequency of GG (AlaAla) genotype was observed in cases [27 (18.0 %) vs. 5 (3.3 %); χ2 18.54; p Pro12Ala (rs1801282), a coding variant in the PPARG gene, is associated with Rheumatoid Arthritis in Pakistanis.

  5. Incorporation of Flaxseed Flour as a Dietary Source for ALA Increases Bone Density and Strength in Post-Partum Female Rats.

    Science.gov (United States)

    Ribeiro, Danielle Cavalcante; Pereira, Aline D'Avila; de Santana, Fernanda Carvalho; Mancini-Filho, Jorge; da Silva, Eduardo Moreira; da Costa, Carlos Alberto Soares; Boaventura, Gilson Teles

    2017-04-01

    In women, bone mass undergoes changes during pregnancy and the postpartum period, which has a risk for subsequent development of osteoporosis. Thus, the present study aims to evaluate the effects of flaxseed flour in femur quality during post-weaning of dam rats. After weaning, the rats were divided into control (C, n = 7) and experimental (F, n = 7) groups treated with a diet containing 25 g of flaxseed flour in the lactating period and 15 g in the maintenance period. After 51 days post-partum, serum hormone, fatty acids composition, bone compartments, computed tomography, and biomechanical analyses were determined. Food intake, length, body mass, hormone analysis, and total bone compartments showed similar results. For biomechanical and computed tomography analysis and fatty acids composition, the F group showed higher maximum force (+12%, p < 0.05), breaking strength (+25%, p < 0.05), rigidity (+17%, p < 0.0001), and femoral head radiodensity (+15%, p < 0.05) and presented lower total polyunsaturated fatty acids (-17%, p < 0.0001) and arachidonic acid (-44%, p < 0.0001) and higher ALA (+695%, p < 0.0001) and EPA (+160%, p < 0.05). Fatty acids composition of flaxseed flour, as well as its protein profile and calcium content, were able to improve the bone quality, which may be associated with lower serum levels of arachidonic acid and higher EPA, showing an anti-inflammatory profile and increased deposition of organic matrix during the post-weaning period, and may result in prevention of future osteoporosis.

  6. Treatment with alpha-lipoic acid reduces asymmetric dimethylarginine in patients with type 2 diabetes mellitus.

    Science.gov (United States)

    Mittermayer, Friedrich; Pleiner, Johannes; Francesconi, Mario; Wolzt, Michael

    2010-01-01

    Elevated asymmetric dimethylarginine (ADMA) concentrations predict cardiovascular events in patients with type 2 diabetes mellitus (T2DM). It has been shown that alpha-lipoic acid (ALA) improves endothelial function and oxidative stress in these patients. The present study investigated if ALA reduces ADMA in patients with T2DM. Plasma concentrations of ADMA, L-arginine and symmetric dimethylarginine (SDMA) were determined in a double-blind, randomized, placebo-controlled study in patients with T2DM. Intravenous ALA (n = 16) or placebo (n = 14) was administered daily for 3 weeks. ALA reduced ADMA while no change was observed with placebo (mean change -0.05 micromol/1[95% CI: -0.01; -0.09] vs. 0.01 micromol/1 [95% CI: -0.05; -0.03]; ANOVA p = 0.031). SDMA and L-arginine were not affected by ALA. In conclusion ALA treatment reduces ADMA in patients with T2DM. Long-term studies need to demonstrate if ALA may cause cardiovascular risk reduction.

  7. The impact of alpha-lipoic acid on amikacin-induced nephrotoxicity.

    Science.gov (United States)

    Asci, Halil; Saygin, Mustafa; Cankara, Fatma Nihan; Bayram, Dilek; Yesilot, Sukriye; Candan, Ibrahim Aydin; Ilhan, Ilter

    2015-02-01

    Amikacin (AK) is an antibacterial drug, but it has remarkable nephrotoxic and ototoxic side effects due to increase in reactive oxygen radicals. This study was established to determine the possible protective effects of alpha-lipoic acid (ALA), a powerful antioxidant, on AK-induced nephrotoxicity. Three different groups of rats (n = 6) were administered saline (control), AK (1.2 g/kg, intraperitoneally), ALA (100 mg/kg, p.o.) and AK combination (ALA one day before the AK for five days). Renal function, oxidative stress markers and histological changes were evaluated at the end of the experiment. Malondialdehyde was increased as an indicator of free radical formation in AK-induced group and decreased with ALA treatment. While catalase activity was increased significantly, superoxide dismutase and glutathione peroxidase activities were not statistically significant increased with ALA treatment. The result showed that AK enhanced levels of urea, creatinine and blood urea nitrogen in serum significantly. Administration of ALA reduced these levels of biochemical markers. Histopathological observations were confirmed by biochemical findings. In conclusion, ALA is suggested to be a potential candidate to ameliorate AK-induced nephrotoxicity.

  8. The effect of iron ion on the specificity of photodynamic therapy with 5-aminolevulinic acid.

    Directory of Open Access Journals (Sweden)

    Maiko Hayashi

    Full Text Available Recently, photodynamic therapy using 5-aminolevulinic acid (ALA-PDT has been widely used in cancer therapy. ALA administration results in tumor-selective accumulation of the photosensitizer protoporphyrin IX (PpIX via the heme biosynthetic pathway. Although ALA-PDT has selectivity for tumor cells, PpIX is accumulated into cultured normal cells to a small extent, causing side effects. The mechanism of tumor-selective PpIX accumulation is not well understood. The purpose of the present study was to identify the mechanism of tumor-selective PpIX accumulation after ALA administration. We focused on mitochondrial labile iron ion, which is the substrate for metabolism of PpIX to heme. We investigated differences in iron metabolism between tumor cells and normal cells and found that the amount of mitochondrial labile iron ion in cancer was lower than that in normal cells. This finding could be because of the lower expression of mitoferrins, which are the mitochondrial iron transporters. Accordingly, we added sodium ferrous citrate (SFC with ALA as a source of iron. As a result, we observed the accumulation of PpIX only in tumor cells, and only these cells showed sensitivity to ALA-PDT. Taken together, these results suggest that the uptake abilities of iron ion into mitochondria play a key role in tumor-selective PpIX accumulation. Using SFC as a source of iron might thus increase the specificity of ALA-PDT effects.

  9. The effect of iron ion on the specificity of photodynamic therapy with 5-aminolevulinic acid.

    Science.gov (United States)

    Hayashi, Maiko; Fukuhara, Hideo; Inoue, Keiji; Shuin, Taro; Hagiya, Yuichiro; Nakajima, Motowo; Tanaka, Tohru; Ogura, Shun-ichiro

    2015-01-01

    Recently, photodynamic therapy using 5-aminolevulinic acid (ALA-PDT) has been widely used in cancer therapy. ALA administration results in tumor-selective accumulation of the photosensitizer protoporphyrin IX (PpIX) via the heme biosynthetic pathway. Although ALA-PDT has selectivity for tumor cells, PpIX is accumulated into cultured normal cells to a small extent, causing side effects. The mechanism of tumor-selective PpIX accumulation is not well understood. The purpose of the present study was to identify the mechanism of tumor-selective PpIX accumulation after ALA administration. We focused on mitochondrial labile iron ion, which is the substrate for metabolism of PpIX to heme. We investigated differences in iron metabolism between tumor cells and normal cells and found that the amount of mitochondrial labile iron ion in cancer was lower than that in normal cells. This finding could be because of the lower expression of mitoferrins, which are the mitochondrial iron transporters. Accordingly, we added sodium ferrous citrate (SFC) with ALA as a source of iron. As a result, we observed the accumulation of PpIX only in tumor cells, and only these cells showed sensitivity to ALA-PDT. Taken together, these results suggest that the uptake abilities of iron ion into mitochondria play a key role in tumor-selective PpIX accumulation. Using SFC as a source of iron might thus increase the specificity of ALA-PDT effects.

  10. Protective effects of alpha lipoic acid on radiation-induced salivary gland injury in rats

    Science.gov (United States)

    Kim, Jin Hyun; Kim, Kyung Mi; Jung, Myeong Hee; Jung, Jung Hwa; Kang, Ki Mun; Jeong, Bae Kwon; Kim, Jin Pyeong; Park, Jung Je; Woo, Seung Hoon

    2016-01-01

    Purpose Radiation therapy is a treatment for patients with head and neck (HN) cancer. However, radiation exposure to the HN often induces salivary gland (SG) dysfunction. We investigated the effect of α-lipoic acid (ALA) on radiation-induced SG injury in rats. Results ALA preserved acinoductal integrity and acinar cell secretary function following irradiation. These results are related to the mechanisms by which ALA inhibits oxidative stress by inhibiting gp91 mRNA and 8-OHdG expression and apoptosis of acinar cells and ductal cells by inactivating MAPKs in the early period and expression of inflammation-related factors including NF-κB, IκB-α, and TGF-β1 and fibrosis in late irradiated SG. ALA effects began in the acute phase and persisted for at least 56 days after irradiation. Materials and Methods Rats were assigned to followings: control, ALA only (100 mg/kg, i.p.), irradiated, and ALA administered 24 h and 30 min prior to irradiation. The neck area including the SG was evenly irradiated with 2 Gy per minute (total dose, 18 Gy) using a photon 6-MV linear accelerator. Rats were killed at 4, 7, 28, and 56 days after radiation. Conclusions Our results show that ALA could be used to ameliorate radiation-induced SG injury in patients with HN cancer. PMID:27072584

  11. Growth performance, intestinal morphology, and meat quality in relation to alpha-lipoic acid associated with vitamin C and E in broiler chickens under tropical conditions

    Directory of Open Access Journals (Sweden)

    Jaehong Yoo

    2016-03-01

    Full Text Available ABSTRACT This study was conducted to examine the effect of alpha-lipoic acid with vitamin C and E on growth performance, intestinal morphology, and meat quality in broiler chickens under tropical conditions. A total of 288 one-day-old male ROSS 308 chicks (40±0.1 g were used in a completely randomized design and allotted to one of six dietary treatments to form sixe replicates per treatment (eight birds per cage. The six dietary treatments were: a corn-soybean meal-based diet (NC; no antimicrobial compounds added with 8 ppm alpha-lipoic acid (ALA; 150 ppm vitamin C and 75 ppm vitamin E (E-75; E-75 plus ALA (E-75-ALA; 150 ppm vitamin C and 50 ppm vitamin E (E-50 plus ALA (E-50-ALA; and 150 ppm vitamin C and 25 ppm vitamin E (E-25 plus ALA (E-25-ALA. All dietary treatments were continuously provided in liquid form, dissolved in water. Birds were housed in a battery cage (n = 36, and were offered dietary treatments on an ad libitum basis. The ambient temperature was maintained at 32±1 ºC for the first three weeks and reduced gradually to 28 ºC by the end of the experiment (day 35 to induce moderate tropical condition. One bird per pen (n = 6, and another bird per pen (n = 6 were euthanized via cervical dislocation to obtain terminal ileum to measure villus height and crypt depth at day 21, and to harvest breast meat and drumsticks to evaluate meat quality traits at day 35, respectively. Dietary treatment E-75-ALA improved body weight and average daily gain compared with birds fed other dietary treatments from day 1 to day 35. Birds fed dietary treatment E-75-ALA and E-50-ALA had higher villus height than those fed the other dietary treatments at day 21. Dietary treatments E-75-ALA and E-50-ALA reduced thiobarbituric acid reactive substance (TBARS in drumsticks compared with other dietary treatments, but only treatment E-75-ALA decreased TBARS in breast meat at day 35. Liquid form of antioxidant compounds such as E-75-ALA can improve growth

  12. A gas chromatography-mass spectrometry method for the determination of delta-aminolevulinic acid in plant leaves.

    Science.gov (United States)

    Hijaz, Faraj; Killiny, Nabil

    2016-05-20

    Delta-aminolevulinic (δ-ALA) acid is an important intermediate for tetrapyrroles biosynthesis and it has recently received great attention in plant physiology and human toxicology. However, the colorimetric method which is the most common method for determination of δ-ALA is time consuming and is not specific. In this study, a method for determination of δ-ALA in plant tissues was developed based on the trimethylsilyl (TMS) derivative of the pyrrole formed from the reaction of δ-ALA with ethyl acetoacetate via Knorr condensation. The δ-ALA in the HCl extract was reacted with ethyl acetoacetate to form a pyrrole. Then, the pyrrole compound was extracted using ethyl acetate and the solvent was evaporated to dryness. The dried sample was derivatized to its TMS ester and analyzed using GC-MS. The concentration of δ-ALA in citrus leaves incubated with levulinic acid was also determined by the conventional colorimetric method. The linear range was 10-200ppm in the full scan mode and 0.1-20ppm in the selected ion monitoring (SIM). The limit of detection was 6ppm in the full scan and 0.05ppm in SIM mode, representing a four-fold increase in sensitivity compared to the colorimetric method. The GC-MS method developed in this study is simple, accurate, sensitive, and could also be used to measure δ-ALA in other biological samples.

  13. Optimization of Biomass and 5-Aminolevulinic Acid Production by Rhodobacter sphaeroides ATCC17023 via Response Surface Methodology.

    Science.gov (United States)

    Liu, Shuli; Zhang, Guangming; Li, Jianzheng; Li, Xiangkun; Zhang, Jie

    2016-06-01

    Microbial 5-aminolevulinic acid (ALA) produced from wastewater is considered as potential renewable energy. However, many hurdles are needed to be overcome such as the regulation of key influencing factors on ALA yield. Biomass and ALA production by Rhodobacter sphaeroides was optimized using response surface methodology. The culturing medium was artificial volatile fatty acids wastewater. Three additives were optimized, namely succinate and glycine that are precursors of ALA biosynthesis, and D-glucose that is an inhibitor of ALA dehydratase. The optimal conditions were achieved by analyzing the response surface plots. Statistical analysis showed that succinate at 8.56 mmol/L, glycine at 5.06 mmol/L, and D-glucose at 7.82 mmol/L were the best conditions. Under these optimal conditions, the highest biomass production and ALA yield of 3.55 g/L and 5.49 mg/g-biomass were achieved. Subsequent verification experiments at optimal values had the maximum biomass production of 3.41 ± 0.002 g/L and ALA yield of 5.78 ± 0.08 mg/g-biomass.

  14. The effect of linoleic acid on the whole body synthesis rates of polyunsaturated fatty acids from α-linolenic acid and linoleic acid in free-living rats.

    Science.gov (United States)

    Domenichiello, Anthony F; Kitson, Alex P; Chen, Chuck T; Trépanier, Marc-Olivier; Stavro, P Mark; Bazinet, Richard P

    2016-04-01

    Docosahexaenoic acid (DHA) is thought to be important for brain function. The main dietary source of DHA is fish, however, DHA can also be synthesized from precursor omega-3 polyunsaturated fatty acids (n-3 PUFA), the most abundantly consumed being α-linolenic acid (ALA). The enzymes required to synthesize DHA from ALA are also used to synthesize longer chain omega-6 (n-6) PUFA from linoleic acid (LNA). The large increase in LNA consumption that has occurred over the last century has led to concern that LNA and other n-6 PUFA outcompete n-3 PUFA for enzymes involved in DHA synthesis, and therefore, decrease overall DHA synthesis. To assess this, rats were fed diets containing LNA at 53 (high LNA diet), 11 (medium LNA diet) or 1.5% (low LNA diet) of the fatty acids with ALA being constant across all diets (approximately 4% of the fatty acids). Rats were maintained on these diets from weaning for 8 weeks, at which point they were subjected to a steady-state infusion of labeled ALA and LNA to measure DHA and arachidonic acid (ARA) synthesis rates. DHA and ARA synthesis rates were generally highest in rats fed the medium and high LNA diets, while the plasma half-life of DHA was longer in rats fed the low LNA diet. Therefore, increasing dietary LNA, in rats, did not impair DHA synthesis; however, low dietary LNA led to a decrease in DHA synthesis with tissue concentrations of DHA possibly being maintained by a longer DHA half-life.

  15. Relationship between PPARγ Pro12Ala gene polymorphism and type 2 diabetic nephropathy risk in Asian population: results from a meta-analysis.

    Science.gov (United States)

    Liu, Guohui; Zhou, Tian-Biao; Jiang, Zongpei; Zheng, Dongwen; Yuan, Fei; Li, Yi; Hu, Haoqiang; Chen, Zijun

    2014-04-01

    The relationship between peroxisome proliferator-activated receptor gamma (PPARγ) Pro12Ala gene polymorphism and type 2 diabetic nephropathy (T2DN) risk in Asians is still unclear. This study was performed to evaluate if there was an association between the PPARγ Pro12Ala gene polymorphism and T2DN risk in Asians using meta-analysis. The relevant reports were searched and identified from PubMed, Cochrane Library and CBM-disc (China Biological Medicine Database) on 1 October 2013, and eligible studies were included and synthesized. Ten reports were recruited into this meta-analysis for the association of the PPARγ Pro12Ala gene polymorphism with T2DN risk. The Pro12Ala gene polymorphism in the Asian population was shown to be not associated with T2DN risk (Ala/Ala: OR = 0.67, 95% CI: 0.22-2.00, p = 0.47; Pro/Pro: OR = 1.77, 95% CI: 0.82-1.65, p = 0.39; Ala allele: OR = 0.74, 95% CI: 0.47-1.16, p = 0.19). In the sensitivity analysis according to Hardy-Weinberg equilibrium (HWE), the control source from hospital, the control source from population, the genotyping methods using PCR-RFLP, the genotyping methods using Taqman, sample size of case (≥ 100), the association of the PPARγ Pro12Ala gene polymorphism with T2DN risk was also not found. Interestingly, in the sensitivity analysis according to sample size of case (Pro12Ala gene polymorphism was not associated with T2DN risk in Asians. However, Ala allele was associated with T2DN risk when the sample size of case was less than 100. Nonetheless, additional studies are required to firmly establish a correlation between the PPARγ Pro12Ala gene polymorphism and T2DN risk in Asians.

  16. Impact of the Pro12Ala polymorphism of the PPARγ2 gene on diabetes and obesity in a highly consanguineous population.

    Science.gov (United States)

    Bener, Abdulbari; Zirie, M; Al-Hamaq, Aoaa; Nawaz, Z; Samson, N; Mohammad, R

    2015-01-01

    The peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor subfamily of transcription factors. It has been reported that they play important roles in obesity and the development of type 2 diabetes mellitus (T2DM). This case-control study was carried out among 764 Qatari patients with diabetes and 764 healthy subjects above 20 years of age at Primary Healthcare Clinics (PHCs) from January 2011 to December 2012. Face-to-face interviews were based on a questionnaire that included variables such as age, sex, sociodemographic status, body mass index (BMI) and other clinical parameters. The Pro12Ala in the PPARγ2 gene was detected on the LightCycler using two specific probes. Univariate and multivariate statistical analysis were performed. The study revealed that in the diabetes group, Pro/(10.2% vs 9.4%; P = 0.606) and Ala/Ala (1.4% vs 0.9%; P = 0.343) were higher than in controls, whereas Pro/Pro (88.4% vs 89.7%;P = 0.413) was lower in diabetes patients, but no significant difference was observed among the genotype groups. In obese patients with diabetes, Pro/Pro (89% vs 89.9%;P = 0.792) and Pro/Ala (8.9% vs 10.1%;P = 0.671) were lower than in obese healthy subjects. No homozygous Ala/Ala was found in obese healthy subjects, whereas 6 Ala/Ala homozygotes were in obese diabetes group. But in diabetes group, obese patients had higher homozygous of Pro/Pro (89.3% vs 87.8%;P = 0.523) and Ala/Ala (1.8% vs 1.2%;P = 0.771) compared to non-obese patients. The current study did not reveal an association between the Pro12Ala polymorphism of the PPAR γ2 gene and type 2 diabetes (T2D) in Qatari's population.

  17. Aktivitas Manusia dan Distribusi Banteng (Bos Javanicus D’alton 1832 di Taman Nasional Alas Purwo

    Directory of Open Access Journals (Sweden)

    Muhammad Ali Imron

    2013-01-01

    Full Text Available Human Activities and Distribution of Banteng (Bos Javanicus D’alton 1832 in Alas Purwo National Park This study aims to comprehend whether human activities contribute to the presence of banteng (Bos sundaicus d’Alton 1836 in the Alas Purwo National Park (APNP. We laid continuous strip line transects from centre of human activities to the direction of core area of APNP. Three locations were selected: Sadengan grazing area, Giri Salaka Hinduism praying area, and Kutorejo village; representing low to high human disturbance respectively. We collected both direct and indirect presence of banteng as well as human activities within 20 metre strip lines with 10 metre width. Data were compiled each 100 metres and analyzed with means comparison to observe difference among locations. Correlation analyses were used to assess the relation between distance from centre of human activities, human activities and banteng presence. Regression analysis was used when  significant correlations found. Our non parametric test showed that human disturbances are significantly different among sites (Kruskal Wallis Test; df 2 = 6.220, p< 0.05. In similar tendency but different manner, it is showed that the different levels of human disturbance conveyed significant difference in number of banteng’s tracks (Kruskal Wallis Test; df 2 = 18.888, p< 0.05. The distance from centre of human activities is negatively related to number of human tracks (Spearman rho; r2= -0.307 N= 64, p<0.05* and also to number of banteng’s tracks (Spearman rho, r2= -0.728 N= 30, p<0.05**. The regression analysis showed that number of human tracks explained 18.6% of total variation on number of Banteng’s tracks, while distance from centre of human activities explained 59%.

  18. Aktivitas Manusia dan Distribusi Banteng (Bos Javanicus D’alton 1832 di Taman Nasional Alas Purwo

    Directory of Open Access Journals (Sweden)

    Muhammad Ali Imron

    2013-01-01

    Full Text Available Human Activities and Distribution of Banteng (Bos Javanicus D’alton 1832 in Alas Purwo National Park This study aims to comprehend whether human activities contribute to the presence of banteng (Bos sundaicus d’Alton 1836 in the Alas Purwo National Park (APNP. We laid continuous strip line transects from centre of human activities to the direction of core area of APNP. Three locations were selected: Sadengan grazing area, Giri Salaka Hinduism praying area, and Kutorejo village; representing low to high human disturbance respectively. We collected both direct and indirect presence of banteng as well as human activities within 20 metre strip lines with 10 metre width. Data were compiled each 100 metres and analyzed with means comparison to observe difference among locations. Correlation analyses were used to assess the relation between distance from centre of human activities, human activities and banteng presence. Regression analysis was used when  significant correlations found. Our non parametric test showed that human disturbances are significantly different among sites (Kruskal Wallis Test; df 2 = 6.220, p< 0.05. In similar tendency but different manner, it is showed that the different levels of human disturbance conveyed significant difference in number of banteng’s tracks (Kruskal Wallis Test; df 2 = 18.888, p< 0.05. The distance from centre of human activities is negatively related to number of human tracks (Spearman rho; r2= -0.307 N= 64, p<0.05* and also to number of banteng’s tracks (Spearman rho, r2= -0.728 N= 30, p<0.05**. The regression analysis showed that number of human tracks explained 18.6% of total variation on number of Banteng’s tracks, while distance from centre of human activities explained 59%.

  19. Dietary Docosahexaenoic Acid and trans-10, cis-12-Conjugated Linoleic Acid Differentially Alter Oxylipin Profiles in Mouse Periuterine Adipose Tissue.

    Science.gov (United States)

    Adkins, Yuriko; Belda, Benjamin J; Pedersen, Theresa L; Fedor, Dawn M; Mackey, Bruce E; Newman, John W; Kelley, Darshan S

    2017-05-01

    Diets containing high n-3 polyunsaturated fatty acids (PUFA) decrease inflammation and the incidence of chronic diseases including cardiovascular disease and nonalcoholic fatty liver disease while trans-fatty acids (TFA) intake increases the incidence of these conditions. Some health benefits of n-3 PUFA are mediated through the impact of their oxygenated metabolites, i.e. oxylipins. The TFA, trans-10, cis-12-conjugated linoleic acid (CLA; 18:2n-6) is associated with adipose tissue (AT) inflammation, oxidative stress, and wasting. We examined the impact of a 4-week feeding of 0, 0.5, and 1.5% docosahexaenoic acid (DHA; 22:6n-3) in the presence and absence of 0.5% CLA on AT oxylipin profiles in female C57BL/6N mice. Esterified oxylipins in AT derived from linoleic acid (LNA), alpha-linolenic acid (ALA), arachidonic acid (ARA), eicosapentaenoic acid (EPA), DHA, and putative from CLA were quantified. CLA containing diets reduced AT mass by ~62%. Compared with the control diet, the DHA diet elevated concentrations of EPA-and DHA-derived alcohols and epoxides and LNA-derived alcohols, reduced ARA-derived alcohols, ketones, epoxides, and 6-keto-prostaglandin (PG) F1α (P < 0.05), and had mixed effects on ALA-derived alcohols. Dietary CLA lowered EPA-, DHA-, and ALA-derived epoxides, ARA-derived ketones and epoxides, and ALA-derived alcohols. While dietary CLA induced variable effects in EPA-, DHA-, and LNA-derived alcohols and LNA-derived ketones, it elevated ARA-derived alcohols and PGF1α, PGF2α, and F2-isoprostanes. DHA counteracted CLA-induced effects in 67, 57, 43, and 29% of total DHA-, ARA-, EPA-, and ALA-derived oxylipins, respectively. Thus, CLA elevated proinflammatory oxylipins while DHA increased anti-inflammatory oxylipins and diminished concentration of CLA-induced pro-inflammatory oxylipins in AT.

  20. Dietary intake of α-linolenic acid and risk of age-related macular degeneration.

    Science.gov (United States)

    Wu, Juan; Cho, Eunyoung; Giovannucci, Edward L; Rosner, Bernard A; Sastry, Srinivas M; Schaumberg, Debra A; Willett, Walter C

    2017-06-01

    Background: The relation between α-linolenic acid (ALA), a plant-derived omega-3 (n-3) fatty acid, and age-related macular degeneration (AMD) is unclear. European researchers reported that ≤40% of ALA can be present as trans forms.Objective: We aimed to evaluate the associations between intake of ALA and intermediate and advanced AMD.Design: Seventy-five thousand eight hundred eighty-nine women from the Nurses' Health Study and 38,961 men from Health Professionals Follow-Up Study were followed up from 1984 to 2012 and from 1986 to 2010, respectively. We assessed dietary intake by a validated food-frequency questionnaire at baseline and every 4 y thereafter. One thousand five hundred eighty-nine incident intermediate and 1356 advanced AMD cases (primarily neovascular AMD) were confirmed by medical record review.Results: The multivariable-adjusted HR for intermediate AMD comparing ALA intake at the top quintile to the bottom quintile was 1.28 (95% CI: 1.05, 1.56; P-trend = 0.01) in the analyses combining 2 cohorts. The HR in each cohort was in the positive direction but reached statistical significance only in the women. However, the positive association was apparent only in the pre-2002 era in each cohort and not afterward (P-time interaction = 0.003). ALA intake was not associated with advanced AMD in either time period. Using gas-liquid chromatography, we identified both cis ALA (mean ± SD: 0.13% ± 0.04%) and trans ALA isomers (0.05% ± 0.01%) in 395 erythrocyte samples collected in 1989-1990. In stepwise regression models, mayonnaise was the leading predictor of erythrocyte concentrations of cis ALA and one isomer of trans ALA. We also found trans ALA in mayonnaise samples.Conclusions: A high intake of ALA was associated with an increased risk of intermediate AMD before 2002 but not afterward. The period before 2002 coincides with the same time period when trans ALA was found in food and participants' blood; this finding deserves further study. © 2017

  1. Danos ao DNA promovidos por ácido 5-aminolevulínico: possível associação com o desenvolvimento de carcinoma hepatocelular em portadores de porfiria aguda intermitente DNA damage induced by 5-aminolevulinic acid: a possible association with the development of hepatocellular carcinoma in acute intermittent porphyria patients

    Directory of Open Access Journals (Sweden)

    Janice Onuki

    2002-07-01

    Full Text Available 5-Aminolevulinic acid (ALA is a heme precursor accumulated in acute intermittent porphyria (AIP, which might be associated with hepatocellular carcinoma (HCC in symptomatic patients. Under metal catalyzed oxidation, ALA and its cyclic dimerization product, 3,6-dihydropyrazine-2,5-dipropanoic acid, produce reactive oxygen species that damage plasmid and calf thymus DNA bases, increase the steady state level of 8-oxo-7,8-dihydro-2´-deoxyguanosine in liver DNA and promote mitochondrial DNA damage. The final product of ALA, 4,5-dioxovaleric acid (DOVA, is able to alkylate guanine moieties, producing adducts. ALA and DOVA are mutagenic in bacteria. This review shows an up-to-date literature data that reinforce the hypothesis that the DNA damage induced by ALA may be associated with the development of HCC in AIP patients.

  2. Constitutive expression of RyhB regulates the heme biosynthesis pathway and increases the 5-aminolevulinic acid accumulation in Escherichia coli.

    Science.gov (United States)

    Li, Fangfang; Wang, Yang; Gong, Kai; Wang, Qian; Liang, Quanfeng; Qi, Qingsheng

    2014-01-01

    In the current study, the small RNA ryhB, which regulates the metabolism of iron in Escherichia coli, was constitutively expressed in engineered E. coli DALA. The resulting strain E. coli DALRA produced 16% more 5-aminolevulinic acid (ALA) than the parent strain E. coli DALA in batch fermentation. Meanwhile, we found that addition of iron in the medium increased heme formation and reduced ALA yield, whereas the presence of iron chelator in the medium decreased heme concentration and increased the ALA production efficiency (ALA yield per OD600). The qRT-PCR analysis showed that the mRNA levels of hemB and hemH were also decreased as well as the known RyhB target genes of acnAB, sdhAB, fumA, and cydAB in E. coli DALRA. These results indicated that small RNA can be used as a tool for regulating ALA accumulation in E. coli.

  3. Evaluation of single nucleotide polymorphisms of Pro12Ala in peroxisome proliferator-activated receptor-γ and Gly308Ala in tumor necrosis factor-α genes in obese Asian Indians: a population-based study

    Directory of Open Access Journals (Sweden)

    Gupta R

    2010-10-01

    Full Text Available Namita Bhagat1,2, Mukta Agrawal1, Kalpana Luthra3, Naval K Vikram4, Anoop Misra4, Rajeev Gupta21Department of Home Science, University of Rajasthan, Jaipur, Rajasthan, India; 2Department of Medicine, Fortis Escorts Hospital, Jaipur, Rajasthan, India; 3Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India; 4Department of Medicine, All India Institute of Medical Sciences, New Delhi, IndiaBackground: A population-based case control study was performed to determine the associations of Pro12Ala polymorphism in peroxisome proliferator-activated receptor-γ (PPARG and Gly308Ala polymorphism in tumor necrosis factor-α (TNFA genes in obese subjects.Patients and methods: Of 1,400 eligible subjects, ≥20 years, we recruited only 1,127. For extreme phenotype case-control design, we evaluated 201 subjects with body mass index (BMI ≥30 kg/m2 (Group 1 and 143 with BMI <20 kg/m2 (Group 2. Clinical, anthropometric, biochemical, and nutritional details and polymorphisms were estimated.Results: In Group 1, the dietary intake of calories and fats was higher, physical activity was lower, and prevalence of truncal obesity, hypertension, high total cholesterol, low high-density lipoprotein cholesterol, and diabetes was greater than in Group 2. There were no homozygous polymorphisms of either gene. Heterozygous Pro12Ala polymorphism in PPARG was found in 15 (7.5% subjects in Group 1 and 3 (2.1% subjects in Group 2 (P = 0.028, and heterozygous Gly308Ala polymorphism in TNFA was found in 19 (9.5% in Group 1 and 7 (4.9% in Group 2 (P = 0.115. Presence of heterozygous polymorphism in PPARG and TNFA-predicted obesity with univariate odds ratio ([OR], 95% confidence intervals of 2.25 (1.32–3.84, P = 0.003 and 1.48 (1.10–1.99, P = 0.009 and with multivariate OR 1.74 (1.03–2.93, P = 0.038 and 1.46 (1.05–2.03, P = 0.024, respectively. The addition of dietary and physical activity variables did not result in significant change

  4. Metabolic Response of Pakchoi Leaves to Amino Acid Nitrogen

    Institute of Scientific and Technical Information of China (English)

    WANG Xiao-li; YU Wen-juan; ZHOU Qian; HAN Rui-feng; HUANG Dan-feng

    2014-01-01

    Different nitrogen (N) forms may cause changes in the metabolic profiles of plants. However, few studies have been conducted on the effects of amino acid-N on plant metabolic proifles. The main objective of this study was to identify primary metabolites associated with amino acid-N (Gly, Gln and Ala) through metabolic proifle analysis using gas chromatography-mass spectrometry (GC-MS). Plants of pakchoi (Brassica campestris L. ssp. chinensis L.), Huawang and Wuyueman cultivars, were grown with different nitrogen forms (i.e., Gly, Gln, Ala, NO3--N, and N starvation) applied under sterile hydroponic conditions. The fresh weight and plant N accumulation of Huawang were greater than those of Wuyueman, which indicates that the former exhibited better N-use efficiency than the latter. The physiological performances of the applied N forms were generally in the order of NO3--N>Gln>Gly>Ala. The metabolic analysis of leaf polar extracts revealed 30 amino acid N-responsive metabolites in the two pakchoi cultivars, mainly consisting of sugars, amino acids, and organic acids. Changes in the carbon metabolism of pakchoi leaves under amino acid treatments occurred via the accumulation of fructose, glucose, xylose, and arabinose. Disruption of amino acid metabolism resulted in accumulation of endogenous Gly in Gly treatment, Pro in Ala treatment, and Asn in three amino acid (Gly, Gln and Ala) treatments. By contrast, the levels of endogenous Gln and Leu decreased. However, this reduction varied among cultivars and amino acid types. Amino acid-N supply also affected the citric acid cycle, namely, the second stage of respiration, where leaves in Gly, Gln and Ala treatments contained low levels of malic, citric and succinic acids compared with leaves in NO3--N treatments. No signiifcant difference in the metabolic responses was observed between the two cultivars which differed in their capability to use N. The response of primary metabolites in pakchoi leaves to amino acid-N supply

  5. Alpha-Linolenic Acid: An Omega-3 Fatty Acid with Neuroprotective Properties—Ready for Use in the Stroke Clinic?

    Directory of Open Access Journals (Sweden)

    Nicolas Blondeau

    2015-01-01

    Full Text Available Alpha-linolenic acid (ALA is plant-based essential omega-3 polyunsaturated fatty acids that must be obtained through the diet. This could explain in part why the severe deficiency in omega-3 intake pointed by numerous epidemiologic studies may increase the brain’s vulnerability representing an important risk factor in the development and/or deterioration of certain cardio- and neuropathologies. The roles of ALA in neurological disorders remain unclear, especially in stroke that is a leading cause of death. We and others have identified ALA as a potential nutraceutical to protect the brain from stroke, characterized by its pleiotropic effects in neuroprotection, vasodilation of brain arteries, and neuroplasticity. This review highlights how chronic administration of ALA protects against rodent models of hypoxic-ischemic injury and exerts an anti-depressant-like activity, effects that likely involve multiple mechanisms in brain, and may be applied in stroke prevention. One major effect may be through an increase in mature brain-derived neurotrophic factor (BDNF, a widely expressed protein in brain that plays critical roles in neuronal maintenance, and learning and memory. Understanding the precise roles of ALA in neurological disorders will provide the underpinnings for the development of new therapies for patients and families who could be devastated by these disorders.

  6. Effects of n-3 fatty acids on cognitive decline: A randomized double-blind, placebo-controlled trial in stable myocardial infarction patients

    NARCIS (Netherlands)

    Geleijnse, J.M.; Giltay, E.J.; Kromhout, D.

    2012-01-01

    Background Epidemiological studies suggest a protective effect of n-3 fatty acids derived from fish (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) against cognitive decline. For a-linolenic acid (ALA) obtained from vegetable sources, the effect on cognitive decline is unknown. We exami

  7. Alleviation of salt-induced oxidative damage by 5-aminolevulinic acid in wheat seedlings

    Science.gov (United States)

    Genişel, Mucip; Erdal, Serkan

    2016-04-01

    The aim of this study was to elucidate how 5-aminolevulinic acid (ALA), the precursor of chlorophyll compounds, affects the defence mechanisms of wheat seedlings induced by salt stress. To determine the possible stimulative effects of ALA against salinity, 11-day old wheat seedlings were sprayed with ALA at two different concentrations (10 and 20 mg.l-1) and then stressed by exposure to salt (150 mM NaCl). The salt stress led to significant changes in the antioxidant activity. While guaiacol peroxidase activity decreased, the activities of superoxide dismutase, catalase, and ascorbate peroxidase markedly increased under salt stress. Compared to the salt stress alone, the application of ALA beforehand further increased the activity of these enzymes. This study is the first time the effects of ALA have been monitored with regard to protein content and the isoenzyme profiles of the antioxidant enzymes. Although the salt stress reduced both the soluble protein content and protein band intensities, pre-treating with ALA significantly mitigated these stress-induced reductions. The data for the isoenzyme profiles of the antioxidant enzymes paralleled that of the ALA-induced increases in antioxidant activity. As a consequence of the high antioxidant activity in the seedlings pre-treated with ALA, the stress-induced elevations in the reactive oxygen species, superoxide anion, and hydrogen peroxide contents and lipid peroxidation levels were markedly diminished. Taken together, this data demonstrated that pre-treating with ALA confers resistance to salt stress by modulating the protein synthesis and antioxidant activity in wheat seedlings.

  8. The Arabidopsis P4-ATPase ALA3 localizes to the golgi and requires a beta-subunit to function in lipid translocation and secretory vesicle formation.

    Science.gov (United States)

    Poulsen, Lisbeth Rosager; López-Marqués, Rosa Laura; McDowell, Stephen C; Okkeri, Juha; Licht, Dirk; Schulz, Alexander; Pomorski, Thomas; Harper, Jeffrey F; Palmgren, Michael Gjedde

    2008-03-01

    Vesicle budding in eukaryotes depends on the activity of lipid translocases (P(4)-ATPases) that have been implicated in generating lipid asymmetry between the two leaflets of the membrane and in inducing membrane curvature. We show that Aminophospholipid ATPase3 (ALA3), a member of the P(4)-ATPase subfamily in Arabidopsis thaliana, localizes to the Golgi apparatus and that mutations of ALA3 result in impaired growth of roots and shoots. The growth defect is accompanied by failure of the root cap to release border cells involved in the secretion of molecules required for efficient root interaction with the environment, and ala3 mutants are devoid of the characteristic trans-Golgi proliferation of slime vesicles containing polysaccharides and enzymes for secretion. In yeast complementation experiments, ALA3 function requires interaction with members of a novel family of plant membrane-bound proteins, ALIS1 to ALIS5 (for ALA-Interacting Subunit), and in this host ALA3 and ALIS1 show strong affinity for each other. In planta, ALIS1, like ALA3, localizes to Golgi-like structures and is expressed in root peripheral columella cells. We propose that the ALIS1 protein is a beta-subunit of ALA3 and that this protein complex forms an important part of the Golgi machinery required for secretory processes during plant development.

  9. Application of evolutionary algorithm methods to polypeptide folding: comparison with experimental results for unsolvated Ac-(Ala-Gly-Gly)5-LysH+

    DEFF Research Database (Denmark)

    Damsbo, Martin; Kinnear, Brian S; Hartings, Matthew R

    2004-01-01

    two complementary representations of the structures and uses the CHARMM force field for evaluating the energies. The method is applied to unsolvated Met-enkephalin and Ac-(Ala-Gly-Gly)(5)-Lys(+)H(+). Unsolvated Ac-(Ala-Gly-Gly)(5)-Lys(+)H(+) has been the object of recent experimental studies using ion...

  10. Congenital sideroblastic anemia—a new family with identification of K156E mutation of ALAS2 gene and literature review%一个遗性铁粒幼细胞贫血家系ALAS2基因K156E突变报道并文献复习

    Institute of Scientific and Technical Information of China (English)

    崔蕊; 徐泽锋; 秦铁军; 张悦; 肖志坚

    2014-01-01

    hemoglobin 16.5 pg),and iron overload (serum iron 44.7 μmol/L,serum ferritin 3 123 μg/L and transferrin saturation 0.84).A mutation 466 A>G predicting a Lysl56Glu amino acid change was identified in the proband and 3 females from the family.The proband was hemizygous for this mutation and presented with microcytic anemia and iron overload,while all 3 heterozygous females showed marginally increased redcell distribution width without any other symptoms.The proband treated with 300 mg of pyridoxine per day and iron chelation therapy with deferoxamine for one year had durable hematopoietic improvements,including increase in hemoglobin to 98 g/L and decrease in serum ferritin to 1 580 μg/L.Conclusion This was a novel K156E substitution in ALAS2 gene identified in a 3-generation pedigree in China.Our findings emphasized the importance of gene based diagnosis of CSA,and CSA patient with ALAS2 mutation responded to pyridoxine treatment.

  11. Isolation of L-3-phenyllactyl-Phe-Lys-Ala-NH2 (Antho-KAamide), a novel neuropeptide from sea anemones

    DEFF Research Database (Denmark)

    Nothacker, H P; Rinehart, K L; Grimmelikhuijzen, C J

    1991-01-01

    We have isolated and sequenced the neuropeptide L-3-phenyllactyl-Phe-Lys-Ala-NH2 from the sea anemone Anthopleura elegantissima. This neuropeptide (named Antho-KAamide) has the unusual N-terminal L-3-phenyllactyl blocking group which has recently also been discovered in 2 other neuropeptides from...

  12. Tunnustati parimaid üliõpilasteadlasi / Elsa Suuster, Marit Alas, Annely Aleksejev ; küsitlenud Vilma Rauniste

    Index Scriptorium Estoniae

    Putku, Elsa, 1984-

    2009-01-01

    Vestlus üliõpilaste teadustööde riikliku konkursi kolme laureaadiga, kelle uurimistöö oli tehtud Saare maakonnas. Nendeks on Elsa Suuster ja Annely Aleksejev Eesti Maaülikoolist ning Marit Alas Tallinna Ülikoolist

  13. Evaluation of the Relationship between Upper and lower Occlusal Plane with Ala-Tragus and Retromolar Pad

    Directory of Open Access Journals (Sweden)

    Bahrani F.

    2011-04-01

    Full Text Available Statement of Problem: Orientation of the occlusal plan in complete denture prostheses therapies plays an important role, leading to appropriate esthetics, stability and mastication.Purpose: The aim of the present study was to define the best soft tissue index, by which the location and inclination of the occlusal plane in complete dentures could be established.Materials and Method: This cross-sectional study consisted of 200 individuals (76 male, 124 female, with the mean age of 26.05 (SD±4.39. In order to determine the relationship between maxillary occlusal plane and ala-tragus line, fox plane and J plane were used. The relationships between maxillary occlusal plane and ALT1 (ala-superior border of tragus, ALT2 (ala-mid-tragus and ALT3 (ala-inferior border of tragus were evaluated. In the lower jaw, the occlusal plane was evaluated with the line between the upper and middle parts (ret1 and that between the middle and lower part of retromolar pad (ret2. Data were analyzed by Chi-square test.Results: Evaluation of the difference between the number and percentage using Chi–square test ( p ret2. Conclusion: Superior one third of the tragus and the upper and middle one third of the retromolar pad are suggested as a reference points for determining the posterior part of the occlusal plane in comparison with the middle and lower one third of the tragus and middle and inferior one third of the retromolarpad.

  14. Tunnustati parimaid üliõpilasteadlasi / Elsa Suuster, Marit Alas, Annely Aleksejev ; küsitlenud Vilma Rauniste

    Index Scriptorium Estoniae

    Putku, Elsa, 1984-

    2009-01-01

    Vestlus üliõpilaste teadustööde riikliku konkursi kolme laureaadiga, kelle uurimistöö oli tehtud Saare maakonnas. Nendeks on Elsa Suuster ja Annely Aleksejev Eesti Maaülikoolist ning Marit Alas Tallinna Ülikoolist

  15. Peroxisome proliferator-activated receptor-gamma (PPARgamma) Pro12Ala polymorphism and risk for pediatric obesity

    NARCIS (Netherlands)

    Dedoussis, George V; Vidra, Nikoleta; Butler, Johannah; Papoutsakis, Constantina; Yannakoulia, Mary; Hirschhorn, Joel N; Lyon, Helen N; Vidra, Nikoletta

    2009-01-01

    BACKGROUND: Variation in the peroxisome-proliferator-activated receptor gamma (PPARgamma) gene has been reported to alter the risk for adiposity in adults. METHODS: We investigated the gender related association between the Pro12Ala variant (rs1801282) in obesity and insulin resistance traits in 794

  16. Suppression of a mitotic mutant by tRNA-Ala anticodon mutations that produce a dominant defect in late mitosis.

    Science.gov (United States)

    Kimata, Yuu; Yanagida, Mitsuhiro

    2004-05-01

    Cold-sensitive dominant mutants scn1 and scn2 of Schizosaccharomyces pombe were isolated by their ability to suppress temperature-sensitive cut9-665 defective in an essential subunit (human Apc6/budding yeast Cdc16 ortholog) of anaphase promoting complex/cyclosome (APC/C). APC/C mutants were defective in metaphase/anaphase transition, whereas single scn mutants showed the delay in anaphase spindle elongation at 20 degrees C. The scn mutants lost viability because of chromosome missegregation, and were sensitive to a tubulin poison. To understand the scn phenotypes, mutant genes were identified. Surprisingly, scn1 and scn2 have the same substitution in the anticodon of two different tRNA-Ala (UGC) genes. UGC was altered to UGU so that the binding of the tRNA-Ala to the ACA Thr codon in mRNA became possible. As cut9-665 contained an Ala535Thr substitution, wild-type Cut9 protein was probably produced in scn mutants. Indeed, plasmid carrying tRNA-Ala (UGU) conferred cold-sensitivity to wild-type and suppressed cut9-665 in a dominant fashion. The previously identified scn1(+) (renamed as scn3(+)) turned out to be a high copy suppressor for scn1 and scn2. These are the first tRNA mutants that cause a mitotic defect.

  17. Comparison of the crystal structure and function to wild-type and His25Ala mutant human heme oxygenase-1.

    Science.gov (United States)

    Zhou, Wen-Pu; Zhong, Wen-Wei; Zhang, Xue-Hong; Ding, Jian-Ping; Zhang, Zi-Li; Xia, Zhen-Wei

    2009-03-01

    Human heme oxygenase-1 (hHO-1) is a rate-limiting enzyme in heme metabolism. It regulates serum bilirubin level. Site-directed mutagenesis studies indicate that the proximal residue histidine 25 (His25) plays a key role in hHO-1 activity. A highly purified hHO-1 His25Ala mutant was generated and crystallized with a new expression system. The crystal structure of the mutant was determined by X-ray diffraction technology and molecular replacement at the resolution of 2.8 A, and the model of hHO-1 His25Ala mutant was refined. The final crystallographic and free R factors were 0.245 and 0.283, respectively. The standard bond length deviation was 0.007 A, and the standard bond angle deviation was 1.3 degrees . The mutation of His25 to Ala led to an empty pocket underneath the ferric ion in the heme, leading to loss of binding iron ligand. Although this did not cause an overall structural change, the enzymatic activity of the mutant hHO-1 was reduced by 90%. By supplementing imidazole, the HO-1 activity was restored approximately 90% to its normal level. These data suggest that Ala25 remains unchanged in the structure compared to His25, but the important catalytic function of hHO-1 is lost. Thus, it appears that His25 is a crucial residue for proper hHO-1 catalysis.

  18. Professor Trechsel : Eesti e-valimiste aeg on liiga lühike / Alexander H. Trechsel ; interv. Askur Alas

    Index Scriptorium Estoniae

    Trechsel, Alexander H.

    2006-01-01

    e-valimistele pühendatud rahvusvahelisel konverentsil esinenud Genfi ülikooli e-demokraatia keskuse juhataja, poliitikateaduste professor Eesti e-valimistest ja e-valimiste tulevikust. Vt. samas: Askur Alas. Konverentsil analüüsiti e-valimiste kogemusi; Eestis hääletas digitaalselt 9317 valijat

  19. Professor Trechsel : Eesti e-valimiste aeg on liiga lühike / Alexander H. Trechsel ; interv. Askur Alas

    Index Scriptorium Estoniae

    Trechsel, Alexander H.

    2006-01-01

    e-valimistele pühendatud rahvusvahelisel konverentsil esinenud Genfi ülikooli e-demokraatia keskuse juhataja, poliitikateaduste professor Eesti e-valimistest ja e-valimiste tulevikust. Vt. samas: Askur Alas. Konverentsil analüüsiti e-valimiste kogemusi; Eestis hääletas digitaalselt 9317 valijat

  20. Studies of the common DIO2 Thr92Ala polymorphism and metabolic phenotypes in 7342 Danish white subjects

    DEFF Research Database (Denmark)

    Grarup, Niels; Andersen, Mette K; Andreasen, Camilla H

    2007-01-01

    The type 2 iodothyronine deiodinase (D2) catalyzes the conversion of T(4) to the active form of thyroid hormone, which is a critical regulator of thermogenesis and glucose metabolism. A Thr92Ala polymorphism in the gene encoding D2 (DIO2) has been reported to associate with insulin resistance....

  1. Met144Ala mutation of the copper-containing nitrite reductase from Alcaligenes xylosoxidans reverses the intramolecular electron transfer

    DEFF Research Database (Denmark)

    Farver, Ole; Eady, Robert R; Sawers, Gary

    2004-01-01

    Pulse radiolysis has been employed to investigate the intramolecular electron transfer (ET) between the type 1 (T1) and type 2 (T2) copper sites in the Met144Ala Alcaligenes xylosoxidans nitrite reductase (AxCuNiR) mutant. This mutation increases the reduction potential of the T1 copper center...

  2. Association between PPARγ2 Pro12Ala polymorphism and myocardial infarction and obesity in Han Chinese in Hohhot, China.

    Science.gov (United States)

    Wang, L P; Zhao, L R; Cui, H W; Yan, M R; Yang, L; Su, X L

    2012-08-29

    Activation of the peroxisome proliferator-activated receptor g (PPARg) improves insulin sensitivity and inhibits atherosclerosis. Whether PPARg2 Pro12Ala polymorphism affects myocardial infarction is not clearly understood. We investigated a possible association of PPARg2 Pro12Ala polymorphism with obesity and myocardial infarction in Han Chinese in Hohhot, Inner Mongolia, China. We included 121 subjects with myocardial infarction and 137 healthy controls in our study. Triglycerides, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol were measured. The following information was recorded for each subject: age, gender, body height, body weight, systolic blood pressure, and diastolic blood pressure; the body mass index was calculated. PCR-RFLP was used to examine Pro12Ala polymorphism. There were significant differences in clinical characteristics between myocardial infarction patients and healthy controls, except for diastolic blood pressure and triglycerides. The PP, PA/AA genotype frequencies were 88.4 and 11.6% in myocardial infarction patients and 95.6 and 4.4% in controls, respectively (P = 0.031). Individuals with the A allele had a significantly higher risk of myocardial infarction. The A allele was not an independent risk factor for obesity. We conclude that PPARg2 Pro12Ala polymorphisms are associated with increased risk for myocardial infarction in Han Chinese in Hohhot.

  3. Genotyping of peroxisome proliferator-activated receptor gamma (PPAR-γ) polymorphism (Pro12Ala) in Iranian population.

    Science.gov (United States)

    Namvaran, Fatemeh; Rahimi-Moghaddam, Parvaneh; Azarpira, Negar

    2011-03-01

    The peroxisome proliferator-activated receptor-γ (PPAR-γ) is a nuclear hormone receptor. It is predominantly expressed in adipose tissue and as a receptor for thiazolidinediones, it has drawn attentions towards itself as a key molecule to trigger pathways involving in some diseases such as cancers, type 2 diabetes, inflammations and osteoporosis. A proline changed to alanine in codon 12 of PPAR-γ gene (Pro12Ala) has been known to be responsible for decreased risk of type 2 diabetes. The aim of the present study is to investigate the frequency of Pro12Ala polymorphism in PPAR-γ in healthy Iranian population to compare with other populations. Understanding this polymorphism may help us in better diagnosis, prevention, and therapeutic approaches toward a better management of diseases such as type 2 diabetes and osteoporosis. 128 healthy volunteers were enrolled in this study. To determine single nucleotide polymorphisms (SNPs), we did real time polymerase chain reaction (RT-PCR), using TaqMan allelic discrimination assays. Genotype frequencies for PPAR-γ gene Pro12Ala (rs1801282) polymorphism were 0.86 for CC, 0.14 for CG, 0.00 for GG while allelic frequencies were 0.93 and 0.0.07 for C and G, respectively. There are statistical differences between the distribution of the PPAR-γ-2 Pro12Ala polymorphism in other populations and Iranian population.

  4. Peroxisome proliferator-activated receptor-gamma (PPARgamma) Pro12Ala polymorphism and risk for pediatric obesity

    NARCIS (Netherlands)

    Dedoussis, George V; Vidra, Nikoleta; Butler, Johannah; Papoutsakis, Constantina; Yannakoulia, Mary; Hirschhorn, Joel N; Lyon, Helen N; Vidra, Nikoletta

    BACKGROUND: Variation in the peroxisome-proliferator-activated receptor gamma (PPARgamma) gene has been reported to alter the risk for adiposity in adults. METHODS: We investigated the gender related association between the Pro12Ala variant (rs1801282) in obesity and insulin resistance traits in 794

  5. Association between the PPARγ Pro12Ala polymorphism and risk of gestational diabetes mellitus: a meta-analysis.

    Science.gov (United States)

    Shuai, H L; Lin, X Z; Chen, D L; Li, P; Luo, X

    2016-11-03

    The relationship between the Pro12Ala polymorphism of PPARγ and the risk of gestational diabetes mellitus remains unresolved. Here, we attempted to resolve this inconsistency. Case-control studies pertaining to the effect of the Pro12Ala polymorphism in the PPARγ protein and risk of gestational diabetes mellitus were extracted from the HuGE, PubMed, Web of Science, CNKI, and SinoMed databases after an extensive literature search. The studies were statistically analyzed using STATA (v.12.0) software. Twelve case-control studies composed of 2968 GDM cases and 5576 controls that fulfilled the inclusion criteria were included in this meta-analysis. We identified no significant relation between the Pro12Ala polymorphism of PPAR-γ and risk of GDM, when analyzed by the allele [G vs C: odds ratio (OR) = 0.85; 95% confidence interval (CI): 0.71-1.01] and dominant (CG+GG vs CC: OR = 0.86; 95% CI: 0.72-1.03) models. Subgroup analysis by ethnicity revealed that East Asian and Middle Eastern females expressing the A allele showed reduced susceptibility to GDM. Additionally, we observed significant differences between the East Asian, Middle Eastern, and Caucasian females (P = 0.008) with respect to GDM susceptibility. The results of this meta-analysis indicated the influence of ethnicity in determining GDM susceptibility, in the presence of a Pro12Ala polymorphism in PPARγ.

  6. Gemini surfactants from natural amino acids.

    Science.gov (United States)

    Pérez, Lourdes; Pinazo, Aurora; Pons, Ramon; Infante, Mrosa

    2014-03-01

    In this review, we report the most important contributions in the structure, synthesis, physicochemical (surface adsorption, aggregation and phase behaviour) and biological properties (toxicity, antimicrobial activity and biodegradation) of Gemini natural amino acid-based surfactants, and some potential applications, with an emphasis on the use of these surfactants as non-viral delivery system agents. Gemini surfactants derived from basic (Arg, Lys), neutral (Ser, Ala, Sar), acid (Asp) and sulphur containing amino acids (Cys) as polar head groups, and Geminis with amino acids/peptides in the spacer chain are reviewed.

  7. Good coupling performance of PyBOP in the solid-phase synthesis of tetrapeptide, OH-Pro-Leu-Ala-Ileu-NH2

    Science.gov (United States)

    Maharani, R.; Ammatillah, N.; Muhammad, G.; Hidayat, A. T.; Zainuddin, A.; Al-Anshori, J.; Subroto, T.

    2017-05-01

    PyBOP (benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate) was found as a good coupling reagent in the solid-phase synthesis of a tetrapeptide, OH-Pro-Leu-Ala-Ile-NH21. The peptide was chosen as the target of synthesis due to its bioactivity as an antibacterial agent. The synthesis was carried out on solid support, 2-chlorotrityl chloride resin with Fmoc strategy. Proline was selected as the first amino acid to be attached on the resin that was followed by the attachment of leucine, alanine and isoleucine. In the synthesis, Fmoc deprotection step was undertaken by taking advantage of 20% piperidine in DMF and coupling reaction was done by the addition of amino acid and PyBOP in a mixture of dichloromethane and DMF (1:1) and in the presence of basic DIPEA. The analytical RP-HPLC of the final product showed a single peak at 22.0 minutes (20-90% of acetonitrile in water with 0.1% of TFA during 30 minutes), indicating that each coupling could give a good coupling performance that resulted in a pure product. The desired product showed the correct molecular weight with m/z 413.3 [M+H]+ and 435.3 [M+Na].

  8. Gas-saturated solution process to obtain microcomposite particles of alpha lipoic acid/hydrogenated colza oil in supercritical carbon dioxide.

    Science.gov (United States)

    Mishima, Kenji; Honjo, Masatoshi; Sharmin, Tanjina; Ito, Shota; Kawakami, Ryo; Kato, Takafumi; Misumi, Makoto; Suetsugu, Tadashi; Orii, Hideaki; Kawano, Hiroyuki; Irie, Keiichi; Sano, Kazunori; Mishima, Kenichi; Harada, Takunori; Ouchi, Mikio

    2016-09-01

    Alpha lipoic acid (ALA), an active substance in anti-aging products and dietary supplements, need to be masked with an edible polymer to obscure its unpleasant taste. However, the high viscosity of the ALA molecules prevents them from forming microcomposites with masking materials even in supercritical carbon dioxide (scCO2). Therefore, the purpose of this study was to investigate and develop a novel production method for microcomposite particles for ALA in hydrogenated colza oil (HCO). Microcomposite particles of ALA/HCO were prepared by using a novel gas-saturated solution (PGSS) process in which the solid-dispersion method is used along with stepwise temperature control (PGSS-STC). Its high viscosity prevents the formation of microcomposites in the conventional PGSS process even under strong agitation. Here, we disperse the solid particles of ALA and HCO in scCO2 at low temperatures and change the temperature stepwise in order to mix the melted ALA and HCO in scCO2. As a result, a homogeneous dispersion of the droplets of ALA in melted HCO saturated with CO2 is obtained at high temperatures. After the rapid expansion of the saturated solution through a nozzle, microcomposite particles of ALA/HCO several micrometers in diameter are obtained.

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

    Science.gov (United States)

    Mahmoud, Y I; Hegazy, H G

    2016-01-01

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

  10. Selective Production of 9R-Hydroxy-10E,12Z,15Z-Octadecatrienoic Acid from α-Linolenic Acid in Perilla Seed Oil Hydrolyzate by a Lipoxygenase from Nostoc Sp. SAG 25.82.

    Science.gov (United States)

    Kim, Kyoung-Rok; An, Jung-Ung; Lee, Seon-Hwa; Oh, Deok-Kun

    2015-01-01

    Hydroxy fatty acids (HFAs) derived from omega-3 polyunsaturated fatty acids have been known as versatile bioactive molecules. However, its practical production from omega-3 or omega-3 rich oil has not been well established. In the present study, the stereo-selective enzymatic production of 9R-hydroxy-10E,12Z,15Z-octadecatrienoic acid (9R-HOTE) from α-linolenic acid (ALA) in perilla seed oil (PO) hydrolyzate was achieved using purified recombinant 9R-lipoxygenase (9R-LOX) from Nostoc sp. SAG 25.82. The specific activity of the enzyme followed the order linoleic acid (LA) > ALA > γ-linolenic acid (GLA). A total of 75% fatty acids (ALA and LA) were used as a substrate for 9R-LOX from commercial PO by hydrolysis of Candida rugosa lipase. The optimal reaction conditions for the production of 9R-HOTE from ALA using 9R-LOX were pH 8.5, 15°C, 5% (v/v) acetone, 0.2% (w/v) Tween 80, 40 g/L ALA, and 1 g/L enzyme. Under these conditions, 9R-LOX produced 37.6 g/L 9R-HOTE from 40 g/L ALA for 1 h, with a conversion yield of 94% and a productivity of 37.6 g/L/h; and the enzyme produced 34 g/L 9R-HOTE from 40 g/L ALA in PO hydrolyzate for 1 h, with a conversion yields of 85% and a productivity of 34 g/L/h. The enzyme also converted 9R-hydroxy-10E,12Z-octadecadienoic acid (9R-HODE) from 40 g/L LA for 1.0 h, with a conversion yield of 95% and a productivity of 38.4 g/L. This is the highest productivity of HFA from both ALA and ALA-rich vegetable oil using LOX ever reported. Therefore, our result suggests an efficient method for the production of 9R-HFAs from LA and ALA in vegetable oil using recombinant LOX in biotechnology.

  11. Loss of the Arabidopsis thaliana P4-ATPase ALA3 Reduces Adaptability to Temperature Stresses and Impairs Vegetative, Pollen, and Ovule Development

    DEFF Research Database (Denmark)

    McDowell, Stephen C.; Lopez Marques, Rosa Laura; Poulsen, Lisbeth Rosager

    2013-01-01

    , a P4-ATPase associated with the trans-Golgi network (ALA3) was previously reported to be important for vegetative growth and reproductive success. Here we show that multiple phenotypes for ala3 knockouts are sensitive to growth conditions. For example, ala3 rosette size was observed to be dependent...... upon both temperature and soil, and varied between 40% and 80% that of wild-type under different conditions. We also demonstrate that ala3 mutants have reduced fecundity resulting from a combination of decreased ovule production and pollen tube growth defects. In-vitro pollen tube growth assays showed...... that ala3 pollen germinated ~2 h slower than wild-type and had approximately 2-fold reductions in both maximal growth rate and overall length. In genetic crosses under conditions of hot days and cold nights, pollen fitness was reduced by at least 90-fold; from ~18% transmission efficiency (unstressed...

  12. Impact of the PPAR-gamma2 Pro12Ala polymorphism and ACE inhibitor therapy on new-onset microalbuminuria in type 2 diabetes: evidence from BENEDICT.

    Science.gov (United States)

    De Cosmo, Salvatore; Motterlini, Nicola; Prudente, Sabrina; Pellegrini, Fabio; Trevisan, Roberto; Bossi, Antonio; Remuzzi, Giuseppe; Trischitta, Vincenzo; Ruggenenti, Piero

    2009-12-01

    Cross-sectional studies found less microalbuminuria in type 2 diabetic patients with the Ala12 allele of the peroxisome proliferator-activated receptor-gamma2 (PPAR-gamma2) Pro12Ala polymorphism. We prospectively evaluated the association between Pro12Ala polymorphism (rs1801282) and new-onset microalbuminuria. Pro12Ala polymorphism was genotyped by TaqMan-based assay in genomic DNA of 1,119 consenting patients from BErgamo NEphrologic DIabetic Complications Trial (BENEDICT)-a prospective, randomized trial evaluating ACE inhibition effect on new-onset microalbuminuria (albuminuria 20-200 microg/min in at least two of three consecutive overnight urine collections in two consecutive visits) in hypertensive type 2 diabetes with albuminuria Pro12Ala polymorphism may help identifying patients at risk who may benefit the most from early renoprotective therapy.

  13. Obesity and Pro12Ala Polymorphism of Peroxisome Proliferator-Activated Receptor-Gamma Gene in Healthy Adults: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Mansoori, Anahita; Amini, Maryam; Kolahdooz, Fariba; Seyedrezazadeh, Ensiyeh

    2015-01-01

    The aim of this systematic review was to evaluate the relationship between obesity and peroxisome proliferator-activated receptor-gamma (PPARx03B3;) Pro12Ala polymorphism in healthy adults. Weighted mean differences (WMDs) of body mass index (BMI) were calculated for different inheritance models and subgroups. Fifty-six studies were eligible for inclusion in the meta-analysis. The result shows that the Ala allele of this polymorphism was associated with increased WMD in mean BMI (WMD = 0.29, 95% CI 0.10-0.48, p = 0.003). The Ala carriers were associated with increased WMD in mean BMI values in both genders and in the Caucasian subgroup. The associations were seen among people with higher levels of BMI (BMI ≥35). The Ala allele of the PPARx03B3; Pro12Ala polymorphism in healthy adults was associated with increased BMI under a dominant model of inheritance. © 2015 S. Karger AG, Basel.

  14. Acute intermittent porphyria presenting as progressive muscular atrophy in a young black man.

    Science.gov (United States)

    Albertyn, C H; Sonderup, M; Bryer, A; Corrigall, A; Meissner, P; Heckmann, J M

    2014-04-01

    Acute intermittent porphyria, the most common porphyria affecting the nervous system, typically presents with neurovisceral crises followed by a motor neuropathy. We describe a 23-year-old black South African man presenting with a progressive stuttering, lower motor neuron syndrome developing over months. He had not experienced pain or neuropsychiatric symptoms. One year after symptom onset he was bed-bound with a flaccid quadriparesis. There was marked amyotrophy, but without fasciculations. Sensation was intact apart from a hypo-aesthetic patch over the thigh. Electrophysiological investigations showed an active motor axonopathy. Urinary porphyrins, delta-aminolaevulinic acid and porphobilinogen were elevated. Mutation analysis revealed the c445C>T (R149X) mutation in the porphobilinogen deaminase gene. The patient responded dramatically to haem arginate and could walk with assistance 2 weeks later. We identified the first molecularly confirmed acute intermittent porphyria in a black South African. The clinical presentation mimicked a progressive lower motor neuron syndrome.

  15. Is it time to reassess alpha lipoic acid and niacinamide therapy in schizophrenia?

    Science.gov (United States)

    Seybolt, Sheila E J

    2010-12-01

    As sulfur containing thiols, alpha lipoic acid (ALA) and its reduced form dihydrolipoic acid (DHLA) are powerful antioxidants and free radical scavengers capable of performing many of the same functions as glutathione (GSH). ALA supplementation may help protect mitochondria from oxidative stress, a possible mechanism contributing to certain forms of brain diseases called schizophrenia. Shortly before the advent of antipsychotic medications, two small studies found ALA relieved psychiatric symptoms in schizophrenia. More recently, animal studies have shown ALA augmentation improves mitochondrial function. At pharmaceutical levels, niacinamide helps preserve mitochondrial membrane integrity and acts as an antioxidant. ALA is a precursor for lipoamide, an essential mitochondrial coenzyme and niacinamide is a component of niacinamide adenine dinucleotide (NAD). NADH, the reduced form of NAD, is involved in the reduction of ALA to DHLA within the mitochondria. This is relevant to contemporary research because DHLA increases GSH and low GSH levels contribute to mitochondrial dysfunction and oxidative stress which have been implicated in the pathophysiology of schizophrenia.

  16. In Vivo Curative and Protective Potential of Orally Administered 5-Aminolevulinic Acid plus Ferrous Ion against Malaria

    Science.gov (United States)

    Suzuki, Shigeo; Hikosaka, Kenji; Balogun, Emmanuel O.; Komatsuya, Keisuke; Niikura, Mamoru; Kobayashi, Fumie; Takahashi, Kiwamu; Tanaka, Tohru; Nakajima, Motowo

    2015-01-01

    5-Aminolevulinic acid (ALA) is a naturally occurring amino acid present in diverse organisms and a precursor of heme biosynthesis. ALA is commercially available as a component of cosmetics, dietary supplements, and pharmaceuticals for cancer diagnosis and therapy. Recent reports demonstrated that the combination of ALA and ferrous ion (Fe2+) inhibits the in vitro growth of the human malaria parasite Plasmodium falciparum. To further explore the potential application of ALA and ferrous ion as a combined antimalarial drug for treatment of human malaria, we conducted an in vivo efficacy evaluation. Female C57BL/6J mice were infected with the lethal strain of rodent malaria parasite Plasmodium yoelii 17XL and orally administered ALA plus sodium ferrous citrate (ALA/SFC) as a once-daily treatment. Parasitemia was monitored in the infected mice, and elimination of the parasites was confirmed using diagnostic PCR. Treatment of P. yoelii 17XL-infected mice with ALA/SFC provided curative efficacy in 60% of the mice treated with ALA/SFC at 600/300 mg/kg of body weight; no mice survived when treated with vehicle alone. Interestingly, the cured mice were protected from homologous rechallenge, even when reinfection was attempted more than 230 days after the initial recovery, indicating long-lasting resistance to reinfection with the same parasite. Moreover, parasite-specific antibodies against reported vaccine candidate antigens were found and persisted in the sera of the cured mice. These findings provide clear evidence that ALA/SFC is effective in an experimental animal model of malaria and may facilitate the development of a new class of antimalarial drug. PMID:26324278

  17. Impact of an AlAs window layer upon the optical properties of Al x Ga1-x As photodiodes

    Science.gov (United States)

    Kang, T.; Chen, X. J.; Johnson, E. B.; Christian, J. F.; Lee, K.; Hammig, M. D.

    2016-05-01

    Recently developed advanced scintillators, which have the ability to distinguish gamma-ray interaction events from those that accompany neutron impact, require improved quantum efficiency in the blue to near UV region of the spectrum. We utilize GaAs/Al0.8Ga0.2As photodiode elements as components in a wide band-gap solid-state photomultiplier as a lower-cost, lower logistical burden, and higher quantum efficiency replacement for the photomultiplier tube. An AlAs window layer is employed as a means to increase the diode’s optical performance. Relative to structures absent the window layer, simulations and measurements demonstrate that the AlAs layer produces a spatial coincidence between regions of large drift fields with regions of high photon absorption. In addition to the AlAs layer, secondary ion mass spectrometry measurements show that an unexpected high degree of inter-diffusion of GaAs and AlAs quenches the photon-detection efficiency, a decrease that can be avoided by its post-growth removal. With the AlAs layer, the peak external quantum efficiency of 49% is achieved at 450 nm with 10 V reverse bias, which does not fully deplete the device. Simulations show that full depletion can result in efficiencies exceeding 90%. In order to enhance the optical response, a simple anti-reflective coating layer is designed using the existing passivation layer components that successfully minimizes the reflection at the wavelength range of interest (300 nm-500 nm).

  18. Fibrinogen Aα Thr312Ala polymorphism specifically contributes to chronic thromboembolic pulmonary hypertension by increasing fibrin resistance.

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    Ji-Feng Li

    Full Text Available BACKGROUND: Polymorphisms are associated with chronic thromboembolic pulmonary hypertension (CTEPH and pulmonary thromboembolism (PTE, but no polymorphism specific to CTEPH but not PTE has yet been reported. Fibrin resistance is associated with CTEPH, but the mechanism has not been elucidated. METHODS: Polymorphisms were analyzed in 101 CTEPH subjects, 102 PTE subjects and 108 healthy controls by Massarray or restriction fragment length polymorphism (RFLP. Plasmin-mediated cleavage of fibrin was characterized in 69 subjects (29 with CTEPH, 21 with PTE and 19 controls. RESULTS: Genotype frequencies and allele frequencies of fibrinogen Aα Thr312Ala were significantly higher in CTEPH subjects than in controls and PTE subjects, while there was no difference between PTE subjects and controls. The odd ratio (OR 2.037 and 95% confidence interval (95% CI, 1.262-3.289 showed that Thr312Ala polymorphism was a risk factor for CTEPH but not PTE. Fibrin from CTEPH subjects was more resistant to lysis than that from PTE subjects and controls. Fibrin resistance was significantly different between Aα Thr312Ala (A/G genotypes within CTEPH subjects, and the fibrin with GG genotype was more resistant than that with AA and AG genotype. CONCLUSIONS: Fibrinogen Aα Thr312Ala (A/G polymorphism was associated with CTEPH, but not PTE, suggesting that the fibrinogen Aα Thr312Ala polymorphism may act as a potential biomarker in identifying CTEPH from PTE. GG genotype polymorphism contributes to CTEPH through increasing fibrin resistance, implying that PTE subjects with fibrinogen Aα GG genotype may need long-term anticoagulation therapy.

  19. Correlation between PPARg2 gene Pro12Ala polymorphism and cerebral infarction in an Inner Mongolian Han Chinese population.

    Science.gov (United States)

    Li, X; Zhang, B L; Zhang, X G; Su, X L

    2016-06-20

    The variant of PPAR-g2 has been shown to promote the increase of carotid IMT in patients suffering from cerebral infarction and the Pro12Ala polymorphism in the peroxisome proliferator-activated receptorg2 (PPARg2) gene may be associated with cerebral infarction. However, due to the different genetic background, race, and regional variations of cerebral infarction patient, the results of investigations into this subject differ. The aim of this study was to investigate this polymorphism in relation to cerebral infarction among the Inner Mongolian Han Chinese population. A total of 574 Han Chinese individuals from Inner Mongolian were selected randomly, including 302 patients with cerebral infarction and 272 healthy controls. Polymerase chain reaction-restriction fragment length polymorphism was used to determine genotypes of the PPARg2 Pro12Ala variant and results were confirmed by direct sequencing. Genotype frequencies were found to be 90.7 and 91.9% for P/P, 8.6 and 7.7% for P/A, and 0.7 and 0.4 for A/A in the cerebral infarction and control groups, respectively. No statistically significant differences in genotype distribution were observed between the two groups (P > 0.05). Moreover, PPARg2 Pro12Ala genotype was not significantly associated with altered fasting blood glucose, blood pressure, or serum lipid profiles. After adjustment for gender, body mass index, and smoking habit, logistic regression was used to analyze the relationship between the Pro12Ala polymorphism and cerebral infarction (odds ratio = 0.888, 95% confidence interval = 0.106-7.460, P > 0.05), revealing that this variant was not the main pathogenic factor involved. Therefore, the Pro12Ala mutation of PPARg2 may not be associated with cerebral infarction in the Inner Mongolian Han Chinese population.

  20. PPARγ Pro12Ala and His447His polymorphisms and susceptibility to Alzheimer's disease: a meta-analysis.

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    Lee, Y H; Song, G G

    2015-06-29

    We investigated whether Pro12Ala (C→G) and His447His (C→T) polymorphisms of the peroxisome proliferator-activated receptor gamma (PPARγ) gene are associated with susceptibility to Alzheimer's disease (AD). We conducted a meta-analysis of the associations between the PPARγ Pro12Ala and His447His polymorphisms and AD in subjects. The meta-analysis was performed according to the apolipoprotein E (APOE) ɛ4 allele status. A total of eight studies were considered in our meta-analysis, comprising 2948 patients with AD and 3753 controls. Meta-analysis showed no association between AD and the PPARγ Pro12Ala G allele in any of the study subjects [odds ratio (OR) = 1.013, 95% confidence interval (95%CI) = 0.906-1.132, P = 0.821] or in the European and Asian populations (OR = 0.997, 95%CI = 0.890-1.118, P = 0.965; OR = 1.409, 95%CI = 0.832-2.387, P = 0.202, respectively). We tested whether the APOE ɛ4 allele affects the association between the PPARγ Pro12Ala polymorphism and AD. Meta-analysis showed no association between AD and the PPARγ G allele in any of the study subjects with or without the APOE ɛ4 allele. Meta-analysis showed no association between AD and the PPARγ His447His T allele in the European population (OR for T allele = 0.912, 95%CI = 0.732-1.136, P = 0.409). This meta-analysis has shown that there is a lack of association between the PPARγ Pro12Ala and His447His polymorphisms and AD risk.

  1. Association of PPARG Pro12Ala polymorphism with insulin sensitivity and body mass index in patients with polycystic ovary syndrome.

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    Baldani, Dinka Pavicic; Skrgatic, Lana; Cerne, Jasmina Z; Ferk, Polonca; Simunic, Velimir; Gersak, Ksenija

    2014-03-01

    Insulin resistance is one of the key factors in the pathogenesis of polycystic ovary syndrome (PCOS). The peroxisome proliferator-activated receptor gamma (PPARG) plays a role in the regulation of insulin sensitivity. The aim of the present study was to establish a possible association of the PPARG Pro12Ala polymorphism with PCOS and its effect on family and personal history, as well as on the metabolic and endocrine parameters in PCOS patients. A total of 151 PCOS patients and 179 healthy women of reproductive age were enrolled. History, body mass index (BMI), waist-to-hip ratio and the presence of phenotypic hyperandrogenism were recorded. Hormonal, metabolic and biochemical profiles were assessed. A molecular analysis for the genetic polymorphism was performed. One third (29.8%) of the PCOS patients were found to be carriers of at least one variant of the Ala allele (X/Ala), while 70.2% carried two wild-type Pro alleles (Pro/Pro), with an equal distribution observed in the control group. The PCOS patients carrying the X/Ala alleles exhibited lower serum fasting insulin levels, homeostatic model assessment of insulin resistance (HOMA-IR) and BMI compared to Pro/Pro carriers. This finding was significant only in the lean PCOS group. The polymorphic genotype exerted no effect on history, hormonal and clinical hyperandrogenism, lipid status or C-reactive protein, leptin, adiponectin, resistin and ghrelin serum levels in women with PCOS. In conclusion, although the PPARG Pro12Ala polymorphism is not a major determinant of PCOS in the Croatian population, it may exert a positive effect on insulin sensitivity and BMI. As these associations were recorded exclusively in the lean group of patients with PCOS, this polymorphism potentially contributes to a protective role against hyperinsulinemia and obesity.

  2. Pro12Ala polymorphism in the peroxisome proliferator-activated receptor-gamma (PPARgamma) gene in inflammatory bowel disease.

    Science.gov (United States)

    Atug, Ozlen; Tahan, Veysel; Eren, Fatih; Tiftikci, Arzu; Imeryuz, Nese; Hamzaoglu, Hulya Over; Tozun, Nurdan

    2008-12-01

    Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) has recently been implicated as an endogenous regulator of cellular proliferation and inflammation. Impaired expression of PPAR-gamma in colonic epithelial cells in ulcerative colitis (UC) and increased expression in hypertrophic mesenteric adipose tissue in Crohn's disease (CD) have been reported. Furthermore, PPAR-gamma ligands have been shown to inhibit tissue injury associated with immune activation in UC. Any mutation in PPAR-gamma gene may be responsible for the increase in inflammatory mediators and hence the perpetuation of inflammation in inflammatory bowel disease (IBD) patients. One common polymorphism in PPAR-gamma gene is proline to alanine substitution (Pro12Ala) which results from a CCA to GCA missense substitution in codon 12 of exon 2 of the PPAR-gamma gene. In this study, we aimed to explore Pro12Ala polymorphism in PPAR-gamma gene in IBD in Turkish patients. 69 patients with CD, 45 with UC and 100 controls of similar age and sex were studied. Genomic DNA was isolated from peripheral blood leucocytes and mutagenically separated-polymerase chain reaction (PCR) analyses were performed to determine the Pro12Ala polymorphism of the PPAR-gamma gene. We observed no significant differences in the frequency of the Pro12Ala polymorphism in the PPAR-gamma gene among subjects with CD, UC and controls (15.9%, 15.5% and 13%, respectively, p>0.05). These results suggest that Pro12Ala polymorphism in the PPAR-gamma gene relates neither to the risk of the development of inflammatory bowel disease nor to the clinical subtypes of CD in the Turkish population.

  3. Dietary alpha-Lipoic Acid Alters Piglet Neurodevelopment

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    Austin T Mudd

    2016-05-01

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

  4. Growth and development of term infants fed with milk with long-chain polyunsaturated fatty acid supplementation

    Institute of Scientific and Technical Information of China (English)

    BEN Xiao-ming 贲晓明; ZHOU Xiao-yu 周晓玉; ZHAO Wei-hua 赵卫华; YU Wen-liang 喻文亮; PAN Wei 潘伟; ZHANG Wei-li 张伟利; WU Sheng-mei 吴圣楣; Christien M. Van Beusekom; Anne Schaafsma

    2004-01-01

    @@ Presently, there is growing interest in long-chain polyunsaturated fatty acids (LCPUFAs), which are considered a major determinant of growth, visual and neural development, and long-term health.1 Two groups of LCPUFAs have received special interest: homologues of linoleic acid (LA) of the n-6 series, which are precursors of arachidonic acid (AA), and homologues of α-linolenic acid (ALA) of the n-3 series, which are precursors of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).

  5. Effects of 5-aminolevulinic acid-mediated sonodynamic therapy on macrophages

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    Cheng J

    2013-02-01

    Full Text Available Jiali Cheng,1,* Xin Sun,1,2,* Shuyuan Guo,1,* Wei Cao,1 Haibo Chen,1 Yinghua Jin,1 Bo Li,1 Qiannan Li,1 Huan Wang,1 Zhu Wang,3 Qi Zhou,3 Peng Wang,3 Zhiguo Zhang,3 Wenwu Cao,3,4 Ye Tian1,21Division of Cardiology, the First Affiliated Hospital, Cardiovascular Institute, Harbin Medical University, Harbin, People’s Republic of China; 2Division of Pathophysiology, the State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, Harbin, People’s Republic of China; 3Laboratory of Photo- and Sono-theranostic Technologies and Condensed Matter Science and Technology Institute, Harbin Institute of Technology, Harbin, People’s Republic of China; 4Materials Research Institute, The Pennsylvania State University, University Park, PA, USA*These authors contributed equally to this workBackground: Inflammatory cells exhibit an elevated level of protoporphyrin IX (PpIX after the administration of 5-aminolevulinic acid (ALA. Here, we investigate the sonodynamic effects of ALA-derived PpIX (ALA-PpIX on macrophages, which are the pivotal inflammatory cells in atherosclerosis.Methods and results: Cultured THP-1 macrophages were incubated with ALA. Fluorescence microscope and fluorescence spectrometer detection showed that intracellular PpIX increased with the concentration of ALA in the incubation solution in a time dependent manner; the highest level of intracellular PpIX was observed after 3-hour incubation. 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assays demonstrated that lower concentrations (less than 2 mM of ALA have no influence on cell viability (more than 90% of cells survived, but sonodynamic therapy (SDT with a low concentration of ALA significantly decreased the survival rate of cells, and the effect was increased with both ALA concentration and ultrasound exposure time. Cell apoptosis and necrosis induced by ALA-mediated SDT (ALA-SDT were measured using

  6. Effects of taurine deficiency and chronic methanol administration on rat retina, optic nerve and brain amino acids and monoamines.

    Science.gov (United States)

    González-Quevedo, A; Obregón, F; Urbina, M; Roussó, T; Lima, L

    2003-08-01

    A chronic methanol (MeOH) intoxication scheme (2 g/kg/day ip for 2 weeks) was carried out in Sprague-Dawley rats, previously depleted of folates with methotrexate (MTX). beta-Alanine (beta-Ala), 5%, was also administered to some animals in the drinking water. Amino acids were determined in plasma, retina, optic nerve, hippocampus and posterior cortex by HPLC with fluorescence detection and monoamines in retina, hippocampus and posterior cortex by electrochemical detection. Beta-Ala administration reduced taurine (Tau) levels in plasma, hippocampus and posterior cortex, but not in retina and optic nerve. Aspartate (Asp) concentration in the optic nerve was increased in MTX-MeOH treated animals, and the administration of beta-Ala did not modify this elevation. The association of beta-Ala with MTX-MeOH produced an increase of threonine, and a decrease of 5-hydroxytryptamine (5-HT) in the retina without modifying 5-hydroxyindoleacetic acid, whereas in the hippocampus an elevation of asparagine was observed. We conclude that, in the retina, beta-Ala in combination with MTX-MeOH increased serotonin and decreased dopamine (DA) turnover rate, and resulted in changes in the amino acid balance, that could affect glycinergic activity. On the other hand, in the hippocampus, Asp metabolism could be affected by Tau depletion with beta-Ala.

  7. Peroxisome proliferator-activated receptor Pro12Ala polymorphism and the risks of gestational diabetes mellitus

    Science.gov (United States)

    Wang, Lihong; Xu, Wenting; Wang, Xu

    2016-01-01

    Abstract Background: Peroxisome proliferator-activated receptors-λ (PPAR-λ) is a member of nuclear receptor superfamily and acts as a ligand-dependent transcription factor often found in the adrenal gland, the spleen, and adipose tissue. The Pro12Ala polymorphism of PPAR-λ has been associated with the risks of gestational diabetes mellitus (GDM); however, association studies have provided conflicting results. The aim of this Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) compliant meta-analysis is to reach a more up-to-date and accurate estimation of the relationship between Pro12Ala genetic polymorphisms and the risks of GDM. Methods: Eligible studies were retrieved by searching PubMed, EMBASE, Web of Science, Ovid, WanFang, and Chinese National Knowledge Databases and selected according to a pre-defined inclusion criterion. The risk of bias was assessed using the Newcastle-Ottawa quality assessment scale. The per-allele odds ratio (OR) of risk allele proline (Pro) was compared between cases and controls in each study to describe the association between the Pro allele and an individual's risk of GDM. The ORs were pooled using both the random-effects model (the DerSimonian and Laird method) and the fixed effects model (the Mantel-Haenszel method) and the 95% confidence interval (95% CI) was calculated using Woolf method. Results: The final meta-analysis included a total of 11 articles of 12 data sets consisting of 7054 controls and 2980 GDM cases. Our results demonstrate that the Pro allele is not associated with GDM [OR: across multiple populations, 95% CI: 0.98–1.24; P(Z) = 0.01; P(Q) = 0.003]. In the stratified analysis by ethnicity, significantly increased risks were found for the Chinese (OR = 2.36; 95% CI: 1.47–3.78) and Korean (OR = 1.39; 95% CI: 1.00–1.93) populations. Conclusion: These data suggest the potential role of Pro allele in the pathogenesis of GDM in Asian populations. Although the funnel plot

  8. 5-Aminolevulinic Acid-Based Sonodynamic Therapy Induces the Apoptosis of Osteosarcoma in Mice.

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    Yongning Li

    Full Text Available Sonodynamic therapy (SDT is promising for treatment of cancer, but its effect on osteosarcoma is unclear. This study examined the effect of 5-Aminolevulinic Acid (5-ALA-based SDT on the growth of implanted osteosarcoma and their potential mechanisms in vivo and in vitro.The dose and metabolism of 5-ALA and ultrasound periods were optimized in a mouse model of induced osteosarcoma and in UMR-106 cells. The effects of ALA-SDT on the proliferation and apoptosis of UMR-106 cells and the growth of implanted osteosarcoma were examined. The levels of mitochondrial membrane potential (ΔψM, ROS production, BcL-2, Bax, p53 and caspase 3 expression in UMR-106 cells were determined.Treatment with 5-ALA for eight hours was optimal for ALA-SDT in the mouse tumor model and treatment with 2 mM 5-ALA for 6 hours and ultrasound (1.0 MHz 2.0 W/cm2 for 7 min were optimal for UMR-106 cells. SDT, but not 5-ALA, alone inhibited the growth of implanted osteosarcoma in mice (P<0.01 and reduced the viability of UMR-106 cells (p<0.05. ALA-SDT further reduced the tumor volumes and viability of UMR-106 cells (p<0.01 for both. Pre-treatment with 5-ALA significantly enhanced the SDT-mediated apoptosis (p<0.01 and morphological changes. Furthermore, ALA-SDT significantly reduced the levels of ΔψM, but increased levels of ROS in UMR-106 cells (p<0.05 or p<0.01 vs. the Control or the Ultrasound. Moreover, ALA-SDT inhibited the proliferation of osteosarcoma cells and BcL-2 expression, but increased levels of Bax, p53 and caspase 3 expression in the implanted osteosarcoma tissues (p<0.05 or p<0.01 vs. the Control or the Ultrasound.The ALA-SDT significantly inhibited osteosarcoma growth in vivo and reduced UMR-106 cell survival by inducing osteosarcoma cell apoptosis through the ROS-related mitochondrial pathway.

  9. Association of Type II 5' Monodeiodinase Thr92Ala Single Nucleotide Gene Polymorphism and Circulating Thyroid Hormones Among Type 2 Diabetes Mellitus Patients.

    Science.gov (United States)

    Yalakanti, Dhanunjaya; Dolia, Pragna B

    2016-04-01

    Diabetes mellitus and thyroid disorders are common endocrinopathies, which often occur parallel. Dyslipidemia is very common in both of these conditions. The development of hypothyroidism is well-known in type 1 diabetics, but it was not distinctly understood in type 2 diabetics. Thus we tried to examine the association between type II deiodinase (D2 or DIO2) Thr92Ala single nucleotide gene polymorphism and thyroid function among type 2 diabetes mellitus patients. A total of 130 type 2 diabetics were screened and genotyped for DIO2 Thr92Ala polymorphism. Fasting plasma glucose, Glycosylated haemoglobin, lipid and thyroid profiles, malondialdehyde (MDA) and paraoxonase were estimated according to standard procedures. A significant altered level of thyroid hormones (TH's) was found in Ala/Ala genotype when compared with Thr/Thr or Thr/Ala genotype. DIO2 and T3:T4 ratio significantly decreased, whereas total T4 and thyroid stimulating hormone levels significantly elevated among Ala/Ala genotype (131 ± 30 ng/ml; 0.12 ± 0.05; 7.17 ± 2.05 µg/dl; 4.77 ± 3.1 µIU/ml, respectively) when compared with Thr/Thr + Thr/Ala genotypes (176 ± 33 ng/ml; 0.21 ± 0.05; 5.21 ± 1.1 µg/dl; 2.59 ± 1.61 µIU/ml respectively). Moreover, D2 levels were significantly negatively correlated with TH's levels except total T4 among Ala/Ala genotypes. All the patients were having a poor glycemic control, and their glycemic status was positively correlating with MDA levels. On the other hand, serum paraoxonase activity decreased among Ala/Ala genotype (104 ± 21 vs. 118 ± 18 nmol/min/ml). In conclusion, DIO2 Ala92 homozygous variant found to be associated with altered levels of DIO2, Thyroid profile and paraoxonase. Hence, we recommend to do detail study of genetic factors related to thyroid function and prevent additional diabetic complications.

  10. Alpha-lipoic acid-mediated activation of muscarinic receptors improves hippocampus- and amygdala-dependent memory.

    Science.gov (United States)

    Mahboob, Aamra; Farhat, Syeda Mehpara; Iqbal, Ghazala; Babar, Mustafeez Mujtaba; Zaidi, Najam-us-Sahar Sadaf; Nabavi, Seyed Mohammad; Ahmed, Touqeer

    2016-04-01

    Aluminum (Al) is a neurotoxic agent which readily crosses the blood-brain-barrier (BBB) and accumulates in the brain leading to neurodegenerative disorders, characterised by cognitive impairment. Alpha-lipoic acid (ALA) is an antioxidant and has a potential to improve cognitive functions. This study aimed to evaluate the neuroprotective effect of ALA in AlCl3-induced neurotoxicity mouse model. Effect of ALA (25mg/kg/day) was evaluated in the AlCl3-induced neurotoxicity (AlCl3 150 mg/kg/day) mouse model on learning and memory using behaviour tests and on the expression of muscarinic receptor genes (using RT-PCR), in hippocampus and amygdala. Following ALA treatment, the expression of muscarinic receptor genes M1, M2 and choline acetyltransferase (ChaT) were significantly improved (pnovelty preference (p<0.001) comparative to the AlCl3-treated group. Fear extinction memory was remarkably restored (p<0.001) in ALA-treated group demonstrated by reduced freezing response as compared to the AlCl3-treated group which showed higher freezing. In-silico analysis showed that racemic mixture of ALA has higher binding affinity for M1 and M2 compared to acetylcholine. These novel findings highlight the potential role of ALA in cognitive functions and cholinergic system enhancement thus presenting it an enviable therapeutic candidate for the treatment of neurodegenerative disorders.

  11. Improved 5-Aminolevulinic Acid Production with Recombinant Escherichia coli by a Short-term Dissolved Oxygen Shock in Fed-batch Fermentation

    Institute of Scientific and Technical Information of China (English)

    杨俊; 朱力; 傅维琦; 林逸君; 林建平; 岑沛霖

    2013-01-01

    5-Aminolevulinic acid (ALA) is a common precursor for tetrapyrrole compounds in all kinds of organ-isms and has wide applications in agriculture and medicines. In this study, a new strategy, i.e. short-term dissolved oxygen (DO) shock during aerobic fermentation, was introduced to produce 5-aminolevulinic acid with a recombi-nant E. coli. Effects of duration time of DO shock operation on plasmid concentration, intracellular ALA synthase (ALAS) activity and ALA production were investigated in Erlenmeyer shake flasks. The results indicated that both ALAS activity and ALA yield were enhanced in an anaerobic operation of 45 min in the early exponential phase during fermentation, while they decreased when the anaerobic operation time was further increased to 60 min. The DO shock protocol was confirmed with the fed-batch fermentation in a 15 L fermenter and the ALA production achieved 9.4 g·L-1 (72 mmol·L-1), which is the highest yield in the fermentation broth reported up to now.

  12. Myeloperoxidase 463 G>A and superoxide dismutase Ala16Val gene polymorphisms in obese children.

    Science.gov (United States)

    Özgen, İlker Tolga; Torun, Emel; Ergen, Arzu; Cesur, Yaşar; Karagedik, Hande; Zeybek, Ümit; Aksu, Mehmet Şirin; Öktem, Faruk

    2014-01-01

    The aim of the study was to determine the role of MnSOD Ala16Val and MPO G-463A gene polymorphisms in the pathogenesis of metabolic syndrome in obese children. A total of 97 obese children with insulin resistance and, as a control group, 96 healthy children were enrolled in the study. In the obese group, AA, AV and VV genotype frequencies of the MnSOD gene and GG, GA and AA genotype frequencies of the MPO gene were not significantly different from the frequencies found in the control group (p=0.555 and 0.530, respectively). In the obese group, children who carry both VV (for MnSOD) and GG (for MPO) alleles (n= 26) had higher HOMA-IR levels (6.51 ± 3.91 vs 5.03 ± 2.12) than those of all other genotype combinations (n=71) (p=0.013). Children who have the maximum risk of developing oxidative stress with the combination of the VV (for MnSOD) and GG (for MPO) genotypes had higher HOMA-IR levels, suggesting these polymorphisms may lead to insulin resistance.

  13. Polymorphism (ALA16VAL) correlates with regional lymph node status in breast cancer.

    Science.gov (United States)

    Bica, Claudia Giuliano; da Silva, Leonardo Leiria de Moura; Toscani, Nadima Vieira; Zettler, Cláudio Galleano; Gottlieb, Maria Gabriela do Valle; Alexandre, Cláudio Osmar Pereira; Graudenz, Márcia Silveira; Mânica da Cruz, Ivana Beatrice

    2010-01-15

    We studied the possible association between Ala16Val manganese-dependent superoxide dismutase (MnSOD) gene genotypes and breast cancer lymph node status because previous investigations suggested an association between the AA genotype and breast cancer. We included 281 women (188 controls and 93 cases of invasive breast cancer with axillary lymph node metastasis (LN+) and without lymph node metastasis (LN-). DNA was extracted from paraffin-embedded tumor tissue or peripheral blood leukocytes, and MnSOD polymorphism was determined by polymerase chain reaction-restriction fragment length polymorphism techniques. In addition, the immunohistochemical profile (p53, Ki-67 and estrogen/progesterone receptors) was also compared between invasive breast cancer groups and different MnSOD genotypes. The frequency of the VV genotype was higher in the LN+ group than in the control and LN- groups (chi(2)=5.081, P=0.02). Subjects with LN+ breast cancer (LN+ group) showed a higher incidence of VV genotype carriers associated with positive Ki-67 marker. Subjects with LN+ breast cancer (LN+ group) showed a higher incidence of VV genotype carriers associated with negative p53 marker. Despite the fact that the AA genotype is well established as being associated with an increased risk of breast cancer, the VV genotype may be associated with a higher metastatic potential, suggesting that MnSOD imbalance is the condition associated with carcinogenesis.

  14. Is SOD2 Ala16Val polymorphism associated with migraine with aura phenotype?

    Science.gov (United States)

    Palmirotta, Raffaele; Barbanti, Piero; De Marchis, Maria Laura; Egeo, Gabriella; Aurilia, Cinzia; Fofi, Luisa; Ialongo, Cristiano; Valente, Maria Giovanna; Ferroni, Patrizia; Della-Morte, David; Guadagni, Fiorella

    2015-01-20

    Several studies suggest a role of oxidative stress in the physiopathology of migraine, particularly in the form with aura. In a case-control study, we investigated the association between migraine and superoxide dismutase 1 (SOD1) and superoxide dismutase 2 (SOD2) genes in a cohort of 490 consecutive unrelated Caucasian migraineurs (migraine with aura [MwA], n=107; migraine without aura [MwoA], n=246; chronic migraine [CM], n=137) and 246 healthy controls recruited at our Headache and Pain Unit and stored in the Interinstitutional Multidisciplinary BioBank (BioBIM). Migraine phenotype was carefully detailed using face-to-face interviews. We examined polymorphisms of SOD1 gene (A/C substitution-rs2234694) and SOD2 gene (C/T transition-rs4880-Ala16Val). The rs4880 TT (Val/Val) genotype was associated (p=0.042) with the presence of unilateral cranial autonomic symptoms (UAs) in MwA patients. We also found a mild correlation between SOD2 rs4880 genotype and the type of acute migraine treatment (p=0.048) in MwA patients. Our findings suggest that SOD2 is a disease-modifier gene influencing oxidative mechanisms in MwA. These observations lead to the hypothesis that SOD2 polymorphism may cause a defective control of the oxidative phenomena linked to cortical spreading depression, the neurophysiological hallmark of migraine aura, causing an overstimulation of trigeminal neurons and UAs triggering.

  15. Quiste subaracnoideo y displasia del ala mayor del esfenoides en neurofibromatosis

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    J. Cortés-Arreguín

    Full Text Available Los quistes subaracnoideos representan menos del 1% de los tumores de ocupación intracraneal. Hay pocas publicaciones acerca de quistes subaracnoideos del lóbulo temporal con remodelación de la cavidad orbitaria, pero no existen en relación al tratamiento reconstructivo de la cavidad orbitaria en esta patología. Presentamos el caso clínico de un varón de 44 años de edad con diagnóstico de neurofibromatosis tipo 1, aumento progresivo de volumen del ojo y párpado izquierdos de 40 años de evolución y dolor retro-ocular intermitente desde hacía 10 años, al que se le diagnostica un quiste subaracnoideo del lóbulo temporal que invade la cavidad orbitaria con displasia del ala mayor del esfenoides. Realizamos drenaje y cistocisternostomía del quiste subaracnoideo, con reconstrucción de paredes orbitarias con malla de titanio y cobertura con un colgajo de pericráneo así como elevación y reposicionamiento del globo ocular mediante cantopexias, seguida de una osteotomía de la órbita para reducir el volumen de la misma.

  16. Fibrinogen Seoul (FGG Ala341Asp): a novel mutation associated with hypodysfibrinogenemia.

    Science.gov (United States)

    Song, Kyung Soon; Park, Noh Jin; Choi, Jong Rak; Doh, Hyun Joo; Chung, Kwang Hoe

    2006-07-01

    Dysfibrinogenemia is a coagulation disorder caused by a variety of structural abnormalities in the fibrinogen molecule that result in fibrinogen function. The molecular basis of hypodysfibrinogenemia was investigated in a 66-year-old woman with peripheral artery obstructive disease and in her family members. Plasma level of functional fibrinogen determined using the Clauss method was lower (75 mg/dL; normal, 140-460 mg/dL) than that measured with immunologic nephelometric assay (137 mg/dL; normal, 180-400 mg/dL). Similar results were also observed in two family members through two generations. DNA was extracted from whole blood, and the coding regions and intron/exon boundaries of gamma chain gene (FGG) were amplified. A novel (Fibrinogen Seoul) heterozygous FGG mutation (GCT->GAT, Ala341Asp) was identified in all three affected family members. Thrombin-catalyzed polymerization was found to be defective on the analysis of purified fibinogen from the propositus. Molecular modeling also showed a conformational change of fibrinogen structure.

  17. PENGEMBANGAN MANAJEMEN DAYA TARIK WISATA BERBASIS QUALITY EXPERIENCES DI OBJEK WISATA ALAS KEDATON TABANAN

    Directory of Open Access Journals (Sweden)

    Yayu Indrawati

    2013-12-01

    Full Text Available In the recent days, to understanding the consumers behaviour is becoming a primary concern in marketing.This is also including in tourism marketing particularly tourism destination. The phenomenon of understandingthe consumer taste in tourism is popularly known as quality experience. It has a meaning that when tourist spendstheir money on a certain destination they expect for quality experience. It can be seen on their satisfaction thatappear on their willingness to revisit or giving the positive impression to their friends and relatives. Today, thereis a downward point in tourist destination in the last five years. Previously there were 1500 visitors per day, butlately it is only 10.000 both for international and domestic visitors. It is caused by the raise of competitor’s numberand the tourist responses towards Alas Kedaton site. Such impression comes from its cleanliness, the hospitalityof the staff, the price of entrance fee, and lack of facilities. Other instances are the uncomfortable way to get tothe site, as well as the absence of spiritual facilities for Muslim visitors for praying during their visit to this place.

  18. Fatty acids in mountain gorilla diets: implications for primate nutrition and health.

    Science.gov (United States)

    Reiner, Whitney B; Petzinger, Christina; Power, Michael L; Hyeroba, David; Rothman, Jessica M

    2014-03-01

    Little is known about the fatty acid composition of foods eaten by wild primates. A total of 18 staple foods that comprise 97% of the annual dietary intake of the mountain gorilla (Gorilla beringei) were analyzed for fatty acid concentrations. Fruits and herbaceous leaves comprise the majority of the diet, with fruits generally having a higher mean percentage of fat (of dry matter; DM), as measured by ether extract (EE), than herbaceous leaves (13.0% ± SD 13.0% vs. 2.3 ± SD 0.8%). The mean daily EE intake by gorillas was 3.1% (DM). Fat provided ≈14% of the total dietary energy intake, and ≈22% of the dietary non-protein energy intake. Saturated fatty acids accounted for 32.4% of the total fatty acids in the diet, while monounsaturated fatty acids accounted for 12.5% and polyunsaturated fatty acids (PUFA) accounted for 54.6%. Both of the two essential PUFA, linoleic acid (LA, n-6) and α-linolenic acid (ALA, n-3), were found in all of the 17 staple foods containing crude fat and were among the three most predominant fatty acids in the diet: LA (C18:2n-6) (30.3%), palmitic acid (C16:0) (23.9%), and ALA (C18:3n-3) (21.2%). Herbaceous leaves had higher concentrations of ALA, while fruit was higher in LA. Fruits provided high amounts of fatty acids, especially LA, in proportion to their intake due to the higher fat concentrations; despite being low in fat, herbaceous leaves provided sufficient ALA due to the high intake of these foods. As expected, we found that wild mountain gorillas consume a diet lower in EE, than modern humans. The ratio of LA:ALA was 1.44, closer to agricultural paleolithic diets than to modern human diets. © 2013 Wiley Periodicals, Inc.

  19. Association of serum lipid/lipoprotein with Pro12Ala polymorphism in PPAR-γ2 among Chinese nonagenarians/centenarians.

    Science.gov (United States)

    Chang-Quan, Huang; Hui, Wang; Qing-Xiu, Liu; Gang, Cheng

    2011-10-01

    In previous studies, the Pro12Ala polymorphism in the peroxisome proliferator-activated receptor gamma 2 (PPAR-γ2) was shown to be associated with both lipid metabolism and longevity. We examined whether the polymorphism continued to be associated with abnormal levels of serum lipid/lipoprotein among elderly subjects (≥90 years). The Pro12Ala variant was examined using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Abnormal levels of serum lipid/lipoprotein were defined according to the criteria provided by the Chinese Medical Association (2004). Abnormal criteria were triglyceride (TG) >5.18 mmol/l, total cholesterol (TC) >1.7 mmol/l, low-density lipoprotein cholesterol (LDL-C) >3.37 mmol/l and high-density lipoprotein cholesterol (HDL-C) Pro12Ala polymorphism were 0% Ala12Ala, 8.9% Pro12Ala, 91.1% Pro12Pro. Neither differences in the levels of serum lipid/lipoprotein nor the prevalence of their abnormal levels was significant between subjects who were or were not 12Ala carriers. Unadjusted and adjusted multiple logistic regressions showed that the odds ratios (OR) for abnormal levels of serum lipid/lipoprotein were not associated with the Pro12Ala polymorphism in PPAR-γ2. Levels of serum lipid/lipoprotein were not associated with the Pro12Ala polymorphism in PPAR-γ2 among Chinese nonagenarians and centenarians, which was different from the general population. Copyright © 2011 IMSS. Published by Elsevier Inc. All rights reserved.

  20. The influence of 5-ALA-IPL-PDT on the secretion of MMP-1 and TGF-β1 in fibroblasts pathway mechanisms%5-氨基酮戊酸联合IPL 光动力疗法对成纤维细胞分泌MMP-1、TGF-β1的影响及信号机制研究

    Institute of Scientific and Technical Information of China (English)

    黄进华; 郭爱元; 陈静; 鲁建云; 向亚平; 左成忻; 杨盛波; 谭丽娜; 康健

    2011-01-01

    目的:研究观察5-氨基酮戊酸(5-ALA)联合强脉冲光(IPL)光动力疗法(5-ALA-IPL-PDT)对成纤维细胞分泌表型的影响及其信号通路机制.方法:成纤维细胞接种至培养板,采用不同浓度的5-ALA处理细胞2 h后给予不同剂量的IPL辐照.免疫印迹法(Western-blot)观察有丝分裂原活化蛋白激酶(MAPK)相关家族成员[细胞外信号调节激酶(ERK)、c-Jun氨基末端激酶(JNK)、P38]的蛋白磷酸化水平.ELISA法检测转化生长因子(TGF)-β1、基质金属蛋白酶(MMP)-1水平的变化.结果:①与空白组比较,IPL+ALA(0.5 mmol/L)组、IPL+ALA(1.0 mmol/L)组,MMP-1浓度分别增加94.7%和111.4%,而TGF-β1浓度分别降低34.8%和39.1%(P < 0.05);②IPL+ALA(0.5 mmol/L)组与IPL组比较,ERK、P38和JNK分别增加113.1%、36.1%和67.3%(P < 0.05).结论:5-ALA-IPL-PDT可刺激MAPK家族分子(ERK、P38、JNK)的活化,诱导成纤维细胞MMP-1的分泌,而抑制TGF-β1的分泌.%Objectives: To study the influence of 5-ALA-IPL-PDT on the MAPK pathway and the secretion of MMP-1, TGF-(31 in fibroblasts. Methods: The fibroblasts were inoculated onto the culture plates. Two hours before IPL radiation dif ferent doses of 5 -aminolevulinic acid (5-ALA) were added to the plate. The level of MAPK phosphorylation was examined by Western blotting. The levels of TGF-(31 and MMP-1 were assessed with enzyme-linked immunosorbent assay (ELISA). Results: CD Compared with control groups, the expressions of MMP-1 in IPL iO J/cm2)+ALA(0.5 mmol/L) groups and IPL 10 J/cm2)+ALA(1.0 mmol/L) groups were markedly enhanced by 94.7% and 111.4%, While the expressions of TGF-(31 dropped by 34.8% and 39.1%, respectively (P < 0.05). ?Compared with IPL groups, IPL 10 J/cm2)+ALA (0.5 mmol/L) increased the phosphorylation of MAPK(ERK,P38 and JNK), up to 113.1%, 36.1% and 67.3%, respectively. Conclusions: 5-ALA-IPL-PDT stimulates MAPK ( ERK, P38 and JNK) phosphorylation in fibroblasts, a potential mechanism involved in downregulating the

  1. Co-Circulation of the Rare CPV-2c with Unique Gln370Arg Substitution, New CPV-2b with Unique Thr440Ala Substitution, and New CPV-2a with High Prevalence and Variation in Heilongjiang Province, Northeast China.

    Directory of Open Access Journals (Sweden)

    Yufei Geng

    Full Text Available To trace evolution of canine parvovirus-2 (CPV-2, a total of 201 stool samples were collected from dogs with diarrhea in Heilongjiang province of northeast China from May 2014 to April 2015. The presence of CPV-2 in the samples was determined by PCR amplification of the VP2 gene (568 bp of CPV-2. The results revealed that 95 samples (47.26% were positive for CPV-2, and they showed 98.8%-100% nucleotide identity and 97.6%-100% amino acid identity. Of 95 CPV-2-positive samples, types new2a (Ser297Ala, new2b (Ser297Ala, and 2c accounted for 64.21%, 21.05%, and 14.74%, respectively. The positive rate of CPV-2 and the distribution of the new2a, new2b and 2c types exhibited differences among regions, seasons, and ages. Immunized dogs accounted for 48.42% of 95 CPV-2-positive samples. Coinfections with canine coronavirus, canine kobuvirus, and canine bocavirus were identified. Phylogenetic analysis revealed that the identified new2a, new2b, and CPV-2c strains in our study exhibited a close relationship with most of the CPV-2 strains from China; type new2a strains exhibited high variability, forming three subgroups; type new2b and CPV-2c strains formed one group with reference strains from China. Of 95 CPV-2 strains, Tyr324Ile and Thr440Ala substitutions accounted for 100% and 64.21%, respectively; all type new2b strains exhibited the Thr440Ala substitution, while the unique Gln370Arg substitution was found in all type 2c strains. Recombination analysis using entire VP2 gene indicated possible recombination events between the identified CPV-2 strains and reference strains from China. Our data revealed the co-circulation of new CPV-2a, new CPV-2b, and rare CPV-2c, as well as potential recombination events among Chinese CPV-2 strains.

  2. Association between PPAR-γ2 Pro12Ala genotype and insulin resistance is modified by circulating lipids in Mexican children

    OpenAIRE

    Carolina Stryjecki; Jesus Peralta-Romero; Akram Alyass; Roberto Karam-Araujo; Fernando Suarez; Jaime Gomez-Zamudio; Ana Burguete-Garcia; Miguel Cruz; David Meyre

    2016-01-01

    The Pro12Ala (rs1801282) polymorphism in peroxisome proliferator-activated receptor-γ2 (PPAR-γ2) has been convincingly associated with insulin resistance (IR) and type 2 diabetes (T2D) among Europeans, in interaction with a high-fat diet. Mexico is disproportionally affected by obesity and T2D however, whether the Pro12Ala polymorphism is associated with early metabolic complications in this population is unknown. We assessed the association of PPAR-γ2 Pro12Ala with metabolic traits in 1457 M...

  3. Persistent photoconductivity in uniforndy and selectively silicon doped AlAs / GaAs short period superlattices

    Science.gov (United States)

    Jeanjean, P.; Sicart, J.; Robert, J. L.; Mollot, F.; Planel, R.

    1991-04-01

    Hall and photo-Hall measurements have been carried out between 4 K et 400 K on MBE deposited AlAs / GaAs superiattices (SPS) with short period (25 Å dopage uniforme, alors que les SPS dopées sélectivement dans GaAs ne présentent qu'une seule barrière (un seul plateau). Ainsi la microstructure GaAs / AlAs apparaît être un outil particulièrement intéressant pour confirmer la validité du modèle multibarrière proposé récemment pour le centre DX dans AlxGal{1-x} As: Si.

  4. Hypofibrinogenemia and the α-Fibrinogen Thr312Ala Polymorphism may be Risk Factors for Early Pregnancy Loss.

    Science.gov (United States)

    Kamimoto, Yuki; Wada, Hideo; Ikejiri, Makoto; Nakatani, Kaname; Sugiyama, Takashi; Osato, Kazuhiro; Murabayashi, Nao; Habe, Koji; Mizutani, Hitoshi; Matsumoto, Takeshi; Ohishi, Kohshi; Ikeda, Tomoaki

    2017-01-01

    We analyzed a cohort of 36 females with pregnancy loss. In addition to 11 patients with antiphospholipid antibody syndrome and 2 patients with congenital antithrombin (AT) or protein C deficiency, we identified 5 patients with low fibrinogen levels (median 110 mg/dL) prior to 10 weeks of gestation. Four of these 5 patients underwent a fibrinogen gene analysis, and all 4 were found to be heterozygotes for the α-fibrinogen (FGA) Thr321Ala polymorphism. One female without hypofibrinogenemia with a history of 8 pregnancy losses was found to be homozygous for the same polymorphism, and she also showed hypercoagulability without thrombosis. In conclusion, there was a relatively high frequency of pregnancy loss in the setting of hypofibrinogenemia and/or the FGA Thr312Ala polymorphism, and this may be an important risk factor for pregnancy loss and a hypercoagulable state in later pregnancy.

  5. Nutritional Effect of Alpha-Linolenic Acid on Honey Bee Colony Development (Apis Mellifera L.

    Directory of Open Access Journals (Sweden)

    Ma Lanting

    2015-12-01

    Full Text Available Alpha-linolenic acid (ALA, which is an n-3 polyunsaturated fatty acid (PUFA, influences honey bee feed intake and longevity. The objective of this study was to research the effect of six dietary ALA levels on the growth and development of Apis mellifera ligustica colonies. In the early spring, a total of 36 honey bee colonies of equal size and queen quality were randomly allocated into 6 groups. The six groups of honey bees were fed a basal diet with supplementation of ALA levels at 0 (group A, 2 (group B, 4 (group C, 6 (group D, 8 (group E, and 10% (group F. In this study, there were significant effects of pollen substitute ALA levels on the feeding amounts of the bee colony, colony population, sealed brood amount, and weight of newly emerged workers (P<0.05. The workers’ midgut Lipase (LPS activity of group C was significantly lower than that of the other groups (P<0.01. The worker bees in groups B, C, and D had significantly longer lifespans than those in the other groups (P<0.05. However, when the diets had ALA concentrations of more than 6%, the mortality of the honey bees increased (P<0.01. These results indicate that ALA levels of 2 ~ 4% of the pollen substitute were optimal for maintaining the highest reproductive performance and the digestion and absorption of fatty acids in honey bees during the period of spring multiplication. Additionally, ALA levels of 2 ~ 6% of the pollen substitute, improved worker bee longevity.

  6. In vitro effects of Ala16Val manganese superoxide dismutase gene polymorphism on human white blood cells exposed to methylmercury.

    Science.gov (United States)

    Algarve, T D; Barbisan, F; Ribeiro, E E; Duarte, M M M F; Mânica-Cattani, M F; Mostardeiro, C P; Lenz, A F; da Cruz, I B M

    2013-10-29

    Environmental contamination by methylmercury (MeHg) is an enormous public health problem in world regions such as Amazonia. MeHg toxic effects seem to be influenced by environmental and genetic factors. However, few studies have evaluated the genetic influences of MeHg toxicity in humans. Therefore, the aim of this study was to evaluate the genetic influence of Ala16Val manganese superoxide dismutase gene polymorphism (Ala16Val-MnSOD) on the cytotoxic effects of in vitro human leukocytes exposed to MeHg. Subjects were selected from 100 individuals aged 26.4 ± 7.3 years genotyped to Ala16Val-MnSOD polymorphism (AA = 6, VV = 6, and AV = 12) to perform in vitro testing using white blood cells (WBCs). Reactive oxygen species production was measured using 2',7'-dichlorofluorescein diacetate fluorimetric assay, and cell viability was measured using MTT assay on WBC samples from the same subjects that were both exposed and not exposed to MeHg (2.5 µM for 6 h). The results showed that AA- and VV-WBCs exposed to MeHg did not display increased reactive oxygen species levels compared to those in cells that were not exposed. However, AV-leukocytes exposed to MeHg displayed increased ROS levels. Cellular viability comparison among genotypes exposed to MeHg showed that the viability of AA-WBCs was lower than that of VV-WBC, with mean values of 3.46 ± 0.13 and 3.08 ± 0.77 (standard error), respectively (P = 0.033), whereas heterozygous cells (AV) displayed intermediate values. This difference was likely due to the higher basal H2O2 production of AA-WBCs compared to that of other genotypes. These results suggest that the Ala16Val-MnSOD polymorphism has toxicogenetic effects in human cells exposed to MeHg.

  7. A new G(gamma) chain variant: Hb F-Bron [gamma20(B2)val-->Ala].

    Science.gov (United States)

    Lacan, Philippe; Burnichon, Nelly; Becchi, Michel; Zanella-Cleon, Isabelle; Aubry, Martine; Couprie, Nicole; Francina, Alain

    2005-01-01

    A new G(gamma) hemoglobin (Hb) variant, Hb F-Bron [gamma20(B2)Val-->Ala] on the first exon of the G(gamma)-globin gene is described. The variant was characterized by DNA sequencing and mass spectrometry (MS). Hematological abnormalities included hypochromia and microcytosis and were probably caused by an interaction with an alpha-thalassemia (thal) (3.7 kb) deletion in the heterozygous state.

  8. PPARγ Pro12Ala polymorphism and risk of acute coronary syndrome in a prospective study of Danes

    OpenAIRE

    Jensen Majken K; Wallin Håkan; Saber Anne; Tjønneland Anne; Dethlefsen Claus; Segel Stine; Vogel Ulla; Schmidt Erik B; Andersen Paal; Overvad Kim

    2009-01-01

    Abstract Background Acute coronary syndrome (ACS) is a major cause of morbidity and mortality in the western world. Peroxisome proliferator-activated receptor γ (PPARγ) plays a key role in the regulation of the energy balance, adipocyte differentiation and lipid biosynthesis. The aim was to investigate if the polymorphism PPARγ2 Pro12Ala, which encodes a less efficient transcription factor, was associated with risk of acute coronary disease and if there were interactions between this polymorp...

  9. Haplotype analysis of the PPARγ Pro12Ala and C1431T variants reveals opposing associations with body weight

    OpenAIRE

    Montgomery Hugh E; World Michael; Flavell David M; Cumming Alastair; Frew David; Fischer Bettina; Doney Alex; Boyle Douglas; Morris Andrew; Palmer Colin NA

    2002-01-01

    Abstract Background Variation at the PPARG locus may influence susceptibility to type 2 diabetes and related traits. The Pro12Ala polymorphism may modulate receptor activity and is associated with protection from type 2 diabetes. However, there have been inconsistent reports of its association with obesity. The silent C1431T polymorphism has not been as extensively studied, but the rare T allele has also been inconsistently linked to increases in weight. Both rare alleles are in linkage diseq...

  10. Peroxisome proliferator-activated receptor-γ (PPARγ) Pro12Ala polymorphism and colorectal cancer (CRC) risk.

    Science.gov (United States)

    Wang, Wei; Shao, Yan; Tang, Shenhua; Cheng, Xianyong; Lian, Haifeng; Qin, Chengyong

    2015-01-01

    The association between the peroxisome proliferator-activated receptor-γ (PPARγ) Pro12Ala polymorphism and colorectal cancer (CRC) risk was inconclusive. We conducted a meta-analysis to evaluate the association between PPARγ Pro12Ala polymorphism and CRC risk. We searched Pubmed, EMBASE, and China National Knowledge Infrastructure databases. Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated. A total of 17 case-control studies with 12635 and 15803 controls were included in this meta-analysis. Overall, PPARγ Pro12Ala polymorphism was associated with CRC risk (OR = 0.84, 95% CI 0.75-0.94, P = 0.003, I(2) = 35%). In the subgroup analysis by ethnicity, a significant association was found among Caucasians (OR = 0.85, 95% CI 0.75-0.96, P = 0.007, I(2) = 38%) but not among Asians (OR = 0.76, 95% CI 0.51-1.12, P = 0.17, I(2) = 28%). In the subgroup analysis by CRC site, a significant association was found among colon cancer (OR = 0.81, 95% CI 0.66-0.98, P = 0.03, I(2) = 16%) but not among rectal cancer (OR = 0.83, 95% CI 0.57-1.21, P = 0.34, I(2) = 63%). The sensitivity analysis did not influence the result by omitting low-quality studies (OR = 0.76, 95% CI 0.63-0.93, P = 0.006, I(2) = 51%). In conclusion, this meta-analysis suggested that PPARγ Pro12Ala polymorphism was significant associated with CRC risk.

  11. Human lactation: oxidation and maternal transfer of dietary (13)C-labelled α-linolenic acid into human milk.

    Science.gov (United States)

    Demmelmair, Hans; Kuhn, Angelika; Dokoupil, Katharina; Hegele, Verena; Sauerwald, Thorsten; Koletzko, Berthold

    2016-06-01

    The origin of fatty acids in milk has not been elucidated in detail. We investigated the contribution of dietary α-linolenic acid (ALA) to human milk fat, its oxidation and endogenous conversion to long-chain polyunsaturated fatty acids. Ten lactating women were given (13)C-ALA orally, and breath and milk samples were collected for a five-day period, while dietary intakes were assessed. 37.5 ± 2.7 % (M ± SE) of the tracer was recovered in breath-CO2, and 7.3 ± 1.1 % was directly transferred into milk. About 0.25 % of the tracer was found in milk long-chain polyunsaturated fatty acids. Combining intake and milk data, we estimate that about 65 % of milk ALA is directly derived from maternal diet. Thus, the major portion of milk ALA is directly derived from the diet, but dietary ALA does not seem to contribute much as a precursor to milk n-3 long-chain polyunsaturated fatty acids within the studied time period.

  12. Amino acid sequences of neuropeptides in the sinus gland of the land crab Cardisoma carnifex: a novel neuropeptide proteolysis site.

    Science.gov (United States)

    Newcomb, R W

    1987-08-01

    The sinus gland is a major neurosecretory structure in Crustacea. Five peptides, labeled C, D, E, F, and I, isolated from the sinus gland of the land crab have been hypothesized to arise from the incomplete proteolysis at two internal sites on a single biosynthetic intermediate peptide "H", based on amino acid composition additivities and pulse-chase radiolabeling studies. The presence of only a single major precursor for the sinus gland peptides implies that peptide H may be synthesized on a common precursor with crustacean hyperglycemic hormone forms, "J" and "L," and a peptide, "K," similar to peptides with molt inhibiting activity. Here I report amino acid sequences of these peptides. The amino terminal sequence of the parent peptide, H, (and the homologous fragments) proved refractory to Edman degradation. Data from amino acid analysis and carboxypeptidase digestion of the naturally occurring fragments and of fragments produced by endopeptidase digestion were used together with Edman degradation to obtain the sequences. Amino acid analysis of fragments of the naturally occurring "overlap" peptides (those produced by internal cleavage at one site on H) was used to obtain the sequences across the cleavage sites. The amino acid sequence of the land crab peptide H is Arg-Ser-Ala-Asp-Gly-Phe-Gly-Arg-Met-Glu-Ser-Leu-Leu-Thr-Ser-Leu-Arg-Gly- Ser-Ala-Glu- Ser-Pro-Ala-Ala-Leu-Gly-Glu-Ala-Ser-Ala-Ala-His-Pro-Leu-Glu. In vivo cleavage at one site involves excision of arginine from the sequence Leu-Arg-Gly, whereas cleavage at the other site involves excision of serine from the sequence Glu-Ser-Leu. Proteolysis at the latter sequence has not been previously reported in intact secretory granules. The aspartate at position 4 is possibly covalently modified.

  13. The role of essential fatty acids in the control of coronary heart disease

    DEFF Research Database (Denmark)

    Vedtofte, Mia Sadowa; Jakobsen, Marianne Uhre; Lauritzen, Lotte

    2012-01-01

    Evidence from various research paradigms supports the cardiovascular benefits of a high intake of n-3 polyunsaturated fatty acids (PUFAs), especially the long-chain, marine-derived n-3 PUFA, eicosapentaenoic acids and docosahexaenoic acids. The effect of the plant-derived alpha-linolenic acid (ALA......) is, however, not clear. Concerns about a high n-6 PUFA intake has been raised, because n-6 PUFA may weaken the effects of n-3 PUFA....

  14. Toxicological effects of ultraviolet radiation on lymphocyte cells with different manganese superoxide dismutase Ala16Val polymorphism genotypes.

    Science.gov (United States)

    dos Santos Montagner, Greice Franciele Feyh; Sagrillo, Michele; Machado, Michel Mansur; Almeida, Renata Chequeller; Mostardeiro, Clarice Pinheiro; Duarte, Marta Maria Medeiros Frescura; da Cruz, Ivana Beatrice Mânica

    2010-08-01

    The aim of this study was to investigate whether there is a differential response of lymphocytes from healthy MnSOD genotype subjects to oxidative stress. We used UV radiation as a toxic agent due to its genotoxic effects associated with chromosome aberrations caused by breaks in the DNA strands. Cellular growth rate, cell viability, mitotic index, chromosomal instability and biomarkers of oxidative metabolism were analysed in lymphocyte cells from healthy adults with different Ala16Val MnSOD polymorphisms that produce tree genotypes: AA, VV and AV. We found a differential response to UV exposure in cultures of lymphocyte cells from Ala16Val genotype donors. In general, AA cell cultures presented higher viability and mitotic index and lower TBARS levels than VV and AV cells for both the control and UV exposure groups. However, when we compared the DNA damage among the three genotypes, AA lymphocyte cells presented the highest damage from UV exposure. These data suggest that the Ala16Val polymorphism affects the response of cellular oxidative metabolism in different ways.

  15. Correct Evaluation of the Effect of Transverse Effective Charges on Phonons in AlAs Quantum Dots

    Institute of Scientific and Technical Information of China (English)

    QIN Guo-Yi

    2003-01-01

    An improved valence force field model (VFFM) is suggested to calculate the phonon modes in both bulk specimens and quantum dots (QDs) of AlAs taking account of the effect of transverse effective charges (TCs) correctly.The resultant dispersions of AlAs bulk phonons are in accord better with the results carefully fitted to the experimental data by using 11-parameters rigid-ion model, than those got by ordinary VFFM, especially in the region of near F point. For AlAs QDs, TCs are evaluated bond by bond for each phonon mode of QD and its effect on the change of the force on atoms is taken into account to modify further the phonon spectrum. The frequency spectra and densities of phonon states of different irreducible representations calculated by using improved VFFM are compared with the results of ordinary VFFM. The correct evaluation of the TCs is not only important in calculating the phonon spectrum of both bulk and QD specimens accurately, but is also in the further discussion of the electron-phonon (e-ph) interaction, which can be directly related to TCs of ions in QD.

  16. Correct Evaluation of the Effect of Transverse Effective Charges on Phonons in AlAs Quantum Dots

    Institute of Scientific and Technical Information of China (English)

    QINGuo-Yi

    2003-01-01

    An improved valence force field model (VFFM) is suggested to calculate the phonon modes in both bulk specimens and quantum dots (QDs) of AlAs taking account of the effect of transverse effective charges (TOs) correctly.The resultant dispersions of AlAs bulk phonons are in accord better with the results carefully fitted to the experimental data by using 11-parameters rigid-ion model, than those got by ordinary VFFM, especially in the region of near Г point. For AlAs QDs, TCs are evaluated bond by bond for each phonon mode of QD and its effect on the change of the force on atoms is taken into account to modify further the phonon spectrum. The frequency spectra and densities ofphonon states of d/fferent irreducible representations calculated by using improved VFFM are compared with the results of ordinary VFFM. The correct evaluation of the TOs is not only important in calculating the phonon spectrum of both bulk and QD specimens accurately, but is also in the further discussion of the electron-phonon (e-ph) interaction, which can be directly related to TCs of ions in QD.

  17. Haplotype analysis of the PPARγ Pro12Ala and C1431T variants reveals opposing associations with body weight

    Directory of Open Access Journals (Sweden)

    Montgomery Hugh E

    2002-11-01

    Full Text Available Abstract Background Variation at the PPARG locus may influence susceptibility to type 2 diabetes and related traits. The Pro12Ala polymorphism may modulate receptor activity and is associated with protection from type 2 diabetes. However, there have been inconsistent reports of its association with obesity. The silent C1431T polymorphism has not been as extensively studied, but the rare T allele has also been inconsistently linked to increases in weight. Both rare alleles are in linkage disequilibrium and the independent associations of these two polymorphisms have not been addressed. Results We have genotyped a large population with type 2 diabetes (n = 1107, two populations of non-diabetics from Glasgow (n = 186 and Dundee (n = 254 and also a healthy group undergoing physical training (n = 148 and investigated the association of genotype with body mass index. This analysis has demonstrated that the Ala12 and T1431 alleles are present together in approximately 70% of the carriers. By considering the other 30% of individuals with haplotypes that only carry one of these polymorphisms, we have demonstrated that the Ala12 allele is consistently associated with a lower BMI, whilst the T1431 allele is consistently associated with higher BMI. Conclusion This study has therefore revealed an opposing interaction of these polymorphisms, which may help to explain previous inconsistencies in the association of PPARG polymorphisms and body weight.

  18. Association of Pro12Ala polymorphism of PPAR-γ2 Gene and diabetic retinopathy in type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Yong-Qing Liu

    2013-06-01

    Full Text Available AIM: To observe the relationship between Prol2Ala polymorphism of peroxisome proliferator activated receptor-γ2(PPAR-γ2gene and diabetic retinopathy(DRwith type 2 diabetic mellitus(T2DMof the Han nationality in Shanxi province. METHODS: Totally 90 patients with T2DM were selected into our research, who were at the age of 40 to 70 years old, diabetic duration from 10 to 20 years, blood pressure PPAR-γ2 gene were determined by polymerase chain reaction-restriction fragment length polymorphisms(PCR-RFLPassay in all the patients. RESULTS: PCR results showed that there were 2 alleles and 3 genotypes in the groups. The frequency of genotype PP, PA, AA were 40.0%, 53.3%, 6.7% in NDR group, 70.0%, 30.0%, 0.0% in BDR group, 76.7%, 23.3%, 0% in PDR group, respectively. The allele frequency(χ2=10.208and gene frequency(χ2=10.351were statistically significant(PCONCLUSION: The alanine variant of Prol2Ala polymorphism of PPAR-γ2 gene is associated with DR in type 2 diabetes among the Hans in Shanxi area, and the Ala allele might be a protective factor for the development of diabetic retinopathy.

  19. Haplotype analysis of the PPARγ Pro12Ala and C1431T variants reveals opposing associations with body weight

    Science.gov (United States)

    Doney, Alex; Fischer, Bettina; Frew, David; Cumming, Alastair; Flavell, David M; World, Michael; Montgomery, Hugh E; Boyle, Douglas; Morris, Andrew; Palmer, Colin NA

    2002-01-01

    Background Variation at the PPARG locus may influence susceptibility to type 2 diabetes and related traits. The Pro12Ala polymorphism may modulate receptor activity and is associated with protection from type 2 diabetes. However, there have been inconsistent reports of its association with obesity. The silent C1431T polymorphism has not been as extensively studied, but the rare T allele has also been inconsistently linked to increases in weight. Both rare alleles are in linkage disequilibrium and the independent associations of these two polymorphisms have not been addressed. Results We have genotyped a large population with type 2 diabetes (n = 1107), two populations of non-diabetics from Glasgow (n = 186) and Dundee (n = 254) and also a healthy group undergoing physical training (n = 148) and investigated the association of genotype with body mass index. This analysis has demonstrated that the Ala12 and T1431 alleles are present together in approximately 70% of the carriers. By considering the other 30% of individuals with haplotypes that only carry one of these polymorphisms, we have demonstrated that the Ala12 allele is consistently associated with a lower BMI, whilst the T1431 allele is consistently associated with higher BMI. Conclusion This study has therefore revealed an opposing interaction of these polymorphisms, which may help to explain previous inconsistencies in the association of PPARG polymorphisms and body weight. PMID:12429071

  20. COMT Val158Met and PPARγ Pro12Ala polymorphisms and susceptibility to Alzheimer's disease: a meta-analysis.

    Science.gov (United States)

    Lee, Young Ho; Song, Gwan Gyu

    2014-05-01

    The aim of this study was to explore whether the catechol-O-methyltransferase (COMT) Val158Met or the peroxisome proliferator-activated receptor-gamma (PPARγ) Pro12Ala polymorphisms are associated with susceptibility to Alzheimer's disease (AD). We conducted a meta-analysis of the associations between the COMT Val158Met and the PPARγ Pro12Ala polymorphisms and AD in subjects. Meta-analysis showed no association between AD and the COMT G allele in any of the study subjects [odds ratio (OR) = 0.972, 95 % confidence intervals (95 % CI) = 0.893-1.059, p = 0.515]. Stratification by ethnicity indicated an association between the COMT GG+GA genotype and AD in an Asian group (OR = 0.702, 95 % CI = 0.517-0.953, p = 0.023), but not in Europeans (OR = 1.058, 95 % CI = 0.868-1.289, p = 0.579). Homozygote contrast analysis showed the same pattern for the COMT GG+GA genotype. Meta-analysis showed no association between AD and the PPARγ polymorphism (OR for the C allele = 0.963, 95 % CI = 0.818-1.134, p = 0.649). This meta-analysis identified an association between AD and the COMT Val158Met polymorphism in Asians but not in Europeans, but it revealed no association between AD and the PPARγ Pro12Ala polymorphism.

  1. Protective effect of alpha-lipoic acid on cypermethrin-induced oxidative stress in Wistar rats.

    Science.gov (United States)

    Mignini, F; Nasuti, C; Fedeli, D; Mattioli, L; Cosenza, M; Artico, M; Gabbianelli, R

    2013-01-01

    Cypermethrin (CY), a class II pyrethroid pesticide, is globally used to control insects in the household and in agriculture. Despite beneficial roles, its uncontrolled and repetitive application leads to unintended effects in non-target organisms. In light of the relevant anti-oxidant properties of alpha-lipoic acid (ALA), in the work described herein we tested the effect of a commercially available ALA formulation on cypermethrin CY)-induced oxidative stress in Wistar rats. The rats were orally administered with 53.14 mg/kg of ALA and 35.71 mg/kg of CY for 60 days. The treatment with CY did not induce changes in either locomotor activities or in body weight. Differences were observed on superoxide dismutase (SOD), catalase (CAT) and lipid peroxidation that were re-established by ALA treatment at similar levels of the placebo group. Furthermore, ALA formulation increased glutathione (GSH) level and glutathione peroxidase (GPx) activity. Because of the widespread use of CY, higher amounts of pesticide residues are present in food, and a diet supplementation with ALA could be an active free radical scavenger protecting against diseases associated with oxidative stress.

  2. Regulation of ion homeostasis by aminolevulinic acid in salt-stressed wheat seedlings

    Energy Technology Data Exchange (ETDEWEB)

    Türk, Hülya, E-mail: hulyaa.turk@hotmail.com [Biology Department, Science Faculty, Ataturk University, Erzurum (Turkey); East Anatolian High Technology Research and Application Center, Ataturk University, Erzurum (Turkey); Genişel, Mucip, E-mail: m.genisel@hotmail.com [Department of Crop and Animal Production, Vocational High School, Agri (Turkey); Erdal, Serkan, E-mail: serkanerdal25@hotmail.com [Biology Department, Science Faculty, Ataturk University, Erzurum (Turkey)

    2016-04-18

    Salinity is regarded as a worldwide agricultural threat, as it seriously limits plant development and productivity. Salt stress reduces water uptake in plants by disrupting the osmotic balance of soil solution. In addition, it creates a damaged metabolic process by causing ion imbalance in cells. In this study, we aim to examine the negative effects of 5-aminolevulinic acid (ALA) (20 mg/l) on the ion balance in wheat seedling leaves exposed to salt stress (150 mM). Sodium is known to be highly toxic for plant cells at high concentrations, and is significantly increased by salt stress. However, it can be reduced by combined application of ALA and salt, compared to salt application alone. On the other hand, while the K{sup +}/Na{sup +} ratio was reduced by salt stress, ALA application changed this ratio in favor of K{sup +}. Manganese, iron, and copper were also able to reduce stress. However, ALA pre-treatment resulted in mineral level increments. Conversely, the stress-induced rise in magnesium, potassium, calcium, phosphorus, zinc, and molybdenum were further improved by ALA application. These data clearly show that ALA has an important regulatory effect of ion balance in wheat leaves.

  3. Regulation of ion homeostasis by aminolevulinic acid in salt-stressed wheat seedlings

    Science.gov (United States)

    Türk, Hülya; Genişel, Mucip; Erdal, Serkan

    2016-04-01

    Salinity is regarded as a worldwide agricultural threat, as it seriously limits plant development and productivity. Salt stress reduces water uptake in plants by disrupting the osmotic balance of soil solution. In addition, it creates a damaged metabolic process by causing ion imbalance in cells. In this study, we aim to examine the negative effects of 5-aminolevulinic acid (ALA) (20 mg/l) on the ion balance in wheat seedling leaves exposed to salt stress (150 mM). Sodium is known to be highly toxic for plant cells at high concentrations, and is significantly increased by salt stress. However, it can be reduced by combined application of ALA and salt, compared to salt application alone. On the other hand, while the K+/Na+ ratio was reduced by salt stress, ALA application changed this ratio in favor of K+. Manganese, iron, and copper were also able to reduce stress. However, ALA pre-treatment resulted in mineral level increments. Conversely, the stress-induced rise in magnesium, potassium, calcium, phosphorus, zinc, and molybdenum were further improved by ALA application. These data clearly show that ALA has an important regulatory effect of ion balance in wheat leaves.

  4. Methotrexate-related response on human peripheral blood mononuclear cells may be modulated by the Ala16Val-SOD2 gene polymorphism.

    Science.gov (United States)

    Barbisan, Fernanda; Motta, Jéssica de Rosso; Trott, Alexis; Azzolin, Verônica; Dornelles, Eduardo Bortoluzzi; Marcon, Matheus; Algarve, Thaís Doeler; Duarte, Marta Maria Medeiros Frescura; Mostardeiro, Clarice Pinheiro; Unfer, Taís Cristina; Schott, Karen Lilian; da Cruz, Ivana Beatrice Mânica

    2014-01-01

    Methotrexate (MTX) is a folic acid antagonist used in high doses as an anti-cancer treatment and in low doses for the treatment of some autoimmune diseases. MTX use has been linked to oxidative imbalance, which may cause multi-organ toxicities that can be attenuated by antioxidant supplementation. Despite the oxidative effect of MTX, the influence of antioxidant gene polymorphisms on MTX toxicity is not well studied. Therefore, we analyzed here whether a genetic imbalance of the manganese-dependent superoxide dismutase (SOD2) gene could have some impact on the MTX cytotoxic response. An in vitro study using human peripheral blood mononuclear cells (PBMCs) obtained from carriers with different Ala16Val-SOD2 genotypes (AA, VV and AV) was carried out, and the effect on cell viability and proliferation was analyzed, as well as the effect on oxidative, inflammatory and apoptotic markers. AA-PBMCs that present higher SOD2 efficiencies were more resistance to high MTX doses (10 and 100 µM) than were the VV and AV genotypes. Both lipoperoxidation and ROS levels increased significantly in PBMCs exposed to MTX independent of Ala16Val-SOD2 genotypes, whereas increased protein carbonylation was observed only in PBMCs from V allele carriers. The AA-PBMCs exposed to MTX showed decreasing SOD2 activity, but a concomitant up regulation of the SOD2 gene was observed. A significant increase in glutathione peroxidase (GPX) levels was observed in all PBMCs exposed to MTX. However, this effect was more intense in AA-PBMCs. Caspase-8 and -3 levels were increased in cells exposed to MTX, but the modulation of these genes, as well as that of the Bax and Bcl-2 genes involved in the apoptosis pathway, presented a modulation that was dependent on the SOD2 genotype. MTX at a concentration of 10 µM also increased inflammatory cytokines (IL-1β, IL-6, TNFα and Igγ) and decreased the level of IL-10 anti-inflammatory cytokine, independent of SOD2 genetic background. The results suggest that

  5. Methotrexate-related response on human peripheral blood mononuclear cells may be modulated by the Ala16Val-SOD2 gene polymorphism.

    Directory of Open Access Journals (Sweden)

    Fernanda Barbisan

    Full Text Available Methotrexate (MTX is a folic acid antagonist used in high doses as an anti-cancer treatment and in low doses for the treatment of some autoimmune diseases. MTX use has been linked to oxidative imbalance, which may cause multi-organ toxicities that can be attenuated by antioxidant supplementation. Despite the oxidative effect of MTX, the influence of antioxidant gene polymorphisms on MTX toxicity is not well studied. Therefore, we analyzed here whether a genetic imbalance of the manganese-dependent superoxide dismutase (SOD2 gene could have some impact on the MTX cytotoxic response. An in vitro study using human peripheral blood mononuclear cells (PBMCs obtained from carriers with different Ala16Val-SOD2 genotypes (AA, VV and AV was carried out, and the effect on cell viability and proliferation was analyzed, as well as the effect on oxidative, inflammatory and apoptotic markers. AA-PBMCs that present higher SOD2 efficiencies were more resistance to high MTX doses (10 and 100 µM than were the VV and AV genotypes. Both lipoperoxidation and ROS levels increased significantly in PBMCs exposed to MTX independent of Ala16Val-SOD2 genotypes, whereas increased protein carbonylation was observed only in PBMCs from V allele carriers. The AA-PBMCs exposed to MTX showed decreasing SOD2 activity, but a concomitant up regulation of the SOD2 gene was observed. A significant increase in glutathione peroxidase (GPX levels was observed in all PBMCs exposed to MTX. However, this effect was more intense in AA-PBMCs. Caspase-8 and -3 levels were increased in cells exposed to MTX, but the modulation of these genes, as well as that of the Bax and Bcl-2 genes involved in the apoptosis pathway, presented a modulation that was dependent on the SOD2 genotype. MTX at a concentration of 10 µM also increased inflammatory cytokines (IL-1β, IL-6, TNFα and Igγ and decreased the level of IL-10 anti-inflammatory cytokine, independent of SOD2 genetic background. The results

  6. A dynamic model for ALA-PDT of skin: simulation of temporal and spatial distributions of ground-state oxygen, photosensitizer and singlet oxygen

    Energy Technology Data Exchange (ETDEWEB)

    Liu Baochang [Department of Medical Physics and Applied Radiation Sciences, McMaster University, 1280 Main Street West, Hamilton, Ontario L8S 4K1 (Canada); Farrell, Thomas J; Patterson, Michael S, E-mail: Baochang.Liu@jcc.hhsc.c, E-mail: Mike.Patterson@jcc.hhsc.c [Department of Medical Physics, Juravinski Cancer Centre, 699 Concession Street, Hamilton, Ontario L8V 5C2 (Canada)

    2010-10-07

    Singlet oxygen ({sup 1}O{sub 2}) direct dosimetry and photosensitizer fluorescence photobleaching are being investigated and applied as dosimetric tools during 5-aminolevulinic acid (ALA)-induced protophorphyrin IX (PpIX) photodynamic therapy (PDT) of normal skin and skin cancers. The correlations of photosensitizer fluorescence and singlet oxygen luminescence (SOL) emission signals to {sup 1}O{sub 2} distribution and cumulative {sup 1}O{sub 2} dose are difficult to interpret because of the temporal and spatial variations of three essential components (light fluence rate, photosensitizer concentration and oxygen concentration) in PDT. A one-dimensional model is proposed in this paper to simulate the dynamic process of ALA-PDT of normal human skin in order to investigate the time-resolved evolution of PpIX, ground-state oxygen ({sup 3}O{sub 2}) and {sup 1}O{sub 2} distributions. The model incorporates a simplified three-layer semi-infinite skin tissue, Monte Carlo simulations of excitation light fluence and both PpIX fluorescence and SOL emission signals reaching the skin surface, {sup 1}O{sub 2}-mediated photobleaching mechanism for updating PpIX, {sup 3}O{sub 2} and {sup 1}O{sub 2} distributions after the delivery of each light dose increment, ground-state oxygen supply by diffusion from the atmosphere and perfusion from blood vessels, a cumulative {sup 1}O{sub 2}-dependent threshold vascular response, and the initial non-uniform distribution of PpIX. The PpIX fluorescence simulated using this model is compared with clinical data reported by Cottrell et al (2008 Clin. Cancer Res. 14 4475-83) for a range of irradiances (10-150 mW cm{sup -2}). Except for the vascular response, one set of parameters is used to fit data at all irradiances. The time-resolved depth-dependent distributions of PpIX, {sup 3}O{sub 2} and {sup 1}O{sub 2} at representative irradiances are presented and discussed in this paper, as well as the PDT-induced vascular response at different depths

  7. Manganese Superoxide Dismutase Val-9Ala Polymorphism and Breast Cancer Susceptibility: A Meta-analysis%MnSOD基因Val-9Ala多态性与乳腺癌易感性关系的Meta分析

    Institute of Scientific and Technical Information of China (English)

    孙国贵; 王雅棣; 王士杰; 郑明民; 程云杰; 李成林; 柴红

    2011-01-01

    Objective To explore the association between manganese superoxide dismutase (MnSOD) Val-9Ala polymorphism and breast cancer risk and to investigate the interaction with menopausal status by meta-analysis. Methods Such databases as The Cochrane Libtary (Issuel, 2010), Pubmed, CBM, CNKI and WanFang Data were searched from the date of their establishment to October, 2010, and the case-control studies of MnSOD Val-9Ala polymorphism and breast cancer risk were collected according to the inclusion and exclusion criteria. Then the quality of the included trials was assessed and meta-analysis was performed by RevMan 4.2.10 software. Results A total of 14 studies involving 17 842 patients were included. The results of meta-analyses showed no significant relation between MnSOD Val-9Ala polymorphism and the breast cancer susceptibility (Val/Ala vs. Val/Val: OR=1.04, 9596CI 0.93 to 1.17; Ala/Ala vs. Val/ Val: OR=1.12, 95%CI 0.95 to 1.33; Ala/Ala vs. Val/Ala+Val/Val: OR=1.06, 95%CI 0.93 to 1.20; Val/Ala+ Ala/Ala vs. Val/ Val: OR=1.06, 9596CI 0.94 to 1.10). However, in the subgroup analysis, the breast cancer risk significantly increased for premenopausal women (Val/Ala+Ala/Ala vs. Val/Val: OR=1.15, 95%CI 1.01 tol.31). Conclusion This meta-analysis suggests that the MnSOD Val-9Ala polymorphism is not significantly associated with the breast cancer susceptibility, but it may increase the risk of breast cancer in the presence of menopausal state.%目的 评价锰超氧化物歧化酶(MnSOD)基因Val-9Ala多态性与乳腺癌易感性及经期状态的关系.方法 计算机检索Cochrane Library(2010年第1期)、PubMed、CNKI、CBM和万方数据库,按照纳入与排除标准选择相关的病例对照试验,检索时限均为建库至2010年10月.在提取资料和评价质量后,采用RevMan 4.2.10软件进行Meta分析.结果 共纳入14个研究,合计17 842例患者.Meta分析结果显示,MnSOD基因Val-9Ala多态性与乳腺癌易感性无关[ Val/Ala vs.Val/Val:OR=1

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

    Directory of Open Access Journals (Sweden)

    Lee Jung Eun

    2012-09-01

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

  9. Erythrocyte stearidonic acid and other n-3 fatty acids and CHD in the Physicians' Health Study.

    Science.gov (United States)

    Matsumoto, Chisa; Matthan, Nirupa R; Wilk, Jemma B; Lichtenstein, Alice H; Michael Gaziano, J; Djoussé, Luc

    2013-06-01

    Intake of marine-based n-3 fatty acids (EPA, docosapentaenoic acid and DHA) is recommended to prevent CHD. Stearidonic acid (SDA), a plant-based n-3 fatty acid, is a precursor of EPA and may be more readily converted to EPA than a-linolenic acid (ALA). While transgenic soyabeans might supply SDA at low cost, it is unclear whether SDA is associated with CHD risk. Furthermore, associations of other n-3 fatty acids with CHD risk remain inconsistent. The present ancillary study examined the association of erythrocyte SDA as well as other n-3 fatty acids with the risk of CHD. In a prospective nested case-control study of the Physicians' Health Study, we randomly selected 1000 pairs of incident CHD with matching controls. Erythrocyte fatty acids were measured using GC. We used conditional logistic regression to estimate relative risks. Mean age was 68·7 (SD 8·7) years. In a multivariable model controlling for matching factors and established CHD risk factors, OR for CHD for each standard deviation increase of log-SDA was 1·03 (95% CI 0·90, 1·18). Corresponding values for log-ALA and log-marine n-3 fatty acids were 1·04 (95% CI 0·94, 1·16) and 0·97 (95% CI 0·88, 1·07), respectively. In conclusion, the present data did not show an association among erythrocyte SDA, ALA or marine n-3 fatty acids and the risk of CHD in male physicians.

  10. Effect of essential fatty acids on glucose-induced cytotoxicity to retinal vascular endothelial cells

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    Shen Junhui

    2012-07-01

    Full Text Available Abstract Background Diabetic retinopathy is a major complication of dysregulated hyperglycemia. Retinal vascular endothelial cell dysfunction is an early event in the pathogenesis of diabetic retinopathy. Studies showed that hyperglycemia-induced excess proliferation of retinal vascular endothelial cells can be abrogated by docosahexaenoic acid (DHA, 22:6 ω-3 and eicosapentaenoic acid (EPA, 20:5 ω-3. The influence of dietary omega-3 PUFA on brain zinc metabolism has been previously implied. Zn2+ is essential for the activity of Δ6 desaturase as a co-factor that, in turn, converts essential fatty acids to their respective long chain metabolites. Whether essential fatty acids (EFAs α-linolenic acid and linoleic acid have similar beneficial effect remains poorly understood. Methods RF/6A cells were treated with different concentrations of high glucose, α-linolenic acid and linoleic acid and Zn2+. The alterations in mitochondrial succinate dehydrogenase enzyme activity, cell membrane fluidity, reactive oxygen species generation, SOD enzyme and vascular endothelial growth factor (VEGF secretion were evaluated. Results Studies showed that hyperglycemia-induced excess proliferation of retinal vascular endothelial cells can be abrogated by both linoleic acid (LA and α-linolenic acid (ALA, while the saturated fatty acid, palmitic acid was ineffective. A dose–response study with ALA showed that the activity of the mitochondrial succinate dehydrogenase enzyme was suppressed at all concentrations of glucose tested to a significant degree. High glucose enhanced fluorescence polarization and microviscocity reverted to normal by treatment with Zn2+ and ALA. ALA was more potent that Zn2+. Increased level of high glucose caused slightly increased ROS generation that correlated with corresponding decrease in SOD activity. ALA suppressed ROS generation to a significant degree in a dose dependent fashion and raised SOD activity significantly. ALA suppressed

  11. EDUCACIÓN Y RESILIENCIA: ALAS DE LA TRANSFORMACIÓN SOCIAL

    Directory of Open Access Journals (Sweden)

    Viviana López Torres

    2010-01-01

    Full Text Available Tratándose de un nuevo paradigma de desarrollo, la resiliencia propone que no todas las personas que crecen en condiciones de adversidad, pobreza y desigualdad social serán adultos condenados al fracaso, a la delincuencia o a la locura; por el contrario, este concepto enfatiza en el potencial humano y hace un llamado a la esperanza y a la responsabilidad colectiva en la promoción de cambio social. El presente ensayo parte de una revisión analítica de literatura reciente sobre resiliencia, en el marco del trabajo realizado durante el año 2009 por el grupo "Esperanza y Vida", en la línea de investigación denominada "Resiliencia y contextos psicosociales", perteneciente al programa de Psicología de la Universidad Antonio Nariño (UAN Bogotá, Colombia. Este ejercicio reflexivo tiene como propósito analizar el concepto de resiliencia en el contexto escolar, considerando que este es uno de los primeros contactos de la infancia con la cultura, el lugar en donde las niñas y los niños van a preguntarse cómo funciona el mundo, el sitio donde pueden encontrar respuestas honestas y sugerencias útiles sobre cómo comprenderlo y cómo transformarlo; además, señala cómo acciones pedagógicas fundamentadas en el reconocimiento del estudiante como un agente responsable y activo en el proceso de aprendizaje, favorecen actitudes de compromiso en la promoción de la transformación social positiva.

  12. Changes of lipid and fatty acid absorption induced by high dose of citric acid ester and lecithin emulsifiers.

    Science.gov (United States)

    Sadouki, Mohamed; Bouchoucha, Michel

    2014-09-01

    To describe the effect of two food emulsifiers, lecithin (E322) and citric acid esters of mono-and diglycerides of fatty acids (E472c), on the intestinal absorption of lipids. The experiment was conducted on 24 male Wistar rats randomly assigned in three groups. For two groups of six rats, 30% of the lipid intake was replaced with lecithin (L) or citric acid ester of mono and diglycerides, (E);