Sample records for acid based homocysteine

  1. The effect of folic acid based homocysteine lowering on cardiovascular events in people with kidney disease: systematic review and meta-analysis.

    PubMed

    Jardine, Meg J; Kang, Amy; Zoungas, Sophia; Navaneethan, Sankar D; Ninomiya, Toshiharu; Nigwekar, Sagar U; Gallagher, Martin P; Cass, Alan; Strippoli, Giovanni; Perkovic, Vlado

    2012-06-13

    To systematically review the effect of folic acid based homocysteine lowering on cardiovascular outcomes in people with kidney disease. Systematic review and meta-analysis. Medline, Embase, the Cochrane Library, and ClinicalTrials.gov to June 2011. Randomised trials in people with non-dialysis dependent chronic kidney disease or end stage kidney disease or with a functioning kidney transplant reporting at least 100 patient years of follow-up and assessing the effect of folic acid based homocysteine lowering therapy. No language restrictions were applied. Two reviewers independently extracted data on study setting, design, and outcomes using a standardised form. The primary endpoint was cardiovascular events (myocardial infarction, stroke, and cardiovascular mortality, or as defined by study author). Secondary endpoints included the individual composite components, all cause mortality, access thrombosis, requirement for renal replacement therapy, and reported adverse events, including haematological and neurological events. The effect of folic acid based homocysteine lowering on outcomes was assessed with meta-analysis using random effects models. 11 trials were identified that reported on 4389 people with chronic kidney disease, 2452 with end stage kidney disease, and 4110 with functioning kidney transplants (10,951 participants in total). Folic acid based homocysteine therapy did not prevent cardiovascular events (relative risk 0.97, 95% confidence interval 0.92 to 1.03, P = 0.326) or any of the secondary outcomes. There was no evidence of heterogeneity in subgroup analyses, including those of kidney disease category, background fortification, rates of pre-existing disease, or baseline homocysteine level. The definitions of chronic kidney disease varied widely between the studies. Non-cardiovascular events could not be analysed as few studies reported these outcomes. Folic acid based homocysteine lowering does not reduce cardiovascular events in people with kidney

  2. Relationship between Total Homocysteine, Folic Acid, and Thyroid Hormones in Hypothyroid Dogs.

    PubMed

    Gołyński, M; Lutnicki, K; Krumrych, W; Szczepanik, M; Gołyńska, M; Wilkołek, P; Adamek, Ł; Sitkowski, Ł; Kurek, Ł

    2017-09-01

    Both elevated homocysteine and decreased folic acid concentrations are observed in human patients with hypothyroidism and can influence the development of numerous secondary disorders. The aim of the study was to assess total homocysteine concentration in serum and to examine its relationship with the concentration of folic acid and thyroid hormones (tT4 and fT4). Ten healthy and 19 hypothyroid client-owned dogs. Dogs with clinical signs of hypothyroidism had the diagnosis confirmed by additional tests. Total homocysteine, folic acid, total thyroxine, and free thyroxine concentrations in serum were evaluated. Hypothyroid dogs were diagnosed with increased homocysteine (median 22.20 μmol/L; range, 16.50-37.75) and decreased folic acid (median 20.62 nmol/L; range, 10.54-26.35) concentrations, as compared to healthy dogs (11.52 μmol/L; range, 10.00-16.65 and 30.68 nmol/L; range, 22.84-38.52, respectively). In sick dogs, total homocysteine was inversely correlated with folic acid (ρ = -0.47, P < 0.001), total thyroxine (ρ = -0.69, P = 0.0092), and free thyroxine (ρ = -0.56, P = 0.0302). Hypothyroidism in dogs causes hyperhomocysteinemia. Concomitant mild folic acid decrease in hypothyroid dogs might be as a result of hyperhomocysteinemia. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  3. Folic acid inhibits homocysteine-induced cell apoptosis in human umbilical vein endothelial cells.

    PubMed

    Cui, Shanshan; Li, Wen; Wang, Pengyan; Lv, Xin; Gao, Yuxia; Huang, Guowei

    2017-12-18

    Homocysteine may be responsible for vascular endothelial cell injury, which occurs early in the pathology of cardiovascular disease. Homocysteine metabolism requires enzymatic interaction with vitamins such as folic acid, vitamin B12, and vitamin B6. We hypothesized that folic acid alleviated homocysteine-induced vascular injury by regulating the metabolic pathway of apoptosis. Human umbilical vein endothelial cells were incubated for 48 h with folic acid at the concentrations of 0-1000 nmol/L, in combination with either 1000 μmol/L homocysteine or vehicle for the first 24 h. We then assessed cell viability and apoptosis by methyl thiazolyl tetrazolium assay and flow cytometry, respectively. To further investigate how folic acid influenced cell apoptosis, we also analyzed the activities of caspase-3/7 and the mRNA and protein expressions of BCL2, BAX, TP53, CASP3, and CASP8 in human umbilical vein endothelial cells. We showed that folic acid increased cell viability and decreased apoptosis in a dose-dependent manner, and that this effect was mediated by decreased caspase-3/7 activity, upregulated BCL2/BAX ratio, and downregulated TP53, CASP3, and CASP8 expressions. Thus, we conclude that folic acid inhibits cell apoptosis and ameliorates homocysteine toxicity by regulating the expression of apoptosis-related genes in human umbilical vein endothelial cells.

  4. Polyunsaturated fatty acids in serum and homocysteine concentrations in Japanese men and women: a cross-sectional study.

    PubMed

    Kume, Ayami; Kurotani, Kayo; Sato, Masao; Ejima, Yuko; Pham, Ngoc Minh; Nanri, Akiko; Kuwahara, Keisuke; Mizoue, Tetsuya

    2013-06-10

    Supplementation studies have suggested a role of n-3 polyunsaturated fatty acids (PUFAs) in homocysteine metabolism, but the evidence is limited and inconsistent among studies that measured blood levels of n-3 and n-6 PUFAs. We examined the association between blood levels of PUFAs and homocysteine in Japanese men and women. The subjects were 496 employees (290 men and 206 women) of 2 municipal offices in Japan. Fatty acid composition in serum phospholipids and cholesterol ester (CE) was measured using gas-liquid chromatography. Multiple regression was used to calculate means of homocysteine concentrations according to PUFA tertile with adjustment for potential confounders. Serum homocysteine concentration decreased with increasing levels of total n-3 PUFA, eicosapentaenoic acid and docosahexaenoic acid (DHA) in serum phospholipids and CE with adjustment for age, sex and workplace. However, only DHA in serum phospholipids remained statistically significant after additional adjustment for other potential confounders including serum folate (P-trend = 0.04). N-6 PUFAs were not significantly associated with homocysteine concentrations. Higher proportion of DHA in serum phospholipids may be associated with lower homocysteine concentrations in Japanese men and women.

  5. Comparative case-control study of homocysteine, vitamin B12, and folic acid levels in patients with epilepsy.

    PubMed

    Pulido Fontes, L; Pulido Fontes, M; Quesada Jiménez, P; Muruzabal Pérez, J; Mendioroz Iriarte, M

    2017-09-01

    Increased blood homocysteine levels are a known cardiovascular risk factor. Epileptic patients on long-term treatment with antiepileptic drugs may present higher homocysteine levels and, consequently, a potential increase in cardiovascular risk. We conducted an observational case-control study to compare plasma levels of homocysteine, folic acid, and vitamin B 12 . Our study included a total of 88 subjects: 52 patients with epilepsy and 36 controls. Epileptic patients showed higher homocysteine levels (P=.084) and lower levels of folic acid (P<.05). Homocysteine levels should be monitored in epileptic patients on long-term treatment with antiepileptic drugs. We suggest starting specific treatment in patients with high homocysteine levels. Copyright © 2016 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  6. Folic acid and the methylation of homocysteine by Bacillus subtilis

    PubMed Central

    Salem, A. R.; Pattison, J. R.; Foster, M. A.

    1972-01-01

    1. Cell-free extracts of Bacillus subtilis synthesize methionine from serine and homocysteine without added folate. The endogenous folate may be replaced by tetrahydropteroyltriglutamate or an extract of heated Escherichia coli for the overall C1 transfer, but tetrahydropteroylmonoglutamate is relatively inactive. 2. Extracts of B. subtilis contain serine transhydroxymethylase and 5,10-methylenetetrahydrofolate reductase, which are non-specific with respect to the glutamate content of the folate substrates. Methyl transfer to homocysteine requires a polyglutamate folate as methyl donor. These properties are not affected by growth of the organism with added vitamin B12. 3. The synthesis of methionine from 5-methyltetrahydropteroyltriglutamate and homocysteine has the characteristics of the cobalamin-independent reaction of E. coli. No evidence for a cobalamin-dependent transmethylation was obtained. 4. S-Adenosylmethionine was not a significant precursor of the methyl group of methionine with cell-free extracts, neither was S-adenosylmethionine generated by methylation of S-adenosylhomocysteine by 5-methyltetrahydrofolate. 5. A procedure for the isolation and analysis of folic acid derivatives from natural sources is described. 6. The folates isolated from lysozyme extracts of B. subtilis are sensitive to folic acid conjugase. One has been identified as 5-formyltetrahydropteroyltriglutamate; the other is possibly a diglutamate folate. 7. A sequence is proposed for methionine biosynthesis in B. subtilis in which methyl groups are generated from serine and transferred to homocysteine by means of a cobalamin-independent pathway mediated by conjugated folate coenzymes. PMID:4627401

  7. [Does diet affect our mood? The significance of folic acid and homocysteine].

    PubMed

    Karakuła, Hanna; Opolska, Aneta; Kowal, Anna; Domański, Maciej; Płotka, Aniela; Perzyński, Janusz

    2009-02-01

    In recent years, there has been growing interest in the association between national diet and the possibility of developing various mental disorders, as well as between deficiency of such vitamins as, e.g. folic acid, vitamin B12, B6, and others (e.g., omega-3 fatty acids), elevated serum homocysteine level and the functioning of human brain as well as the occurrence of such disorders as dementia, central nervous system vascular disorders and depression. was to present the current state of knowledge about the role of folic acid and homocysteine in the human organism as well as the significance of vitamin deficiency, mainly folic acid and hyperhomocysteinemy for the occurrence of mood disorders. The authors conducted the search of the Internet database Medline (www.pubmed.com) using as key words: depression, mood, homocysteine, vitamin deficiencies: folic acid, B6 and 812 and time descriptors: 1990-2007. In depression, folate, vitamins B12 and B6, as well as unsaturated omega-3 fatty acids deficiency affects the biochemical processes in the CNS, as folic acid and vitamin B12, participate in the metabolism of S-adenosylmethionine (SAM), a donator of methyl groups, which play a decisive role in the functioning of the nervous system; they are, among others, active in the formation of neurotransmitters (e.g. serotonin), phospholipids that are a component of neuronal myelin sheaths, and cell receptors. The deficiency of the vitamins in question results in hyperhomocysteinemia (the research shows that approximately 45-55% of patients with depression develop significantly elevated serum homocysteine), which causes a decrease in SAM, followed by impaired methylation and, consequently, impaired metabolism of neurotransmitters, phospholipids, myelin, and receptors. Hyperhomocysteinemia also leads to activation of NMDA receptors, lesions in vascular endothelium, and oxidative stress. All this effects neurotoxicity and promotes the development of various disorders, including

  8. Effect of folic acid supplementation on plasma homocysteine in obese children: a randomized, double-blind, placebo-controlled trial.

    PubMed

    Iamopas, Orawan; Ratanachu-ek, Suntaree; Chomtho, Sirinuch

    2014-06-01

    Obese children tend to consume less dietary folate, which is an important cofactor in remethylation of homocysteine to methionine. The deficiency of folate can lead to hyperhomocysteinemia. To determine whether folic acid supplementation could reduce plasma homocysteine in obese children. Obese children, aged 9-15 years with body mass index > median plus 2 SD according to WHO reference, were randomly assigned to 2 groups: receiving either 5 mg folic acid or placebo for 2 months. Fasting homocysteine, creatinine, folate, vitamin B12, insulin, glucose and lipid profiles were taken at baseline and the end of the study. Dietary vitamin B12, folate intake and physical activity were assessed using validated questionnaires. Fifty obese children (31 boys and 19 girls) took part in the study. Their mean age was 10.9 ± 1.6 years and mean BMI Z-score was 3.41 ± 0.69. After the intervention, plasma homocysteine decreased by 15.75% and 6.99% in the folic acid and placebo group, respectively (mean difference 8.76%; 95% CI: 0.26%, 17.25%, p = 0.044). This divergence was more pronounced in boys and it remained significant after adjusting for baseline homocysteine and other confounders. Subgroup analysis showed a larger magnitude of plasma homocysteine reduction in the low folate group (mean difference 12.24%; 95% CI: 1.39%, 23.09%). The homocysteine lowering effect of folic acid supplementation was found in obese children, especially in boys and those with low serum folate. Further long-term interventional studies are needed to determine the effects of the lowered plasma homocysteine on the cardiovascular outcomes of obese children. This trial was registered on clinicaltrials.gov (NCT01766310).

  9. Methoxistasis: Integrating the Roles of Homocysteine and Folic Acid in Cardiovascular Pathobiology

    PubMed Central

    Joseph, Jacob; Loscalzo, Joseph

    2013-01-01

    Over the last four decades, abnormalities in the methionine-homocysteine cycle and associated folate metabolism have garnered great interest due to the reported link between hyperhomocysteinemia and human pathology, especially atherothrombotic cardiovascular disease. However, clinical trials of B-vitamin supplementation including high doses of folic acid have not demonstrated any benefit in preventing or treating cardiovascular disease. In addition to the fact that these clinical trials may have been shorter in duration than appropriate for modulating chronic disease states, it is likely that reduction of the blood homocysteine level may be an oversimplified approach to a complex biologic perturbation. The methionine-homocysteine cycle and folate metabolism regulate redox and methylation reactions and are, in turn, regulated by redox and methylation status. Under normal conditions, a normal redox-methylation balance, or “methoxistasis”, exists, coordinated by the methionine-homocysteine cycle. An abnormal homocysteine level seen in pathologic states may reflect a disturbance of methoxistasis. We propose that future research should be targeted at estimating the deviation from methoxistasis and how best to restore it. This approach could lead to significant advances in preventing and treating cardiovascular diseases, including heart failure. PMID:23955381

  10. Homocysteine regulates fatty acid and lipid metabolism in yeast.

    PubMed

    Visram, Myriam; Radulovic, Maja; Steiner, Sabine; Malanovic, Nermina; Eichmann, Thomas O; Wolinski, Heimo; Rechberger, Gerald N; Tehlivets, Oksana

    2018-04-13

    S -Adenosyl-l-homocysteine hydrolase (AdoHcy hydrolase; Sah1 in yeast/AHCY in mammals) degrades AdoHcy, a by-product and strong product inhibitor of S -adenosyl-l-methionine (AdoMet)-dependent methylation reactions, to adenosine and homocysteine (Hcy). This reaction is reversible, so any elevation of Hcy levels, such as in hyperhomocysteinemia (HHcy), drives the formation of AdoHcy, with detrimental consequences for cellular methylation reactions. HHcy, a pathological condition linked to cardiovascular and neurological disorders, as well as fatty liver among others, is associated with a deregulation of lipid metabolism. Here, we developed a yeast model of HHcy to identify mechanisms that dysregulate lipid metabolism. Hcy supplementation to wildtype cells up-regulated cellular fatty acid and triacylglycerol content and induced a shift in fatty acid composition, similar to changes observed in mutants lacking Sah1. Expression of the irreversible bacterial pathway for AdoHcy degradation in yeast allowed us to dissect the impact of AdoHcy accumulation on lipid metabolism from the impact of elevated Hcy. Expression of this pathway fully suppressed the growth deficit of sah1 mutants as well as the deregulation of lipid metabolism in both the sah1 mutant and Hcy-exposed wildtype, showing that AdoHcy accumulation mediates the deregulation of lipid metabolism in response to elevated Hcy in yeast. Furthermore, Hcy supplementation in yeast led to increased resistance to cerulenin, an inhibitor of fatty acid synthase, as well as to a concomitant decline of condensing enzymes involved in very long-chain fatty acid synthesis, in line with the observed shift in fatty acid content and composition. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

  11. Homocysteine regulates fatty acid and lipid metabolism in yeast

    PubMed Central

    Visram, Myriam; Radulovic, Maja; Steiner, Sabine; Malanovic, Nermina; Eichmann, Thomas O.; Wolinski, Heimo; Rechberger, Gerald N.; Tehlivets, Oksana

    2018-01-01

    S-Adenosyl-l-homocysteine hydrolase (AdoHcy hydrolase; Sah1 in yeast/AHCY in mammals) degrades AdoHcy, a by-product and strong product inhibitor of S-adenosyl-l-methionine (AdoMet)-dependent methylation reactions, to adenosine and homocysteine (Hcy). This reaction is reversible, so any elevation of Hcy levels, such as in hyperhomocysteinemia (HHcy), drives the formation of AdoHcy, with detrimental consequences for cellular methylation reactions. HHcy, a pathological condition linked to cardiovascular and neurological disorders, as well as fatty liver among others, is associated with a deregulation of lipid metabolism. Here, we developed a yeast model of HHcy to identify mechanisms that dysregulate lipid metabolism. Hcy supplementation to wildtype cells up-regulated cellular fatty acid and triacylglycerol content and induced a shift in fatty acid composition, similar to changes observed in mutants lacking Sah1. Expression of the irreversible bacterial pathway for AdoHcy degradation in yeast allowed us to dissect the impact of AdoHcy accumulation on lipid metabolism from the impact of elevated Hcy. Expression of this pathway fully suppressed the growth deficit of sah1 mutants as well as the deregulation of lipid metabolism in both the sah1 mutant and Hcy-exposed wildtype, showing that AdoHcy accumulation mediates the deregulation of lipid metabolism in response to elevated Hcy in yeast. Furthermore, Hcy supplementation in yeast led to increased resistance to cerulenin, an inhibitor of fatty acid synthase, as well as to a concomitant decline of condensing enzymes involved in very long-chain fatty acid synthesis, in line with the observed shift in fatty acid content and composition. PMID:29414770

  12. Capillary electrophoresis tandem mass spectrometry determination of glutamic acid and homocysteine's metabolites: Potential biomarkers of amyotrophic lateral sclerosis.

    PubMed

    Cieslarova, Zuzana; Lopes, Fernando Silva; do Lago, Claudimir Lucio; França, Marcondes Cavalcante; Colnaghi Simionato, Ana Valéria

    2017-08-01

    Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects both lower and upper motor neurons, leading to muscle atrophy, paralysis, and death caused by respiratory failure or infectious complications. Altered levels of homocysteine, cysteine, methionine, and glutamic acid have been observed in plasma of ALS patients. In this context, a method for determination of these potential biomarkers in plasma by capillary electrophoresis tandem mass spectrometry (CE-MS/MS) is proposed herein. Sample preparation was carefully investigated, since sulfur-containing amino acids may interact with plasma proteins. Owing to the non-thiol sulfur atom in methionine, it was necessary to split sample preparation into two methods: i) determination of homocysteine and cysteine as S-acetyl amino acids; ii) determination of glutamic acid and methionine. All amino acids were separated within 25min by CE-MS/MS using 5molL -1 acetic acid as background electrolyte and 5mmolL -1 acetic acid in 50% methanol/H 2 O (v/v) as sheath liquid. The proposed CE-MS/MS method was validated, presenting RSD values below 6% and 11% for intra- and inter-day precision, respectively, for the middle concentration level within the linear range. The limits of detection ranged from 35 (homocysteine) to 268nmolL -1 (glutamic acid). The validated method was applied to the analysis of plasma samples from a group of healthy individuals and patients with ALS, showing the potential of glutamic acid and homocysteine metabolites as biomarkers of ALS. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Efficacy of homocysteine lowering therapy with folic acid in stroke prevention: a meta-analysis

    PubMed Central

    Lee, Meng; Hong, Keun-Sik; Chang, Shen-Chih; Saver, Jeffrey L.

    2010-01-01

    Background and Purpose Although lower serum homocysteine concentration is associated with a reduced risk of stroke in epidemiologic studies, randomized controlled trials (RCTs) have yielded mixed findings regarding the effect of therapeutic homocysteine lowering on stroke prevention. We performed a meta-analysis of RCTs to assess the efficacy of folic acid supplementation in the prevention of stroke. Methods Salient trials were identified by formal literature search. Relative risk (RR) with 95% confidence interval (CI) was used as a measure of the association between folic acid supplementation and risk of stroke, pooling data across trials using a fixed-effects model. Results The search identified 13 RCTs of folic acid therapy to reduce homocysteine, enrolling 39,005 participants, in which stroke was reported as an outcome measure. Across all trials, folic acid supplementation was associated with a trend toward mild benefit that did not reach statistical significance in reducing the risk of stroke (RR 0.93, 95% CI 0.85-1.03; p=0.16). The RR for non-secondary prevention trials was 0.89 (95% CI 0.79-0.99; p=0.03). In stratified analyses, a greater beneficial effect was seen in the trials testing combination therapy of folic acid plus vitamins B6 and B12 (RR 0.83, 0.71-0.97; p=0.02) and in the trials which disproportionately enrolled male patients (men/women > 2, RR 0.84, 0.74-0.94; p=0.003). Conclusions Folic acid supplementation did not demonstrate a major effect in averting stroke. However, potential mild benefits in primary stroke prevention, especially when folate is combined with B vitamins and in male patients, merit further investigation. PMID:20413740

  14. Effect of plasma homocysteine level and urinary monomethylarsonic acid on the risk of arsenic-associated carotid atherosclerosis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wu, M.-M.; Graduate Institute of Medicine, College of Medicine, Fu-Jen Catholic University, Taipei, Taiwan; Chiou, H.-Y.

    2006-10-01

    Arsenic-contaminated well water has been shown to increase the risk of atherosclerosis. Because of involving S-adenosylmethionine, homocysteine may modify the risk by interfering with the biomethylation of ingested arsenic. In this study, we assessed the effect of plasma homocysteine level and urinary monomethylarsonic acid (MMA{sup V}) on the risk of atherosclerosis associated with arsenic. In total, 163 patients with carotid atherosclerosis and 163 controls were studied. Lifetime cumulative arsenic exposure from well water for study subjects was measured as index of arsenic exposure. Homocysteine level was determined by high-performance liquid chromatography (HPLC). Proportion of MMA{sup V} (MMA%) was calculated bymore » dividing with total arsenic species in urine, including arsenite, arsenate, MMA{sup V}, and dimethylarsinic acid (DMA{sup V}). Results of multiple linear regression analysis show a positive correlation of plasma homocysteine levels to the cumulative arsenic exposure after controlling for atherosclerosis status and nutritional factors (P < 0.05). This correlation, however, did not change substantially the effect of arsenic exposure on the risk of atherosclerosis as analyzed in a subsequent logistic regression model. Logistic regression analyses also show that elevated plasma homocysteine levels did not confer an independent risk for developing atherosclerosis in the study population. However, the risk of having atherosclerosis was increased to 5.4-fold (95% CI, 2.0-15.0) for the study subjects with high MMA% ({>=}16.5%) and high homocysteine levels ({>=}12.7 {mu}mol/l) as compared to those with low MMA% (<9.9%) and low homocysteine levels (<12.7 {mu}mol/l). Elevated homocysteinemia may exacerbate the formation of atherosclerosis related to arsenic exposure in individuals with high levels of MMA% in urine.« less

  15. [Homocysteine, vitamin B-12, folic acid and the cognitive decline in the elderly].

    PubMed

    Smach, M A; Naffeti, S; Charfeddine, B; Ben Abdallah, J; Othmen, L B; Letaef, A; Limem, K

    2013-10-01

    Hyperhomocysteinemia is a risk factor for neurological diseases, but the underlying pathophysiology has not been adequately explained. Mild hyperhomocysteinemia, which is sometimes associated with a low plasma level of vitamin B9, B12 and folic acid, is responsible in the toxicity in neural cell by activating NMDA receptor. Indeed, even if vitamin supplementation has clearly proven its efficiency on lowering plasma levels of homocysteine, recent studies do not show any positive effect of vitamin therapy on cognitive function. The hypothesis that this therapy is inefficient has been recently reinforced by two randomized trials on the effects of vitamin supplementation. Several hypotheses still need to be explored: Mechanisms of homocysteine toxicity and that of total uselessness of vitamin supplementation; the possible need to complete the actual data with further, more powerful studies in order to prove the role of homocysteine in the development of neurodegenerative diseases and a clinical effect of vitamin therapy. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  16. Folic acid supplementation does not reduce intracellular homocysteine, and may disturb intracellular one-carbon metabolism.

    PubMed

    Smith, Desirée E C; Hornstra, Jacqueline M; Kok, Robert M; Blom, Henk J; Smulders, Yvo M

    2013-08-01

    In randomized trails, folic acid (FA) lowered plasma homocysteine, but failed to reduce cardiovascular risk. We hypothesize this is due to a discrepancy between plasma and intracellular effects of FA. In a double-blind trial, 50 volunteers were randomized to received 500 µg FA daily for 8 weeks, or placebo. Plasma and peripheral blood mononuclear cell (PBMC) concentrations of homocysteine, S-adenosylmethionine (SAM), S-adenosylhomocysteine, methionine, cystathionine and 5-methyltetrahydrofolate (bioactive folate) were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). PBMCs were used as a cellular model since they display the full spectrum of one-carbon (1C) enzymes and reactions. At baseline, plasma concentrations were a poor reflection of intracellular concentrations for most 1C metabolites, except 5-methyltetrahydrofolate (R=0.33, p=0.02), homocysteine (Hcy) (R=0.35, p=0.01), and cystathionine (R=0.45, p=0.001). FA significantly lowered plasma homocysteine (p=0.00), but failed to lower intracellular homocysteine or change the concentrations of any of the other PBMC 1C metabolites. At baseline, PBMC homocysteine concentrations correlated to PBMC SAM. After FA supplementation, PBMC homocysteine no longer correlated with PBMC SAM, suggesting a loss of SAM's regulatory function. In vitro experiments in lymphoblasts confirmed that at higher folate substrate concentrations, physiological concentrations of SAM no longer effectively inhibit the key regulatory enzyme methylenetetrahydrofolate reductase (MTHFR). FA supplementation does not reduce intracellular concentrations of Hcy or any of its closely related substances. Rather, FA may disturb physiological regulation of intracellular 1C metabolism by interfering with SAM's inhibitory effect on MTHFR activity.

  17. Choline Supplementation Alters Some Amino Acid Concentrations with No Change in Homocysteine in Children with Cystic Fibrosis and Pancreatic Insufficiency

    PubMed Central

    Alshaikh, Belal; Schall, Joan I.; Maqbool, Asim; Mascarenhas, Maria; Bennett, Michael J.; Stallings, Virginia A.

    2016-01-01

    The present study determined the plasma amino acid status in children with cystic fibrosis (CF) and pancreatic insufficiency (PI) in the modern medical and nutritional care setting and investigated the effect of choline supplementation on amino acid status. A total of 110 children, ages 5 to 18 years, with CF and PI were randomized to receive choline-enriched structured lipid (LYM-X-SORB™, LXS) or placebo with similar calorie and fat content. Plasma amino acids were measured at baseline, 3, and 12 months. We hypothesized that choline supplementation would result in lower plasma homocysteine concentrations in children with CF. At baseline, dietary protein intake was high and the amino acid profile was within laboratory reference ranges in most subjects. Alanine and cysteine were elevated in 24% and 36% of subjects, respectively. Children with baseline alanine above reference range had improved weight, body mass index, and fat-free mass. Low homocysteine was found in 62% of children 11 years and older. After 3 and 12 months, there was no effect of choline supplementation on methionine or homocysteine status. Compared to placebo, choline supplementation resulted in increased glycine and decreased threonine, histidine, valine and total branch chained amino acids at 12 months. In conclusion, daily choline supplementation with LXS did not alter methionine-homocysteine metabolism but did result in alterations in other amino acids in children with CF and PI. PMID:27101760

  18. Fluorescent coumarin-based probe for cysteine and homocysteine with live cell application

    NASA Astrophysics Data System (ADS)

    Wei, Ling-Fang; Thirumalaivasan, Natesan; Liao, Yu-Cheng; Wu, Shu-Pao

    2017-08-01

    Cysteine (Cys) and homocysteine (Hcy) are two of important biological thiols and function as important roles in several biological processes. The development of Cys and Hcy probes will help to explore the functions of biothiols in biological systems. In this work, a new coumarin-based probe AC, containing an acryloyl moiety, was developed for Cys and Hcy detection in cells. Cys and Hcy undergo a nucleophilic addition and subsequent cyclization reaction to remove to the acryloyl group and yield a fluorescent product, 7-hydroxylcomuarin. The probe AC showed good selectivity for cysteine and homocysteine over glutathione and other amino acids and had low detection limits of 65 nM for Cys and 79 nM for Hcy, respectively. Additionally, confocal imaging experiments demonstrated that the probe AC can be applied to visualize Cys and Hcy in living cells.

  19. Choline supplementation alters some amino acid concentrations with no change in homocysteine in children with cystic fibrosis and pancreatic insufficiency.

    PubMed

    Alshaikh, Belal; Schall, Joan I; Maqbool, Asim; Mascarenhas, Maria; Bennett, Michael J; Stallings, Virginia A

    2016-05-01

    The present study determined the plasma amino acid status in children with cystic fibrosis (CF) and pancreatic insufficiency (PI) in the modern medical and nutritional care setting and investigated the effect of choline supplementation on amino acid status. A total of 110 children aged 5 to 18 years with CF and PI were randomized to receive choline-enriched structured lipid (LYM-X-SORB) or placebo with similar energy and fat content. Plasma amino acids were measured at baseline and 3 and 12 months. We hypothesized that choline supplementation would result in lower plasma homocysteine concentrations in children with CF. At baseline, dietary protein intake was high and the amino acid profile was within laboratory reference ranges in most participants. Alanine and cysteine were elevated in 24% and 36% of participants, respectively. Children with baseline alanine above reference range had improved weight, body mass index, and fat-free mass. Low homocysteine was found in 62% of children 11 years and older. After 3 and 12 months, there was no effect of choline supplementation on methionine or homocysteine status. Compared with placebo, choline supplementation resulted in increased glycine and decreased threonine, histidine, valine, and total branch chained amino acids at 12 months. In conclusion, daily choline supplementation with LYM-X-SORB did not alter methionine-homocysteine metabolism but did result in alterations in other amino acids in children with CF and PI. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Effects of folic acid and N-acetylcysteine on plasma homocysteine levels and endothelial function in patients with coronary artery disease.

    PubMed

    Yilmaz, Hale; Sahin, Sinan; Sayar, Nurten; Tangurek, Burak; Yilmaz, Mehmet; Nurkalem, Zekeriya; Onturk, Ebru; Cakmak, Nazmiye; Bolca, Osman

    2007-12-01

    Hyperhomocysteinaemia is related with premature coronary artery disease and adverse cardiac events in patients with coronary artery disease (CAD). It is assumed that hyper-homocysteinaemia causes endothelial dysfunction. In this study, the effect of folic acid and oral N-acetylcysteine (NAC) therapies on plasma homocysteine levels and endothelial function were evaluated in hyperhomocysteinaemic patients with CAD. 60 patients were randomized to either folic acid 5 mg or NAC 600 mg or placebo daily for eight weeks. Brachial artery endothelial functions were studied by using high-resolution ultrasound and assessed by measuring endothelium-dependent dilation (EDD) and endothelium-independent dilation (NEDD). Folic acid and NAC therapies decreased plasma homocysteine (from 21.7 +/- 8.7 micromol/l to 12.5 +/- 2.5 micromol/l, P < 0.001; from 20.9 +/- 7.6 micromol/l to 15.6 +/- 4.3 micromol/l, P = 0.03, respectively), and increased EDD (6.7 +/- 6.1% P = 0.002, 4.4 +/- 2.6% P < 0.001, respectively) compared with placebo. There was no significant difference in improving EDD between the folic acid and the NAC group (6.7 +/- 6.1%, 4.4 +/- 2.6%, P = 0. 168). In the univariate analyses there was an inverse correlation between the post-treatment homocysteine level and the percent change in EDD with folic acid therapy (r= -0.490, P = 0.028), but there was no correlation with the NAC therapy (r = 0.259, P = 0.333) In patients with hyperhomocysteinaemic CAD, folic acid and NAC lowered plasma homocysteine levels and improved endothelial function. The effects of both treatments in improvement of EDD were similar.

  1. Serum levels of lipoprotein(a) and homocysteine in patients on hemodialysis who take hydroxymethylglutaryl-CoA reductase inhibitors, vitamin B6, and folic acid.

    PubMed

    Shojaei, Mir Hatef; Djalali, Mamhmoud; Siassi, Fereydoun; Khatami, Mohammad Reza; Boroumand, Mohammad Ali; Eshragian, Mohammad Reza

    2009-07-01

    High serum levels of lipoprotein(a) and homocysteine are risk factors of cardiovascular disease which are prevalent in patients on hemodialysis. Controversy exists about the effects of hydroxymethylglutaryl-CoA reductase inhibitors on serum lipoprotein(a) levels in patients on hemodialysis. Also, deficiency of some water soluble vitamins and administration of statins may raise serum levels of homocysteine in these patients. This study was designed to investigate serum levels of lipoprotein(a) and homocysteine in patients on hemodialysis who were taking a statin, vitamin B6, and folic acid. We investigated on 152 patients with maintenance hemodialysis who were taking atorvastatin or lovastatin, vitamin B6, and folic acid for at least 6 months. Their serum levels were obtained to measure lipoprotein(a) and homocysteine levels, as well as triglyceride, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. The mean serum values of total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol and triglyceride were significantly less than the maximum reference values (P < .001). The mean serum level of lipoprotein(a) was also less than the reference value (P = .009), but homocysteine level was 33% higher on average than the reference value (P < .001). Our study demonstrated that in our patients on hemodialysis, the mean serum level of homocysteine was about 30% higher than the reference value although they were receiving vitamin B6 and folic acid. Hence, they were still exposed to the risk of cardiovascular disease.

  2. Hepatic betaine-homocysteine methyltransferase activity in the chicken is influenced by dietary intake of sulfur amino acids, choline and betaine.

    PubMed

    Emmert, J L; Garrow, T A; Baker, D H

    1996-08-01

    There is much interest in the metabolism of homocysteine, because elevated plasma homocysteine [hyperhomocyst(e)inemia] is an independent risk factor for the development of cardiovascular disease. Four chick assays were conducted to determine the effects of varying dietary sulfur amino acids, choline and betaine on the activity of hepatic betaine-homocysteine methyltransferase (BHMT), an enzyme likely to be important in modulating plasma homocysteine. In Experiment 1, chicks were fed a purified crystalline amino acid diet containing adequate sulfur amino acids and choline. Excess dietary methionine, or the combination of excess cystine with choline or betaine, caused a small increase (P < 0.05) in BHMT activity. In Experiment 2, use of a methionine-deficient purified diet resulted in a threefold increase (P < 0.05) in BHMT activity, and addition of choline or betaine further increased (P < 0.05) BHMT activity. In Experiment 3, use of a methionine-deficient corn-peanut meal diet increased BHMT (P < 0.05) relative to that of chicks supplemented with adequate methionine, and addition of surfeit choline to the methionine-deficient basal diet caused a further increase (P < 0.05). In Experiment 4, addition of both surfeit choline and surfeit betaine to the methionine-deficient corn-peanut meal diet caused an increase (P < 0.05) in BHMT activity relative to that observed in chicks fed the methionine-deficient basal diet. These assays show that large increases in BHMT activity can be produced under methionine-deficient conditions, especially in the presence of excess choline or betaine.

  3. Transmethylation of homocysteine to methionine: efficiency in the rat and chick.

    PubMed

    Baker, D H; Czarnecki, G L

    1985-10-01

    Experiments were conducted with young chicks and rats to quantify the efficacy of L-homocysteine as a methionine precursor. Linear growth responses were obtained to both L-methionine and L-homocysteine when added to a methionine-deficient intact-protein diet containing a plethora of cystine. Slope-ratio multiple regression methodology indicated L-homocysteine to be 64.5% as efficacious as L-methionine in rats and 62.5% as efficacious in chicks. Plasma-free methionine also increased linearly as graded levels of either L-methionine or L-homocysteine were added to the diet of rats. At higher dosages of L-homocysteine, betaine, but not choline, showed some efficacy in enhancing the conversion of homocysteine to methionine. In the linear response surface of the growth curve, however, supplemental betaine was without effect on L-homocysteine bioefficacy, as was also the case for supplemental sarcosine and N5-methyltetrahydrofolic acid.

  4. Exercise, nutrition, and homocysteine.

    PubMed

    Joubert, Lanae M; Manore, Melinda M

    2006-08-01

    Homocysteine is an independent cardiovascular disease (CVD) risk factor modifiable by nutrition and possibly exercise. While individuals participating in regular physical activity can modify CVD risk factors, such as total blood cholesterol levels, the impact physical activity has on blood homocysteine concentrations is unclear. This review examines the influence of nutrition and exercise on blood homocysteine levels, the mechanisms of how physical activity may alter homocysteine levels, the role of homocysteine in CVD, evidence to support homocysteine as an independent risk factor for CVD, mechanisms of how homocysteine increases CVD risk, and cut-off values for homocysteinemia. Research examining the impact of physical activity on blood homocysteine levels is equivocal, which is partially due to a lack of control for confounding variables that impact homocysteine. Duration, intensity, and mode of exercise appear to impact blood homocysteine levels differently, and may be dependent on individual fitness levels.

  5. MAT1A variants modulate the effect of dietary fatty acids on plasma homocysteine concentrations and DNA damage

    USDA-ARS?s Scientific Manuscript database

    Dietary n-3 polyunsaturated fatty acids (PUFA) are associated with decreased plasma homocysteine (Hcy), an important biomarker for cardiovascular disease. Methionine adenosyltransferase (MAT1A) is an enzyme involved in formation of form S-adenosylmethionine during methionine metabolism. The objectiv...

  6. Effect of Folic Acid, Betaine, Vitamin B6, and Vitamin B12 on Homocysteine and Dimethylglycine Levels in Middle-Aged Men Drinking White Wine

    PubMed Central

    Rajdl, Daniel; Racek, Jaroslav; Trefil, Ladislav; Stehlik, Pavel; Dobra, Jana; Babuska, Vaclav

    2016-01-01

    Moderate regular consumption of alcoholic beverages is believed to protect against atherosclerosis but can also increase homocysteine or dimethylglycine, which are putative risk factors for atherosclerosis. We aimed (1) to investigate the effect of alcohol consumption on vitamins and several metabolites involved in one-carbon metabolism; and (2) to find the most effective way of decreasing homocysteine during moderate alcohol consumption. Methods: Male volunteers (n = 117) were randomly divided into five groups: the wine-only group (control, 375 mL of white wine daily for one month) and four groups combining wine consumption with one of the supplemented substances (folic acid, betaine, and vitamins B12 or B6). Significant lowering of homocysteine concentration after the drinking period was found in subjects with concurrent folate and betaine supplementation. Vitamin B12 and vitamin B6 supplementation did not lead to a statistically significant change in homocysteine. According to a multiple linear regression model, the homocysteine change in the wine-only group was mainly determined by the interaction between the higher baseline homocysteine concentration and the change in dimethylglycine levels. Folate and betaine can attenuate possible adverse effects of moderate alcohol consumption. Dimethylglycine should be interpreted together with data on alcohol consumption and homocysteine concentration. PMID:26771632

  7. Some amino acids levels: glutamine,glutamate, and homocysteine, in plasma of children with chronic kidney disease.

    PubMed

    Fadel, Fatina I; Elshamaa, Manal F; Essam, Rascha G; Elghoroury, Eman A; El-Saeed, Gamila S M; El-Toukhy, Safinaz E; Ibrahim, Mona Hamed

    2014-03-01

    The high prevalence of protein-energy malnutrition is a critical issue for patients with chronic kidney disease (CKD). Serum albumin is the most commonly used nutritional marker. Another index is plasma amino acid (AA) profile. Of these, the plasma levels of glutamine, glutamate and homocysteine, correlate well with nutritional status. We measured some plasma AAs in children with different stages CKD to provide information in monitoring the therapeutic strategy, particularly in AA supplementary therapy or protein restriction. Three amino acids were evaluated along with albumin and high sensitivity C-reactive protein (hs-CRP) in 30 patients with advanced CKD stages 4 and 5. They were divided into two groups undergoing conservative treatment (CT) (n=15) or hemodialysis (HD) (n=15). An additional group of patients with nephrotic syndrome [CKD stage 2] was also studied to assess the alterations of plasma free amino acids with the early stage of CKD. Another 30 age- and sex-matched healthy children served as controls. A significant increase in plasma concentration of amino acid glutamine was observed in children with advanced CKD stages 4 and 5 when compared with controls (P=0.02).Plasma glutamine level was significantly higher in ESRD children on HD than in children with nephrotic syndrome (P=0.02). We did not find a significant difference between HD children and CT children as regard to glutamine level. Notable differences were in the plasma homocysteine level detected in the CKD groups patients, which was greater than that in controls (P=0.0001). Plasma homocysteine level was significantly higher in children on HD than in children with nephrotic syndrome (P=0.01). A significant differences was observed in hs-CRP levels between the CKD groups and the controls (P=0.04). Albumin levels were lower in CKD groups than in controls (p=0.01). Glutamine showed significant positive correlations with blood urea level (r=0.84, P=0.002) and blood ammonia level (r=0.72, P=0

  8. Study on relationships among deep vein thrombosis, homocysteine & related B group vitamins.

    PubMed

    Ekim, Meral; Ekim, Hasan; Yilmaz, Yunus Keser; Kulah, Bahadir; Polat, M Fevzi; Gocmen, A Yesim

    2015-01-01

    Hyperhomocysteinemia has been considered as a potential risk factor for deep venous thrombosis (DVT) but it is still controversy. We aimed to evaluate the prevalence of hyperhomocysteinemia in patients with DVT. Our second objective was to document the prevalence of folate, Vitamin B6, and Vitamin B12 level in this patient population. Sixty patients with DVT aged from 23 to 84 years, were assessed regarding demographic characteristics, serum levels of homocysteine, folate, vitamin B12, and vitamin B6. The diagnosis of DVT was based upon Wells scoring system and serum D-dimer level and confirmed by deep venous Doppler ultrasonography of the lower limbs. Mean serum homocysteine levels were found significantly higher in patients over the age of 40 years (10.81±4.26 µmol/L vs 9.13±3.23 µmol/L). Of all the patients, 9 patients had homocysteine level above the 15µmol/L, 26 had folic acid level below 3 ng/ml, one had vitamin B12 level below 150 pmol/L, and two had vitamin B6 level below 30 nmol/L. In the hyperhomocysteinemic group, five patients had low folic acid level, one had low vitamin B12 level, and two had low vitamin B6 level. Hyperhomocysteinemia, in women older than 40 years, may be a risk factor for DVT. Folic acid deficiency may also influence serum homocysteine concentrations. Folate therapy may be offered to the patients with DVT. However further studies are required to clarify the underlying molecular mechanisms.

  9. Increased serum level of homocysteine correlates with retinal nerve fiber layer thinning in diabetic retinopathy

    PubMed Central

    Srivastav, Khushboo; Mahdi, Abbas A.; Shukla, Rajendra K.; Meyer, Carsten H.; Akduman, Levent; Khanna, Vinay K.

    2016-01-01

    Purpose To study the correlation between serum levels of vitamin B12, folic acid, and homocysteine and the severity of diabetic retinopathy and the correlation with retinal nerve fiber layer (RNFL) thinning on spectral domain optical coherence tomography (SD-OCT). Methods In a tertiary care center–based prospective cross-sectional study, 60 consecutive cases and 20 healthy controls in the age group of 40–65 years were included. The eyes of the cases were divided into three groups according to Early Treatment Diabetic Retinopathy Study (ETDRS) classification: diabetes mellitus without retinopathy (n = 20), non-proliferative diabetic retinopathy with macular edema (n = 20), and proliferative diabetic retinopathy with macular edema (n = 20). The serum levels of vitamin B12 and folic acid were measured using a standard protocol. The serum homocysteine assay was performed using an enzyme-linked immunosorbent assay (ELISA) kit. Average RNFL thickness was measured using SD-OCT. Statistical analysis was used to assess the correlations between the study variables. Results Increased severity of diabetic retinopathy was found to correlate with an increase in the serum levels of homocysteine (F = 53.79; p<0.001). The mean serum levels of vitamin B12 and folic acid were found to be within the normal reference range. A positive correlation was found between retinal nerve fiber layer thinning and serum levels of homocysteine (p<0.001). Conclusions This study, for the first time, demonstrated a correlation between increased homocysteine with a decrease in RNFL thickness and increased severity of diabetic retinopathy. PMID:27994434

  10. Are dietary choline and betaine intakes determinants of total homocysteine concentration?

    PubMed

    Lee, Jung Eun; Jacques, Paul F; Dougherty, Lauren; Selhub, Jacob; Giovannucci, Edward; Zeisel, Steven H; Cho, Eunyoung

    2010-05-01

    Elevated homocysteine concentrations are associated with an increased risk of cardiovascular disease and a decline in cognitive function. Intakes of choline and betaine, as methyl donors, may affect homocysteine concentrations. The objective was to examine whether choline and betaine intakes, assessed from food-frequency questionnaires, are associated with total plasma homocysteine concentrations under both fasting and post-methionine-load conditions in both pre- and post-folic acid fortification periods in the United States. We assessed the association between choline and betaine intakes and fasting and post-methionine-load homocysteine concentrations using the US Department of Agriculture revised food-composition tables and evaluated whether the associations varied by folic acid fortification periods in 1325 male and 1407 female participants in the sixth examination (1995-1998) of the Framingham Offspring Study. A higher choline-plus-betaine intake was associated with lower concentrations of post-methionine-load homocysteine; the multivariate geometric means were 24.1 micromol/L (95% CI: 23.4, 24.9 micromol/L) in the top quintile of intake and 25.0 micromol/L (95% CI: 24.2, 25.7 micromol/L) in the bottom quintile (P for trend = 0.01). We found an inverse association between choline-plus-betaine intake and fasting homocysteine concentrations; the multivariate geometric mean fasting homocysteine concentrations were 9.6 micromol/L (95% CI: 9.3, 9.9 micromol/L) in the top quintile and 10.1 micromol/L (95% CI: 9.8, 10.4 micromol/L) in the bottom quintile (P for trend < 0.001). When we stratified by plasma folate and vitamin B-12 concentrations, the inverse association was limited to participants with low plasma folate or vitamin B-12 concentrations. In the postfortification period, the inverse association between choline-plus-betaine intake and either fasting or post-methionine-load homocysteine was no longer present. Choline and betaine intakes were associated with

  11. Homocysteine-Lowering and Cardiovascular Disease Outcomes in Kidney Transplant Recipients: Primary Results from the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) Trial

    PubMed Central

    Bostom, Andrew G.; Carpenter, Myra A.; Kusek, John W.; Levey, Andrew S.; Hunsicker, Lawrence; Pfeffer, Marc A.; Selhub, Jacob; Jacques, Paul F.; Cole, Edward; Gravens-Mueller, Lisa; House, Andrew A.; Kew, Clifton; McKenney, Joyce L.; Pacheco-Silva, Alvaro; Pesavento, Todd; Pirsch, John; Smith, Stephen; Solomon, Scott; Weir, Matthew

    2015-01-01

    Background Kidney transplant recipients, like other patients with chronic kidney disease (CKD), experience excess risk of cardiovascular disease (CVD) and elevated total homocysteine (tHcy) concentrations. Observational studies of patients with CKD suggest increased homocysteine is a risk factor for CVD. The impact of lowering total homocysteine (tHcy) levels in kidney transplant recipients is unknown. Methods and Results In a double-blind controlled trial, we randomized 4110 stable kidney transplant recipients to a multivitamin that included either a high dose (n=2056) or low dose (n=2054) of folic acid, vitamin B6, and vitamin B12 to determine whether decreasing tHcy concentrations reduced the rate of the primary composite arteriosclerotic CVD outcome (myocardial infarction, stroke, CVD death, resuscitated sudden death, coronary artery or renal artery revascularization, lower extremity arterial disease, carotid endarterectomy or angioplasty, or abdominal aortic aneurysm repair). Mean follow-up was 4.0 years. Treatment with the high dose multivitamin reduced homocysteine but did not reduce the rates of the primary outcome (n= 547 total events; hazards ratio [95% confidence interval] = 0.99 [0.84–1.17]), or secondary outcomes of all-cause mortality (n=431 deaths; 1.04 [0.86–1.26]) or dialysis-dependent kidney failure (n=343 events; 1.15 [0.93–1.43]) compared to the low dose multivitamin. Conclusions Treatment with a high dose folic acid, B6, and B12 multivitamin in kidney transplant recipients did not reduce a composite cardiovascular disease outcome, all-cause mortality, or dialysis-dependent kidney failure despite significant reduction in homocysteine level. PMID:21482964

  12. Diets high in palmitic acid (16:0), lauric and myristic acids (12:0 + 14:0), or oleic acid (18:1) do not alter postprandial or fasting plasma homocysteine and inflammatory markers in healthy Malaysian adults.

    PubMed

    Voon, Phooi Tee; Ng, Tony Kock Wai; Lee, Verna Kar Mun; Nesaretnam, Kalanithi

    2011-12-01

    Dietary fat type is known to modulate the plasma lipid profile, but its effects on plasma homocysteine and inflammatory markers are unclear. We investigated the effects of high-protein Malaysian diets prepared with palm olein, coconut oil (CO), or virgin olive oil on plasma homocysteine and selected markers of inflammation and cardiovascular disease (CVD) in healthy adults. A randomized-crossover intervention with 3 dietary sequences of 5 wk each was conducted in 45 healthy subjects. The 3 test fats, namely palmitic acid (16:0)-rich palm olein (PO), lauric and myristic acid (12:0 + 14:0)-rich CO, and oleic acid (18:1)-rich virgin olive oil (OO), were incorporated at two-thirds of 30% fat calories into high-protein Malaysian diets. No significant differences were observed in the effects of the 3 diets on plasma total homocysteine (tHcy) and the inflammatory markers TNF-α, IL-1β, IL-6, and IL-8, high-sensitivity C-reactive protein, and interferon-γ. Diets prepared with PO and OO had comparable nonhypercholesterolemic effects; the postprandial total cholesterol for both diets and all fasting lipid indexes for the OO diet were significantly lower (P < 0.05) than for the CO diet. Unlike the PO and OO diets, the CO diet was shown to decrease postprandial lipoprotein(a). Diets that were rich in saturated fatty acids prepared with either PO or CO, and an OO diet that was high in oleic acid, did not alter postprandial or fasting plasma concentrations of tHcy and selected inflammatory markers. This trial was registered at clinicaltrials.gov as NCT00941837.

  13. A Protein Extract from Chicken Reduces Plasma Homocysteine in Rats.

    PubMed

    Lysne, Vegard; Bjørndal, Bodil; Vik, Rita; Nordrehaug, Jan Erik; Skorve, Jon; Nygård, Ottar; Berge, Rolf K

    2015-06-04

    The present study aimed to evaluate effects of a water-soluble protein fraction of chicken (CP), with a low methionine/glycine ratio, on plasma homocysteine and metabolites related to homocysteine metabolism. Male Wistar rats were fed either a control diet with 20% w/w casein as the protein source, or an experimental diet where 6, 14 or 20% w/w of the casein was replaced with the same amount of CP for four weeks. Rats fed CP had reduced plasma total homocysteine level and markedly increased levels of the choline pathway metabolites betaine, dimethylglycine, sarcosine, glycine and serine, as well as the transsulfuration pathway metabolites cystathionine and cysteine. Hepatic mRNA level of enzymes involved in homocysteine remethylation, methionine synthase and betaine-homocysteine S-methyltransferase, were unchanged, whereas cystathionine gamma-lyase of the transsulfuration pathway was increased in the CP treated rats. Plasma concentrations of vitamin B2, folate, cobalamin, and the B-6 catabolite pyridoxic acid were increased in the 20% CP-treated rats. In conclusion, the CP diet was associated with lower plasma homocysteine concentration and higher levels of serine, choline oxidation and transsulfuration metabolites compared to a casein diet. The status of related B-vitamins was also affected by CP.

  14. A Protein Extract from Chicken Reduces Plasma Homocysteine in Rats

    PubMed Central

    Lysne, Vegard; Bjørndal, Bodil; Vik, Rita; Nordrehaug, Jan Erik; Skorve, Jon; Nygård, Ottar; Berge, Rolf K.

    2015-01-01

    The present study aimed to evaluate effects of a water-soluble protein fraction of chicken (CP), with a low methionine/glycine ratio, on plasma homocysteine and metabolites related to homocysteine metabolism. Male Wistar rats were fed either a control diet with 20% w/w casein as the protein source, or an experimental diet where 6, 14 or 20% w/w of the casein was replaced with the same amount of CP for four weeks. Rats fed CP had reduced plasma total homocysteine level and markedly increased levels of the choline pathway metabolites betaine, dimethylglycine, sarcosine, glycine and serine, as well as the transsulfuration pathway metabolites cystathionine and cysteine. Hepatic mRNA level of enzymes involved in homocysteine remethylation, methionine synthase and betaine-homocysteine S-methyltransferase, were unchanged, whereas cystathionine gamma-lyase of the transsulfuration pathway was increased in the CP treated rats. Plasma concentrations of vitamin B2, folate, cobalamin, and the B-6 catabolite pyridoxic acid were increased in the 20% CP-treated rats. In conclusion, the CP diet was associated with lower plasma homocysteine concentration and higher levels of serine, choline oxidation and transsulfuration metabolites compared to a casein diet. The status of related B-vitamins was also affected by CP. PMID:26053618

  15. Modulation of homocysteine toxicity by S-nitrosothiol formation: a mechanistic approach.

    PubMed

    Morakinyo, Moshood K; Strongin, Robert M; Simoyi, Reuben H

    2010-08-05

    The metabolic conversion of homocysteine (HCYSH) to homocysteine thiolactone (HTL) has been reported as the major cause of HCYSH pathogenesis. It was hypothesized that inhibition of the thiol group of HCYSH by S-nitrosation will prevent its metabolic conversion to HTL. The kinetics, reaction dynamics, and mechanism of reaction of HCYSH and nitrous acid to produce S-nitrosohomocysteine (HCYSNO) was studied in mildly to highly acidic pHs. Transnitrosation of this non-protein-forming amino acid by S-nitrosoglutathione (GSNO) was also studied at physiological pH 7.4 in phosphate buffer. In both cases, HCYSNO formed quantitatively. Copper ions were found to play dual roles, catalyzing the rate of formation of HCYSNO as well as its rate of decomposition. In the presence of a transition-metal ions chelator, HCYSNO was very stable with a half-life of 198 h at pH 7.4. Nitrosation by nitrous acid occurred via the formation of more powerful nitrosating agents, nitrosonium cation (NO(+)) and dinitrogen trioxide (N(2)O(3)). In highly acidic environments, NO(+) was found to be the most effective nitrosating agent with a first-order dependence on nitrous acid. N(2)O(3) was the most relevant nitrosating agent in a mildly acidic environment with a second-order dependence on nitrous acid. The bimolecular rate constants for the direct reactions of HCYSH and nitrous acid, N(2)O(3), and NO(+) were 9.0 x 10(-2), 9.50 x 10(3), and 6.57 x 10(10) M(-1) s(-1), respectively. These rate constant values agreed with the electrophilic order of these nitrosating agents: HNO(2) < N(2)O(3) < NO(+). Transnitrosation of HCYSH by GSNO produced HCYSNO and other products including glutathione (reduced and oxidized) and homocysteine-glutathione mixed disulfide. A computer modeling involving eight reactions gave a good fit to the observed formation kinetics of HCYSNO. This study has shown that it is possible to modulate homocysteine toxicity by preventing its conversion to a more toxic HTL by S-nitrosation.

  16. The development and amino acid binding ability of nano-materials based on azo derivatives: theory and experiment.

    PubMed

    Shang, Xuefang; Du, Jinge; Yang, Wancai; Liu, Yun; Fu, Zhiyuan; Wei, Xiaofang; Yan, Ruifang; Yao, Ningcong; Guo, Yaping; Zhang, Jinlian; Xu, Xiufang

    2014-05-01

    Two nano-material-containing azo groups have been designed and developed, and the binding ability of nano-materials with various amino acids has been characterized by UV-vis and fluorescence titrations. Results indicated that two nano-materials showed the strongest binding ability for homocysteine among twenty normal kinds of amino acids (alanine, valine, leucine, isoleucine, methionine, aspartic acid, glutamic acid, arginine, glycine, serine, threonine, asparagine, phenylalanine, histidine, tryptophan, proline, lysine, glutamine, tyrosine and homocysteine). The reason for the high sensitivity for homocysteine was that two nano-materials containing an aldehyde group reacted with SH in homocysteine and afforded very stable thiazolidine derivatives. Theoretical investigation further illustrated the possible binding mode in host-guest interaction and the roles of molecular frontier orbitals in molecular interplay. Thus, the two nano-materials can be used as optical sensors for the detection of homocysteine. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Effects of blood lead and cadmium levels on homocysteine level in plasma.

    PubMed

    Cai, R; Zheng, Y-F; Bu, J-G; Zhang, Y-Y; Fu, S-L; Wang, X-G; Guo, L-L; Zhang, J-R

    2017-01-01

    We studied the effect of non-occupational exposure to lead and cadmium on homocysteine level in plasma. Homocysteine is a marker for plasma folate folic acid metabolism in urban populations. 159 individuals from Beijing, Guangzhou, Shenzhen and Shanghai with no history of close exposure to heavy metals and no history of metabolic diseases were enrolled to participate in this study. Blood lead and cadmium levels were detected using ICP-MS method and the level of homocysteine was also measured using enzyme method. Our results showed that blood lead and cadmium levels in males were significantly higher than those in females. Also, blood lead and cadmium levels in smokers were higher than those in non-smokers; homocysteine level was significantly higher in smokers as well. According to blood lead and cadmium levels, cases were divided into four groups. Our results showed that a surge in blood lead and cadmium levels could result in an increase in homocysteine level. We concluded that in the Chinese population, smoking and gender might be the risk factors for elevated levels of lead and cadmium. Meanwhile, blood lead and cadmium levels may influence the homocysteine levels in the body. It is possible to speculate that non-occupational exposure to lead and cadmium, by increasing the homocysteine levels, negatively affect the cardiovascular and nervous system.

  18. Homocysteine and venous thrombosis: outline of a vitamin intervention trial.

    PubMed

    Willems, H P; den Heijer, M; Bos, G M

    2000-01-01

    In the past years several case-control studies established the association of an elevated plasma homocysteine concentration and the risk of venous thromboembolism. It is still unclear if elevated homocysteine concentrations can cause venous thrombosis. The VITRO (VItamins and ThROmbosis) trial is the first multicenter, randomized, double-blind and placebo-controlled study to evaluate the effect of homocysteine-lowering therapy by means of 5 mg folic acid, 0.4 mg vitamin B12 and 50 mg vitamin B6. The study is a secondary prevention trial in 600 patients who suffered from a first episode of idiopathic deep vein thrombosis (DVT) or pulmonary embolism (PE), or both. There will be 300 hyperhomocysteinemic and 300 normohomocysteinemic patients included, all with an objectivated venous thrombosis. The end point is recurrence of venous thrombosis.

  19. Effect of L-methionine supplementation on plasma homocysteine and other free amino acids: a placebo-controlled double-blind cross-over study.

    PubMed

    Ditscheid, B; Fünfstück, R; Busch, M; Schubert, R; Gerth, J; Jahreis, G

    2005-06-01

    The essential amino acid L-methionine is a potential compound in the prophylaxis of recurrent or relapsing urinary tract infection due to acidification of urine. As an intermediate of L-methionine metabolism, homocysteine is formed. The objective was to study the metabolism of L-methionine and homocysteine, and to assess whether there are differences between patients with chronic urinary tract infection and healthy control subjects. A randomized placebo-controlled double-blind intervention study with cross-over design. Department of Nutritional Physiology, Institute of Nutrition in cooperation with the Department of Internal Medicine III, Friedrich Schiller University of Jena, Germany. Eight female patients with chronic urinary tract infection and 12 healthy women (controls). After a methionine-loading test, the volunteers received 500 mg L-methionine or a placebo three times daily for 4 weeks. Serum and urinary concentrations of methionine, homocysteine, cystathionine, cystine, serine, glycine and serum concentrations of vitamin B12, B6 and the state of folate. Homocysteine plasma concentrations increased from 9.4+/-2.7 micromol/l (patients) and 8.9+/-1.8 micromol/l (controls) in the placebo period to 11.2+/-4.1 micromol/l (P=0.031) and 11.0+/-2.3 micromol/l (P=0.000), respectively, during L-methionine supplementation. There were significant increases in serum methionine (53.6+/-22.0 micromol/l; P=0.003; n=20) and cystathionine (0.62+/-0.30 micromol/l; P=0.000; n=20) concentrations compared with the placebo period (33.0+/-12.0 and 0.30+/-0.10 micromol/l; n=20). Simultaneously, renal excretion of methionine and homocysteine was significantly higher during L-methionine intake. Despite an adequate vitamin status, the supplementation of 1500 mg of L-methionine daily significantly increases homocysteine plasma concentrations by an average of 2.0 micromol/l in patients and in control subjects. An optimal vitamin supplementation, especially with folate, might prevent

  20. A flavone-based turn-on fluorescent probe for intracellular cysteine/homocysteine sensing with high selectivity.

    PubMed

    Zhang, Jian; Lv, Yanlin; Zhang, Wei; Ding, Hui; Liu, Rongji; Zhao, Yongsheng; Zhang, Guangjin; Tian, Zhiyuan

    2016-01-01

    A new type of flavone-based fluorescent probe (DMAF) capable of cysteine (Cys)/homocysteine (Hcy) sensing with high selectivity over other amino acids was developed. Such type of probe undergoes Cys/Hcy-mediated cyclization reaction with the involvement of its aldehyde group, which suppresses of the photoinduced electron transfer (PET) process of the probe molecule and consequently leads to the enhancement of fluorescence emission upon excitation using visible light. The formation of product of the Cys/Hcy-mediated cyclization reaction was confirmed and the preliminary fluorescence imaging experiments revealed the biocompatibility of the as-prepared probe and validated its practicability for intracellular Cys/Hcy sensing. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Effects of homocysteine-lowering with folic acid plus vitamin B12 vs placebo on mortality and major morbidity in myocardial infarction survivors: a randomized trial.

    PubMed

    Armitage, Jane M; Bowman, Louise; Clarke, Robert J; Wallendszus, Karl; Bulbulia, Richard; Rahimi, Kazem; Haynes, Richard; Parish, Sarah; Sleight, Peter; Peto, Richard; Collins, Rory

    2010-06-23

    Blood homocysteine levels are positively associated with cardiovascular disease, but it is uncertain whether the association is causal. To assess the effects of reducing homocysteine levels with folic acid and vitamin B(12) on vascular and nonvascular outcomes. Double-blind randomized controlled trial of 12,064 survivors of myocardial infarction in secondary care hospitals in the United Kingdom between 1998 and 2008. 2 mg folic acid plus 1 mg vitamin B(12) daily vs matching placebo. First major vascular event, defined as major coronary event (coronary death, myocardial infarction, or coronary revascularization), fatal or nonfatal stroke, or noncoronary revascularization. Allocation to the study vitamins reduced homocysteine by a mean of 3.8 micromol/L (28%). During 6.7 years of follow-up, major vascular events occurred in 1537 of 6033 participants (25.5%) allocated folic acid plus vitamin B(12) vs 1493 of 6031 participants (24.8%) allocated placebo (risk ratio [RR], 1.04; 95% confidence interval [CI], 0.97-1.12; P = .28). There were no apparent effects on major coronary events (vitamins, 1229 [20.4%], vs placebo, 1185 [19.6%]; RR, 1.05; 95% CI, 0.97-1.13), stroke (vitamins, 269 [4.5%], vs placebo, 265 [4.4%]; RR, 1.02; 95% CI, 0.86-1.21), or noncoronary revascularizations (vitamins, 178 [3.0%], vs placebo, 152 [2.5%]; RR, 1.18; 95% CI, 0.95-1.46). Nor were there significant differences in the numbers of deaths attributed to vascular causes (vitamins, 578 [9.6%], vs placebo, 559 [9.3%]) or nonvascular causes (vitamins, 405 [6.7%], vs placebo, 392 [6.5%]) or in the incidence of any cancer (vitamins, 678 [11.2%], vs placebo, 639 [10.6%]). Substantial long-term reductions in blood homocysteine levels with folic acid and vitamin B(12) supplementation did not have beneficial effects on vascular outcomes but were also not associated with adverse effects on cancer incidence. isrctn.org Identifier: ISRCTN74348595.

  2. Anti-inflammatory compound resveratrol suppresses homocysteine formation in stimulated human peripheral blood mononuclear cells in vitro.

    PubMed

    Schroecksnadel, Katharina; Winkler, Christiana; Wirleitner, Barbara; Schennach, Harald; Weiss, Günter; Fuchs, Dietmar

    2005-01-01

    Inflammation, immune activation and oxidative stress play a major role in the pathogenesis of cardiovascular disorders. In addition to markers of inflammation, moderate hyperhomocysteinemia is an independent risk factor for cardiovascular disease, and there is a link between the activation of immunocompetent cells and the enhanced formation of homocysteine in vitro. Likewise, anti-inflammatory drugs and nutrients rich in antioxidant vitamins are able to reduce cardiovascular risk and to slow down the atherogenic process. Resveratrol, a phenolic antioxidant synthesized in grapes and vegetables and present in wine, has also been supposed to be beneficial for the prevention of cardiovascular events. Apart from its strong antioxidant properties, resveratrol has also been demonstrated to act as an anti-inflammatory agent. In this study the influence of resveratrol on the production of homocysteine by stimulated human peripheral blood mononuclear cells (PBMCs) was investigated. Results were compared to earlier described effects of the anti-inflammatory compounds aspirin and salicylic acid and of the lipid-lowering drug atorvastatin. Stimulation of PBMCs with the mitogens concanavalin A and phytohemagglutinin induced significantly higher homocysteine accumulation in supernatants compared with unstimulated cells. Treatment with 10-100 muM resveratrol suppressed homocysteine formation in a dose-dependent manner. Resveratrol did not influence the release of homocysteine from resting PBMCs. The data suggest that resveratrol may prevent homocysteine accumulation in the blood by suppressing immune activation cascades and the proliferation of mitogen-driven T-cells. The effect of resveratrol to down-regulate the release of homo-cysteine was comparable to the decline of neopterin concentrations in the same experiments. The suppressive effect of resveratrol was very similar to results obtained earlier with aspirin, salicylic acid and atorvastatin; however, it appeared that doses

  3. Influence of folic acid, pyridoxal phosphate and cobalamin on plasma homocyst(e)ine levels and the susceptibility of low-density lipoprotein to ex-vivo oxidation.

    PubMed

    Weiss, N; Feussner, A; Hailer, S; Spengel, F A; Keller, C; Wolfram, G

    1999-10-15

    Mild hyperhomocyst(e)inaemia is a risk factor for atherosclerotic vascular disease. In-vitro studies have shown that autooxidation of homocyst(e)ine is accompanied by the generation of oxygen radicals. This may lead to oxidative modification of low-density lipoproteins (LDL) and promote atherosclerotic vascular lesions. In male patients with peripheral arterial occlusive disease we determined fasting and post methionine load homocyst(e)ine levels by high performance liquid chromatography and the susceptibility of their LDL particles to ex-vivo oxidation by continously measuring the conjugated diene production induced by incubation with copper ions. Oxidation resistance (expressed as lag time), maximal oxidation rate, and extent of oxidation (expressed of total diene production) of LDL from patients with normal or mildly elevated homocyst(e)ine levels did not differ significantly. Folic acid, pyridoxal phosphate and cobalamin supplementation significantly decreased plasma homocyst(e)ine levels in hyperhomocyst(e)inaemic patients. This went along with a significant decrease in the extent of LDL oxidation and additionally increased HDL-cholesterol levels. The clinical relevance of these findings for the long-term course of atherosclerotic vascular disorders has to be determined by intervention studies.

  4. Homocysteine threshold value based on cystathionine beta synthase and paraoxonase 1 activities in mice.

    PubMed

    Hamelet, J; Aït-Yahya-Graison, E; Matulewicz, E; Noll, C; Badel-Chagnon, A; Camproux, A-C; Demuth, K; Paul, J-L; Delabar, J M; Janel, N

    2007-12-01

    Hyperhomocysteinaemia is a metabolic disorder associated with the development of premature atherosclerosis. Among the determinants which predispose to premature thromboembolic and atherothrombotic events, serum activity of paraoxonase 1, mainly synthesized in the liver, has been shown to be a predictor of cardiovascular disease and to be negatively correlated with serum homocysteine levels in human. Even though treatments of hyperhomocysteinaemic patients ongoing cardiovascular complications are commonly used, it still remains unclear above which homocysteine level a preventive therapy should be started. In order to establish a threshold of plasma homocysteine concentration we have analyzed the hepatic cystathionine beta synthase and paraoxonase 1 activities in a moderate to intermediate murine model of hyperhomocysteinaemia. Using wild type and heterozygous cystathionine beta synthase deficient mice fed a methionine enriched diet or a control diet, we first studied the link between cystathionine beta synthase and paraoxonase 1 activities and plasma homocysteine concentration. Among the animals used in this study, we observed a negative correlation between plasma homocysteine level and cystathionine beta synthase activity (rho=-0.52, P=0.0008) or paraoxonase 1 activity (rho=-0.49, P=0.002). Starting from these results, a homocysteine cut-off value of 15 microm has been found for both cystathionine beta synthase (P=0.0003) and paraoxonase 1 (P=0.0007) activities. Our results suggest that both cystathionine beta synthase and paraoxonase 1 activities are significantly decreased in mice with a plasma homocysteine value greater than 15 microm. In an attempt to set up preventive treatment for cardiovascular disease our results indicate that treatments should be started from 15 microm of plasma homocysteine.

  5. The Effect of High Dose Folic Acid throughout Pregnancy on Homocysteine (Hcy) Concentration and Pre-Eclampsia: A Randomized Clinical Trial

    PubMed Central

    Sayyah-Melli, Manizheh; Ghorbanihaghjo, Amir; Alizadeh, Mahasti; Kazemi-Shishvan, Maryamalsadat; Ghojazadeh, Morteza; Bidadi, Sanam

    2016-01-01

    Pre-eclampsia is a pregnancy-related multi-systemic hypertensive disorder and affects at least 5% of pregnancies. This randomized clinical trial aimed at assessing the effect of low doses and high doses of folic acid on homocysteine (Hcy) levels, blood pressure, urea, creatinine and neonatal outcome. A randomized clinical trial was done at Alzahra Teaching Hospital, Tabriz University of Medical Sciences from April 2008 to March 2013. Four-hundred and sixty nulliparous pregnant women were randomly assigned into two groups. Group 1 (n = 230) received 0.5 mg of folic acid and group 2 (n = 230) received 5 mg of folic acid per daily. They were followed until delivery. Blood pressure and laboratory changes, including plasma Hcy levels, were measured and compared between the groups. Homocysteine concentrations were significantly higher at the time of delivery in group 1 (13.17±3.89 μmol/l) than in group 2 (10.31±3.54, μmol/l) (p<0.001). No statistically significant differences were observed in systolic and diastolic blood pressure (p = 0.84 and 0.15, respectively). Birth weight was significantly higher in group 2 (p = 0.031) and early abortion was significantly higher in group 1 than group 2 (p = 0.001). This study has provided evidence that a high dosage of folic acid supplements throughout pregnancy reduces Hcy concentrations at the time of delivery. Trial Registration: Iranian Registry of Clinical Trials IRCT201402175283N9 PMID:27166794

  6. Homocysteine: overview of biochemistry, molecular biology, and role in disease processes.

    PubMed

    Fowler, Brian

    2005-05-01

    Homocysteine is derived from the essential amino acid methionine and plays a vital role in cellular homeostasis in man. Homocysteine levels depend on its synthesis, involving methionine adenosyltransferase, S-adenosylmethionine-dependent methyltransferases such as glycine N-methyltransferase, and S-adenosylhomocysteine hydrolase; its remethylation to methionine by methionine synthase, which requires methionine synthase reductase, vitamin B (12), and 5-methyltetrahydrofolate produced by methylenetetrahydrofolate reductase or betaine methyltransferase; and its degradation by transsulfuration involving cystathionine beta-synthase. The control of homocysteine metabolism involves changes of tissue content or inherent kinetic properties of the enzymes. In particular, S-adenosylmethionine acts as a switch between remethylation and transsulfuration through its allosteric inhibition of methylenetetrahydrofolate reductase and activation of cystathionine beta-synthase. Mutant alleles of genes for these enzymes can lead to severe loss of function and varying severity of disease. Several defects lead to severe hyperhomocysteinemia, the most common form being cystathionine beta-synthase deficiency, with more than a hundred reported mutations. Less severe elevations of plasma homocysteine are caused by folate and vitamin B (12) deficiency, and renal disease and moderate hyperhomocysteinemia are associated with several common disease states such as cardiovascular disease. Homocysteine toxicity is likely direct or caused by disturbed levels of associated metabolites; for example, methylation reactions through elevated S-adenosylhomocysteine.

  7. Nutriepigenetic regulation by folate-homocysteine-methionine axis: a review.

    PubMed

    Bhargava, Seema; Tyagi, S C

    2014-02-01

    Although normally folic acid is given during pregnancy, presumably to prevent neural tube defects, the mechanisms of this protection are unknown. More importantly it is unclear whether folic acid has other function during development. It is known that folic acid re-methylates homocysteine (Hcy) to methionine by methylene tetrahydrofolate reductase-dependent pathways. Folic acid also generates high-energy phosphates, behaves as an antioxidant and improves nitric oxide (NO) production by endothelial NO synthase. Interestingly, during epigenetic modification, methylation of DNA/RNA generate homocysteine unequivocally. The enhanced overexpression of methyl transferase lead to increased yield of Hcy. The accumulation of Hcy causes vascular dysfunction, reduces perfusion in the muscles thereby causing musculopathy. Another interesting fact is that children with severe hyperhomocysteinaemia (HHcy) have skeletal deformities, and do not live past teenage. HHcy is also associated with the progeria syndrome. Epilepsy is primarily caused by inhibition of gamma-amino-butyric-acid (GABA) receptor, an inhibitory neurotransmitter in the neuronal synapse. Folate deficiency leads to HHcy which then competes with GABA for binding on the GABA receptors. With so many genetic and clinical manifestations associated with folate deficiency, we propose that folate deficiency induces epigenetic alterations in the genes and thereby results in disease.

  8. Betaine:homocysteine methyltransferase--a new assay for the liver enzyme and its absence from human skin fibroblasts and peripheral blood lymphocytes.

    PubMed

    Wang, J A; Dudman, N P; Lynch, J; Wilcken, D E

    1991-12-31

    Chronic elevation of plasma homocysteine is associated with increased atherogenesis and thrombosis, and can be lowered by betaine (N,N,N-trimethylglycine) treatment which is thought to stimulate activity of the enzyme betaine:homocysteine methyltransferase. We have developed a new assay for this enzyme, in which the products of the enzyme-catalysed reaction between betaine and homocysteine are oxidised by performic acid before being separated and quantified by amino acid analysis. This assay confirmed that human liver contains abundant betaine:homocysteine methyltransferase (33.4 nmol/h/mg protein at 37 degrees C, pH 7.4). Chicken and lamb livers also contain the enzyme, with respective activities of 50.4 and 6.2 nmol/h/mg protein. However, phytohaemagglutinin-stimulated human peripheral blood lymphocytes and cultured human skin fibroblasts contained no detectable betaine:homocysteine methyltransferase (less than 1.4 nmol/h/mg protein), even after cells were pre-cultured in media designed to stimulate production of the enzyme. The results emphasize the importance of the liver in mediating the lowering of elevated circulating homocysteine by betaine.

  9. Correlation between plasma homocysteine levels and craving in alcohol dependent stabilized patients.

    PubMed

    Coppola, Maurizio; Mondola, Raffaella

    2018-06-01

    Homocysteine is a sulfur amino acid strictly related with alcohol consumption. In alcoholics, hyperhomocysteinemia can increase the risk of various alcohol-related disorders such as: brain atrophy, epileptic seizures during withdrawal, and mood disorders. To evaluate the correlation among serum homocysteine concentrations, craving, hazardous and harmful patterns of alcohol consumption in patients stabilized for withdrawal symptoms. Participants were adult outpatients accessed at the Addiction Treatment Unit. Alcoholism was assessed using the following tools: Mini-International Neuropsychiatric Interview Plus (MINI Plus), Alcohol Use Disorder Identification test (AUDIT), Visual Analogic Scale for craving (VAS). Furthermore, during the first visit a blood sample was taken from all patients to measure the plasma concentration of both homocysteine and Carboxy Deficient Transferrin (CDT). Differences between groups in socio-demographic and clinical characteristics were analyzed using the t-test and the Mann-Whitney's U test for normally and non-normally distributed data, respectively. Correlation between clinical scale scores and plasma concentration of homocysteine and CDT was evaluated using the Pearson's correlation coefficient and the Kendall's Tau-b bivariate correlation coefficient for normally and non-normally distributed data, respectively. Our study included 92 patients. No difference was found in socio-demographic characteristics between groups. The group with high homocysteine had higher prevalence of mood disorders (p < 0.001), plasma CDT percentage (p < 0.001), VAS score (p < 0.001) and AUDIT score (p < 0.001) than group with normal homocysteine. Plasma homocysteine showed a positive correlation with both VAS score (p < 0.001), and AUDIT score (p < 0.05). In our study, plasma homocysteine concentration is associated with craving, hazardous and harmful patterns of alcohol consumption. In particular, homocysteine is correlated with alcoholism in a

  10. Hyperhomocysteinemia in polycystic ovary syndrome: decreased betaine-homocysteine methyltransferase and cystathionine β-synthase-mediated homocysteine metabolism.

    PubMed

    Li, Da; Liu, Hong-Xiang; Fang, Yuan-Yuan; Huo, Jia-Ning; Wu, Qi-Jun; Wang, Tian-Ren; Zhou, Yi-Ming; Wang, Xiu-Xia; Ma, Xiao-Xin

    2018-05-22

    What are the metabolic characteristics of homocysteine in polycystic ovary syndrome (PCOS)? Homocysteine concentrations were determined in serum samples from non-obese and obese control subjects and PCOS patients. Homocysteine metabolism was studied in a rat model of PCOS established using dehydroepiandrosterone (DHEA) or DHEA in combination with a high-fat diet (HFD). It was shown that (i) serum homocysteine concentrations were greater in PCOS patients than in control subjects in the obese group (P < 0.05) and serum homocysteine concentrations were significantly higher in the obese group than in the non-obese group, regardless of PCOS status (both P < 0.05); (ii) serum homocysteine concentrations were significantly increased in DHEA + HFD-induced rats compared with controls (P < 0.05); (iii) when compared with the control group, mRNA concentrations of homocysteine metabolic enzymes Bhmt and Cbs were significantly reduced in the liver tissues of DHEA + HFD-induced rats (both P < 0.0001); (iv) when compared with the control group, there was a significant decrease in the methylation concentrations of the Cbs (P < 0.05) and Bhmt (P < 0.05 and P < 0.0001) promoter in the DHEA + HFD group. The methylation patterns, together with previous data, indicate that hypomethylated promoter-mediated transcriptional activation of Bhmt and Cbs might be a defence mechanism against PCOS-related hyperhomocysteinemia. These findings indicate that decreased liver Bhmt and Cbs-mediated homocysteine metabolism might have a role in hyperhomocysteinemia in PCOS and provides further evidence for a potential role of decreased liver function in PCOS. Copyright © 2018 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

  11. Hepatitis C virus co-infection and sexual risk behaviour are associated with a high homocysteine serum level in HIV-infected patients.

    PubMed

    Roca, Bernardino; Bennasar, Marián; Ferrero, José Antonio; del Monte, Mari Cruz; Resino, Elena

    2012-01-11

    A better understanding of the relationship of homocysteine with cardiovascular risk factors is needed. The objectives of this study were to assess the serum level of homocysteine in HIV-infected patients and to analyse the possible association of increased levels of the amino acid with cardiovascular risk factors, demographic and clinical characteristics of participants. Cross-sectional study carried out as a supplementary task to the usual controls necessary in HIV-infected patients in the outpatient clinic of the Hospital General of Castellon, Spain. For two consecutive visits the demographic, clinical and HIV-related characteristics and blood analyses results were obtained for each participant. Homocysteine serum level was documented and the possible association of the amino acid with all the other study variables was assessed with a multiple linear regression analysis. A total of 145 patients were included. The mean homocysteine serum level of all participants was 11.9 ± 5.9 µmol/L. A total of 54 patients (37%) presented homocysteine serum levels higher than the upper limit of normal. An association was found between higher homocysteine serum level and the following variables: family history of early coronary disease (P = 0.027), sexual HIV risk behaviour (P = 0.016), hepatitis C virus co-infection (P = 0.002), higher height (P = 0.002), higher diastolic blood pressure (P = 0.049), lower serum level of folic acid (P <0.001), and lower serum level of vitamin B12 (P = <0.001). In the HIV population, increased homocysteine serum level is associated with sexual risk behaviour and hepatitis C virus coinfection.

  12. Interactions Between Nuclear Receptor SHP and FOXA1 Maintain Oscillatory Homocysteine Homeostasis in Mice.

    PubMed

    Tsuchiya, Hiroyuki; da Costa, Kerry-Ann; Lee, Sangmin; Renga, Barbara; Jaeschke, Hartmut; Yang, Zhihong; Orena, Stephen J; Goedken, Michael J; Zhang, Yuxia; Kong, Bo; Lebofsky, Margitta; Rudraiah, Swetha; Smalling, Rana; Guo, Grace; Fiorucci, Stefano; Zeisel, Steven H; Wang, Li

    2015-05-01

    Hyperhomocysteinemia is often associated with liver and metabolic diseases. We studied nuclear receptors that mediate oscillatory control of homocysteine homeostasis in mice. We studied mice with disruptions in Nr0b2 (called small heterodimer partner [SHP]-null mice), betaine-homocysteine S-methyltransferase (Bhmt), or both genes (BHMT-null/SHP-null mice), along with mice with wild-type copies of these genes (controls). Hyperhomocysteinemia was induced by feeding mice alcohol (National Institute on Alcohol Abuse and Alcoholism binge model) or chow diets along with water containing 0.18% DL-homocysteine. Some mice were placed on diets containing cholic acid (1%) or cholestyramine (2%) or high-fat diets (60%). Serum and livers were collected during a 24-hour light-dark cycle and analyzed by RNA-seq, metabolomic, and quantitative polymerase chain reaction, immunoblot, and chromatin immunoprecipitation assays. SHP-null mice had altered timing in expression of genes that regulate homocysteine metabolism compared with control mice. Oscillatory production of S-adenosylmethionine, betaine, choline, phosphocholine, glyceophosphocholine, cystathionine, cysteine, hydrogen sulfide, glutathione disulfide, and glutathione, differed between SHP-null mice and control mice. SHP inhibited transcriptional activation of Bhmt and cystathionine γ-lyase by FOXA1. Expression of Bhmt and cystathionine γ-lyase was decreased when mice were fed cholic acid but increased when they were placed on diets containing cholestyramine or high-fat content. Diets containing ethanol or homocysteine induced hyperhomocysteinemia and glucose intolerance in control, but not SHP-null, mice. In BHMT-null and BHMT-null/SHP-null mice fed a control liquid, lipid vacuoles were observed in livers. Ethanol feeding induced accumulation of macrovesicular lipid vacuoles to the greatest extent in BHMT-null and BHMT-null/SHP-null mice. Disruption of Shp in mice alters timing of expression of genes that regulate

  13. Blood lead is a predictor of homocysteine levels in a population-based study of older adults.

    PubMed

    Schafer, Jyme H; Glass, Thomas A; Bressler, Joseph; Todd, Andrew C; Schwartz, Brian S

    2005-01-01

    Lead and homocysteine are both associated with cardiovascular disease and cognitive dysfunction. We evaluated the relations among blood lead, tibia lead, and homocysteine levels by cross-sectional analysis of data among subjects in the Baltimore Memory Study, a longitudinal study of 1,140 randomly selected residents in Baltimore, Maryland, who were 50-70 years of age. Tibia lead was measured by (superscript)109(/superscript)Cd K-shell X-ray fluorescence. The subject population had a mean +/- SD age of 59.3 +/- 5.9 years and was 66.0% female, 53.9% white, and 41.4% black or African American. Mean +/- SD blood lead, tibia lead, and homocysteine levels were 3.5 +/- 2.4 microg/dL, 18.9 +/- 12.5 microg/g, and 10.0 +/- 4.1 micromol/L, respectively. In unadjusted analysis, blood lead and homocysteine were moderately correlated (Pearson's r = 0.27, p < 0.01). After adjustment for age, sex, race/ethnicity, educational level, tobacco and alcohol consumption, and body mass index using multiple linear regression, results revealed that homocysteine levels increased 0.35 micromol/L per 1.0 microg/dL increase in blood lead (p < 0.01). The relations of blood lead with homocysteine levels did not differ in subgroups distinguished by age, sex, or race/ethnicity. Tibia lead was modestly correlated with blood lead (Pearson's r = 0.12, p < 0.01) but was not associated with homocysteine levels. To our knowledge, these are the first data to reveal an association between blood lead and homocysteine. These results suggest that homocysteine could be a mechanism that underlies the effects of lead on the cardiovascular and central nervous systems, possibly offering new targets for intervention to prevent the long-term consequences of lead exposure.

  14. Metabolic evidence of vitamin B-12 deficiency, including high homocysteine and methylmalonic acid and low holotranscobalamin, is more pronounced in older adults with elevated plasma folate123

    PubMed Central

    Miller, Joshua W; Garrod, Marjorie G; Allen, Lindsay H; Haan, Mary N

    2009-01-01

    Background: An analysis of data from the National Health and Nutrition Examination Survey indicated that in older adults exposed to folic acid fortification, the combination of low serum vitamin B-12 and elevated folate is associated with higher concentrations of homocysteine and methylmalonic acid and higher odds ratios for cognitive impairment and anemia than the combination of low vitamin B-12 and nonelevated folate. These findings await confirmation in other populations. Objective: The purpose was to compare metabolic indicators of vitamin B-12 status, cognitive function, and depressive symptoms among elderly Latinos with elevated and nonelevated plasma folate. Design: Cross-sectional data were analyzed for 1535 subjects (age: ≥60 y) from the Sacramento Area Latino Study on Aging. Subjects were divided into 4 groups on the basis of plasma vitamin B-12 (< or ≥148 pmol/L) and folate (≤ or >45.3 nmol/L). Homocysteine, methylmalonic acid, holotranscobalamin, ratio of holotranscobalamin to vitamin B-12, Modified Mini-Mental State Examination, delayed recall, and depressive symptom scores were compared between the groups. Results: Individuals with low vitamin B-12 and elevated folate (n = 22) had the highest concentrations of homocysteine and methylmalonic acid and the lowest concentration of holotranscobalamin and ratio of holotranscobalamin to vitamin B-12 when compared with all other groups (P ≤ 0.003). No differences in Modified Mini-Mental State Examination, delayed recall, and depressive symptom scores were observed between the low vitamin B-12 and elevated-folate group compared with other groups. Conclusions: Low vitamin B-12 is associated with more pronounced metabolic evidence of vitamin B-12 deficiency when folate is elevated than when folate is not elevated. These data should be considered when assessing the potential costs, risks, and benefits of folic acid and vitamin B-12 fortification programs. PMID:19726595

  15. Homocysteine, Cortisol, Diabetes Mellitus, and Psychopathology

    PubMed Central

    Kontoangelos, K.; Papageorgiou, C. C.; Raptis, A. E.; Tsiotra, P.; Lambadiari, V.; Papadimitriou, G. N.; Rabavilas, A. D.; Dimitriadis, G.; Raptis, S. A.

    2015-01-01

    Objective. This study investigates the association of homocysteine and cortisol with psychological factors in type 2 diabetic patients. Method. Homocysteine, cortisol, and psychological variables were analyzed from 131 diabetic patients. Psychological factors were assessed with the Eysenck Personality Questionnaire (EPQ), Hostility and Direction of Hostility Questionnaire (HDHQ), the Symptom Checklist 90-R (SCL 90-R), the Zung Self-Rating Depression Scale (ZDRS), and the Maudsley O-C Inventory Questionnaire (MOCI). Blood samples were taken by measuring homocysteine and cortisol in both subgroups during the initial phase of the study (T0). One year later (T1), the uncontrolled diabetic patients were reevaluated with the use of the same psychometric instruments and with an identical blood analysis. Results. The relation of psychoticism and homocysteine is positive among controlled diabetic patients (P value = 0.006 < 0.05) and negative among uncontrolled ones (P value = 0.137). Higher values of cortisol correspond to lower scores on extraversion subscale (r p = −0.223, P value = 0.010). Controlled diabetic patients showed a statistically significant negative relationship between homocysteine and the act-out hostility subscale (r sp = −0.247, P = 0.023). There is a statistically significant relationship between homocysteine and somatization (r sp = −0.220, P = 0.043). Conclusions. These findings support the notion that homocysteine and cortisol are related to trait and state psychological factors in patients with diabetes mellitus type 2. PMID:25722989

  16. Folic acid mitigated cardiac dysfunction by normalizing the levels of tissue inhibitor of metalloproteinase and homocysteine-metabolizing enzymes postmyocardial infarction in mice

    PubMed Central

    Qipshidze, Natia; Tyagi, Neetu; Sen, Utpal; Givvimani, Srikanth; Metreveli, Naira; Lominadze, David

    2010-01-01

    Myocardial infarction (MI) results in significant metabolic derangement, causing accumulation of metabolic by product, such as homocysteine (Hcy). Hcy is a nonprotein amino acid generated during nucleic acid methylation and demethylation of methionine. Folic acid (FA) decreases Hcy levels by remethylating the Hcy to methionine, by 5-methylene tetrahydrofolate reductase (5-MTHFR). Although clinical trials were inconclusive regarding the role of Hcy in MI, in animal models, the levels of 5-MTHFR were decreased, and FA mitigated the MI injury. We hypothesized that FA mitigated MI-induced injury, in part, by mitigating cardiac remodeling during chronic heart failure. Thus, MI was induced in 12-wk-old male C57BL/J mice by ligating the left anterior descending artery, and FA (0.03 g/l in drinking water) was administered for 4 wk after the surgery. Cardiac function was assessed by echocardiography and by a Millar pressure-volume catheter. The levels of Hcy-metabolizing enzymes, cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), and 5-MTHFR, were estimated by Western blot analyses. The results suggest that FA administered post-MI significantly improved cardiac ejection fraction and induced tissue inhibitor of metalloproteinase, CBS, CSE, and 5-MTHFR. We showed that FA supplementation resulted in significant improvement of myocardial function after MI. The study eluted the importance of homocysteine (Hcy) metabolism and FA supplementation in cardiovascular disease. PMID:20802128

  17. Dose-response effects of oral guanidinoacetic acid on serum creatine, homocysteine and B vitamins levels.

    PubMed

    Ostojic, Sergej M; Stojanovic, Marko; Drid, Patrik; Hoffman, Jay R

    2014-12-01

    Guanidinoacetic acid (GAA) is an intermediate in the biosynthesis of creatine (Cr), yet its use in human nutrition is limited due to a lack of a clear understanding of its' dose-response effect. Thus, the purpose of this study was to investigate the effect of three different dosages of GAA (1.2, 2.4 and 4.8 g/day) administered for 6 weeks on serum and urinary variables related to GAA metabolism. Forty-eight healthy volunteers participated in the randomized, placebo-controlled, double-blind, repeated-measure study. At baseline, after 1, 2, 4 and 6 weeks, participants provided both fasting blood samples and 24-h urine. GAA intervention significantly increased serum and urinary GAA, Cr and creatinine as compared to placebo (P < 0.05). Differences were found for serum GAA and Cr responses between the three GAA dosages, with high-dose GAA resulting in a greater increase (P < 0.05) in the plasma concentration of both variables as compared to other GAA dosages. In GAA groups, fasting plasma total homocysteine (T-Hcy) increased by 3.5 μmol/L on average at post-administration, yet no dose-response differences were found between trials. Serum B vitamins were not affected by either placebo or GAA intervention (P > 0.05). Results indicate that low-to-high dosages of exogenous GAA can increase serum concentrations of Cr and T-Hcy while not depleting the B vitamins pool available for remethylation of homocysteine. ClinicalTrials.gov, identification number NCT01133899.

  18. Homocysteine and cerebrovascular accidents.

    PubMed

    Datta, Saikat; Pal, Salil K; Mazumdar, Hirak; Bhandari, Biswanath; Bhattacherjee, Sharmistha; Pandit, Sudipta

    2009-06-01

    Hyperhomocysteinaemia is rapidly emerging as an important risk factor for coronary artery disease, possibly because of its propensity to accelerate atherosclerosis. Whether it is also a risk factor for cerebrovascular accidents (CVA) is a matter of debate till now, as there are conflicting results of the various prospective studies. The present study was performed to correlate the levels of plasma homocysteine levels with that of ischaemic and haemorrhagic CVA. Forty-two cases of CVA were randomly selected over a period of one year, and their risk factors were assessed. It was observed that serum homocysteine levels were significantly raised in those with intracerebral infarcts when compared to those with intracerebral haemorrhage, although homocysteine levels didn't prove to be prognostically significant.

  19. Liquid chromatographic determination of total homocysteine in blood plasma with photometric detection.

    PubMed

    Zhloba, Alexander A; Blashko, Eduard L

    2004-02-05

    A rapid and sensitive method for quantification of homocysteine total forms and glutathione levels in blood plasma via HPLC was developed. Dithiotreitol as a water soluble agent has been used as a reductant for both protein and nonprotein disulphides. Dithiotreitol reacts with the mixed disulphides under 60 degrees C treatment within 10 min. Reduced aminothiols and homocystein were easily derivated with 5,5'-dithiobis-(2-nitrobenzoic acid) and the resultant ultraviolet absorbance within 330 nm was detected by the HPLC method. The concentration of total plasma homocysteine was significantly higher in groups of patients: with the end stage of renal disease: 45.5+/-40.9 micromol/l (n=79), with cerebral vascular disorders 12.3+/-7.0 micromol/l (n=65), and with coronary atherosclerosis 15.4+/-10.9 micromol/l (n=15) than that in healthy subjects (6.2+/-1.74 micromol/l, n=20). Some major advantages of the method include: simultaneous measurement of both total homocysteine and total glutathione, no loss of oxidized form during processing of blood plasma for aminothiols measurement, use of protein-bound aminothiols solution as a calibrator.

  20. Dietary intake of S-(α-carboxybutyl)-DL-homocysteine induces hyperhomocysteinemia in rats

    PubMed Central

    Strakova, Jana; Williams, Kelly T.; Gupta, Sapna; Schalinske, Kevin L.; Kruger, Warren D.; Rozen, Rima; Jiracek, Jiri; Li, Lucas; Garrow, Timothy A.

    2010-01-01

    Betaine homocysteine S-methyltransferase (BHMT) catalyzes the transfer of a methyl group from betaine to homocysteine forming dimethylglycine and methionine. We previously showed that inhibiting BHMT in mice by intraperitoneal injection of S-(α-carboxybutyl)-DL-homocysteine (CBHcy) results in hyperhomocysteinemia. In the present study, CBHcy was fed to rats to determine whether it could be absorbed and cause hyperhomocysteinemia as observed for the intraperitoneal administration of the compound in mice. We hypothesized that dietary administered CBHcy will be absorbed and will result in the inhibition of BHMT and cause hyperhomocysteinemia. Rats were meal-fed every 8 hours an L-amino acid-defined diet either containing or devoid of CBHcy (5 mg/meal) for 3 days. The treatment decreased liver BHMT activity by 90% and had no effect on methionine synthase, methylenetetrahydrofolate reductase, phosphatidylethanolamine N-methyltransferase and CTP:phosphocholine cytidylyltransferase activities. In contrast, cystathionine β-synthase activity and immunodetectable protein decreased (56 and 26%, respectively) and glycine N-methyltransferase activity increased (52%) in CBHcy-treated rats. Liver S-adenosylmethionine levels decreased by 25% in CBHcy-treated rats and S-adenosylhomocysteine levels did not change. Further, plasma choline decreased (22%) and plasma betaine increased (15-fold) in CBHcy-treated rats. The treatment had no effect on global DNA and CpG island methylation, liver histology and plasma markers of liver damage. We conclude that CBHcy mediated BHMT inhibition causes an elevation in total plasma homocysteine that is not normalized by the folate-dependent conversion of homocysteine to methionine. Further, metabolic changes caused by BHMT inhibition affect cystathionine β-synthase and glycine N-methyltransferase activities, which further deteriorate plasma homocysteine levels. PMID:20797482

  1. The Sigma Receptor Ligand (+)-Pentazocine Prevents Apoptotic Retinal Ganglion Cell Death induced in vitro by Homocysteine and Glutamate

    PubMed Central

    Martin, Pamela Moore; Ola, Mohammad S.; Agarwal, Neeraj; Ganapathy, Vadivel; Smith, Sylvia B.

    2013-01-01

    Recent studies demonstrated that the excitotoxic amino acid homocysteine induces apoptotic death of retinal ganglion cells in vivo. In the present study, an in vitro rat retinal ganglion cell (RGC-5) culture system was used to analyze the toxicity of acute exposure to high levels of homocysteine, the mechanism of homocysteine-induced toxicity and the usefulness of σR1 ligands as neuroprotectants. When cultured RGC-5 cells were subjected to treatment with 1 mM D, L- homocysteine, a significant increase in cell death was detected by TUNEL analysis and analysis of activated caspase. When cells were treated with homocysteine- or glutamate in the presence of MK-801, an antagonist of the NMDA receptor, the cell death was inhibited significantly. In contrast, NBQX, an antagonist of the AMPA/Kainate receptor, and nifedipine, a calcium channel blocker, did not prevent the homocysteine- or glutamate-induced cell death. Semi-quantitative RT-PCR and immunocytochemical analysis demonstrated that RGC-5 cells exposed to homocysteine or glutamate express type 1 sigma receptor at levels similar to control cells. Treatment of RGC-5 cells with 3 µM or 10 µM concentrations of the σR1-specific ligand (+)-pentazocine inhibited significantly the apoptotic cell death induced by homocysteine or glutamate. The results suggest that homocysteine is toxic to ganglion cells in vitro, that the toxicity is mediated via NMDA receptor activation, and that the σR1-specific ligand (+)-pentazocine can block the RGC-5 cell death induced by homocysteine and glutamate. PMID:15046867

  2. Alleviation of hepatic fat accumulation by betaine involves reduction of homocysteine via up-regulation of betaine-homocysteine methyltransferase (BHMT).

    PubMed

    Ahn, Chul Won; Jun, Doo Sung; Na, Jong Deok; Choi, Yeo Jin; Kim, Young Chul

    2016-08-26

    We investigated the anti-lipogenic effect of betaine in rats fed methionine and choline-deficient diet (MCD). Intake of MCD for 3 wk resulted in a significant accumulation of hepatic lipids, which was prevented by betaine supplementation in drinking water (1%). Phosphorylation of AMP-activated protein kinase (AMPK), acetyl-CoA carboxylase (ACC), sterol regulatory element-binding protein-1c (SREBP-1c), and liver kinase B1 (LKB1) was inhibited by MCD intake, and these changes were all inhibited by betaine feeding. Meanwhile, betaine supplementation reversed the reduction of methionine and S-adenosylmethionine (SAM), and the elevation of homocysteine levels in the liver, which could be attributable to the induction of betaine-homocysteine methyltransferase (BHMT) and methionine adenosyltransferase (MAT). Different cell lines were used to clarify the role of homocysteine on activation of the AMPK pathway. Homocysteine treatment decreased pAMPK, pACC, pSREBP-1c and pLKB1 in HepG2 cells. Metformin-induced activation of AMPK was also inhibited by homocysteine. Treatment with hydroxylamine, a cystathionine β-synthase inhibitor, resulted in a reduction of pAMPK, pACC and pSREBP-1c, accompanied by an elevation of intracellular homocysteine. Betaine treatment prevented the homocysteine-induced reduction of pAMPK, pACC, pSREBP-1c and pLKB1 in H4IIE cells, but not in HepG2 cells. Also the elevation of cellular homocysteine and inhibition of protein expression of BHMT were prevented by betaine only in H4IIE cells which express BHMT. The results suggest that the beneficial effect of betaine against hepatic lipid accumulation may be attributed, at least in part, to the depletion of homocysteine via up-regulation of BHMT in hepatocytes. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Status of Homocysteine in Polycystic Ovary Syndrome (PCOS).

    PubMed

    Maleedhu, Priyanka; M, Vijayabhaskar; S S B, Sharma; Kodumuri, Praveen K; Devi D, Vasundhara

    2014-02-01

    Polycystic ovary syndrome (PCOS) is the most common endocrine disease in women of reproductive age and is estimated to affect 5-10 % of the population. Women with PCOS have a clustering of cardiovascular risk factors, such as obesity, dyslipidemia, impaired glucose tolerance and hypertension. Homocysteine has been recognized recently as a risk factor for cardiovascular diseases. Preliminary investigations suggest that high sensitivity C-reactive protein, homocysteine and adiponectin are abnormal in women with PCOS. The possible determinants of elevated homocysteine concentration are still debated among authors who found significant correlations between homocysteine and insulin resistance or hyperandrogenism. The purpose of this study is to evaluate homocysteine levels in the PCOS population compared with controls. Study group comprised of 142 women with PCOS and 65 healthy non-PCOS controls. Body mass index (BMI), Waist circumference and serum homocysteine were measured in PCOS subjects and age matched controls. Statastical Analysis: All values are expressed as mean α SD. The results obtained are analysed statistically using the unpaired student t-test to evaluate the significance of differences between the mean values. The mean BMI, Waist circumference and serum homocysteine values are significantly increased in PCOS subjects when compared with non PCOS controls. The present study has demonstrated increase in mean serum homocysteine concentrations in women with PCOS.

  4. L-Cysteine/D,L-homocysteine-regulated ileum motility via system L and B°(,+) transporter: Modification by inhibitors of hydrogen sulfide synthesis and dietary treatments.

    PubMed

    Yamane, Satoshi; Nomura, Ryouya; Yanagihara, Madoka; Nakamura, Hiroyuki; Fujino, Hiromichi; Matsumoto, Kenjiro; Horie, Syunji; Murayama, Toshihiko

    2015-10-05

    Previous studies including ours demonstrated that L-cysteine treatments decreased motility in gastrointestinal tissues including the ileum via hydrogen sulfide (H2S), which is formed from sulfur-containing amino acids such as L-cysteine and L-homocysteine. However, the amino acid transport systems involved in L-cysteine/L-homocysteine-induced responses have not yet been elucidated in detail; therefore, we investigated these systems pharmacologically by measuring electrical stimulation (ES)-induced contractions with amino acids in mouse ileum preparations. The treatments with L-cysteine and D,L-homocysteine inhibited ES-induced contractions in ileum preparations from fasted mice, and these responses were decreased by the treatment with 2-aminobicyclo[2.2.1]heptane-2-carboxylate (BCH), an inhibitor of systems L and B°(,+). The results obtained using ileum preparations and a model cell line (PC12 cells) with various amino acids and BCH showed that not only L-cysteine, but also aminooxyacetic acid and D,L-propargylglycine, which act as H2S synthesis inhibitors, appeared to be taken up by these preparations/cells in L and B°(,+) system-dependent manners. The L-cysteine and D,L-homocysteine responses were delayed and abolished, respectively, in ileum preparations from fed mice. Our results suggested that the regulation of ileum motility by L-cysteine and D,L-homocysteine was dependent on BCH-sensitive systems, and varied depending on feeding in mice. Therefore, the effects of aminooxyacetic acid and D,L-propargylglycine on transport systems need to be considered in pharmacological analyses. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. B-vitamin status and concentrations of homocysteine in Austrian omnivores, vegetarians and vegans.

    PubMed

    Majchrzak, D; Singer, I; Männer, M; Rust, P; Genser, D; Wagner, K-H; Elmadfa, I

    2006-01-01

    A vegetarian diet is considered to promote health and longevity and reduce the risk of cardiovascular diseases and cancer. However, a vegetarian diet may be deficient in some nutrients. Exclusion of animal products in vegetarian diets may affect the status of certain B-vitamins, and further cause the rise of plasma homocysteine concentration. The nutritional status of various B-vitamins (B(1), B(2), B(6), B(12), folic acid) and the concentration of homocysteine in blood plasma of omnivores (n = 40), vegetarians (n = 36) and vegans (n = 42) in Austria was evaluated. The evaluation was done using the functional parameters erythrocyte transketolase (ETK), glutathione reductase (EGR) and glutamic oxaloacetic transaminase (EGOT) activation coefficients. Enzyme activity was measured photometrically. The quantity of vitamins B(1), B(2) and B(6) in urine and the concentrations of vitamin B(6) and homocysteine in plasma were determined by HPLC methods with fluorescence detection. Plasma concentration of vitamin B(12) and folic acid were measured with radioimmunoassay. Most of the subjects showed a satisfying vitamin B(1) status. Vegans presented a significantly lower mean plasma vitamin B(12) concentration than omnivores and vegetarians and deficiency in 2.4% of the volunteers but the highest mean value of plasma folate among the investigated groups. A deficient status of folate was found in 18% of omnivores and in approximately 10% of vegans and vegetarians. The status of riboflavin is considered to be deficient in about 10% of omnivores and vegetarians and in over 30% of vegans. According to the activation coefficient of GOT, approximately one third of all subjects showed vitamin B(6) deficiency. Elevated homocysteine concentration in plasma was observed in 66% of the vegans and about 45-50% of the omnivores and vegetarians. Vegan subjects had significantly higher mean plasma homocysteine levels than omnivores. Thiamin and folate need not be a problem in a well

  6. Homocysteine Test

    MedlinePlus

    ... Time and International Normalized Ratio (PT/INR) PSEN1 Quantitative Immunoglobulins Red Blood Cell (RBC) Antibody Identification Red ... and heart disease remains an active area of research. At present, however, the use of homocysteine levels ...

  7. Preparation of CuO/ZnO nanocomposite and its application as a cysteine/homocysteine colorimetric and fluorescence detector.

    PubMed

    Šimšíková, Michaela; Čechal, Jan; Zorkovská, Anna; Antalík, Marián; Šikola, Tomáš

    2014-11-01

    Cysteine and homocysteine play a crucial role in many biological functions but abnormal levels of these amino acids may lead to various forms of pathogenesis. Therefore, selective and easy-to-use methods for the detection of cysteine and homocysteine are essential for the early diagnosis of developing diseases. In this paper we report on a rapid, straightforward and highly selective method for the detection of cysteine (Cys) and homocysteine (Hcy) which uses a CuO/ZnO nanocomposite as a dual colorimetric and fluorometric assay. The presence of Cys and Hcy in a solution of these nanorods (NRs) induces a change in its color from light blue to dark grey which is visible to the naked eye. This is accompanied by a blue shift in the absorption spectra from 725 nm to 650 nm and a decrease in the intensity of CuO/ZnO nanocomposite emission. These changes are ascribed to the reduction of Cu(II) to Cu(0), and the oxidation of cysteine (homocysteine) and subsequent formation of the disulfide bond. This novel assay method does not respond to any other amino-acid which is present in living organisms; therefore the selective determination of cysteine (homocysteine) with a lower analyte limit of 40 μM (4.8 μg mL(-1)) can be carried out in aqueous solutions without the need for any sophisticated instrumentation, fluorophore molecules or complicated procedures. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Homocysteine remethylation in young broilers fed varying levels of methionine, choline, and betaine.

    PubMed

    Pillai, P B; Fanatico, A C; Beers, K W; Blair, M E; Emmert, J L

    2006-01-01

    Methionine is critical in amino acid nutrition for chickens, yet details of the flux of Met metabolites in the avian system are lacking. This study explored the interactions among dietary choline (CHO), betaine (BET), and sulfur amino acid levels on growth and hepatic homocysteine (HCY) remethylation. Graded levels (0, 0.07, 0.11, and 0.24%) of DL-Met were added to diets adequate in CHO and deficient in sulfur amino acids (0.26% digestible Met, 0.26% digestible Cys). Each Met level was tested alone or with the addition of CHO (0.25%) or BET (0.28%). Broilers were reared from 8 to 22 d in raised wire floor battery cages, and the 12 dietary treatments were fed to 3 replicate pens containing 5 birds per pen. Weight gain and feed efficiency were maximized (P < 0.05) with addition of 0.11% supplemental Met, whereas feed intake was maximized (P < 0.05) with addition of 0.07% supplemental Met. Overall, growth parameters were not affected (P > 0.05) by CHO or BET addition. Hepatic tissue primed by the different dietary treatments was subjected to a newly developed stable isotope methodology and HPLC-mass spectrometry to quantify the impact of diet on HCY remethylation. Dietary Met level did not (P > 0.05) affect HCY remethylation, but remethylation through the Met synthase pathway was increased (P < 0.05) by addition of CHO or BET to diets containing deficient or excess levels of Met. Minimal changes in hepatic HCY remethylation through the betaine-homocysteine methyltransferase pathway occurred in response to dietary changes; therefore, data failed to support previous suggestions that BHMT might have a regulatory role when diets containing deficient or excess Met levels are fed. In contrast to previous suppositions based on enzyme activity, under most dietary conditions, the quantity of HCY remethylated by Met synthase appeared to exceed that remethylated by the alternate betaine-homocysteine methyltransferase pathway.

  9. Methyl Vitamin B12 but not methylfolate rescues a motor neuron-like cell line from homocysteine-mediated cell death

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hemendinger, Richelle A., E-mail: richelle.hemendinger@carolinashealthcare.org; Armstrong, Edward J.; Brooks, Benjamin Rix

    Homocysteine is an excitatory amino acid implicated in multiple diseases including amyotrophic lateral sclerosis (ALS). Information on the toxicity of homocysteine in motor neurons is limited and few studies have examined how this toxicity can be modulated. In NSC-34D cells (a hybrid cell line derived from motor neuron-neuroblastoma), homocysteine induces apoptotic cell death in the millimolar range with a TC{sub 50} (toxic concentration at which 50% of maximal cell death is achieved) of 2.2 mM, confirmed by activation of caspase 3/7. Induction of apoptosis was independent of short-term reactive oxygen species (ROS) generation. Methyl Vitamin B12 (MeCbl) and methyl tetrahydrofolatemore » (MTHF), used clinically to treat elevated homocysteine levels, were tested for their ability to reverse homocysteine-mediated motor neuron cell death. MeCbl in the micromolar range was able to provide neuroprotection (2 h pretreatment prior to homocysteine) and neurorescue (simultaneous exposure with homocysteine) against millimolar homocysteine with an IC{sub 50} (concentration at which 50% of maximal cell death is inhibited) of 0.6 {mu}M and 0.4 {mu}M, respectively. In contrast, MTHF (up to 10 {mu}M) had no effect on homocysteine-mediated cell death. MeCbl inhibited caspase 3/7 activation by homocysteine in a time- and dose-dependent manner, whereas MTHF had no effect. We conclude that MeCbl is effective against homocysteine-induced cell death in motor neurons in a ROS-independent manner, via a reduction in caspase activation and apoptosis. MeCbl decreases Hcy induced motor neuron death in vitro in a hybrid cell line derived from motor neuron-neuroblastoma and may play a role in the treatment of late stage ALS where HCy levels are increased in animal models of ALS.« less

  10. Does Serum Homocysteine Explain the Connection Between Sexual Frequency and Cardiovascular Risk?

    PubMed

    Yang, Hui-Fang; Kao, Tung-Wei; Lin, Yuan-Yung; Shih, Mu-Tsun; Wu, Li-Wei; Liaw, Fang-Yih; Peng, Tao-Chun; Chen, Wei-Liang

    2017-07-01

    Sexual activity correlates with various health issues, and homocysteine is considered an independent risk factor for cardiovascular events and atherosclerosis. Research on the relation of sexual activity to sexual frequency and homocysteine is sparse. To examine the association between sexual frequency and homocysteine in the general population in the United States. In total, 2,267 eligible participants 20 to 59 years old who had serum homocysteine data and completed a sexual behavior questionnaire were enrolled from the National Health and Nutrition Examination Survey of 2005 to 2006. The correlation between sexual frequency and serum homocysteine levels was analyzed using a linear regression model and an extended-model approach was performed for covariate adjustment. Individuals, especially men, in the lower quartiles of sexual frequency had significantly higher serum homocysteine levels, and a sex difference was identified in subgroup analysis. In a model of quartile-based analysis after adjustment for age, sex, and race and ethnicity, the regression coefficient of the highest quartile of sexual frequency compared with the lowest quartile was -1.326 (P = .012). After further adjustment for multiple covariates, the inverse association between sexual frequency and serum homocysteine levels remained unchanged. Negative trends maintained statistical significance (P for trend < .05). In subgroup analysis by sex, a negative association between sexual frequency and serum homocysteine levels remained unchanged in men even after adjusting for multiple covariates, but not in women. Clinical physicians in primary care should support patients' sexual activity, and there are implications for health promotion programs. This is the first observational investigation stratified by sex to evaluate the correlation between sexual frequency and serum homocysteine levels. The study was a cross-sectional observational investigation and the causal relation should be evaluated in a

  11. Association between Homocysteine and Cerebral Small Vessel Disease: A Meta-Analysis.

    PubMed

    Piao, Xiangyu; Wu, Guangyao; Yang, Pei; Shen, Jing; De, Ailing; Wu, Jianlin; Qu, Qiumin

    2018-05-22

    This study aimed to evaluate whether elevated homocysteine levels is associated with risk of different subtypes of cerebral small vessel disease (CSVD) by using meta-analysis. Electronic databases were systematically searched up to April 2018 for collecting the studies reporting homocysteine levels in CSVD or CSVD subtypes. After an inclusion and exclusion criteria, the data was extracted. All data was analyzed using Stata software v.12.0 (Stata Corp LP, College Station, TX). The standardized mean difference (SMD) and 95% confidence interval (CI) were used to compare continuous variables. Eighteen studies met eligibility criteria with 5088 participants (1987 patients with CSVD and 3101 controls) included in the meta-analysis. Meta-analysis revealed that, compared with the controls group, the CSVD group had significantly higher homocysteine levels, with the SMD of .50 and 95% CI (.36-.64). Subgroup analyses suggested white matter lesion had significantly higher levels of homocysteine compared with controls (SMD = .56, 95% CI .39-.73), followed by silent brain infarction (SMD = .33, 95% CI .24-.42) and lacunar infarction (SMD = .17, 95% CI -.06 to .40). This meta-analysis found that CSVD or CSVD subtypes have a significantly higher homocysteine levels than in controls. Further prospective population-based studies are needed to longitudinally evaluate the association between homocysteine levels and progression of different CSVD subtypes. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  12. Role of homocysteine for thromboembolic complication in patients with non-valvular atrial fibrilation.

    PubMed

    Cingozbay, B Y; Yiginer, O; Cebeci, B S; Kardesoglu, E; Demiralp, E; Dincturk, M

    2002-10-01

    Thromboembolism is the most important complication in patients with atrial fibrilation (AF). Homocysteine is a toxic amino acid that has been recently accepted as a risk factor for atherosclerosis and stroke. The aim of the present study is to show whether there is a relation between hyperhomocysteinemia and thromboembolic complications in patients with non-valvular AF. We admitted 38 patients with non-valvular AF. The patients were divided into two groups: group A (n = 20; mean age, 75.7 +/- 10.4 years; three males/17 females), and group B (n = 18; mean age, 68.0 +/- 10.6 years; 11 males/seven females). While group A consisted of the patients with AF and stroke, group B was composed of the patients with AF but without stroke. The patients having sinus rhythm (15 subjects) were used as the reference group to obtain the cut-off value. Homocysteine was measured by the immunoassay method. The means of the homocysteine levels were 12.4 +/- 3.3 micromol/l in group A, 8.3 +/- 2.3 micromol/l in group B and 9.3 +/- 1.8 micromol/l in the reference group. The cut-off value was 10.6 micromol/l. Group A had a statistically higher homocysteine level than not only group B, but also the reference group (P < 0.05). While 60% of group A (n = 12) had the elevated homocysteine level, the rate was only 22% for group B (n = 4). In conclusion, hyperhomocysteinemia may be one of the explanations for the increased rate of thromboembolic complications in older patients with AF.

  13. Higher homocysteine associated with thinner cortical gray matter in 803 ADNI subjects

    PubMed Central

    Madsen, Sarah K.; Rajagopalan, Priya; Joshi, Shantanu H.; Toga, Arthur W.; Thompson, Paul M.

    2014-01-01

    A significant portion of our risk for dementia in old age is associated with lifestyle factors (diet, exercise, and cardiovascular health) that are modifiable, at least in principle. One such risk factor – high homocysteine levels in the blood – is known to increase risk for Alzheimer’s disease and vascular disorders. Here we set out to understand how homocysteine levels relate to 3D surface-based maps of cortical gray matter distribution (thickness, volume, surface area) computed from brain MRI in 803 elderly subjects from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset. Individuals with higher plasma levels of homocysteine had lower gray matter thickness in bilateral frontal, parietal, occipital and right temporal regions; and lower gray matter volumes in left frontal, parietal, temporal, and occipital regions, after controlling for diagnosis, age, and sex, and after correcting for multiple comparisons. No significant within-group associations were found in cognitively healthy people, mild cognitive impairment, or Alzheimer’s disease. These regional differences in gray matter structure may be useful biomarkers to assess the effectiveness of interventions, such as vitamin B supplements, that aim to prevent homocysteine-related brain atrophy by normalizing homocysteine levels. PMID:25444607

  14. A novel enzymatic method for determination of homocysteine using electrochemical hydrogen sulfide sensor.

    PubMed

    Zhao, Dong; Liu, Tsan-Zon; Chan, Err-Cheng; Fein, Harry; Zhang, Xueji

    2007-05-01

    Homocysteine is a sulfur-containing compound produced during metabolism process of methionine. Its uptake in human plasma is believed to be the cause of cardiovascular diseases and many other diseases. An electrochemical method was proposed for selective and quantitative measurement of homocysteine by employing hydrogen sulfide sensor coupled with methionine a, g-lyase. The principle of this method is to measure the evolved hydrogen sulfide from the enzymatic reaction between homocysteine and methionine a, g-lyase. The sensitivities of the measurements at different pH values of the tris buffer solutions and at room temperature peaked to 275 pA/mM at pH 6.5 with detection limit of 150 nM (based on 3 s cutoff). The linearity measurements at pH 6.5 were performed for the homocysteine concentrations range from 0.5 to 200 mM, which is wider than the human blood plasma total homocysteine level of 5 to 100 mM, and the regressive analysis of the experiments gave R2=0.9987. The enzyme also showed the fastest response to homocysteine in the tris buffer solution of pH 7.5 with the current approaching its maximum at 134 seconds. The interference tests against several common agents were carried out, and found that cysteine and methionine were the major two species to introduce measurement problem. The solution to this interference problem was explored and discussed thoroughly based on the preliminary tests. The sensitivities of the experiments against several enzyme concentrations were also performed.

  15. A folate-rich diet is as effective as folic acid from supplements in decreasing plasma homocysteine concentrations

    PubMed Central

    2005-01-01

    Background & Aims: At least 500 μg of folic acid are required daily to treat hyperhomocysteinemia. To reach this amount by dietary changes alone may be difficult because food has a low folic acid content and bioavailability. No studies have compared the effects of similar amounts of additional folate derived from a combination of folate-rich and fortified foods or folic acid from supplements on plasma total homocysteine (tHcy) concentrations, which was the aim of this study. Methods: Twenty male patients with hyperhomocysteinemia and coronary artery disease were included in a randomized, crossover intervention trial. Patients were treated daily with a combination of foods containing approximately 500 μg of folate or with one 500 μg capsule of synthetic folic acid over two five-week periods separated by a five-week wash-out period. Results: Plasma folate increased markedly (p<0.001) and plasma tHcy decreased (p<0.001) with both therapies. Folate-rich foods decreased tHcy by 8.6% (95% CI: –15.9 to –1.2) and synthetic folic acid capsules by 8% (95% CI: –13.3 to –2.7). Conclusions: This study shows, for the first time in the literature, that a folate-rich diet is as effective as folic acid capsules in decreasing plasma tHcy concentrations and adds further support to the recommendation of those diets to prevent cardiovascular disease. PMID:15968341

  16. Serum homocysteine levels in cerebrovascular accidents.

    PubMed

    Zongte, Zolianthanga; Shaini, L; Debbarma, Asis; Singh, Th Bhimo; Devi, S Bilasini; Singh, W Gyaneshwar

    2008-04-01

    Hyperhomocysteinemia has been considered an independent risk factor in the development of stroke. The present study was undertaken to evaluate serum homocysteine levels in patients with cerebrovascular accidents among the Manipuri population and to compare with the normal cases. Ninety-three cerebrovascular accident cases admitted in the hospital were enrolled for the study and twenty-seven age and sex matched individuals free from cerebrovascular diseases were taken as control group. Serum homocysteine levels were estimated by ELISA method using Axis homocysteine EIA kit manufactured by Ranbaxy Diagnostic Ltd. India. The finding suggests that hyperhomocysteinemia is associated with cerebrovascular accident with male preponderance, which increases with advancing age. However, whether hyperhomocysteinemia is the cause or the result of cerebrovascular accidents needs further investigations.

  17. Homocysteine and Cognitive Performance in Elders with Self-Neglect

    NASA Technical Reports Server (NTRS)

    Burnett, J.; Smith, S.M.; Aung, K.; Dyer, C.

    2009-01-01

    Elevated plasma homocysteine has been associated with altered cognitive performance in older adults. Elders referred to Adult Protective Services (APS) for self-neglect have been reported to have elevated plasma homocysteine levels and to suffer from cognitive impairment. This study assesses the association, if any, between plasma homocysteine and cognitive performance among elders with self-neglect. Methods: Sixty-five community-living adults, 65 years of age and older, reported to Adult Protective Services for self-neglect and 55 matched controls (matched for age, ethnicity, gender and socio-economic status) consented and participated in this study. The research team conducted in-home comprehensive geriatric assessments which included the mini-mental state exam (MMSE), the 15-item geriatric depression scale (GDS), the Wolf-Klein Clock Drawing Tests (CDT) and a comprehensive nutritional biochemistry panel, which included plasma homocysteine. Student s t tests and Pearson correlations were conducted to assess for bivariate associations. Results: Elders with self-neglect had significantly higher plasma homocysteine levels (M=12.68umol/L, sd=4.4) compared to the controls (M=10.40umol/L, sd=3.61;t=3.21, df=127, p=.002). There were no statistically significant associations between cognitive performance and plasma homocysteine in the self-neglect group, however there was a significant correlation between plasma homocysteine and the CDT among the controls (r=-.296, p=.022). Conclusion: Mean plasma homocysteine levels were significantly higher in elders with self-neglect, however, they do not appear to be related to cognitive performance, indicating that cognitive impairment in elder self-neglect involve mechanisms other than hyperhomocysteinemia. These findings warrant further investigation

  18. [Homocysteine metabolism disorders as a potential predictor of preeclamsia].

    PubMed

    Kajdy, Anna; Niemiec, Tomasz

    2008-11-01

    Preeclampsia is one of the main causes of maternal and fetal mortality. We lack a reliable test that would identify the "at risk" group of pregnant women, thus allowing us to implement a specific prevention, management and treatment program. Recently, a number of theories regarding the pathophysiology of preeclampsia has been published. The role of vascular pathology as a result of an increase in homocysteine level is often mentioned. The aim of this paper is to review the current literature related to the pathology of preeclampsia and to evaluate the usefulness of assessment of homocysteine level and homocysteine metabolism disorders as a potential predictor of preeclamsia. Hiperhomocysteinemia is a known risk factor of cardiovascular diseases and hypertension. Different sources report a similar correlation between an increase in homocysteine level and the incidence of preeclampsia. As far as the topic of homocysteine in pregnancy is concerned, numerous questions and problems remain unanswered and unsolved. Although there exists a relationship between an increased values of homocysteine and the incidence of preeclampsia, there is not enough information about what group of patients should be included in the screening test to increase the rate of diagnosis and prevention of the most dangerous sequele.

  19. Blood lead levels, iron metabolism gene polymorphisms and homocysteine: a gene-environment interaction study.

    PubMed

    Kim, Kyoung-Nam; Lee, Mee-Ri; Lim, Youn-Hee; Hong, Yun-Chul

    2017-12-01

    Homocysteine has been causally associated with various adverse health outcomes. Evidence supporting the relationship between lead and homocysteine levels has been accumulating, but most prior studies have not focused on the interaction with genetic polymorphisms. From a community-based prospective cohort, we analysed 386 participants (aged 41-71 years) with information regarding blood lead and plasma homocysteine levels. Blood lead levels were measured between 2001 and 2003, and plasma homocysteine levels were measured in 2007. Interactions of lead levels with 42 genotyped single-nucleotide polymorphisms (SNPs) in five genes ( TF , HFE , CBS , BHMT and MTR ) were assessed via a 2-degree of freedom (df) joint test and a 1-df interaction test. In secondary analyses using imputation, we further assessed 58 imputed SNPs in the TF and MTHFR genes. Blood lead concentrations were positively associated with plasma homocysteine levels (p=0.0276). Six SNPs in the TF and MTR genes were screened using the 2-df joint test, and among them, three SNPs in the TF gene showed interactions with lead with respect to homocysteine levels through the 1-df interaction test (p<0.0083). Seven SNPs in the MTHFR gene were associated with homocysteine levels at an α-level of 0.05, but the associations did not persist after Bonferroni correction. These SNPs did not show interactions with lead levels. Blood lead levels were positively associated with plasma homocysteine levels measured 4-6 years later, and three SNPs in the TF gene modified the association. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  20. Homocysteine and disease: Causal associations or epiphenomenons?

    PubMed

    Hannibal, Luciana; Blom, Henk J

    2017-02-01

    Nutritional and genetic deficiencies of folate and vitamin B 12 lead to elevation of cellular homocysteine (Hcy), which translates in increased plasma Hcy. The sources and role of elevated plasma Hcy in pathology continues to be a subject of intense scientific debate. Whether a cause, mediator or marker, little is known about the molecular mechanisms and interactions of Hcy with cellular processes that lead to disease. The use of folic acid reduces the incidence of neural tube defects, but the effect of Hcy-lowering interventions with folic acid in cardiovascular disease and cognitive impairment remains controversial. The fact that levels of Hcy in plasma do not always reflect cellular status of this amino acid may account for the substantial gaps that exist between epidemiological, intervention and basic research studies. Understanding whether plasma Hcy is a mechanistic player or an epiphenomenon in pathogenesis requires further investigation, and this research is essential to improve the assessment and potential treatment of hyperhomocysteinemias. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Effect of folic acid supplementation on homocysteine concentration and association with training in handball players

    PubMed Central

    2013-01-01

    Background Strenuous physical activity can alter the status of folic acid, a vitamin directly associated with homocysteine (Hcy); alterations in this nutrient are a risk factor for cardiovascular disease. Handball players are a population at risk for nutrient deficiency because of poor dietary habits. Objective The aims of this study were to evaluate nutritional status for macronutrients and folic acid in members of a high-performance handball team, and determine the effect of a nutritional intervention with folic acid supplementation and education. Design A total of 14 high-performance handball players were monitored by recording training time, training intensity (according to three levels of residual heart rate (RHR): <60%, 60%–80% and >80%), and subjective perceived exertion (RPE) during a 4-month training period. Nutritional, laboratory and physical activity variables were recorded at baseline (Week 0), after 2 months of dietary supplementation with 200 μg folic acid (50% of the recommended daily allowance) (Week 8) and after 2 months without supplementation (Week 16). We compared training load and analyzed changes in plasma concentrations of Hcy before and after the intervention. Results Bivariate analysis showed a significant negative correlation (P < 0.01) between Hcy and folic acid concentrations (r = −0.84) at Week 8, reflecting a significant change in Hcy concentration (P < 0.05) as a result of hyperhomocysteinemia following the accumulation of high training loads. At Week 16 we observed a significant negative correlation (P < 0.01) between Hcy concentration and training time with an RHR <60%, indicating that aerobic exercise avoided abrupt changes in Hcy and may thus reduce the risk of cardiovascular accidents in high-performance athletes. Conclusion Integral monitoring and education are needed for practitioners of handball sports to record their folic acid status, a factor that directly affects Hcy metabolism. Folic acid

  2. Preferred Conformers of Non-Proteinogenic Amino Acids Homoserine and Homocysteine

    NASA Astrophysics Data System (ADS)

    Díez, Verónica; Rodríguez, Miguel A.; Mata, Santiago; Alonso, E. R.; Cabezas, Carlos; Alonso, José L.

    2016-06-01

    Vaporization of solid homoserine and homocysteine by laser ablation in combination with Fourier transform microwave spectroscopy techniques made possible the detection of their most stable structures in a supersonic expansion. All detected conformers have been identified through their rotational and 14N quadrupole coupling constants. They show hydrogen bonds linking the amino and carboxylic group through N-H\\cdot\\cdot\\cdotO=C (type I) or N\\cdot\\cdot\\cdotH-O (type II) interactions. In some of them there are additional hydrogen bonds established between the amino group and the hydroxyl/thiol groups in the gamma position. Entropic effects related to the side chain have been found to be significant in determining the most populated conformations.

  3. Folic acid supplement decreases the homocysteine increasing effect of filtered coffee. A randomised placebo-controlled study.

    PubMed

    Strandhagen, E; Landaas, S; Thelle, D S

    2003-11-01

    Elevated levels of plasma total homocysteine (tHcy) are identified as independent risk factors for coronary heart disease and for fetal neural tube defects. tHcy levels are negatively associated with folic acid, pyridoxine and cobalamine, and positively associated with coffee consumption and smoking. A total of 600 ml of filtered coffee results in a tHcy increase that 200 mug of folic acid or 40 mg of pyridoxine supplementation might eliminate. Randomised, blinded study with two consecutive trial periods. Free living population. Volunteers. A total of 121 healthy, nonsmoking men and women (78%) aged 29-65 y. (1) A coffee-free period of 3 weeks, (2) 600 ml coffee/day and a supplement of 200 mug folic acid/day or placebo for 4 weeks, (3) 3-week coffee-free period, (4) 600 ml coffee/day and 40 mg pyridoxine/day or placebo for 4 weeks. The difference between the change in tHcy in the supplement group and the change in tHcy in the placebo group during the 4-week trial period. Coffee abstention resulted in a tHcy decrease of 1.04 mumol/l for the whole group. In the subsequent coffee period, a further decrease of 0.17 mumol/l was observed in the folic acid group whereas an increase of 1.26 mumol/l was observed in the placebo group, the difference was 1.43 mumol/l (95% CI: 0.80, 2.07). Pyridoxine supplement had no impact on tHcy levels. Supplementation of 200 mug folic acid/day eliminates the tHcy increasing effect of 600 ml filtered coffee in subjects not already on folic acid supplements. A supplement of 40 mg pyridoxine/day does not have the same effect.

  4. Homocystein as a Risk Factor for Developing Complications in Chronic Renal Failure

    PubMed Central

    Jakovljevic, Biljana; Gasic, Branislav; Kovacevic, Pedja; Rajkovaca, Zvezdana; Kovacevic, Tijana

    2015-01-01

    Aim: Cardiovascular diseases are leading cause of death in patients with chronic renal failure. The aim of our study was to establish connection between levels of homocysteine and traditional and nontraditional risk factors for developing cardiovascular diseases in dialysis and pre dialysis patients. Methods: We included 33 pre dialysis (23 in stage three and 10 in stage four of chronic kidney disease) and 43 patients receiving hemodialysis longer than six months. Besides standard laboratory parameters, levels of homocysteine and blood pressure were measured in all patients. Glomerular filtration rate was measured in pre dialysis patients and dialysis quality parameters in dialysis patients. Results: Homocysteine levels were elevated in all patients (19±5.42mmol/l). The connection between homocysteine levels and other cardiovascular diseases risk factors was not established in pre dialysis patients. In patients treated with hemodialysis we found negative correlation between homocysteine levels and patients’ age (p<0.05) and positive correlation between homocysteine levels and length of dialysis (p<0.01) as well as between homocysteine and anemia parameters (erythrocytes, hemoglobin), (p<0.01). Homocysteine and LDL (and total cholesterol) were in negative correlation (p<0.01). Conclusion: Homocysteine, as one of nontraditional cardiovascular diseases risk factors, is elevated in all patients with chronic renal failure and it’s positive correlation with some other risk factors was found. PMID:26005384

  5. Purification, crystallization and preliminary crystallographic studies of plant S-adenosyl-l-homocysteine hydrolase (Lupinus luteus)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Brzezinski, Krzysztof; Department of Crystallography, Faculty of Chemistry, A. Mickiewicz University, Poznan; Bujacz, Grzegorz

    2008-07-01

    Single crystals of recombinant S-adenosyl-l-homocysteine hydrolase from L. luteus in complex with adenosine diffract X-rays to 1.17 Å resolution at 100 K. The crystals are tetragonal, space group P4{sub 3}2{sub 1}2, and contain one copy of the dimeric enzyme in the asymmetric unit. By degrading S-adenosyl-l-homocysteine, which is a byproduct of S-adenosyl-l-methionine-dependent methylation reactions, S-adenosyl-l-homocysteine hydrolase (SAHase) acts as a regulator of cellular methylation processes. S-Adenosyl-l-homocysteine hydrolase from the leguminose plant yellow lupin (Lupinus luteus), LlSAHase, which is composed of 485 amino acids and has a molecular weight of 55 kDa, has been cloned, expressed in Escherichia coli and purified.more » Crystals of LlSAHase in complex with adenosine were obtained by the hanging-drop vapour-diffusion method using 20%(w/v) PEG 4000 and 10%(v/v) 2-propanol as precipitants in 0.1 M Tris–HCl buffer pH 8.0. The crystals were tetragonal, space group P4{sub 3}2{sub 1}2, with unit-cell parameters a = 122.4, c = 126.5 Å and contained two protein molecules in the asymmetric unit, corresponding to the functional dimeric form of the enzyme. Atomic resolution (1.17 Å) X-ray diffraction data have been collected using synchrotron radiation.« less

  6. Association between homocyst(e)ine levels and risk of vascular events.

    PubMed

    Kaplan, Eugene D

    2003-03-01

    Homocyst(e)ine is a novel risk factor in vascular disease. First observations of vascular lesions in children with high blood homocyst(e)ine levels due to severe inborn enzyme deficiencies led to the hypothesis that elevated blood homocyst(e)ine levels might be a risk factor for vascular disease. A substantial body of evidence on the role of the homocyst(e)ine in the development of coronary and carotid artery disease, myocardial infarction, stroke, deep vein thrombosis and other disorders has been accumulated over the last 30 years. Cross-sectional and case-control studies provide initial and the strongest support for the hypothesis, followed by results from the prospective cohorts. Infrequent cases of homozygous mutations of the key enzymes in the homocyst(e)ine metabolism chain are able to produce extreme homocyst(e)inemia and early vascular lesions. More frequently, heterozygous enzyme mutations and deficiencies of folate and vitamins B6 and B12 cause mild to moderate homocyst(e)inemia, which is still strongly associated with the increased risk of vascular events. Elevated homocyst(e)ine levels may be effectively managed with adequate folate, B12 and B6 intake in doses comparable to or above FDA recommendations. Whether correction of elevated homocyst(e)ine levels with vitamins is helpful in prevention and treatment of vascular events remains unknown and is under investigation in ongoing clinical trials (VISP, VITATOPS). No consensus on homocyst(e)ine management is available at the present time.

  7. Association between Plasma Homocysteine Levels and Neuronal Injury in HIV Infection.

    PubMed

    Ahlgren, Erika; Hagberg, Lars; Fuchs, Dietmar; Andersson, Lars-Magnus; Nilsson, Staffan; Zetterberg, Henrik; Gisslén, Magnus

    2016-01-01

    To investigate the role of homocysteine in neuronal injury in HIV infection. Using a cross-sectional design and archived samples, we compared concentrations of plasma homocysteine and cerebrospinal fluid (CSF) neurofilament light protein (NFL), a sensitive marker of neuronal injury, in 83 HIV-1-infected subjects without antiretroviral treatment. We also analyzed plasma vitamin B12, serum folate, CSF, and plasma HIV RNA, the immune activation marker neopterin in CSF and serum, and albumin ratio as a marker of blood-brain barrier integrity. Twenty-two subjects provided a second sample median of 12.5 months after antiretroviral treatment initiation. A significant correlation was found between plasma homocysteine and CSF NFL concentrations in untreated individuals (r = 0.52, p < 0.0001). As expected, there was a significant inverse correlation between homocysteine and B12 (r = -0.41, p < 0.001) and folate (r = -0.40, p = < 0.001) levels. In a multiple linear regression analysis homocysteine stood out as an independent predictor of CSF NFL in HIV-1-infected individuals. The correlation of plasma homocysteine and CSF NFL was also present in the group receiving antiretroviral therapy (r = 0.51, p = 0.016). A correlation between plasma homocysteine and axonal injury, as measured by CSF NFL, was found in both untreated and treated HIV. While this study is not able to prove a causal link, homocysteine and functional B12/folate deficiency appear to play a role in neural injury in HIV-infected individuals.

  8. Commutability of NIST SRM 1955 Homocysteine and Folate in Frozen Human Serum with selected total homocysteine immunoassays and enzymatic assays.

    PubMed

    Nelson, Bryant C; Pfeiffer, Christine M; Zhang, Ming; Duewer, David L; Sharpless, Katherine E; Lippa, Katrice A

    2008-09-01

    The National Institute of Standards and Technology (NIST) has recently developed Standard Reference Material (SRM) 1955 Homocysteine and Folate in Frozen Human Serum with certified values for total homocysteine (tHcy) and 5-methyl-tetrahydrofolic acid. NIST has performed an international, interlaboratory assessment of SRM 1955 commutability; results are reported for tHcy only. Total Hcy was measured in 20 patient sera and in 3 levels of SRM 1955 using 14 immunoassays and/or enzymatic assays. Liquid chromatography/tandem mass spectrometry was utilized as the reference assay. An "errors-in-variables" statistical model was utilized to assess the commutability of SRM 1955. Normalized residuals ranged from -2.65 to 2.19 for SRM 1955. The median interlaboratory/interassay imprecision (CV) was approximately 4% for patient specimens and ranged from approximately 3% to approximately 7% for SRM 1955. The median intra-assay imprecision ranged from approximately 1% to approximately 13%. Orthogonal residuals, as a descriptor of assay accuracy, ranged from 0.29 to 7.71 and from 0.20 to 2.22 for patient specimens and SRM 1955 samples, respectively. The current study suggests that SRM 1955 is commutable with the investigated tHcy assays; however, a broader specimen set needs to be evaluated to completely substantiate this conclusion.

  9. Plasma homocysteine, dietary B vitamins, betaine, and choline and risk of peripheral artery disease

    PubMed Central

    Bertoia, Monica L.; Pai, Jennifer K.; Cooke, John P.; Joosten, Michel M.; Mittleman, Murray A.; Rimm, Eric B.; Mukamal, Kenneth J.

    2014-01-01

    Objective Few studies have examined the roles of homocysteine and related nutrients in the development of peripheral artery disease (PAD). We examined the associations between plasma homocysteine, dietary B vitamins, betaine, choline, and supplemental folic acid use and incidence of PAD. Methods We used two cohort studies of 72,348 women in the Nurses' Health Study (NHS, 1990-2010) and 44,504 men in the Health Professionals Follow-up Study (HPFS, 1986-2010). We measured plasma homocysteine in nested matched case-control studies of clinically recognized PAD within both cohorts, including 143 PAD cases and 424 controls within the NHS (1990-2010) and 143 PAD cases and 428 controls within the HPFS (1994-2008). We examined the association between diet and risk of incident PAD in the cohorts using a food frequency questionnaire and 790 cases of PAD over 3.1 million person-years of follow-up. Results Higher homocysteine levels were positively associated with risk of PAD in men (adjusted IRR 2.17; 95% CI, 1.08-4.38 for tertile 3 vs. 1). There was no evidence of an association in women (adjusted IRR 1.14; 95% CI, 0.61-2.12). Similarly, higher folate intake, including supplements, was inversely associated with risk of PAD in men (adjusted HR 0.90; 95% CI, 0.82-0.98 for each 250 μg increase) but not women (HR 1.01, 95% CI, 0.88-1.15). Intakes of the other B vitamins, betaine, and choline were not consistently associated with risk of PAD in men or women. Conclusion Homocysteine levels were positively associated and dietary folate intake was inversely associated with risk of PAD in men but not in women. PMID:24819748

  10. Plasma homocysteine, dietary B vitamins, betaine, and choline and risk of peripheral artery disease.

    PubMed

    Bertoia, Monica L; Pai, Jennifer K; Cooke, John P; Joosten, Michel M; Mittleman, Murray A; Rimm, Eric B; Mukamal, Kenneth J

    2014-07-01

    Few studies have examined the roles of homocysteine and related nutrients in the development of peripheral artery disease (PAD). We examined the associations between plasma homocysteine, dietary B vitamins, betaine, choline, and supplemental folic acid use and incidence of PAD. We used two cohort studies of 72,348 women in the Nurses' Health Study (NHS, 1990-2010) and 44,504 men in the Health Professionals Follow-up Study (HPFS, 1986-2010). We measured plasma homocysteine in nested matched case-control studies of clinically recognized PAD within both cohorts, including 143 PAD cases and 424 controls within the NHS (1990-2010) and 143 PAD cases and 428 controls within the HPFS (1994-2008). We examined the association between diet and risk of incident PAD in the cohorts using a food frequency questionnaire and 790 cases of PAD over 3.1 million person-years of follow-up. Higher homocysteine levels were positively associated with risk of PAD in men (adjusted IRR 2.17; 95% CI, 1.08-4.38 for tertile 3 vs. 1). There was no evidence of an association in women (adjusted IRR 1.14; 95% CI, 0.61-2.12). Similarly, higher folate intake, including supplements, was inversely associated with risk of PAD in men (adjusted HR 0.90; 95% CI, 0.82-0.98 for each 250 μg increase) but not women (HR 1.01, 95% CI, 0.88-1.15). Intakes of the other B vitamins, betaine, and choline were not consistently associated with risk of PAD in men or women. Homocysteine levels were positively associated and dietary folate intake was inversely associated with risk of PAD in men but not in women. Copyright © 2014. Published by Elsevier Ireland Ltd.

  11. Beta blocker effects on plasma homocysteine levels in patients with hypertension.

    PubMed

    Atar, Ilyas; Korkmaz, Mehmet Emin; Demircan, Senol; Atar, Inci Asli; Bozbaş, Hüseyin; Aydinalp, Alp; Ozin, Bülent; Yildirir, Aylin; Müderrisoğlu, Haldun

    2005-08-01

    Recent studies have shown that hyperhomocysteinemia might play a role in the pathogenesis of hypertension. The effects of antihypertensive agents on plasma homocysteine levels have not been tested extensively. We investigated the effects of beta-blocker therapy on homocysteine levels in patients with hypertension. In the study, 120 patients with newly diagnosed hypertension were enrolled. All patients received metoprolol succinate 100 mg/day initially. If blood pressure was above normal on the 15th day of follow-up, the metoprolol dosage was doubled. Before initiation of the antihypertensive medication and after the fourth month of treatment, homocysteine levels were measured. Of the 120 patients enrolled, 39 could not complete the study. Homocysteine levels decreased significantly by the end of the fourth month when compared with basal values (13.5+/-4.5 micromol/l versus 12.4+/-4.9 micromol/l; P = 0.001). There was no relation between homocysteine level and blood pressure control. There was a significant decrease in homocysteine levels in the women treated in this study (P = 0.001); however, this effect was absent in men (P = 0.185). We demonstrate that metoprolol succinate treatment significantly decreases plasma homocysteine levels in patients with hypertension, especially in women.

  12. [Relations between serum homocysteine and folic acid levels with congenital heart disease].

    PubMed

    Zhu, Wen-li; Dao, Jing-jing; Cheng, Jun; Li, Shu-qin

    2005-11-01

    To investigate the relations between serum homocysteine (Hcy) and folic acid with congenital heart disease (CHD) in CHD nuclear families. In Liaoning Province 151 CHD patients and their biological parents were selected as the case group, with another 98 normal subjects and their parents as control. For some filial individuals and their mothers the serum total Hcy (tHcy) levels were detected by fluorescence polarization immunoassay. And for all members the serum levels of folic acid and vitamin B12 (VB12) were determined by radio-immunoassay. There were not significantly differences in the serum tHcy and folic acid levels and theirs abnormality prevalence between CHD patients and the control, neither were their parents in the study. Compared with the control group the serum VB12 levels of CHD patients were apparently higher (315.36 pmol/L and 185.34 pmol/L, P < 0.05), and the VB12 deficiency prevalence of patients and their fathers were lower. Analysis of different CHD types showed that in ventricular septal defect patients the serum tHcy levels were lower than the control with VB12 levels higher, and in parents of patent ductus arteriosus patients the serum folic acid levels were increased (P < 0.05). The study also indicated that the folic acid and VB12 of parents were significantly positively associated with that of filial generation. In the case group the tHcy levels of mothers were positively correlated with filial generation, and in CHD patients the tHcy was negatively associated with folic acid. In filial individuals of the control group the tHcy was negatively related with VB12 (P < 0.05). Folic acid and VB12 were important influencing factors of serum Hcy and they were negatively correlated. In this study, the folic acid and Hcy were not significantly related with CHD, and it needs further investigations to confirm it. There were not significant differences in the serum tHcy and folic acid levels and theirs abnormality prevalence between CHD patients and

  13. Association between Plasma Homocysteine Levels and Neuronal Injury in HIV Infection

    PubMed Central

    Ahlgren, Erika; Hagberg, Lars; Fuchs, Dietmar; Andersson, Lars-Magnus; Nilsson, Staffan; Zetterberg, Henrik; Gisslén, Magnus

    2016-01-01

    Objective To investigate the role of homocysteine in neuronal injury in HIV infection. Methods Using a cross-sectional design and archived samples, we compared concentrations of plasma homocysteine and cerebrospinal fluid (CSF) neurofilament light protein (NFL), a sensitive marker of neuronal injury, in 83 HIV-1-infected subjects without antiretroviral treatment. We also analyzed plasma vitamin B12, serum folate, CSF, and plasma HIV RNA, the immune activation marker neopterin in CSF and serum, and albumin ratio as a marker of blood-brain barrier integrity. Twenty-two subjects provided a second sample median of 12.5 months after antiretroviral treatment initiation. Results A significant correlation was found between plasma homocysteine and CSF NFL concentrations in untreated individuals (r = 0.52, p < 0.0001). As expected, there was a significant inverse correlation between homocysteine and B12 (r = –0.41, p < 0.001) and folate (r = –0.40, p = < 0.001) levels. In a multiple linear regression analysis homocysteine stood out as an independent predictor of CSF NFL in HIV-1-infected individuals. The correlation of plasma homocysteine and CSF NFL was also present in the group receiving antiretroviral therapy (r = 0.51, p = 0.016). Conclusion A correlation between plasma homocysteine and axonal injury, as measured by CSF NFL, was found in both untreated and treated HIV. While this study is not able to prove a causal link, homocysteine and functional B12/folate deficiency appear to play a role in neural injury in HIV-infected individuals. PMID:27441551

  14. The effect of hormone therapy on plasma homocysteine levels: a randomized clinical trial.

    PubMed

    Tutuncu, Levent; Ergur, Ali Rustu; Mungen, Ercument; Gun, Ismet; Ertekin, Aktug; Yergok, Yusuf Ziya

    2005-03-01

    An elevated plasma homocysteine level is a risk factor for cardiovascular diseases. Hormone therapy (HT) may reduce fasting plasma homocysteine levels. We studied 80 postmenopausal women to determine the effect of medroxyprogesterone acetate (MPA) combined with conjugated equine estrogens (CEE) on fasting plasma homocysteine levels. In a randomized, double blind, prospective, placebo-controlled study, we randomly assigned 80 healthy postmenopausal women between CEE 0.625 mg/d combined with MPA 2.5 mg/d (n = 20), CEE 0.625 mg/d combined with MPA 5 mg/d (n = 20), unopposed CEE 0.625 mg/d (n = 20), and placebo (n = 20) all given for a duration of 6 months. Fasting plasma homocysteine levels were measured before and at the end of the treatment. Before treatment, plasma homocysteine concentrations were similar in all groups. After 6 months of unopposed CEE, the mean fasting plasma homocysteine levels decreased by 19.02% when compared with baseline levels (P < 0.05). The mean fasting plasma homocysteine concentrations decreased by 17.63% and 19.56% from baseline in both the CEE plus MPA 2.5 mg/d and CEE plus MPA 5 mg/d groups, respectively (P < 0.05 for each group). In contrast, plasma homocysteine levels increased by 11.66% in the placebo group. The homocysteine lowering effect did not differ significantly among the three groups of women receiving unopposed CEE alone and CEE plus MPA at two different doses. Six months of estrogen therapy (ET) and combined estrogen-progestogen therapy (EPT) significantly lower fasting plasma homocysteine levels in healthy postmenopausal women with equal efficacy.

  15. Association of serum homocysteine with major depressive disorder: results from a large population-based study.

    PubMed

    Nabi, Hermann; Bochud, Murielle; Glaus, Jennifer; Lasserre, Aurélie M; Waeber, Gérard; Vollenweider, Peter; Preisig, Martin

    2013-10-01

    Studies on the association between homocysteine levels and depression have shown conflicting results. To examine the association between serum total homocysteine (tHcy) levels and major depressive disorder (MDD) in a large community sample with an extended age range. A total of 3392 men and women aged 35-66 years participating in the CoLaus study and its psychiatric arm (PsyCoLaus) were included in the analyses. High tHcy measured from fasting blood samples was defined as a concentration ≥15μmol/L. MDD was assessed using the semi-structured Diagnostic Interview for Genetics Studies. In multivariate analyses, elevated tHcy levels were associated with greater odds of meeting the diagnostic criteria for lifetime MDD among men (OR=1.71; 95% CI, 1.18-2.50). This was particularly the case for remitted MDD. Among women, there was no significant association between tHcy levels and MDD and the association tended to be in the opposite direction (OR=0.61; 95% CI, 0.34-1.08). In this large population-based study, elevated tHcy concentrations are associated with lifetime MDD and particularly with remitted MDD among men. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Cochlear Homocysteine Metabolism at the Crossroad of Nutrition and Sensorineural Hearing Loss.

    PubMed

    Partearroyo, Teresa; Vallecillo, Néstor; Pajares, María A; Varela-Moreiras, Gregorio; Varela-Nieto, Isabel

    2017-01-01

    Hearing loss (HL) is one of the most common causes of disability, affecting 360 million people according to the World Health Organization (WHO). HL is most frequently of sensorineural origin, being caused by the irreversible loss of hair cells and/or spiral ganglion neurons. The etiology of sensorineural HL (SNHL) is multifactorial, with genetic and environmental factors such as noise, ototoxic substances and aging playing a role. The nutritional status is central in aging disability, but the interplay between nutrition and SNHL has only recently gained attention. Dietary supplementation could therefore constitute the first step for the prevention and potential repair of hearing damage before it reaches irreversibility. In this context, different epidemiological studies have shown correlations among the nutritional condition, increased total plasma homocysteine (tHcy) and SNHL. Several human genetic rare diseases are also associated with homocysteine (Hcy) metabolism and SNHL confirming this potential link. Accordingly, rodent experimental models have provided the molecular basis to understand the observed effects. Thus, increased tHcy levels and vitamin deficiencies, such as folic acid (FA), have been linked with SNHL, whereas long-term dietary supplementation with omega-3 fatty acids improved Hcy metabolism, cell survival and hearing acuity. Furthermore, pharmacological supplementations with the anti-oxidant fumaric acid that targets Hcy metabolism also improved SNHL. Overall these results strongly suggest that cochlear Hcy metabolism is a key player in the onset and progression of SNHL, opening the way for the design of prospective nutritional therapies.

  17. Cochlear Homocysteine Metabolism at the Crossroad of Nutrition and Sensorineural Hearing Loss

    PubMed Central

    Partearroyo, Teresa; Vallecillo, Néstor; Pajares, María A.; Varela-Moreiras, Gregorio; Varela-Nieto, Isabel

    2017-01-01

    Hearing loss (HL) is one of the most common causes of disability, affecting 360 million people according to the World Health Organization (WHO). HL is most frequently of sensorineural origin, being caused by the irreversible loss of hair cells and/or spiral ganglion neurons. The etiology of sensorineural HL (SNHL) is multifactorial, with genetic and environmental factors such as noise, ototoxic substances and aging playing a role. The nutritional status is central in aging disability, but the interplay between nutrition and SNHL has only recently gained attention. Dietary supplementation could therefore constitute the first step for the prevention and potential repair of hearing damage before it reaches irreversibility. In this context, different epidemiological studies have shown correlations among the nutritional condition, increased total plasma homocysteine (tHcy) and SNHL. Several human genetic rare diseases are also associated with homocysteine (Hcy) metabolism and SNHL confirming this potential link. Accordingly, rodent experimental models have provided the molecular basis to understand the observed effects. Thus, increased tHcy levels and vitamin deficiencies, such as folic acid (FA), have been linked with SNHL, whereas long-term dietary supplementation with omega-3 fatty acids improved Hcy metabolism, cell survival and hearing acuity. Furthermore, pharmacological supplementations with the anti-oxidant fumaric acid that targets Hcy metabolism also improved SNHL. Overall these results strongly suggest that cochlear Hcy metabolism is a key player in the onset and progression of SNHL, opening the way for the design of prospective nutritional therapies. PMID:28487633

  18. Folate network genetic variation, plasma homocysteine, and global genomic methylation content: a genetic association study

    PubMed Central

    2011-01-01

    Background Sequence variants in genes functioning in folate-mediated one-carbon metabolism are hypothesized to lead to changes in levels of homocysteine and DNA methylation, which, in turn, are associated with risk of cardiovascular disease. Methods 330 SNPs in 52 genes were studied in relation to plasma homocysteine and global genomic DNA methylation. SNPs were selected based on functional effects and gene coverage, and assays were completed on the Illumina Goldengate platform. Age-, smoking-, and nutrient-adjusted genotype--phenotype associations were estimated in regression models. Results Using a nominal P ≤ 0.005 threshold for statistical significance, 20 SNPs were associated with plasma homocysteine, 8 with Alu methylation, and 1 with LINE-1 methylation. Using a more stringent false discovery rate threshold, SNPs in FTCD, SLC19A1, and SLC19A3 genes remained associated with plasma homocysteine. Gene by vitamin B-6 interactions were identified for both Alu and LINE-1 methylation, and epistatic interactions with the MTHFR rs1801133 SNP were identified for the plasma homocysteine phenotype. Pleiotropy involving the MTHFD1L and SARDH genes for both plasma homocysteine and Alu methylation phenotypes was identified. Conclusions No single gene was associated with all three phenotypes, and the set of the most statistically significant SNPs predictive of homocysteine or Alu or LINE-1 methylation was unique to each phenotype. Genetic variation in folate-mediated one-carbon metabolism, other than the well-known effects of the MTHFR c.665C>T (known as c.677 C>T, rs1801133, p.Ala222Val), is predictive of cardiovascular disease biomarkers. PMID:22103680

  19. Assessing the association between homocysteine and cognition: reflections on Bradford Hill, meta-analyses, and causality.

    PubMed

    McCaddon, Andrew; Miller, Joshua W

    2015-10-01

    Hyperhomocysteinemia is a recognized risk factor for cognitive decline and incident dementia in older adults. Two recent reports addressed the cumulative epidemiological evidence for this association but expressed conflicting opinions. Here, the evidence is reviewed in relation to Sir Austin Bradford Hill's criteria for assessing "causality," and the latest meta-analysis of the effects of homocysteine-lowering on cognitive function is critically examined. The meta-analysis included 11 trials, collectively assessing 22,000 individuals, that examined the effects of B vitamin supplements (folic acid, vitamin B12, vitamin B6) on global or domain-specific cognitive decline. It concluded that homocysteine-lowering with B vitamin supplements has no significant effect on cognitive function. However, careful examination of the trials in the meta-analysis indicates that no conclusion can be made regarding the effects of homocysteine-lowering on cognitive decline, since the trials typically did not include individuals who were experiencing such decline. Further definitive trials in older adults experiencing cognitive decline are still urgently needed. © The Author(s) 2015. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  20. Metal-Catalyzed Oxidation of Protein Methionine Residues in Human Parathyroid Hormone (1-34): Formation of Homocysteine and a Novel Methionine-Dependent Hydrolysis Reaction

    PubMed Central

    Mozziconacci, Olivier; Ji, Junyan A.; Wang, Y. John; Schöneich, Christian

    2013-01-01

    The oxidation of PTH(1-34) catalyzed by ferrous ethylenediaminetetraacetic acid (EDTA) is site-specific. The oxidation of PTH(1-34) is localized primarily to the residues Met[8] and His[9]. Beyond the transformation of Met[8] and His[9] into methionine sulfoxide and 2-oxo-histidine, respectively, we observed a hydrolytic cleavage between Met[8] and His[9]. This hydrolysis requires the presence of FeII and oxygen and can be prevented by diethylenetriaminepentaacetic acid (DTPA) and phosphate buffer. Conditions leading to this site-specific hydrolysis also promote the transformation of Met[8] into homocysteine, indicating that the hydrolysis and transformation of homocysteine may proceed through a common intermediate. PMID:23289936

  1. Increased homocysteine levels impair reference memory and reduce cortical levels of acetylcholine in a mouse model of vascular cognitive impairment.

    PubMed

    Dam, Kevin; Füchtemeier, Martina; Farr, Tracy D; Boehm-Sturm, Philipp; Foddis, Marco; Dirnagl, Ulrich; Malysheva, Olga; Caudill, Marie A; Jadavji, Nafisa M

    2017-03-15

    Folates are B-vitamins that are vital for normal brain function. Deficiencies in folates either genetic (methylenetetrahydrofolate reductase, MTHFR) or dietary intake of folic acid result in elevated levels of homocysteine. Clinical studies have shown that elevated levels of homocysteine (Hcy) may be associated with the development of dementia, however this link remains unclear. The purpose of this study was to evaluate the impact of increased Hcy levels on a mouse model of vascular cognitive impairment (VCI) produced by chronic hypoperfusion. Male and female Mthfr +/+ and Mthfr +/- mice were placed on either control (CD) or folic acid deficient (FADD) diets after which all animals underwent microcoil implantation around each common carotid artery or a sham procedure. Post-operatively animals were tested on the Morris water maze (MWM), y-maze, and rotarod. Animals had no motor impairments on the rotarod, y-maze, and could learn the location of the platform on the MWM. However, on day 8 of testing of MWM testing during the probe trial, Mthfr +/- FADD microcoil mice spent significantly less time in the target quadrant when compared to Mthfr +/- CD sham mice, suggesting impaired reference memory. All FADD mice had elevated levels of plasma homocysteine. MRI analysis revealed arterial remodeling was present in Mthfr +/- microcoil mice not Mthfr +/+ mice. Acetylcholine and related metabolites were reduced in cortical tissue because of microcoil implantation and elevated levels of homocysteine. Deficiencies in folate metabolism resulting in increased Hcy levels yield a metabolic profile that increases susceptibility to neurodegeneration in a mouse model of VCI. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Plasma homocysteine is associated with increased oxidative stress and antioxidant enzyme activity in welders.

    PubMed

    Liu, Hung-Hsin; Shih, Tung-Sheng; Huang, Hsin-Ru; Huang, Shih-Chien; Lee, Lien-Hsiung; Huang, Yi-Chia

    2013-01-01

    The purpose of this study was to examine the association of vitamin B6 status and plasma homocysteine with oxidative stress and antioxidant capacities in welders. Workers were divided into either the welding exposure group (n = 57) or the nonexposure controls (n = 42) based on whether they were employed as welders. There were no significant differences in vitamin B₆ status and plasma homocysteine concentration between the welding exposure group and the nonexposure controls. The welding exposure group had significantly higher levels of oxidized low-density lipoprotein cholesterol and lower erythrocyte glutathione concentration and superoxide dismutase (SOD) activities when compared to nonexposure controls. Plasma pyridoxal 5'-phosphate concentration did not correlate with oxidative stress indicators or antioxidant capacities in either group. However, plasma homocysteine significantly correlated with total antioxidant capacity (TAC) (partial r(s) = -0.34, P < 0.05) and erythrocyte SOD activities (partial r(s) = 0.29, P < 0.05) after adjusting for potential confounders in the welding exposure group. In the welding exposure group, adequate vitamin B₆ status was not associated with oxidative stress or antioxidant capacities. However, elevated plasma homocysteine seemed to be a major contributing factor to antioxidant capacities (TAC and erythrocyte SOD activities) in welders.

  3. Role of homocysteine in the treatment of Parkinson's disease.

    PubMed

    Müller, Thomas

    2008-06-01

    The saga of harmful administration of levodopa (LD) in the treatment of Parkinson's disease (PD) resulted from outcomes of animal trials and cell culture studies. They were initiated after the clinical observation of onset of motor complications related to the short plasma half-life of the drug in PD patients. This discussion only partially considered a further aspect, which is associated with the long-term administration of LD. Chronic LD intake increases homocysteine plasma levels. This may support progression of the disease due to concomitant onset of neuropsychiatric symptoms and comorbidities (i.e., vascular disease). In the periphery, therapeutic approaches for this LD-mediated homocysteine increase are vitamin supplementation (i.e., folic acid or application of LD with an inhibitor of catechol-O-methyltransferase [COMT]). In the brain, a blood-brain trespassing precursor of folic acid or a centrally acting COMT inhibitor may represent hypothetical therapeutic approaches. This COMT inhibitor should be applied together with an oxidative stress reducing monoamine oxidase-B inhibitor, in order to force central dopamine metabolism further down via the methylation path. However, this may turn out to be a double-edged sword, since the inhibition of O-methylation with the COMT inhibitor may hypothetically contribute to increased N-methylation. Thus, endogenous tetrahydroisoquinolines may be transformed to neurotoxic N-methylated tetrahydroisoquinolines. These neurotoxic compounds were observed in cerebrospinal fluid and plasma of long-term LD-treated PD patients. They have a structure similar to 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine or its ion 1-methyl-4-phenylpyridinium, both of which are known to induce PD-like motor symptoms.

  4. Predictive value of homocysteine for depression after acute coronary syndrome

    PubMed Central

    Kang, Hee Ju; Stewart, Robert; Bae, Kyung Yeol; Kim, Sung Wan; Shin, Il Seon; Kang, Hyuno; Moon, Won Jin; Hong, Young Joon; Ahn, Youngkeun; Jeong, Myung Ho; Yoon, Jin Sang; Kim, Jae Min

    2016-01-01

    We investigated roles of plasma homocysteine and MTHFR gene in relation to risks and treatment responses of depression in ACS. A sample of 969 patients with recent ACS were recruited and 711 followed 1 year later. In addition, of 378 baseline participants with depressive disorder, 255 were randomized to a 24-week double blind trial of escitalopram (N = 127) or placebo (N = 128). A higher homocysteine concentration was independently associated with prevalent depressive disorder at baseline irrespective of MTHFR genotype; and with both incident and persistent depressive disorder at follow-up only in the presence of TT genotype. MTHFR genotype was not itself associated with depressive disorder after ACS. No associations were found with 24-week antidepressant treatment responses. Plasma homocysteine could be a biomarker for depressive disorder particularly in the acute phase of ACS. Focused interventions for those with higher homocysteine level and MTHFR TT genotype might reduce the risk of later depressive disorder. PMID:27626182

  5. A nutrient-dense, high-fiber, fruit-based supplement bar increases HDL cholesterol, particularly large HDL, lowers homocysteine, and raises glutathione in a 2-wk trial

    PubMed Central

    Mietus-Snyder, Michele L.; Shigenaga, Mark K.; Suh, Jung H.; Shenvi, Swapna V.; Lal, Ashutosh; McHugh, Tara; Olson, Don; Lilienstein, Joshua; Krauss, Ronald M.; Gildengoren, Ginny; McCann, Joyce C.; Ames, Bruce N.

    2012-01-01

    Dietary intake modulates disease risk, but little is known how components within food mixtures affect pathophysiology. A low-calorie, high-fiber, fruit-based nutrient-dense bar of defined composition (e.g., vitamins and minerals, fruit polyphenolics, β-glucan, docosahexaenoic acid) appropriate for deconstruction and mechanistic studies is described and evaluated in a pilot trial. The bar was developed in collaboration with the U.S. Department of Agriculture. Changes in cardiovascular disease and diabetes risk biomarkers were measured after 2 wk twice-daily consumption of the bar, and compared against baseline controls in 25 healthy adults. Plasma HDL-cholesterol (HDL-c) increased 6.2% (P=0.001), due primarily to a 28% increase in large HDL (HDL-L; P<0.0001). Total plasma homocysteine (Hcy) decreased 19% (P=0.017), and glutathione (GSH) increased 20% (P=0.011). The changes in HDL and Hcy are in the direction associated with decreased risk of cardiovascular disease and cognitive decline; increased GSH reflects improved antioxidant defense. Changes in biomarkers linked to insulin resistance and inflammation were not observed. A defined food-based supplement can, within 2 wk, positively impact metabolic biomarkers linked to disease risk. These results lay the groundwork for mechanistic/deconstruction experiments to identify critical bar components and putative synergistic combinations responsible for observed effects.—Mietus-Snyder, M. L., Shigenaga, M. K., Suh, J. H., Shenvi, S. V., Lal, A., McHugh, T., Olson, D., Lilienstein, J., Krauss, R. M., Gildengoren, G., McCann, J. C., Ames, B. N. A nutrient-dense, high-fiber, fruit-based supplement bar increases HDL cholesterol, particularly large HDL, lowers homocysteine, and raises glutathione in a 2-wk trial. PMID:22549511

  6. Increased CSF Homocysteine in Pathological Gamblers Compared with Healthy Controls

    ERIC Educational Resources Information Center

    Nordin, Conny; Sjodin, Ingemar

    2009-01-01

    Neurocognitive disturbances suggesting a frontal lobe dysfunction have been observed in pathological gamblers and alcohol dependents. Given that a high homocysteine level has been suggested to be a mediating factor in alcohol-related cognitive decline, we have determined homocysteine and cobalamine in cerebrospinal fluid (CSF) obtained from 11…

  7. Are dietary choline and betaine intakes determinants of total homocysteine concentration?

    USDA-ARS?s Scientific Manuscript database

    Elevated homocysteine concentrations are associated with an increased risk of cardiovascular disease and a decline in cognitive function. Intakes of choline and betaine, as methyl donors, may affect homocysteine concentrations. The objective was to examine whether choline and betaine intakes, assess...

  8. High-performance liquid chromatography assay of cysteine and homocysteine using fluorosurfactant-functionalized gold nanoparticles as postcolumn resonance light scattering reagents.

    PubMed

    Xiao, Qunyan; Gao, Huiling; Yuan, Qipeng; Lu, Chao; Lin, Jin-Ming

    2013-01-25

    Herein, a new postcolumn resonance light scattering (RLS) detection approach coupled with high-performance liquid chromatography (HPLC) was developed to detect cysteine and homocysteine. In the established system, the fluorosurfactant-capped gold nanoparticles (AuNPs) were first employed as postcolumn RLS reagents. The detection principle was based on the enhancement of RLS intensity of AuNPs upon the addition of cysteine/homocysteine. The RLS signals were detected by a common fluorescence detector at λ(EX)=λ(EM)=560 nm. The linear ranges for both cysteine and homocysteine were in the range of 5.0-50 μM. The detection limits were 5.9 pmol for cysteine and 12 pmol for homocysteine at a signal-to-noise ratio of 3. HPLC separation and RLS detection conditions were optimized in detail. The applicability of the proposed method has been validated by detecting cysteine and homocysteine in human urine samples. Recoveries from spiked urine samples were 95.0-103.0%. Copyright © 2012 Elsevier B.V. All rights reserved.

  9. Homocysteine-Lowering by B Vitamins Slows the Rate of Accelerated Brain Atrophy in Mild Cognitive Impairment: A Randomized Controlled Trial

    PubMed Central

    Smith, Stephen M.; de Jager, Celeste A.; Whitbread, Philippa; Johnston, Carole; Agacinski, Grzegorz; Oulhaj, Abderrahim; Bradley, Kevin M.; Jacoby, Robin

    2010-01-01

    Background An increased rate of brain atrophy is often observed in older subjects, in particular those who suffer from cognitive decline. Homocysteine is a risk factor for brain atrophy, cognitive impairment and dementia. Plasma concentrations of homocysteine can be lowered by dietary administration of B vitamins. Objective To determine whether supplementation with B vitamins that lower levels of plasma total homocysteine can slow the rate of brain atrophy in subjects with mild cognitive impairment in a randomised controlled trial (VITACOG, ISRCTN 94410159). Methods and Findings Single-center, randomized, double-blind controlled trial of high-dose folic acid, vitamins B6 and B12 in 271 individuals (of 646 screened) over 70 y old with mild cognitive impairment. A subset (187) volunteered to have cranial MRI scans at the start and finish of the study. Participants were randomly assigned to two groups of equal size, one treated with folic acid (0.8 mg/d), vitamin B12 (0.5 mg/d) and vitamin B6 (20 mg/d), the other with placebo; treatment was for 24 months. The main outcome measure was the change in the rate of atrophy of the whole brain assessed by serial volumetric MRI scans. Results A total of 168 participants (85 in active treatment group; 83 receiving placebo) completed the MRI section of the trial. The mean rate of brain atrophy per year was 0.76% [95% CI, 0.63–0.90] in the active treatment group and 1.08% [0.94–1.22] in the placebo group (P = 0.001). The treatment response was related to baseline homocysteine levels: the rate of atrophy in participants with homocysteine >13 µmol/L was 53% lower in the active treatment group (P = 0.001). A greater rate of atrophy was associated with a lower final cognitive test scores. There was no difference in serious adverse events according to treatment category. Conclusions and Significance The accelerated rate of brain atrophy in elderly with mild cognitive impairment can be slowed by treatment with homocysteine

  10. No effect of folic acid supplementation on global DNA methylation in men and women with moderately elevated homocysteine.

    PubMed

    Jung, Audrey Y; Smulders, Yvo; Verhoef, Petra; Kok, Frans J; Blom, Henk; Kok, Robert M; Kampman, Ellen; Durga, Jane

    2011-01-01

    A global loss of cytosine methylation in DNA has been implicated in a wide range of diseases. There is growing evidence that modifications in DNA methylation can be brought about by altering the intake of methyl donors such as folate. We examined whether long-term daily supplementation with 0.8 mg of folic acid would increase global DNA methylation compared with placebo in individuals with elevated plasma homocysteine. We also investigated if these effects were modified by MTHFR C677T genotype. Two hundred sixteen participants out of 818 subjects who had participated in a randomized double-blind placebo-controlled trial were selected, pre-stratified on MTHFR C677T genotype and matched on age and smoking status. They were allocated to receive either folic acid (0.8 mg/d; n = 105) or placebo treatment (n = 111) for three years. Peripheral blood leukocyte DNA methylation and serum and erythrocyte folate were assessed. Global DNA methylation was measured using liquid chromatography-tandem mass spectrometry and expressed as a percentage of 5-methylcytosines versus the total number of cytosine. There was no difference in global DNA methylation between those randomized to folic acid and those in the placebo group (difference = 0.008, 95%CI = -0.05,0.07, P = 0.79). There was also no difference between treatment groups when we stratified for MTHFR C677T genotype (CC, n = 76; CT, n = 70; TT, n = 70), baseline erythrocyte folate status or baseline DNA methylation levels. In moderately hyperhomocysteinemic men and women, long-term folic acid supplementation does not increase global DNA methylation in peripheral blood leukocytes.ClinicalTrials.gov NCT00110604.

  11. Homocysteine and C-reactive protein as useful surrogate markers for evaluating CKD risk in adults.

    PubMed

    Chuang, Chung-Hsun; Lee, Yi-Yen; Sheu, Bor-Fuh; Hsiao, Cheng-Ting; Loke, Song-Seng; Chen, Jih-Chang; Li, Wen-Cheng

    2013-01-01

    This study aimed to evaluate the effectiveness of homocysteine and C-reactive protein (CRP) as potential markers for chronic kidney disease (CKD) in adults in Taiwan, and to identify associations between these factors and CKD, stratifying by gender. This cross-sectional study analyzed multi-center data retrospectively. Data were collected from 22,043 adult Taiwanese at Chang-Gung Memorial Hospital from 2005 to 2011. Smoking/drinking history, personal medical/medication history, pregnancy, fasting times as well as laboratory parameters, including homocysteine and CRP were measured and analyzed. Significant differences were observed between four homocysteine and CRP quartiles in eGFR and CKD. For males, only one model showed significant associations between plasma homocysteine and CKD, while in females, all three models showed significant associations with CKD. On the contrary, the gender difference in the case of CRP was opposite. Combined homocysteine and CRP were associated with CKD in males but not in females. Among Taiwanese adults, plasma homocysteine is associated with CKD in females and plasma hsCRP is associated with CKD in males. High hsCRP/high homocysteine is associated with elevated CKD risk in male. Our results suggest that homocysteine and hsCRP may be useful surrogate markers for evaluating CKD risk in adults. © 2013 S. Karger AG, Basel.

  12. Plasma Homocysteine Is Associated with Increased Oxidative Stress and Antioxidant Enzyme Activity in Welders

    PubMed Central

    Liu, Hung-Hsin; Shih, Tung-Sheng; Huang, Hsin-Ru; Huang, Shih-Chien; Lee, Lien-Hsiung; Huang, Yi-Chia

    2013-01-01

    The purpose of this study was to examine the association of vitamin B6 status and plasma homocysteine with oxidative stress and antioxidant capacities in welders. Workers were divided into either the welding exposure group (n = 57) or the nonexposure controls (n = 42) based on whether they were employed as welders. There were no significant differences in vitamin B6 status and plasma homocysteine concentration between the welding exposure group and the nonexposure controls. The welding exposure group had significantly higher levels of oxidized low-density lipoprotein cholesterol and lower erythrocyte glutathione concentration and superoxide dismutase (SOD) activities when compared to nonexposure controls. Plasma pyridoxal 5′-phosphate concentration did not correlate with oxidative stress indicators or antioxidant capacities in either group. However, plasma homocysteine significantly correlated with total antioxidant capacity (TAC) (partial r s = −0.34, P < 0.05) and erythrocyte SOD activities (partial r s = 0.29, P < 0.05) after adjusting for potential confounders in the welding exposure group. In the welding exposure group, adequate vitamin B6 status was not associated with oxidative stress or antioxidant capacities. However, elevated plasma homocysteine seemed to be a major contributing factor to antioxidant capacities (TAC and erythrocyte SOD activities) in welders. PMID:24106453

  13. Total homocysteine and cognition in a tri-ethnic cohort

    PubMed Central

    Wright, C.B.; Lee, H.-S.; Paik, M.C.; Stabler, S.P.; Allen, R.H.; Sacco, R.L.

    2005-01-01

    Objective: Several studies implicate elevated homocysteine as a risk factor for dementia and cognitive decline, but most studies have involved subjects older than 55 years from homogeneous populations. The authors examined homocysteine and cognition in a tri-ethnic community sample 40 years and older. Method: The Northern Manhattan Study includes 3,298 stroke-free subjects. Of these 2,871 had baseline fasting total homocysteine (tHcy) levels and Mini-Mental State Examination (MMSE) scores available. The authors used multiple linear regression to examine the cross-sectional association between baseline tHcy levels and mean MMSE scores adjusting for sociodemographic and vascular risk factors. Results: Homocysteine levels were related to age, renal function, and B12 deficiency. Those with B12 deficiency had tHcy levels five points higher (9.4 vs 14.4 nmol/L). Mean MMSE scores differed by age, sex, and race-ethnic group. Those with hypertension, diabetes, cardiac disease, and B12 deficiency had lower MMSE scores. In multivariate analyses, elevated tHcy was associated with lower mean MMSE scores for those older than 65 but not for those 40 to 64. Adjusting for B12 deficiency and sociodemographic factors the mean MMSE was 2.2 points lower for each unit increase in the log tHcy level (95% CI −3.6, −0.9). Adding vascular risk factors to the model did not attenuate this effect (mean MMSE −2.2 points; 95% CI −3.5, −0.9). Conclusions: Elevated homocysteine was independently associated with decreased cognition in subjects older than 65 in this tri-ethnic cohort, adjusting for sociodemographic and vascular risk factors. PMID:15277617

  14. MTHFR Gene and Serum Folate Interaction on Serum Homocysteine Lowering: Prospect for Precision Folic Acid Treatment.

    PubMed

    Huang, Xiao; Qin, Xianhui; Yang, Wenbin; Liu, Lishun; Jiang, Chongfei; Zhang, Xianglin; Jiang, Shanqun; Bao, Huihui; Su, Hai; Li, Ping; He, Mingli; Song, Yun; Zhao, Min; Yin, Delu; Wang, Yu; Zhang, Yan; Li, Jianping; Yang, Renqang; Wu, Yanqing; Hong, Kui; Wu, Qinhua; Chen, Yundai; Sun, Ningling; Li, Xiaoying; Tang, Genfu; Wang, Binyan; Cai, Yefeng; Hou, Fan Fan; Huo, Yong; Wang, Hong; Wang, Xiaobin; Cheng, Xiaoshu

    2018-03-01

    This post hoc analysis of the CSPPT (China Stroke Primary Prevention Trial) assessed the individual variation in total homocysteine (tHcy)-lowering response after an average 4.5 years of 0.8 mg daily folic acid therapy in Chinese hypertensive adults and evaluated effect modification by methylenetetrahydrofolate reductase ( MTHFR ) C677T genotypes and serum folate levels. This analysis included 16 413 participants from the CSPPT, who were randomly assigned to 2 double-blind treatment groups: either 10-mg enalapril+0.8-mg folic acid or 10-mg enalapril, daily and had individual measurements of serum folate and tHcy levels at baseline and exit visits and MTHFR C677T genotypes. Mean baseline tHcy levels were comparable between the 2 treatment groups (14.5±8.5 versus 14.4±8.1 μmol/L; P =0.561). After 4.5 years of treatment, mean tHcy levels were reduced to 12.7±6.1 μmol/L in the enalapril+folic acid group, but almost stayed the same in the enalapril group (14.4±7.9 μmol/L, group difference: 1.61 μmol/L; 11% reduction). More importantly, tHcy lowering varied by MTHFR genotypes and serum folate levels. Compared with CC and CT genotypes, participants with the TT genotype had a more prominent L-shaped curve between tHcy and serum folate levels and required higher folate levels (at least 15 ng/mL) to eliminate the differences in tHcy by genotypes. Compared with CC or CT, tHcy in the TT group manifested a heightened L-shaped curve from low to high folate levels, but this difference in tHcy by genotype was eliminated when plasma folate levels reach ≈15 ng/mL or higher. Our data raised the prospect to tailor folic acid therapy according to individual MTHFR C677T genotype and folate status. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00794885. © 2018 American Heart Association, Inc.

  15. DNA/nickel oxide nanoparticles/osmium(III)-complex modified electrode toward selective oxidation of l-cysteine and simultaneous detection of l-cysteine and homocysteine.

    PubMed

    Sharifi, Ensiyeh; Salimi, Abdollah; Shams, Esmaeil

    2012-08-01

    The modification of glassy carbon (GC) electrode with electrodeposited nickel oxide nanoparticles (NiOxNPs) and deoxyribonucleic acid (DNA) is utilized as a new efficient platform for entrapment of osmium (III) complex. Surface morphology and electrochemical properties of the prepared nanocomposite modified electrode (GC/DNA/NiOxNPs/Os(III)-complex) were investigated by FESEM, cyclic voltammetry and electrochemical impedance spectroscopy techniques. Cyclic voltammetric results indicated the excellent electrocatalytic activity of the resulting electrode toward oxidation of l-cysteine (CySH) at reduced overpotential (0.1 V vs. Ag/AgCl). Using chronoamperometry to CySH detection, the sensitivity and detection limit of the biosensor are obtained as 44 μA mM(-1) and 0.07 μM with a concentration range up to 1000 μM. The electrocatalytic activity of the modified electrode not only for oxidation of low molecular-mass biothiols derivatives such as, glutathione, l-cystine, l-methionine and electroactive biological species ( dopamine, uric acid, glucose) is negligible but also for very similar biothiol compound (homocysteine) no recognizable response is observed at the applied potential window. Furthermore, the simultaneous voltammetric determination of l-cysteine and homocysteine compounds without any separation or pretreatment process was reported for the first time in this work. Finally, the applicability of sensor for the analysis of CySH concentration in complex serum samples was successfully demonstrated. Highly selectivity, excellent electrocatalytic activity and stability, remarkable antifouling property toward thiols and their oxidation products, as well as the ability for simultaneous detection of l-cysteine and homocysteine are remarkably advantageous of the proposed DNA based biosensor. Copyright © 2012 Elsevier B.V. All rights reserved.

  16. Glomerular filtration rate as measured by serum cystatin C is an important determinant of plasma homocysteine and serum methylmalonic acid in the elderly.

    PubMed

    Lewerin, C; Ljungman, S; Nilsson-Ehle, H

    2007-01-01

    To explore the dependence of glomerular filtration rate (GFR) on plasma total homocysteine (tHcy) and serum methylmalonic acid (MMA), as well as the consequences for the diagnosis of cobalamin and/or folic acid deficiency in an elderly community-dwelling population. Population-based study of 209 community-dwelling subjects, mean age 76 years. Four months' treatment study with oral vitamin B(12), folic acid and B(6) or placebo. Determinants of tHcy and MMA: cystatin C as a marker of GFR and serum/plasma concentrations of vitamin B(12) and folate, age and sex. Elevated cystatin C (>1.55 mg L(-1)) was found in 31.3% (men) and 13.0% (women). Elevated tHcy (> or = 16 micromol L(-1)) occurred in 53% and elevated MMA (> or = 0.34 micromol L(-1)) in 11% of all subjects. When GFR was taken into consideration, the proportion of elevated tHcy was reduced to 10% (20/209), whilst the proportion of elevated MMA was unchanged. Cystatin C was correlated with tHcy (r = 0.45, P < 0.001) and with MMA (r =0.28, P < 0.001), independently of vitamin B(12)- and folate status. According to multiple regression, independent predictors for tHcy were plasma folate (15%), cystatin C (11%) and vitamin B(12) (4%), and for MMA, cystatin C (8%) and vitamin B(12) (2%). The prevalence of elevated tHcy may be overestimated in elderly populations unless GFR is taken into account. Nomograms for evaluation of tHcy and MMA in relation to both cystatin C and serum creatinine are presented.

  17. Homocysteine as a Diagnostic and Etiopathogenic Factor in Children with Autism Spectrum Disorder.

    PubMed

    Józefczuk, Jan; Kasprzycka, Wiktoria; Czarnecki, Rafał; Graczyk, Alfreda; Józefczuk, Paweł; Magda, Krzysztof; Lampart, Urszula

    2017-08-01

    Substantial characteristics of autism are cognitive and psychophysical disorders. Etiopathogenetic factors are thought to be responsible for development of autism in children with genetic predisposition as well as have their effect on the severity of the disorders. The main problem of early identification of patients affected by autism spectrum disorder is that there are no clear diagnostic criteria. The aim of our study was assessment of hair magnesium and serum homocysteine concentrations in children with autism. The presented work is a continuation of previous study in which we investigated the influence of disturbances in magnesium and homocysteine levels in children with autism, performed on a new, larger group of patients. One hundred and forty children had hair magnesium levels analyzed, as well as blood serum levels of homocysteine and magnesium. Hair magnesium analysis was performed using a flame atomic absorption spectrometer, blood serum homocysteine determination was performed using a radioimmunological method, and blood serum magnesium level was determined using a biochemical method. Our research showed normal magnesium blood levels and significantly high homocysteine levels and very low hair magnesium levels. Low concentration of hair magnesium progresses with age. Our hypothesis is that magnesium deficiency, as a relevant epigenetic factor, might be decreasing methylation of homocysteine, therefore decreasing genome transcription and lowering the synaptic plasticity. We suggest that analysis of hair magnesium and serum homocysteine levels might be useful in identification of children with autism spectrum disorder, as well as control of its treatment. Obtained results and performed analysis might therefore justify supplementation of magnesium among children with autism.

  18. High homocysteine induces betaine depletion

    PubMed Central

    Imbard, Apolline; Benoist, Jean-François; Esse, Ruben; Gupta, Sapna; Lebon, Sophie; de Vriese, An S; de Baulny, Helene Ogier; Kruger, Warren; Schiff, Manuel; Blom, Henk J.

    2015-01-01

    Betaine is the substrate of the liver- and kidney-specific betaine-homocysteine (Hcy) methyltransferase (BHMT), an alternate pathway for Hcy remethylation. We hypothesized that BHMT is a major pathway for homocysteine removal in cases of hyperhomocysteinaemia (HHcy). Therefore, we measured betaine in plasma and tissues from patients and animal models of HHcy of genetic and acquired cause. Plasma was collected from patients presenting HHcy without any Hcy interfering treatment. Plasma and tissues were collected from rat models of HHcy induced by diet and from a mouse model of cystathionine β-synthase (CBS) deficiency. S-adenosyl-methionine (AdoMet), S-adenosyl-homocysteine (AdoHcy), methionine, betaine and dimethylglycine (DMG) were quantified by ESI—LC–MS/MS. mRNA expression was quantified using quantitative real-time (QRT)-PCR. For all patients with diverse causes of HHcy, plasma betaine concentrations were below the normal values of our laboratory. In the diet-induced HHcy rat model, betaine was decreased in all tissues analysed (liver, brain, heart). In the mouse CBS deficiency model, betaine was decreased in plasma, liver, heart and brain, but was conserved in kidney. Surprisingly, BHMT expression and activity was decreased in liver. However, in kidney, BHMT and SLC6A12 expression was increased in CBS-deficient mice. Chronic HHcy, irrespective of its cause, induces betaine depletion in plasma and tissues (liver, brain and heart), indicating a global decrease in the body betaine pool. In kidney, betaine concentrations were not affected, possibly due to overexpression of the betaine transporter SLC6A12 where betaine may be conserved because of its crucial role as an osmolyte. PMID:26182429

  19. High homocysteine induces betaine depletion.

    PubMed

    Imbard, Apolline; Benoist, Jean-François; Esse, Ruben; Gupta, Sapna; Lebon, Sophie; de Vriese, An S; de Baulny, Helene Ogier; Kruger, Warren; Schiff, Manuel; Blom, Henk J

    2015-04-28

    Betaine is the substrate of the liver- and kidney-specific betaine-homocysteine (Hcy) methyltransferase (BHMT), an alternate pathway for Hcy remethylation. We hypothesized that BHMT is a major pathway for homocysteine removal in cases of hyperhomocysteinaemia (HHcy). Therefore, we measured betaine in plasma and tissues from patients and animal models of HHcy of genetic and acquired cause. Plasma was collected from patients presenting HHcy without any Hcy interfering treatment. Plasma and tissues were collected from rat models of HHcy induced by diet and from a mouse model of cystathionine β-synthase (CBS) deficiency. S-adenosyl-methionine (AdoMet), S-adenosyl-homocysteine (AdoHcy), methionine, betaine and dimethylglycine (DMG) were quantified by ESI-LC-MS/MS. mRNA expression was quantified using quantitative real-time (QRT)-PCR. For all patients with diverse causes of HHcy, plasma betaine concentrations were below the normal values of our laboratory. In the diet-induced HHcy rat model, betaine was decreased in all tissues analysed (liver, brain, heart). In the mouse CBS deficiency model, betaine was decreased in plasma, liver, heart and brain, but was conserved in kidney. Surprisingly, BHMT expression and activity was decreased in liver. However, in kidney, BHMT and SLC6A12 expression was increased in CBS-deficient mice. Chronic HHcy, irrespective of its cause, induces betaine depletion in plasma and tissues (liver, brain and heart), indicating a global decrease in the body betaine pool. In kidney, betaine concentrations were not affected, possibly due to overexpression of the betaine transporter SLC6A12 where betaine may be conserved because of its crucial role as an osmolyte. © 2015 Author(s).

  20. Plasma Homocysteine, Serum Folic Acid, Serum Vitamin B12, Serum Vitamin B6, MTHFR, and Risk of Normal-Tension Glaucoma.

    PubMed

    Li, Jinmiao; Xu, Fan; Zeng, Rui; Gong, Haijun; Lan, Yuqing

    2016-02-01

    This meta-analysis aims to comprehensively evaluate the association between total homocysteine (tHcy) levels, serum folic acid, vitamin B12, vitamin B6 levels, methylenetetrahydrofolate reductase (MTHFR) C677T genotype, and risk of normal-tension glaucoma (NTG). A systematic search of the EMBASE and PubMed databases was performed to evaluate plasma tHcy levels, serum folic acid, B vitamins' mean difference, and odds ratios of MTHFR C677T genotype between cases and controls. A total of 7 studies including 458 cases and 555 controls meeting the inclusion criteria were involved in this meta-analysis. There were 4 studies for tHcy (149 cases and 148 controls), 2 studies for vitamin B6, vitamin B12, and folate (90 cases and 82 controls), and 4 studies for MTHFR (343 cases and 449 controls). Overall, the mean plasma tHcy levels, serum folic acids, vitamin B12, and vitamin B6 levels were 1.16 μmol/L [95% confidence interval (CI), -0.13, 2.45], -0.62 μmol/L (95% CI, -1.98, 0.74), 5.81 μmol/L (95% CI, -3.53, 15.14), and -16.79 μmol/L (95% CI, -86.09, 52.51). MTHFR TT genotype was found to be unrelated to NTG risk (odds ratio=1.08; 95% CI, 0.69, 1.69). NTG is not associated with elevated plasma tHcy, serum folic acid, serum vitamin B12, serum vitamin B6, and MTHFR C677T genotype.

  1. Common genetic loci influencing plasma homocysteine concentrations and their effect on risk of coronary artery disease

    USDA-ARS?s Scientific Manuscript database

    The strong observational association between total homocysteine (tHcy) concentrations and risk of coronary artery disease (CAD) and the null associations in the homocysteine-lowering trials have prompted the need to identify genetic variants associated with homocysteine concentrations and risk of CA...

  2. Quantitation of total homocysteine in human plasma by derivatization to its N(O,S)-propoxycarbonyl propyl ester and gas chromatography-mass spectrometry analysis.

    PubMed

    Sass, J O; Endres, W

    1997-08-01

    Much evidence supports the hypothesis that mild or moderate hyperhomocysteinaemia represents an important and independent risk factor for occlusive vascular diseases. Therefore, the accurate and reliable determination of total plasma homocysteine has gained major importance for risk assessment. Furthermore, it can help in the detection of folate and vitamin B12 deficiency. This has prompted us to develop a sensitive gas chromatography-mass spectrometry (GC-MS) method in order to quantify total homocysteine in human plasma. Prior to chromatography, reduced homocysteine was released from disulfide bonds by incubation with excess dithiothreitol and converted into its N(O,S)-propoxycarbonyl propyl ester by derivatization with n-propyl chloroformate. Aminoethylcysteine served as internal standard. The method proved to be highly linear over the entire concentration range examined (corresponding to 0-266 microM homocysteine) and showed intra-assay and inter-assay variation (relative standard deviations) of approximately 5 and 5-10%, respectively. External quality control by comparison with duplicate analysis performed on a HPLC-based system revealed satisfactory correlation. The newly developed GC-MS based method provides simple, reliable and fast quantification of total homocysteine and requires only inexpensive chemicals, which are easy to obtain.

  3. Sulfur amino acid metabolism in doxorubicin-resistant breast cancer cells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ryu, Chang Seon; Kwak, Hui Chan; Lee, Kye Sook

    2011-08-15

    Although methionine dependency is a phenotypic characteristic of tumor cells, it remains to be determined whether changes in sulfur amino acid metabolism occur in cancer cells resistant to chemotherapeutic medications. We compared expression/activity of sulfur amino acid metabolizing enzymes and cellular levels of sulfur amino acids and their metabolites between normal MCF-7 cells and doxorubicin-resistant MCF-7 (MCF-7/Adr) cells. The S-adenosylmethionine/S-adenosylhomocysteine ratio, an index of transmethylation potential, in MCF-7/Adr cells decreased to {approx} 10% relative to that in MCF-7 cells, which may have resulted from down-regulation of S-adenosylhomocysteine hydrolase. Expression of homocysteine-clearing enzymes, such as cystathionine beta-synthase, methionine synthase/methylene tetrahydrofolate reductase,more » and betaine homocysteine methyltransferase, was up-regulated in MCF-7/Adr cells, suggesting that acquiring doxorubicin resistance attenuated methionine-dependence and activated transsulfuration from methionine to cysteine. Homocysteine was similar, which is associated with a balance between the increased expressions of homocysteine-clearing enzymes and decreased extracellular homocysteine. Despite an elevation in cysteine, cellular GSH decreased in MCF-7/Adr cells, which was attributed to over-efflux of GSH into the medium and down-regulation of the GSH synthesis enzyme. Consequently, MCF-7/Adr cells were more sensitive to the oxidative stress induced by bleomycin and menadione than MCF-7 cells. In conclusion, our results suggest that regulating sulfur amino acid metabolism may be a possible therapeutic target for chemoresistant cancer cells. These results warrant further investigations to determine the role of sulfur amino acid metabolism in acquiring anticancer drug resistance in cancer cells using chemical and biological regulators involved in sulfur amino acid metabolism. - Research Highlights: > MCF-7/Adr cells showed decreases in

  4. Homocysteine is the confounding factor of metabolic syndrome-confirmed by siMS score.

    PubMed

    Srećković, Branko; Soldatovic, Ivan; Colak, Emina; Mrdovic, Igor; Sumarac-Dumanovic, Mirjana; Janeski, Hristina; Janeski, Nenad; Gacic, Jasna; Dimitrijevic-Sreckovic, Vesna

    2018-04-06

    Abdominal adiposity has a central role in developing insulin resistance (IR) by releasing pro-inflammatory cytokines. Patients with metabolic syndrome (MS) have higher values of homocysteine. Hyperhomocysteinemia correlates with IR, increasing the oxidative stress. Oxidative stress causes endothelial dysfunction, hypertension and atherosclerosis. The objective of the study was to examine the correlation of homocysteine with siMS score and siMS risk score and with other MS co-founding factors. The study included 69 obese individuals (age over 30, body mass index [BMI] >25 kg/m2), classified into two groups: I-with MS (33 patients); II-without MS (36 patients). Measurements included: anthropometric parameters, lipids, glucose regulation parameters and inflammation parameters. IR was determined by homeostatic model assessment for insulin resistance (HOMA-IR). ATP III classification was applied for diagnosing MS. SiMS score was used as continuous measure of metabolic syndrome. A significant difference between groups was found for C-reactive protein (CRP) (p<0.01) apolipoprotein (Apo) B, HOMA-IR and acidum uricum (p<0.05). siMS risk score showed a positive correlation with homocysteine (p=0.023), while siMS score correlated positively with fibrinogen (p=0.013), CRP and acidum uricum (p=0.000) and homocysteine (p=0.08). Homocysteine correlated positively with ApoB (p=0.036), HbA1c (p=0.047), HOMA-IR (p=0.008) and negatively with ApoE (p=0.042). Correlation of siMS score with homocysteine, fibrinogen, CRP and acidum uricum indicates that they are co-founding factors of MS. siMS risk score correlation with homocysteine indicates that hyperhomocysteinemia increases with age. Hyperhomocysteinemia is linked with genetic factors and family nutritional scheme, increasing the risk for atherosclerosis.

  5. Serum Homocysteine Level in Parkinson's Disease and Its Association with Duration, Cardinal Manifestation, and Severity of Disease.

    PubMed

    Saadat, Payam; Ahmadi Ahangar, Alijan; Samaei, Seyed Ehsan; Firozjaie, Alireza; Abbaspour, Fatemeh; Khafri, Sorrayya; Khoddami, Azam

    2018-01-01

    Due to the high prevalence of Parkinson's disease (PD) in the elderly, a large financial burden is imposed on the families and health systems of countries in addition to the problems related to the mobility impairment caused by the disease for the patients. Studies on controversial issues in this disease are taken into consideration, and one of these cases is the role of serum homocysteine level in Parkinson's patients. In this study, the serum level of homocysteine and its association with various variables in relation to this disease was compared with healthy individuals. In this study, 100 patients with PD and 100 healthy individuals as control group were investigated. Serum homocysteine level and demographic and clinical data were included in the checklist. Data were analyzed by SPSS version 23. In all tests, the significance level was below 0.05. The mean level of serum homocysteine in case and control groups was 14.93 ± 8.30 and 11.52 ± 2.86  µ mol/L, respectively (95% CI: 1.68; 5.14, P < 0.001). In total patients, 85 had normal serum homocysteine level, while 15 had high serum homocysteine level. In controls, the homocysteine level was 98 and 2, respectively ( P =0.002). In multivariate logistic regression analysis, serum homocysteine level higher than 20  µ mol/L was accompanied by 8.64-fold in Parkinson's disease involvement (95% CI: 1.92; 38.90, P =0.005). Increasing serum homocysteine level elevates the rate to having PD. Serum homocysteine levels did not have any relationship with the duration of the disease, type of cardinal manifestation, and the severity of Parkinson's disease.

  6. Methylmalonic Acid and Homocysteine as Indicators of Vitamin B-12 Deficiency in Cancer

    PubMed Central

    Vashi, Pankaj; Edwin, Persis; Popiel, Brenten; Lammersfeld, Carolyn; Gupta, Digant

    2016-01-01

    Background/Aims Normal or high serum vitamin B-12 levels can sometimes be seen in a B-12 deficient state, and can therefore be misleading. High levels of Methymalonic Acid (MMA) and Homocysteine (HC) have been identified as better indicators of B-12 deficiency than the actual serum B-12 level itself. We evaluated the prevalence of vitamin B-12 deficiency using appropriate cut-off levels of vitamin B-12, MMA and HC, and determined the relationship between serum levels of vitamin B-12, MMA and HC in cancer. Methods This is a cross-sectional study using a consecutive case series of 316 cancer patients first seen at Cancer Treatment Centers of America® (CTCA) at Midwestern Regional Medical Center between April 2014 and June 2014. All patients were evaluated at baseline for vitamin B-12 (pg/mL), MMA (nmol/L) and HC (μmol/L) levels. In accordance with previously published research, the following cut-offs were used to define vitamin B-12 deficiency: <300 pg/mL for vitamin B-12, >260 nmol/L for MMA and >12 μmol/L for HC. The relationship between B-12, MMA and HC was evaluated using Spearman's rho correlation coefficient and cross-tabulation analysis. Receiver Operating Characteristic (ROC) curves were estimated using the non-parametric method to further evaluate the diagnostic accuracy of vitamin B-12 using Fedosov quotient as the "gold standard". Results Mean age at presentation was 52.5 years. 134 (42.4%) patients were males while 182 (57.6%) were females. Median vitamin B-12, MMA and HC levels were 582.5 pg/mL, 146.5 nmol/L and 8.4 μmol/L respectively. Of 316 patients, 28 (8.9%) were vitamin B-12 deficient based on vitamin B-12 (<300pg/mL), 34 (10.8%) were deficient based on MMA (>260 nmol/L) while 55 (17.4%) were deficient based on HC (>12 μmol/L). Correlation analysis revealed a significant weak negative correlation between vitamin B-12 and MMA (rho = -0.22) as well as B-12 and HC (rho = -0.35). ROC curves suggested MMA to have the best discriminatory power in

  7. Contribution of caffeine to the homocysteine-raising effect of coffee: a randomized controlled trial in humans.

    PubMed

    Verhoef, Petra; Pasman, Wilrike J; Van Vliet, Trinette; Urgert, Rob; Katan, Martijn B

    2002-12-01

    A high plasma total homocysteine concentration is associated with increased risk of cardiovascular disease. Consumption of unfiltered or filtered coffee raises total homocysteine concentrations in healthy volunteers. The responsible compound, however, is unknown. The objective was to determine whether caffeine explains the homocysteine-raising effect of coffee. Forty-eight subjects aged 19-65 y completed this randomized crossover study with 3 treatments, each lasting 2 wk. Subjects consumed 6 capsules providing 870 mg caffeine/d (test treatment), 0.9 L paper-filtered coffee providing approximately 870 mg caffeine/d, or 6 placebo capsules. Blood samples were drawn fasting and 4 h after consumption of 0.45 L coffee or 3 capsules. The mean fasting plasma homocysteine concentration after the placebo treatment was 9.6 +/- 3.1 micro mol/L. The caffeine and coffee treatments increased fasting homocysteine by 0.4 micro mol/L (95% CI: 0.1, 0.7; P = 0.04), or 5%, and by 0.9 micro mol/L (95% CI: 0.6, 1.2; P = 0.0001), or 11%, respectively, compared with placebo. The increase in homocysteine concentrations 4 h after consumption of 0.45 L coffee relative to consumption of 3 placebo capsules was 19% (P = 0.0001). Caffeine treatment had a much weaker acute effect on homocysteine (4%; P = 0.09). Effects of caffeine were stronger in women than in men, but the effects of coffee did not differ significantly between men and women. Caffeine is partly responsible for the homocysteine-raising effect of coffee. Coffee, but not caffeine, affects homocysteine metabolism within hours after intake, although the effect is still substantial after an overnight fast.

  8. Homocysteine in small-for-gestational age and appropriate-for-gestational age preterm neonates from mothers receiving folic acid supplementation.

    PubMed

    Gomes, Thushari S; Lindner, Ulrike; Tennekoon, Kamani H; Karandagoda, Wimal; Gortner, Ludwig; Obeid, Rima

    2010-08-01

    Prematurity and small-for-gestational age (SGA) neonates are at risk for postnatal complications. Concentrations of total homocysteine (tHcy) might be related to neonatal outcome. We hypothesized that concentrations of tHcy are not related to growth restriction in neonates from mothers receiving 5 mg/day folic acid. We studied a total of 133 preterm neonates from normotensive mothers; SGA (n=96) and appropriate-for-gestational age (AGA, n=37). Concentrations of tHcy, folate and vitamin B12 were measured in venous umbilical cord plasma. AGA preterm neonates had higher mean birth weight (BW) compared to SGA preterms (2472 g vs. 2007 g; p<0.001) of comparable mean gestational age (GA) (35.1 vs. 35.7 weeks; p=0.059). Concentrations of tHcy (4.86 vs. 4.95 micromol/L), folate (63.3 vs. 55.7 nmol/L), and vitamin B12 (409 vs. 394 pmol/L) were not significantly different between the groups. GA was a strong positive predictor, BW was a significant negative predictor of cord plasma folate. Vitamin B12 concentration was a significant negative predictor of cord tHcy. Concentrations of tHcy did not differ between SGA and AGA preterm neonates born to mothers supplemented with folic acid. This finding argues against a causal role for folate deficiency or increased tHcy in growth restriction.

  9. Uremic restless legs syndrome (RLS) and sleep quality in patients with end-stage renal disease on hemodialysis: potential role of homocysteine and parathyroid hormone.

    PubMed

    Gade, Katrin; Blaschke, Sabine; Rodenbeck, Andrea; Becker, Andreas; Anderson-Schmidt, Heike; Cohrs, Stefan

    2013-01-01

    The aetiology of uremic restless legs syndrome (RLS) remains unclear. Our research investigated whether an elevated plasma concentration of the excitatory amino acid homocysteine might be associated with RLS occurrence in patients with chronic renal insufficiency on hemodialysis. Total plasma homocysteine as well as creatinine, urea, folate, parathyroid hormone, hemoglobin, iron, ferritin, phosphate, calcium, magnesium, and albumin levels were compared between 26 RLS-affected (RLSpos) and 26 non-affected (RLSneg) patients on chronic hemodialysis. We further compared subjective sleep quality between RLSpos and RLSneg patients using the Pittsburgh-Sleep-Quality-Index and investigated possible relationships between laboratory parameters and sleep quality. Taking individual albumin concentrations into account, a significant positive correlation between total plasma homocysteine and RLS occurrence was observed (r= 0.246; p=0.045). Sleep quality was significantly more reduced in RLSpos compared to RLSneg patients and RLS severity correlated positively with impairment of sleep quality. Bad sleep quality in all patients was associated with higher concentrations of parathyroid hormone. Our results suggest a possible aetiological role of homocysteine in uremic RLS. They confirm that uremic RLS is an important factor causing sleep impairment in patients on hemodialysis. Higher parathyroid hormone levels might also be associated with bad sleep quality in these patients. © 2013 S. Karger AG, Basel.

  10. Stroke: roles of B vitamins, homocysteine and antioxidants.

    PubMed

    Sánchez-Moreno, Concepción; Jiménez-Escrig, Antonio; Martín, Antonio

    2009-06-01

    In the present review concerning stroke, we evaluate the roles of B vitamins, homocysteine and antioxidant vitamins. Stroke is a leading cause of death in developed countries. However, current therapeutic strategies for stroke have been largely unsuccessful. Several studies have reported important benefits on reducing the risk of stroke and improving the post-stroke-associated functional declines in patients who ate foods rich in micronutrients, including B vitamins and antioxidant vitamins E and C. Folic acid, vitamin B6 and vitamin B12 are all cofactors in homocysteine metabolism. Growing interest has been paid to hyperhomocysteinaemia as a risk factor for CVD. Hyperhomocysteinaemia has been linked to inadequate intake of vitamins, particularly to B-group vitamins and therefore may be amenable to nutritional intervention. Hence, poor dietary intake of folate, vitamin B6 and vitamin B12 are associated with increased risk of stroke. Elevated consumption of fruits and vegetables appears to protect against stroke. Antioxidant nutrients have important roles in cell function and have been implicated in processes associated with ageing, including vascular, inflammatory and neurological damage. Plasma vitamin E and C concentrations may serve as a biological marker of lifestyle or other factors associated with reduced stroke risk and may be useful in identifying those at high risk of stroke. After reviewing the observational and intervention studies, there is an incomplete understanding of mechanisms and some conflicting findings; therefore the available evidence is insufficient to recommend the routine use of B vitamins, vitamin E and vitamin C for the prevention of stroke. A better understanding of mechanisms, along with well-designed controlled clinical trials will allow further progress in this area.

  11. l-Homocysteine-induced cathepsin V mediates the vascular endothelial inflammation in hyperhomocysteinaemia.

    PubMed

    Leng, Yi-Ping; Ma, Ye-Shuo; Li, Xiao-Gang; Chen, Rui-Fang; Zeng, Ping-Yu; Li, Xiao-Hui; Qiu, Cheng-Feng; Li, Ya-Pei; Zhang, Zhen; Chen, Alex F

    2018-04-01

    Vascular inflammation, including the expression of inflammatory cytokines in endothelial cells, plays a critical role in hyperhomocysteinaemia-associated vascular diseases. Cathepsin V, specifically expressed in humans, is involved in vascular diseases through its elastolytic and collagenolytic activities. The aim of this study was to determine the effects of cathepsin V on l-homocysteine-induced vascular inflammation. A high methionine diet-induced hyperhomocysteinaemic mouse model was used to assess cathepsin V expression and vascular inflammation. Cultures of HUVECs were challenged with l-homocysteine and the cathepsin L/V inhibitor SID to assess the pro-inflammatory effects of cathepsin V. Transfection and antisense techniques were utilized to investigate the effects of cathepsin V on the dual-specificity protein phosphatases (DUSPs) and MAPK pathways. Cathepsin L (human cathepsin V homologous) was increased in the thoracic aorta endothelial cells of hyperhomocysteinaemic mice; l-homocysteine promoted cathepsin V expression in HUVECs. SID suppressed the activity of cathepsin V and reversed the up-regulation of inflammatory cytokines (IL-6, IL-8 and TNF-α), adhesion and chemotaxis of leukocytes and vascular inflammation induced by l-homocysteine in vivo and in vitro. Increased cathepsin V promoted the degradation of DUSP6 and DUSP7, phosphorylation and subsequent nuclear translocation of ERK1/2, phosphorylation of STAT1 and expression of IL-6, IL-8 and TNF-α. This study has identified a novel mechanism, which shows that l-homocysteine-induced upregulation of cathepsin V mediates vascular endothelial inflammation under high homocysteine condition partly via ERK 1/2 /STAT1 pathway. This mechanism could represent a potential therapeutic target in hyperaemia-associated vascular diseases. This article is part of a themed section on Spotlight on Small Molecules in Cardiovascular Diseases. To view the other articles in this section visit http

  12. Influence of mental stress on the plasma homocysteine level and blood pressure change in young men.

    PubMed

    Sawai, Asuka; Ohshige, Kenji; Kura, Naoki; Tochikubo, Osamu

    2008-04-01

    Objective. This study aimed to determine whether mental stress influences the plasma total homocysteine level or blood pressure in young men. Method. Twenty-seven male university students were assigned to a normal blood pressure group (24-h systolic blood pressure <125 mmHg and diastolic blood pressure <75 mmHg; 13 subjects) or a high blood pressure group (24-h systolic blood pressure > or =125 mmHg, or 24-h diastolic blood pressure > or =75 mmHg; 14 subjects). Wearing an ambulatory blood pressure monitoring device, subjects rested for 30 minutes, underwent an arithmetic test for 15 minutes, and rested again for 15 minutes. Blood samples were taken before and after the test. Plasma total homocysteine levels were measured. Heart rate, blood pressure, and sympathovagal balance were determined during the test. Results. The mean total homocysteine level at rest in the high blood pressure group was slightly, but not significantly, higher than that in the normal blood pressure group. The resting total homocysteine level was significantly higher in subjects with parental history of hypertension than in those without (p < 0.01). Blood pressure, heart rate, and the plasma total homocysteine level were increased significantly by mental stress (p < 0.05). The change in total homocysteine correlated significantly with the changes in systolic blood pressure and sympathovagal balance (p < 0.05). Conclusion. Resting total homocysteine level was significantly higher in male students with a parental history of hypertension than in those without. It was shown that mental stress elevates heart rate, blood pressure, sympathovagal activity, and the plasma total homocysteine level in young men.

  13. Chemoselective synthesis of functional homocysteine residues in polypeptides and peptides.

    PubMed

    Gharakhanian, Eric G; Deming, Timothy J

    2016-04-18

    A methodology was developed for efficient, chemoselective transformation of methionine residues into stable, functional homocysteine derivatives. Methionine residues can undergo highly chemoselective alkylation reactions at low pH to yield stable sulfonium ions, which could then be selectively demethylated to give stable alkyl homocysteine residues. This mild, two-step process is chemoselective, efficient, tolerates many functional groups, and provides a means for creation of new functional biopolymers, site-specific peptide tagging, and synthesis of biomimetic and structural analogs of peptides.

  14. Folic acid, neurodegenerative and neuropsychiatric disease.

    PubMed

    Kronenberg, Golo; Colla, Michael; Endres, Matthias

    2009-04-01

    Folic acid plays an important role in neuroplasticity and in the maintenance of neuronal integrity. Folate is a co-factor in one-carbon metabolism during which it promotes the regeneration of methionine from homocysteine, a highly reactive sulfur-containing amino acid. Methionine may then be converted to S-adenosylmethionine (SAM), the principal methyl donor in most biosynthetic methylation reactions. On the cellular level, folate deficiency and hyperhomocysteinemia exert multiple detrimental effects. These include induction of DNA damage, uracil misincorporation into DNA and altered patterns of DNA methylation. Low folate status and elevated homocysteine increase the generation of reactive oxygen species and contribute to excitotoxicity and mitochondrial dysfunction which may lead to apoptosis. Strong epidemiological and experimental evidence links derangements of one-carbon metabolism to vascular, neurodegenerative and neuropsychiatric disease, including most prominently cerebral ischemia, Alzheimer's dementia and depression. Although firm evidence from controlled clinical trials is largely lacking, B-vitamin supplementation and homocysteine reduction may have a role especially in the primary prevention of stroke and dementia as well as as an adjunct to antidepressant pharmacotherapy.

  15. Homocysteine and other cardiovascular risk factors in patients with lichen planus.

    PubMed

    Saleh, N; Samir, N; Megahed, H; Farid, E

    2014-11-01

    Chronic inflammation was found to play an important role in the development of cardiovascular risk factors. Homocysteine (Hcy) and fibrinogen have been identified as a major independent risk factor for cardiovascular disease. Lichen planus is assumed to be closely related to dyslipidaemia. Several cytokines involved in lichen planus pathogenesis, could explain its association with dyslipidaemia. Also chronic inflammation with lichen planus has been suggested as a component of the metabolic syndrome. The aim of this study was to detect a panel of cardiovascular risk factors in patients of lichen planus. This study was done on 40 patients of lichen planus and 40 healthy controls. All patients and controls were subjected to clinical examination. Serum levels of homocysteine, fibrinogen and high-sensitive C-reactive protein (hs-CRP) were measured by enzyme-linked immunosorbent assay technique (ELISA). Metabolic syndrome parameters including anthropometric measures, lipid profiles, blood sugar and blood pressure were studied. Patients with lichen planus showed significant association with metabolic syndrome parameters than controls (P < 0.001). Serum homocysteine, fibrinogen and hs-CRP were significantly higher in lichen planus patients than controls (P < 0.001). Serum homocysteine correlated with both serum hs-CRP and serum fibrinogen. However, there was no correlation between serum levels of homocysteine and fibrinogen with any metabolic syndrome criteria and related disorders except for a negative correlation of fibrinogen with high-density lipoprotein (HDL). In the present work, patients with lichen planus were found to have higher makers of both metabolic and cardiovascular risk factors in relation to controls most probably due to long standing inflammation. © 2013 European Academy of Dermatology and Venereology.

  16. Effects of polymorphisms in endothelial nitric oxide synthase and folate metabolizing genes on the concentration of serum nitrate, folate, and plasma total homocysteine after folic acid supplementation: a double-blind crossover study.

    PubMed

    Cabo, Rona; Hernes, Sigrunn; Slettan, Audun; Haugen, Margaretha; Ye, Shu; Blomhoff, Rune; Mansoor, M Azam

    2015-02-01

    A number of studies have explored the effects of dietary nitrate on human health. Nitrate in the blood can be recycled to nitric oxide, which is an essential mediator involved in many important biochemical mechanisms. Nitric oxide is also formed in the body from l-arginine by nitric oxide synthase. The aim of this study was to investigate whether genetic polymorphisms in endothelial nitric oxide synthase (eNOS) and genes involved in folate metabolism affect the concentration of serum nitrate, serum folate, and plasma total homocysteine in healthy individuals after folic acid supplementation. In a randomized double-blind, crossover study, participants were given either folic acid 800 μg/d (n = 52) or placebo (n = 51) for 2 wk. Wash-out period was 2 wk. Fasting blood samples were collected, DNA was extracted by salting-out method and the polymorphisms in eNOS synthase and folate genes were genotyped by polymerase chain reaction methods. Measurement of serum nitrate and plasma total homocysteine (p-tHcy) concentration was done by high-performance liquid chromatography. The concentration of serum nitrate did not change in individuals after folic acid supplements (trial 1); however, the concentration of serum nitrate increased in the same individuals after placebo (P = 0.01) (trial 2). The individuals with three polymorphisms in eNOS gene had increased concentration of serum folate and decreased concentration of p-tHcy after folic acid supplementation. Among the seven polymorphisms tested in folate metabolizing genes, serum nitrate concentration was significantly decreased only in DHFR del 19 gene variant. A significant difference in the concentration of serum nitrate was detected among individuals with MTHFR C > T677 polymorphisms. Polymorphisms in eNOS and folate genes affect the concentration of serum folate and p-tHcy but do not have any effect on the concentration of NO3 in healthy individuals after folic acid supplementation. Copyright © 2015 Elsevier Inc. All

  17. Potent homocysteine-induced ERK phosphorylation in cultured neurons depends on self-sensitization via system Xc{sup -}

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Gu Li; Hu Xiaoling; Xue Zhanxia

    2010-01-15

    Homocysteine is increased during pathological conditions, endangering vascular and cognitive functions, and elevated homocysteine during pregnancy may be correlated with an increased incidence of schizophrenia in the offspring. This study showed that millimolar homocysteine concentrations in saline medium cause phosphorylation of extracellular-signal regulated kinases 1 and 2 (ERK{sub 1/2}) in cerebellar granule neurons, inhibitable by metabotropic but not ionotropic glutamate receptor antagonists. These findings are analogous to observations by , that similar concentrations cause neuronal death. However, these concentrations are much higher than those occurring clinically during hyperhomocysteinemia. It is therefore important that a approx 10-fold increase in potency occurredmore » in the presence of the glutamate precursor glutamine, when ERK{sub 1/2} phosphorylation became inhibitable by NMDA or non-NMDA antagonists and dependent upon epidermal growth factor (EGF) receptor transactivation. However, glutamate release to the medium was reduced, suggesting that reversal of the cystine/glutamate antiporter, system X{sub c}{sup -} could be involved in potentiation of the response by causing a localized release of initially accumulated homocysteine. In agreement with this hypothesis further enhancement of ERK{sub 1/2} phosphorylation occurred in the additional presence of cystine. Pharmacological inhibition of system X{sub c}{sup -} prevented the effect of micromolar homocysteine concentrations, and U0126-mediated inhibition of ERK{sub 1/2} phosphorylation enhanced homocysteine-induced death. In conclusion, homocysteine interacts with system X{sub c}{sup -} like quisqualate (Venkatraman et al. 1994), by 'self-sensitization' with initial accumulation and subsequent release in exchange with cystine and/or glutamate, establishing high local homocysteine concentrations, which activate adjacent ionotropic glutamate receptors and cause neurotoxicity.« less

  18. Dealing with methionine/homocysteine sulfur: cysteine metabolism to taurine and inorganic sulfur

    PubMed Central

    Ueki, Iori

    2010-01-01

    Synthesis of cysteine as a product of the transsulfuration pathway can be viewed as part of methionine or homocysteine degradation, with cysteine being the vehicle for sulfur conversion to end products (sulfate, taurine) that can be excreted in the urine. Transsulfuration is regulated by stimulation of cystathionine β-synthase and inhibition of methylene tetrahydrofolate reductase in response to changes in the level of S-adenosylmethionine, and this promotes homocysteine degradation when methionine availability is high. Cysteine is catabolized by several desulfuration reactions that release sulfur in a reduced oxidation state, generating sulfane sulfur or hydrogen sulfide (H2S), which can be further oxidized to sulfate. Cysteine desulfuration is accomplished by alternate reactions catalyzed by cystathionine β-synthase and cystathionine γ-lyase. Cysteine is also catabolized by pathways that require the initial oxidation of the cysteine thiol by cysteine dioxygenase to form cysteinesulfinate. The oxidative pathway leads to production of taurine and sulfate in a ratio of approximately 2:1. Relative metabolism of cysteine by desulfuration versus oxidative pathways is influenced by cysteine dioxygenase activity, which is low in animals fed low-protein diets and high in animals fed excess sulfur amino acids. Thus, desulfuration reactions dominate when cysteine is deficient, whereas oxidative catabolism dominates when cysteine is in excess. In rats consuming a diet with an adequate level of sulfur amino acids, about two thirds of cysteine catabolism occurs by oxidative pathways and one third by desulfuration pathways. Cysteine dioxygenase is robustly regulated in response to cysteine availability and may function to provide a pathway to siphon cysteine to less toxic metabolites than those produced by cysteine desulfuration reactions. PMID:20162368

  19. Transcriptional regulation of methionine synthase by homocysteine and choline in Aspergillus nidulans.

    PubMed Central

    Kacprzak, Magdalena M; Lewandowska, Irmina; Matthews, Rowena G; Paszewski, Andrzej

    2003-01-01

    Roles played by homocysteine and choline in the regulation of MS (methionine synthase) have been examined in fungi. The Aspergillus nidulans metH gene encoding MS was cloned and characterized. Its transcription was not regulated by methionine, but was enhanced by homocysteine and repressed by choline and betaine. MS activity levels were regulated in a similar way. The repression by betaine was due to its metabolic conversion to choline, which was found to be very efficient in A. nidulans. Betaine and choline supplementation stimulated growth of leaky metH mutants apparently by decreasing the demand for methyl groups and thus saving methionine and S -adenosylmethionine. We have also found that homocysteine stimulates transcription of MS-encoding genes in Saccharomyces cerevisiae and Schizosaccharomyces pombe. PMID:12954077

  20. Homocysteine levels and treatment effect in the PROspective Study of Pravastatin in the Elderly at Risk.

    PubMed

    Drewes, Yvonne M; Poortvliet, Rosalinde K E; Blom, Jeanet W; de Ruijter, Wouter; Westendorp, Rudi G J; Stott, David J; Blom, Henk J; Ford, Ian; Sattar, Naveed; Wouter Jukema, J; Assendelft, Willem J J; de Craen, Anton J M; Gussekloo, Jacobijn

    2014-02-01

    To assess the effect of preventive pravastatin treatment on coronary heart disease (CHD) morbidity and mortality in older persons at risk for cardiovascular disease (CVD), stratified according to plasma levels of homocysteine. A post hoc subanalysis in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER), started in 1997, which is a double-blind, randomized, placebo-controlled trial with a mean follow-up of 3.2 years. Primary care setting in two of the three PROSPER study sites (Netherlands and Scotland). Individuals (n = 3,522, aged 70-82, 1,765 male) with a history of or risk factors for CVD were ranked in three groups depending on baseline homocysteine level, sex, and study site. Pravastatin (40 mg) versus placebo. Fatal and nonfatal CHD and mortality. In the placebo group, participants with a high homocysteine level (n = 588) had a 1.8 higher risk (95% confidence interval (CI) = 1.2-2.5, P = .001) of fatal and nonfatal CHD than those with a low homocysteine level (n = 597). The absolute risk reduction in fatal and nonfatal CHD with pravastatin treatment was 1.6% (95% CI = -1.6 to 4.7%) in the low homocysteine group and 6.7% (95% CI = 2.7-10.7%) in the high homocysteine group (difference 5.2%, 95% CI = 0.11-10.3, P = .046). Therefore, the number needed to treat (NNT) with pravastatin for 3.2 years for benefit related to fatal and nonfatal CHD events was 14.8 (95% CI = 9.3-36.6) for high homocysteine and 64.5 (95% CI = 21.4-∞) for low homocysteine. In older persons at risk of CVD, those with high homocysteine are at highest risk for fatal and nonfatal CHD. With pravastatin treatment, this group has the highest absolute risk reduction and the lowest NNT to prevent fatal and nonfatal CHD. © 2014, Copyright the Authors. Journal compilation © 2014, The American Geriatrics Society.

  1. Neuroprotection and mechanisms of atractylenolide III in preventing learning and memory impairment induced by chronic high-dose homocysteine administration in rats.

    PubMed

    Zhao, H; Ji, Z-H; Liu, C; Yu, X-Y

    2015-04-02

    Studies demonstrated that chronic high-dose homocysteine administration induced learning and memory impairment in animals. Atractylenolide III (Aen-III), a neuroprotective constituent of Atractylodis macrocephalae Koidz, was isolated in our previous study. In this study, we investigated potential benefits of Aen-III in preventing learning and memory impairment following chronic high-dose homocysteine administration in rats. Results showed that administration of Aen-III significantly ameliorated learning and memory impairment induced by chronic high-dose homocysteine administration in rats, decreased homocysteine-induced reactive oxygen species (ROS) formation and restored homocysteine-induced decrease of phosphorylated protein kinase C expression level. Moreover, Aen-III protected primary cultured neurons from apoptotic death induced by homocysteine treatment. This study provides the first evidence for the neuroprotective effect of Aen-III in preventing learning and impairment induced by chronic administration of homocysteine. Aen-III may have therapeutic potential in treating homocysteine-mediated cognitive impairment and neuronal injury. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  2. Correlation between serum homocysteine concentration and severity of mitral valve disease in dogs.

    PubMed

    Lee, Chang-Min; Jeong, Da-Min; Kang, Min-Hee; Kim, Seung-Gon; Han, Jae-Ik; Park, Hee-Myung

    2017-04-01

    OBJECTIVE To measure serum homocysteine concentrations in dogs with myxomatous mitral valve disease (MMVD) and identify any association between this variable and stage of MMVD. ANIMALS 53 client-owned dogs with MMVD and 10 healthy control Beagles. PROCEDURES Dogs with MMVD were allocated to 3 groups in accordance with the staging system for chronic valvular heart disease in dogs and cats of the American College of Veterinary Internal Medicine. Blood samples were collected from all dogs, and serum homocysteine and cardiac troponin 1 concentrations were measured by enzyme immunoassay and chemiluminescence immunoassay, respectively. Analyte values were tested for associations with each other and with stage of MMVD. RESULTS A significant correlation was identified between serum homocysteine concentration and stage of MMVD. Mean ± SD concentrations were 6.72 ± 1.65 μmol/L for control dogs, 13.37 ± 4.16 μmol/L for dogs with stage B MMVD, 18.86 ± 6.73 μmol/L for dogs with stage C disease, and 28.26 ± 4.48 μmol/L for dogs with stage D disease. In addition, serum homocysteine concentration was correlated with serum cardiac troponin 1 (r = 0.34) and creatinine (r = 0.46) concentrations, systolic blood pressure (r = 0.57), and left atrium-to-aortic root ratio (r = 0.28), all of which were positively correlated with stage of MMVD. CONCLUSIONS AND CLINICAL RELEVANCE Serum homocysteine concentrations of dogs with MMVD were significantly higher than those of control dogs, and significant correlations were identified between these values and several risk factors for heart failure. Measurement of serum homocysteine concentration may be useful in the prediction of severity of disease in dogs with MMVD.

  3. [Determination of homocysteine level in plasma by high performance liquids chromatography with fluorescence detection].

    PubMed

    Da, Xu; Qian, Ling-Jia

    2005-08-01

    To establish a method for detection of plasma total homocysteine with HPLC. The chromatography analysis was carried out using a Symmetry Shield RP18. The mobile phase was sodium acetate (0.08 mol/L) and methanol (1%) and we utilized a HPLC system with fluorescence detection of plasma homocysteine derivatized from reaction with 7-fluorobenzo-2-oxa-1,3-diazole-4-sulphonate (SBD-F). The average recoveries were 95.8 - 100.8% and the relative standard deviations were 1.2-2.0%. The results showed it to be a rapid and accurate method for the determination of homocysteine level in plasma.

  4. Comparative Assessment of Vitamin-B12, Folic Acid and Homocysteine Levels in Relation to p53 Expression in Megaloblastic Anemia.

    PubMed

    Yadav, Manish K; Manoli, Nandini M; Madhunapantula, SubbaRao V

    2016-01-01

    Megaloblastic anemia (MBA), also known as macrocytic anemia, is a type of anemia characterized by decreased number of RBCs as well as the presence of unusually large, abnormal and poorly developed erythrocytes (megaloblasts), which fail to enter blood circulation due to their larger size. Lack of vitamin-B12 (VB12) and / or folate (Vitamin-B9, VB9) with elevated homocysteine is the key factor responsible for megaloblastic anemia. Prior studies have demonstrated the induction of apoptosis in these abnormal under-developed erythrocytes. However, it is not clear whether this apoptosis induction is due to elevated p53 level or due to any other mechanism. Furthermore, it is also not fully known whether decreased vitamin-B12 and / or folate are responsible for apoptosis induction mediated by p53 in pre-erythroblasts. Levels of serum VB9, VB12 and homocysteine in 50 patients suffering from MBA were compared with 50 non-megaloblastic anemia control subjects, who were referred by the clinicians for bone marrow examination for medical conditions other than MBA. Next, we have measured the p53 expression in the paraffin embedded blocks prepared from bone marrow biopsy, using immunohistochemistry, and the expression levels correlated with VB9 and VB12 levels. Out of 50 MBA patients 40 (80%) and 44 (88%) subjects had very low VB12 and VB9 levels respectively. In contrast, only 2 (4%) and 12 (24%) non-megaloblastic anemia controls, out of 50 subjects, had low VB12 and VB9 respectively. Correlating with low vitamin B9 and B12, the homocysteine levels were high in 80% cases. But, only 20% non-megaloblastic controls exhibited high homocysteine in plasma. Immunohistochemical analysis for p53 expression showed a significantly high level of expression in MBA cases and no-or very low-expression in control subjects. Our correlation studies comparing the VB12 and VB9 levels with p53 expression concludes unusually high p53 levels in patients suffering from VB12 and VB9 deficiency induced

  5. Comparative Assessment of Vitamin-B12, Folic Acid and Homocysteine Levels in Relation to p53 Expression in Megaloblastic Anemia

    PubMed Central

    Yadav, Manish K.; Manoli, Nandini M.

    2016-01-01

    Background Megaloblastic anemia (MBA), also known as macrocytic anemia, is a type of anemia characterized by decreased number of RBCs as well as the presence of unusually large, abnormal and poorly developed erythrocytes (megaloblasts), which fail to enter blood circulation due to their larger size. Lack of vitamin-B12 (VB12) and / or folate (Vitamin-B9, VB9) with elevated homocysteine is the key factor responsible for megaloblastic anemia. Prior studies have demonstrated the induction of apoptosis in these abnormal under-developed erythrocytes. However, it is not clear whether this apoptosis induction is due to elevated p53 level or due to any other mechanism. Furthermore, it is also not fully known whether decreased vitamin-B12 and / or folate are responsible for apoptosis induction mediated by p53 in pre-erythroblasts. Methods Levels of serum VB9, VB12 and homocysteine in 50 patients suffering from MBA were compared with 50 non-megaloblastic anemia control subjects, who were referred by the clinicians for bone marrow examination for medical conditions other than MBA. Next, we have measured the p53 expression in the paraffin embedded blocks prepared from bone marrow biopsy, using immunohistochemistry, and the expression levels correlated with VB9 and VB12 levels. Results Out of 50 MBA patients 40 (80%) and 44 (88%) subjects had very low VB12 and VB9 levels respectively. In contrast, only 2 (4%) and 12 (24%) non-megaloblastic anemia controls, out of 50 subjects, had low VB12 and VB9 respectively. Correlating with low vitamin B9 and B12, the homocysteine levels were high in 80% cases. But, only 20% non-megaloblastic controls exhibited high homocysteine in plasma. Immunohistochemical analysis for p53 expression showed a significantly high level of expression in MBA cases and no—or very low—expression in control subjects. Our correlation studies comparing the VB12 and VB9 levels with p53 expression concludes unusually high p53 levels in patients suffering from VB

  6. Inflammation, homocysteine and carotid intima-media thickness.

    PubMed

    Baptista, Alexandre P; Cacdocar, Sanjiva; Palmeiro, Hugo; Faísca, Marília; Carrasqueira, Herménio; Morgado, Elsa; Sampaio, Sandra; Cabrita, Ana; Silva, Ana Paula; Bernardo, Idalécio; Gome, Veloso; Neves, Pedro L

    2008-01-01

    Cardiovascular disease is the main cause of morbidity and mortality in chronic renal patients. Carotid intima-media thickness (CIMT) is one of the most accurate markers of atherosclerosis risk. In this study, the authors set out to evaluate a population of chronic renal patients to determine which factors are associated with an increase in intima-media thickness. We included 56 patients (F=22, M=34), with a mean age of 68.6 years, and an estimated glomerular filtration rate of 15.8 ml/min (calculated by the MDRD equation). Various laboratory and inflammatory parameters (hsCRP, IL-6 and TNF-alpha) were evaluated. All subjects underwent measurement of internal carotid artery intima-media thickness by high-resolution real-time B-mode ultrasonography using a 10 MHz linear transducer. Intima-media thickness was used as a dependent variable in a simple linear regression model, with the various laboratory parameters as independent variables. Only parameters showing a significant correlation with CIMT were evaluated in a multiple regression model: age (p=0.001), hemoglobin (p=00.3), logCRP (p=0.042), logIL-6 (p=0.004) and homocysteine (p=0.002). In the multiple regression model we found that age (p=0.001) and homocysteine (p=0.027) were independently correlated with CIMT. LogIL-6 did not reach statistical significance (p=0.057), probably due to the small population size. The authors conclude that age and homocysteine correlate with carotid intima-media thickness, and thus can be considered as markers/risk factors in chronic renal patients.

  7. Association between dietary folate intake and blood status of folate and homocysteine in Malaysian adults.

    PubMed

    Chew, Siew-Choo; Khor, Geok-Lin; Loh, Su-Peng

    2011-01-01

    Folate is of prime interest among investigators in nutrition due to its multiple roles in maintaining health, especially in preventing neural tube defects and reducing the risk of cardiovascular diseases. We investigated the effect of dietary folate intake on blood folate, vitamin B(12), vitamin B(6), and homocysteine status. One hundred subjects consisting of Chinese and Malay subjects volunteered to participate in this cross-sectional study. Dietary folate intake was assessed by 24-h dietary recall and a food-frequency questionnaire (FFQ). Serum and red blood cell folate were analyzed using a microbiological assay, while serum vitamin B(12) was determined by electrochemiluminescence immunoassay (ECLIA), and high-performance liquid chromatography (HPLC) was used for the determination of serum vitamin B(6) and homocysteine. The mean folate intake, serum folate, RBC folate, serum vitamin B(12), and B(6), were higher in female subjects, with the exception of serum homocysteine. The Chinese tended to have higher folate intake, serum folate, RBC folate, and vitamin B(12). A positive association was found between folate intake and serum folate while a negative association was found between folate intake and serum homocysteine. Stepwise linear regression of serum folate showed a significant positive coefficient for folate intake whilst a significant negative coefficient was found for serum homocysteine when controlling for age, gender, and ethnicity. In conclusion, high dietary folate intake helps to increase serum folate and to lower the homocysteine levels.

  8. [Blood levels of homocysteine by high pressure liquid chromatography and comparison with two other techniques].

    PubMed

    Ceppa, F; Drouillard, I; Chianea, D; Burnat, P; Perrier, F; Vaillant, C; El Jahiri, Y

    1999-01-01

    Cardio-vascular diseases are the most common cause of death in industrialized countries. A new marker has emerged among offending risk factors in the past few years: homocysteine. This sulphured amino-acid is an important intermediate in transsulphuration and remethylation reactions of methionine's metabolism. We proposed to evaluate a home made method of determination for this parameter by high performance liquid chromatography (HPLC) and to compare it to fluorescence polarization immunoassay technique (FPIA) and to gaz phase chromatography (CG-SM). This method associated with good sensibility and precision remain much less expensive than FPIA technique.

  9. SULPHUR-CONTAINING AMINO ACIDS METABOLISM IN EXPERIMENTAL HYPER- AND HYPOTHYROIDISM IN RATS.

    PubMed

    Nechiporuk, V; Zaichko, N; Korda, М; Melnyk, A; Koloshko, O

    2017-10-01

    Hyper- and hypothyroidism are some of the most common endocrinopathies that cause many metabolic disorders including amino acids metabolism. However, a specific molecular mechanism of thyroid hormones influence on sulphur-containing amino acids metabolism has not been established. The aim of our research was to investigate experimentally the influence of thyroid gland functional state on the main enzymatic systems of sulphur-containing amino acids metabolism in liver and kidneys, the content of homocysteine, cysteine and H2S in blood. The rats were administered with L-thyroxine and mercazolil to simulate the states of hyper- and hypothyroidism, which were confirmed by the content of fT3, fT4 and TSH in the blood. In liver and kidneys of the animals with hypothyroidism we observed the decrease in the activity of enzymes of remethylation cycle of S-adenosylmethioninsyntase, S-adenosylhomocysteinhyhdrolase, betaine-homocysteine methyltransferase. Suppression of transsulfuration transformation of homocysteine to cysteine in hypothyroidism was mainly due to the inhibition of cystathionine synthase activity of cystathionine-β-synthase, wherein cystathionase activity of cystathionine-γ-lyase was not changed. In animals with hypothyroidism we also noticed the inhibition of cysteine desulfunation reactions: the activity of enzymes of cystathionine-β-synthase, cystathionine-γ-lyase and cysteine aminotransferase significantly decreased in liver and kidneys. Experimental hyperthyroidism was accompanied by increase in activity of remethylation cycle enzymes, increase in cystationine synthase activity of cystathionine-β-synthase in liver and activity of these enzymes in kidneys. The simulation of hyperthyroidism led to the decrease of homocysteine concentration, and of hypothyroidism - to the increase of homocysteine and cysteine concentrations and reduced H2S content in blood of the animals. Thus, the significant risk factors for the development of atherosclerosis

  10. Acetylcysteine reduces plasma homocysteine concentration and improves pulse pressure and endothelial function in patients with end-stage renal failure.

    PubMed

    Scholze, Alexandra; Rinder, Christiane; Beige, Joachim; Riezler, Reiner; Zidek, Walter; Tepel, Martin

    2004-01-27

    Increased oxidative stress, elevated plasma homocysteine concentration, increased pulse pressure, and impaired endothelial function constitute risk factors for increased mortality in patients with end-stage renal failure. We investigated the metabolic and hemodynamic effects of intravenous administration of acetylcysteine, a thiol-containing antioxidant, during a hemodialysis session in a prospective, randomized, placebo-controlled crossover study in 20 patients with end-stage renal failure. Under control conditions, a hemodialysis session reduced plasma homocysteine concentration to 58+/-22% predialysis (mean+/-SD), whereas in the presence of acetylcysteine, the plasma homocysteine concentration was significantly more reduced to 12+/-7% predialysis (P<0.01). The reduction of plasma homocysteine concentration was significantly correlated with a reduction of pulse pressure. A 10% decrease in plasma homocysteine concentration was associated with a decrease of pulse pressure by 2.5 mm Hg. Analysis of the second derivative of photoplethysmogram waveform showed changes of arterial wave reflectance during hemodialysis in the presence of acetylcysteine, indicating improved endothelial function. Acetylcysteine-dependent increase of homocysteine removal during a hemodialysis session improves plasma homocysteine concentration, pulse pressure, and endothelial function in patients with end-stage renal failure.

  11. Homocysteine enhances the predictive value of the GRACE risk score in patients with ST-elevation myocardial infarction.

    PubMed

    Fan, Yan; Wang, Jianjun; Zhang, Sumei; Wan, Zhaofei; Zhou, Dong; Ding, Yanhong; He, Qinli; Xie, Ping

    2017-09-01

    The present study aims to investigate whether the addition of homocysteine level to the Global Registry of Acute Coronary Events (GRACE) risk score enhances its predictive value for clinical outcomes in ST-elevation myocardial infarction (STEMI). A total of 1143 consecutive patients with STEMI were included in this prospective cohort study. Homocysteine was detected, and the GRACE score was calculated. The predictive power of the GRACE score alone or combined with homocysteine was assessed by the receiver operating characteristic (ROC) analysis, methods of net reclassification improvement (NRI) and integrated discrimination improvement (IDI). During a median follow-up period of 36.7 months, 271 (23.7%) patients reached the clinical endpoints. It showed that the GRACE score and homocysteine could independently predict all-cause death [GRACE: HR=1.031 (1.024-1.039), p<0.001; homocysteine: HR=1.023 (1.018-1.028), p<0.001] and MACE [GRACE: HR=1.008 (1.005-1.011), p<0.001; homocysteine: HR=1.022 (1.018-1.025), p<0.001]. When they were used in combination to assess the clinical outcomes, the area under the ROC curve significantly increased from 0.786 to 0.884 (95% CI=0.067-0.128, Z=6.307, p<0.001) for all-cause death and from 0.678 to 0.759 (95% CI=0.055-0.108, Z=5.943, p<0.001) for MACE. The addition of homocysteine to the GRACE model improved NRI (all-cause death: 0.575, p<0.001; MACE: 0.621, p=0.008) and IDI (all-cause death: 0.083, p<0.001; MACE: 0.130, p=0.016), indicating effective discrimination and reclassification. Both the GRACE score and homocysteine are significant and independent predictors for clinical outcomes in patients with STEMI. A combination of them can develop a more predominant prediction for clinical outcomes in these patients.

  12. Differential effects of low and high dose folic acid on endothelial dysfunction in a murine model of mild hyperhomocysteinaemia.

    PubMed

    Clarke, Zoe L; Moat, Stuart J; Miller, Alastair L; Randall, Michael D; Lewis, Malcolm J; Lang, Derek

    2006-12-03

    The exact mechanism(s) by which hyperhomocysteinaemia promotes vascular disease remains unclear. Moreover, recent evidence suggests that the beneficial effect of folic acid on endothelial function is independent of homocysteine-lowering. In the present study the effect of a low (400 microg/70 kg/day) and high (5 mg/70 kg/day) dose folic acid supplement on endothelium-dependent relaxation in the isolated perfused mesenteric bed of heterozygous cystathionine beta-synthase deficient mice was investigated. Elevated total plasma homocysteine and impaired relaxation responses to methacholine were observed in heterozygous mice. In the presence of N(G)-nitro-L-arginine methyl ester relaxation responses in wild-type tissues were reduced, but in heterozygous tissues were abolished. Clotrimazole and 18alpha-glycyrrhetinic acid, both inhibitors of non-nitric oxide/non-prostanoid-induced endothelium-dependent relaxation, reduced responses to methacholine in wild-type but not heterozygous tissues. The combination of N(G)-nitro-L-arginine methyl ester and either clotrimazole or 18alpha-glycyrrhetinic acid completely inhibited relaxation responses in wild-type tissues. Both low and high dose folic acid increased plasma folate, reduced total plasma homocysteine and reversed endothelial dysfunction in heterozygous mice. A greater increase in plasma folate in the high dose group was accompanied by a more significant effect on endothelial function. In the presence of N(G)-nitro-L-arginine methyl ester, a significant residual relaxation response was evident in tissues from low and high dose folic acid treated heterozygous mice. These data suggest that the impaired mesenteric relaxation in heterozygous mice is largely due to loss of the non-nitric oxide/non-prostanoid component. While low dose folic acid may restore this response in a homocysteine-dependent manner, the higher dose has an additional effect on nitric oxide-mediated relaxation that would appear to be independent of

  13. Homocysteine, B vitamins, and the incidence of dementia and cognitive impairment: results from the Sacramento Area Latino Study on Aging2

    PubMed Central

    Haan, Mary N; Miller, Joshua W; Aiello, Allison E; Whitmer, Rachel A; Jagust, William J; Mungas, Dan M; Allen, Lindsay H; Green, Ralph

    2007-01-01

    Background High concentrations of homocysteine have been linked to a greater risk of Alzheimer disease, dementia, and cognitive decline. Objective We evaluated the association between homocysteine and 4.5-y combined incidences of dementia and cognitive impairment without dementia (CIND) in a cohort of 1779 Mexican Americans aged 60–101 y. Design Homocysteine, red blood cell (RBC) folate, and plasma vitamin B-12 were measured at baseline. New cases of dementia or CIND were ascertained by neuropsychological and clinical examinations and expert adjudication. We used proportional hazards models to estimate the risk of homocysteine-associated dementia or CIND and the influence of RBC folate and plasma vitamin B-12 on that association. Results High homocysteine concentrations were associated with a greater risk of dementia or CIND: hazard ratio (HR): 2.39; 95% CI: 1.11, 5.16. Plasma vitamin B-12 modified the association between homocysteine and the outcome. The rates of dementia or CIND associated with homocysteine for those in the lowest and highest tertiles of vitamin B-12, respectively, were significantly higher (HR: 1.61, P = 0.04) and lower (HR: 0.94, P = 0.015) than the risk for those in the middle tertile. Conclusions Homocysteine is an independent risk factor for both dementia and CIND. Higher plasma vitamin B-12 may reduce the risk of homocysteine-associated dementia or CIND. PMID:17284751

  14. Prospective study of plasma homocysteine level and risk of age-related macular degeneration in women.

    PubMed

    Christen, William G; Cook, Nancy R; Ridker, Paul M; Buring, Julie E

    2015-04-01

    Prospective data to examine the association of homocysteine with age-related macular degeneration (AMD) are limited. We examined the prospective relation of plasma homocysteine level and AMD in a large cohort of apparently healthy women. We evaluated the relationship between baseline levels of plasma homocysteine and incident AMD among 27,479 female health professionals aged 40 years or older. Main outcome measures were total AMD, defined as self-report documented by medical record evidence of an initial diagnosis after randomization, and visually significant AMD, defined as confirmed incident AMD with visual acuity 20/30 or worse attributable to this condition. During an average 10 years of follow-up, a total of 452 cases of AMD, including 182 cases of visually significant AMD, were documented. Women in the highest versus lowest quartile of plasma homocysteine had modestly, but statistically non-significant, increased risks of total AMD (hazard ratio, HR, 1.24, 95% confidence interval, CI, 0.95-1.63; p for trend 0.07) and visually significant AMD (HR 1.41, 95% CI 0.92-2.17; p for trend 0.052) in age- and treatment-adjusted analyses. These prospective data from a large cohort of apparently healthy women do not support a strong role for homocysteine in AMD occurrence.

  15. Brain biochemical correlates of the plasma homocysteine level: a proton magnetic resonance spectroscopy study in the elderly subjects.

    PubMed

    Chen, Cheng-Sheng; Kuo, Yu-Ting; Tsai, Hui-Yi; Li, Chun-Wei; Lee, Chen-Chang; Yen, Cheng-Fang; Lin, Hsiu-Fen; Ko, Chih-Hung; Juo, Suh-Hang Hank; Yeh, Yi-Chun; Liu, Gin-Chung

    2011-07-01

    An elevated plasma homocysteine level has been reported to be associated with various neuropsychiatric diseases. However, little is known about the brain biochemical changes associated with the higher plasma homocysteine level. The main goal of this study was to examine the sex difference in brain biochemical concentrations using brain proton magnetic resonance spectroscopy (H MRS), and to elucidate the biochemical changes associated with plasma homocysteine levels by sex in healthy elderly subjects. Seventy elderly subjects without any clinical psychiatric and neurological disease underwent 3-T brain H MRS. MRS spectra were acquired from voxels placed on the left side of the basal ganglia, frontal lobe, and hippocampus. Brain biochemical concentrations were compared between the elderly male and female participants. Correlations between these biochemical concentrations and plasma homocysteine levels by sex were analyzed. Female participants had significantly higher levels of choline in the left frontal lobe and hippocampus, and lower creatine and myo-inositol, in the left basal ganglia than did males. A higher homocysteine level was correlated with a lower N-acetylaspartate (NAA) concentration in the left hippocampus in elderly women (r = -0.44; p = 0.03) but not in elderly men. This study found that there was a sex difference in brain biochemical concentrations in the elderly participants. A higher plasma homocysteine level was associated with a lower NAA in the hippocampus of elderly women. The sex difference in association between brain biochemical concentrations and plasma homocysteine levels needs further investigation. We speculate that after menopause, women lose protection of estrogen from the neurotoxic effects of homocysteine in the hippocampus. Future studies are required to examine this speculation.

  16. Inverse association between plasma homocysteine concentrations and type 2 diabetes mellitus among a middle-aged and elderly Chinese population.

    PubMed

    Yu, C; Wang, J; Wang, F; Han, X; Hu, H; Yuan, J; Miao, X; Yao, P; Wei, S; Wang, Y; Liang, Y; Chen, W; Zhang, X; Guo, H; Yang, H; Tang, Y; Zheng, D; Wu, T; He, M

    2018-03-01

    Plasma homocysteine concentrations have been reported to be associated with type 2 diabetes mellitus (T2DM) with controversial findings. The aim of the present study was to investigate the association between plasma homocysteine concentrations and T2DM. A cross-sectional study including 19,085 eligible participants derived from the Dongfeng-Tongji cohort was conducted. Plasma homocysteine concentrations were measured by Abbott Architect i2000 Automatic analyzer and T2DM was defined according to American Diabetes Association criteria. Logistic regression model was used to explore the association between plasma homocysteine concentrations and T2DM. The prevalence of T2DM was 19.0% in the whole population (mean age 62.9 years), 21.8% in males, and 17.1% in females. In the multivariable logistic regression analyses, compared with those in the lowest quintile, the OR (95% CI) of T2DM was 1.05 (0.92-1.21), 0.99 (0.86-1.14), 0.90 (0.78-1.05), and 0.77 (0.66-0.90) for quintile 2 to quintile 5 of homocysteine concentrations after adjustment for potential confounders (P for trend < 0.0001). Homocysteine concentrations were associated with decreased T2DM prevalence risk (OR = 0.88 per SD increase of homocysteine concentration; 95% CI: 0.84-0.93). A significant interaction between homocysteine concentrations and drinking status on T2DM prevalence risk was observed (P for interaction = 0.03). The inverse association of plasma homocysteine concentrations with T2DM prevalence risk was observed in non-drinkers but not in current drinkers. Plasma homocysteine concentrations were inversely correlated with T2DM among a middle-aged and elderly Chinese population. Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

  17. Comparison of folic acid levels in schizophrenic patients and control groups

    NASA Astrophysics Data System (ADS)

    Arthy, C. C.; Amin, M. M.; Effendy, E.

    2018-03-01

    Folic acid deficiency is a risk factor for schizophrenia through epidemiology, biochemistry and gene-related studies. Compared with healthy people, schizophrenic patients may have high homocysteine plasma values and homocysteine or low levels of folic acid, which seems to correlate with extrapyramidal motor symptoms caused by neuroleptic therapy and with symptoms of schizophrenia. In this present study, we focus on the difference of folic acid level between schizophrenic patient and control group. The study sample consisted of schizophrenic patients and 14 people in the control group and performed blood sampling to obtain the results of folic acid levels. The folic acid level in both groups was within normal range, but the schizophrenic patient group had lower mean folic acid values of 5.00 ng/ml (sb 1.66), compared with the control group with mean folic acid values of 10.75 ng/ml (sb 4.33). there was the group of the control group had a higher value of folic acid than the schizophrenic group.

  18. Homocysteine directly interacts and activates the angiotensin II type I receptor to aggravate vascular injury.

    PubMed

    Li, Tuoyi; Yu, Bing; Liu, Zhixin; Li, Jingyuan; Ma, Mingliang; Wang, Yingbao; Zhu, Mingjiang; Yin, Huiyong; Wang, Xiaofeng; Fu, Yi; Yu, Fang; Wang, Xian; Fang, Xiaohong; Sun, Jinpeng; Kong, Wei

    2018-01-02

    Hyperhomocysteinemia (HHcy) is a risk factor for various cardiovascular diseases. However, the mechanism underlying HHcy-aggravated vascular injury remains unclear. Here we show that the aggravation of abdominal aortic aneurysm by HHcy is abolished in mice with genetic deletion of the angiotensin II type 1 (AT1) receptor and in mice treated with an AT1 blocker. We find that homocysteine directly activates AT1 receptor signalling. Homocysteine displaces angiotensin II and limits its binding to AT1 receptor. Bioluminescence resonance energy transfer analysis reveals distinct conformational changes of AT1 receptor upon binding to angiotensin II and homocysteine. Molecular dynamics and site-directed mutagenesis experiments suggest that homocysteine regulates the conformation of the AT1 receptor both orthosterically and allosterically by forming a salt bridge and a disulfide bond with its Arg 167 and Cys 289 residues, respectively. Together, these findings suggest that strategies aimed at blocking the AT1 receptor may mitigate HHcy-associated aneurysmal vascular injuries.

  19. Suppression of homocysteine levels by vitamin B12 and folates: age and gender dependency in the Jackson Heart Study.

    PubMed

    Henry, Olivia R; Benghuzzi, Hamed; Taylor, Herman A; Tucci, Michelle; Butler, Kenneth; Jones, Lynne

    2012-08-01

    To examine factors potentially contributing to premature cardiovascular disease mortality in African Americans (40% versus 20% all other populations), plasma homocysteine, serum vitamin B12 and folate levels were examined for African American participants in the Jackson Heart Study. Of 5192 African American Jackson Heart Study participants (21-94 years), 5064 (mean age, 55 ± 13 years; 63% female) had homocysteine levels measured via fasting blood samples, with further assessments of participants' vitamin B12 (n = 1790) and folate (n = 1788) levels. Regression analyses were used to examine age, gender, vitamin B12 and folate with homocysteine levels. Homocysteine levels, a purported surrogate risk factor for cardiovascular disease, increased with age, were inversely proportional to folate and vitamin B12 levels (P < 0.001) and were higher for men of all ages. The results show that, as with other populations, age, gender, vitamin B12 and folate may predict homocysteine levels for African Americans. Diet may be an important predictive factor as well, given the relationships that were observed between plasma homocysteine and serum B vitamin levels.

  20. Blood lipids, homocysteine, stress factors, and vitamins in clinically stable multiple sclerosis patients

    PubMed Central

    2010-01-01

    Multiple Sclerosis (MS) patients present a decrease of antioxidants and neuroprotective and immunoregulatory vitamins and an increase of total homocysteine (tHcy), cholesterol (CHL), HDL-cholesterol, and of cellular stress markers, variably associated with the different phases of the disease. We compared the blood levels of uric acid, folic acid, vitamins B12, A, and E, tHcy, CHL, HDL-cholesterol, and triglycerides in forty MS patients during a phase of clinical inactivity with those of eighty healthy controls, matched for age and sex. We found higher levels of tHcy (p = 0.032) and of HDL-cholesterol (p = 0.001) and lower levels of vitamin E (p = 0.001) and the ratio vitamin E/CHL (p = 0.001) in MS patients. In conclusion, modifications of some biochemical markers of cell damage were detected in MS patients during a phase of clinical inactivity. PMID:20163740

  1. Body composition in patients with classical homocystinuria: body mass relates to homocysteine and choline metabolism.

    PubMed

    Poloni, Soraia; Leistner-Segal, Sandra; Bandeira, Isabel Cristina; D'Almeida, Vânia; de Souza, Carolina Fischinger Moura; Spritzer, Poli Mara; Castro, Kamila; Tonon, Tássia; Nalin, Tatiéle; Imbard, Apolline; Blom, Henk J; Schwartz, Ida V D

    2014-08-10

    Classical homocystinuria is a rare genetic disease caused by cystathionine β-synthase deficiency, resulting in homocysteine accumulation. Growing evidence suggests that reduced fat mass in patients with classical homocystinuria may be associated with alterations in choline and homocysteine pathways. This study aimed to evaluate the body composition of patients with classical homocystinuria, identifying changes in body fat percentage and correlating findings with biochemical markers of homocysteine and choline pathways, lipoprotein levels and bone mineral density (BMD) T-scores. Nine patients with classical homocystinuria were included in the study. Levels of homocysteine, methionine, cysteine, choline, betaine, dimethylglycine and ethanolamine were determined. Body composition was assessed by bioelectrical impedance analysis (BIA) in patients and in 18 controls. Data on the last BMD measurement and lipoprotein profile were obtained from medical records. Of 9 patients, 4 (44%) had a low body fat percentage, but no statistically significant differences were found between patients and controls. Homocysteine and methionine levels were negatively correlated with body mass index (BMI), while cysteine showed a positive correlation with BMI (p<0.05). There was a trend between total choline levels and body fat percentage (r=0.439, p=0.07). HDL cholesterol correlated with choline and ethanolamine levels (r=0.757, p=0.049; r=0.847, p=0.016, respectively), and total cholesterol also correlated with choline levels (r=0.775, p=0.041). There was no association between BMD T-scores and body composition. These results suggest that reduced fat mass is common in patients with classical homocystinuria, and that alterations in homocysteine and choline pathways affect body mass and lipid metabolism. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Homocysteine levels after nitrous oxide anesthesia for living-related donor renal transplantation: a randomized, controlled, double-blind study.

    PubMed

    Coskunfirat, N; Hadimioglu, N; Ertug, Z; Akbas, H; Davran, F; Ozdemir, B; Aktas Samur, A; Arici, G

    2015-03-01

    Nitrous oxide anesthesia increases postoperative homocysteine concentrations. Renal transplantation candidates present with higher homocysteine levels than patients with no renal disease. We designed this study to investigate if homocysteine levels are higher in subjects receiving nitrous oxide for renal transplantation compared with subjects undergoing nitrous oxide free anesthesia. Data from 59 patients scheduled for living-related donor renal transplantation surgery were analyzed in this randomized, controlled, blinded, parallel-group, longitudinal trial. Patients were assigned to receive general anesthesia with (flowmeter was set at 2 L/min nitrous oxide and 1 L/min oxygen) or without nitrous oxide (2 L/min air and 1 L/min oxygen). We evaluated levels of total homocysteine and known determinants, including creatinine, folate, vitamin B12, albumin, and lipids. We evaluated factor V and von Willebrand factor (vWF) to determine endothelial dysfunction and creatinine kinase myocardial band (CKMB)-mass, troponin T to show myocardial ischemia preoperatively in the holding area (T1), after discontinuation of anesthetic gases (T2), and 24 hours after induction (T3). Compared with baseline, homocysteine concentrations significantly decreased both in the nitrous oxide (22.3 ± 16.3 vs 11.8 ± 9.9; P < .00001) and nitrous oxide-free groups (21.5 ± 15.3 vs 8.0 ± 5.7; P < .0001) at postoperative hour 24. The nitrous oxide group had significantly higher mean plasma homocysteine concentrations than the nitrous oxide-free group (P = .021). The actual homocysteine difference between groups was 3.8 μmol/L. This study shows that homocysteine levels markedly decrease within 24 hours after living-related donor kidney transplantation. Patients receiving nitrous oxide have a lesser reduction, but this finding is unlikely to have a clinical relevance. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Hydrogen Sulfide Ameliorates Homocysteine-Induced Cognitive Dysfunction by Inhibition of Reactive Aldehydes Involving Upregulation of ALDH2.

    PubMed

    Li, Min; Zhang, Ping; Wei, Hai-Jun; Li, Man-Hong; Zou, Wei; Li, Xiang; Gu, Hong-Feng; Tang, Xiao-Qing

    2017-04-01

    Homocysteine, a risk factor for Alzheimer's disease, induces cognitive dysfunction. Reactive aldehydes play an important role in cognitive dysfunction. Aldehyde-dehydrogenase 2 detoxifies reactive aldehydes. Hydrogen sulfide, a novel neuromodulator, has neuroprotective effects and regulates learning and memory. Our previous work confirmed that the disturbance of hydrogen sulfide synthesis is invovled in homocysteine-induced defects in learning and memory. Therefore, the present work was to explore whether hydrogen sulfide ameliorates homocysteine-generated cognitive dysfunction and to investigate whether its underlying mechanism is related to attenuating accumulation of reactive aldehydes by upregulation of aldehyde-dehydrogenase 2. The cognitive function of rats was assessed by the Morris water maze test and the novel object recognition test. The levels of malondialdehyde, 4-hydroxynonenal, and glutathione as well as the activity of aldehyde-dehydrogenase 2 were determined by enzyme linked immunosorbent assay; the expression of aldehyde-dehydrogenase 2 was detected by western blot. The behavior experiments, Morris water maze test and novel objects recognition test, showed that homocysteine induced deficiency in learning and memory in rats, and this deficiency was reversed by treatment of NaHS (a donor of hydrogen sulfide). We demonstrated that NaHS inhibited homocysteine-induced increases in generations of MDA and 4-HNE in the hippocampus of rats and that hydrogen sulfide reversed homocysteine-induced decreases in the level of glutathione as well as the activity and expression of aldehyde-dehydrogenase 2 in the hippocampus of rats. Hydrogen sulfide ameliorates homocysteine-induced impairment in cognitive function by decreasing accumulation of reactive aldehydes as a result of upregulations of glutathione and aldehyde-dehydrogenase 2. © The Author 2016. Published by Oxford University Press on behalf of CINP.

  4. Hydrogen Sulfide Ameliorates Homocysteine-Induced Cognitive Dysfunction by Inhibition of Reactive Aldehydes Involving Upregulation of ALDH2

    PubMed Central

    Li, Min; Zhang, Ping; Wei, Hai-jun; Li, Man-Hong; Li, Xiang; Gu, Hong-Feng

    2017-01-01

    Abstract Background: Homocysteine, a risk factor for Alzheimer’s disease, induces cognitive dysfunction. Reactive aldehydes play an important role in cognitive dysfunction. Aldehyde-dehydrogenase 2 detoxifies reactive aldehydes. Hydrogen sulfide, a novel neuromodulator, has neuroprotective effects and regulates learning and memory. Our previous work confirmed that the disturbance of hydrogen sulfide synthesis is invovled in homocysteine-induced defects in learning and memory. Therefore, the present work was to explore whether hydrogen sulfide ameliorates homocysteine-generated cognitive dysfunction and to investigate whether its underlying mechanism is related to attenuating accumulation of reactive aldehydes by upregulation of aldehyde-dehydrogenase 2. Methods: The cognitive function of rats was assessed by the Morris water maze test and the novel object recognition test. The levels of malondialdehyde, 4-hydroxynonenal, and glutathione as well as the activity of aldehyde-dehydrogenase 2 were determined by enzyme linked immunosorbent assay; the expression of aldehyde-dehydrogenase 2 was detected by western blot. Results: The behavior experiments, Morris water maze test and novel objects recognition test, showed that homocysteine induced deficiency in learning and memory in rats, and this deficiency was reversed by treatment of NaHS (a donor of hydrogen sulfide). We demonstrated that NaHS inhibited homocysteine-induced increases in generations of MDA and 4-HNE in the hippocampus of rats and that hydrogen sulfide reversed homocysteine-induced decreases in the level of glutathione as well as the activity and expression of aldehyde-dehydrogenase 2 in the hippocampus of rats. Conclusion: Hydrogen sulfide ameliorates homocysteine-induced impairment in cognitive function by decreasing accumulation of reactive aldehydes as a result of upregulations of glutathione and aldehyde-dehydrogenase 2. PMID:27988490

  5. Homocysteine measurement in dried blood spot for neonatal detection of homocystinurias.

    PubMed

    Alodaib, Ahmad N; Carpenter, Kevin; Wiley, Veronica; Wotton, Tiffany; Christodoulou, John; Wilcken, Bridget

    2012-01-01

    Expanded newborn screening (NBS) leads to an increased number of false positive results, causing parental anxiety, greater follow-up costs, and the need for further metabolic investigations. We developed and validated a second-tier approach for NBS of homocystinurias by measuring the total homocysteine (tHcy) on the initial dried blood spot (DBS) samples to reduce the need for further investigation, and investigated newborn DBS homocysteine values in patients with homocystinuria. Total DBS homocysteine was measured in normal newborns, and retrospectively in newborns with established disorders, using liquid chromatography tandem mass spectrometry (LC-MS/MS) with stable isotope-labelled internal standards for homocysteine. Analytes were separated using reverse phase chromatography with a total run time of 3 min. The method was linear over the range of 10-100 μmol/L of tHcy and showed excellent precision; intra-batch CV was 4% and inter-batch precision 6.5%. Comparison of 59 plasma values with DBS for tHcy taken at the same time showed excellent correlation, (r (2)>0.97). The reference range for current neonatal samples was 5.4-10.7 μmol/L (n=99), and for the stored neonatal samples (stored dry, sealed in plastic at room temperature for 10 years) was 1.7-5.5 μmol/L, (n=50), both being normally distributed. The clinical utility of this method was checked by retrospective analysis of stored NBS samples from patients with different forms of homocystinuria, including four different remethylating disorders. All had clear elevations of tHcy.

  6. Serum homocysteine, folate, vitamin B12 and total antioxidant status in vegetarian children.

    PubMed

    Ambroszkiewicz, J; Klemarczyk, W; Chełchowska, M; Gajewska, J; Laskowska-Klita, T

    2006-01-01

    The results of several studies point to the positive role of vegetarian diets in reducing the risk of diabetes, some cancers and cardiovascular diseases. However, exclusion of animal products in vegetarian diets may affect the cobalamin status and cause an elevation of the plasma homocysteine level. The aim of this study was to assess the effect of vegetarian diets on serum concentrations of homocysteine, folate, vitamin B12 and total antioxidant status (TAS) in children. The study included 32 vegetarians (including 5 vegans), age 2-10 years. Dietary constituents were analyzed using a local nutritional programme. Serum homocysteine, folate and vitamin B12 were determined with fluorescence and chemiluminescence immunoassays. The concentration of TAS was measured by a colorimetric method. Average daily energy intake and the percentage of energy from protein, fat and carbohydrates in the diets of the studied children were just above or similar to the recommended amounts. It could be shown that vegetarian diets contain high concentrations of folate. In vegan diets it even exceeds the recommended dietary allowance. Mean daily intake of vitamin B12 in the studied diets was adequate but in vegans was below the recommended range. The serum concentrations of homocysteine, folate, vitamin B12 and TAS in vegetarian children remained within the physiological range. The presented data indicate that vegetarian children, contrary to adults, have enough vitamin B12 in their diet (excluding vegans) and normal serum concentrations of homocysteine, folate and vitamin B12. Therefore, in order to prevent deficiencies in the future, close monitoring of vegetarian children (especially on a vegan diet) is important to make sure that they receive adequate quantities of nutrients needed for healthy growth.

  7. Reduction in plasma total homocysteine through increasing folate intake in healthy individuals is not associated with changes in measures of antioxidant activity or oxidant damage.

    PubMed

    Moat, S J; Hill, M H; McDowell, I F W; Pullin, C H; Ashfield-Watt, P A L; Clark, Z E; Whiting, J M; Newcombe, R G; Lewis, M J; Powers, H J

    2003-03-01

    Various mechanisms have been proposed to explain the association between plasma total homocysteine (tHcy) and risk of cardiovascular disease, including oxidative activity of homocysteine. To explore the putative role of reactive oxygen species in the association between plasma tHcy and risk of cardiovascular disease in healthy individuals. A double-blind, placebo-controlled crossover intervention to increase folate intake through diet (increased consumption of folate-rich foods) and supplement (400 micro g folic acid) was carried out in 126 healthy men and women. Measurements were made of antioxidant activity in red blood cells and plasma, and products of oxidant damage in plasma. Diet and supplement-based interventions led to an increase in measures of folate status and a reduction in plasma tHcy. This was not associated with any significant change in measures of antioxidant activity (plasma and red blood cell glutathione peroxidase activity and red blood cell superoxide dismutase activity) or oxidant damage (plasma malondialdehyde), although an improvement in plasma total antioxidant capacity just failed to reach significance. In healthy individuals lowering plasma tHcy does not have any functional implications regarding oxidative damage.

  8. Suppression of Homocysteine Levels by Vitamin B12 and Folates: Age and Gender Dependency in the Jackson Heart Study

    PubMed Central

    Henry, Olivia R.; Benghuzzi, Hamed; Taylor, Herman A.; Tucci, Michelle; Butler, Kenneth; Jones, Lynne

    2011-01-01

    Objectives To examine factors potentially contributing to premature cardiovascular disease mortality in African Americans (40% versus 20% all other populations), plasma homocysteine, serum vitamin B12 and folate levels were examined for African American participants in the Jackson Heart Study. Methods Of 5,192 African American Jackson Heart Study participants (21–94 years), 5,064 (mean age, 55±13 years; 63% female) had homocysteine levels measured via fasting blood samples, with further assessments of participants’ vitamin B12 (n=1,790) and folate (n=1,788) levels. We used regression analyses to examine age, gender, vitamin B12, and folate with homocysteine levels. Results Homocysteine levels, a purported surrogate risk factor for cardiovascular disease, increased with age, were inversely proportional to folate and vitamin B12 levels (p<0.001), and higher for men of all ages. Conclusions Our results show that, as with other populations, age, gender, vitamin B12, and folate may predict homocysteine levels for African Americans. Diet may be an important predictive factor as well, given the relationships we observed between plasma homocysteine and serum B vitamin levels. PMID:22173042

  9. Comparison of parameters of bone profile and homocysteine in physically active and non-active postmenopausal females.

    PubMed

    Tariq, Sundus; Lone, Khalid Parvez; Tariq, Saba

    2016-01-01

    Optimal physical activity is important in attaining a peak bone mass. Physically active women have better bone mineral density and reduce fracture risk as compared to females living a sedentary life. The objective of this study was to compare parameters of bone profile and serum homocysteine levels in physically active and non-active postmenopausal females. In this cross sectional study postmenopausal females between 50-70 years of age were recruited and divided into two groups: Physically inactive (n=133) performing light physical activity and Physically active (n=34) performing moderate physical activity. Physical activity (in metabolic equivalents), bone mineral density and serum homocysteine levels were assessed. Spearman's rho correlation was applied to observe correlations. Two independent sample t test and Mann Whitney U test were applied to compare groups. P-value ≤ 0.05 was taken statistically significant. Parameters of bone profile were significantly higher and serum homocysteine levels were significantly lower in postmenopausal females performing moderate physical activity as compared to females performing light physical activity. Homocysteine was not significantly related to T-score and Z-score in both groups. Improving physical activity could be beneficial for improving the quality of bone, decreasing fracture risk and decreasing serum homocysteine levels.

  10. Folic acid deficiency induces premature hearing loss through mechanisms involving cochlear oxidative stress and impairment of homocysteine metabolism.

    PubMed

    Martínez-Vega, Raquel; Garrido, Francisco; Partearroyo, Teresa; Cediel, Rafael; Zeisel, Steven H; Martínez-Álvarez, Concepción; Varela-Moreiras, Gregorio; Varela-Nieto, Isabel; Pajares, María A

    2015-02-01

    Nutritional imbalance is emerging as a causative factor of hearing loss. Epidemiologic studies have linked hearing loss to elevated plasma total homocysteine (tHcy) and folate deficiency, and have shown that folate supplementation lowers tHcy levels potentially ameliorating age-related hearing loss. The purpose of this study was to address the impact of folate deficiency on hearing loss and to examine the underlying mechanisms. For this purpose, 2-mo-old C57BL/6J mice (Animalia Chordata Mus musculus) were randomly divided into 2 groups (n = 65 each) that were fed folate-deficient (FD) or standard diets for 8 wk. HPLC analysis demonstrated a 7-fold decline in serum folate and a 3-fold increase in tHcy levels. FD mice exhibited severe hearing loss measured by auditory brainstem recordings and TUNEL-positive-apoptotic cochlear cells. RT-quantitative PCR and Western blotting showed reduced levels of enzymes catalyzing homocysteine (Hcy) production and recycling, together with a 30% increase in protein homocysteinylation. Redox stress was demonstrated by decreased expression of catalase, glutathione peroxidase 4, and glutathione synthetase genes, increased levels of manganese superoxide dismutase, and NADPH oxidase-complex adaptor cytochrome b-245, α-polypeptide (p22phox) proteins, and elevated concentrations of glutathione species. Altogether, our findings demonstrate, for the first time, that the relationship between hyperhomocysteinemia induced by folate deficiency and premature hearing loss involves impairment of cochlear Hcy metabolism and associated oxidative stress. © FASEB.

  11. Neural Tube Defects and Maternal Biomarkers of Folate, Homocysteine, and Glutathione Metabolism

    PubMed Central

    Zhao, Weizhi; Mosley, Bridget S.; Cleves, Mario A.; Melnyk, Stepan; James, S. Jill; Hobbs, Charlotte A.

    2010-01-01

    Background Alterations in maternal folate and homocysteine metabolism are associated with neural tube defects (NTDs). The role that specific micronutrients and metabolites play in the causal pathway leading to NTDs is not fully understood. Methods We conducted a case-control study to investigate the association between NTDs and maternal alterations in plasma micronutrients and metabolites in two metabolic pathways, the methionine remethylation and glutathione transsulfuration. Biomarkers were measured in a population-based sample of women who had NTD-affected pregnancies (n = 43) and a control group of women who had a pregnancy unaffected by a birth defect (n = 160). Plasma concentrations of folate, Vitamin B12, Vitamin B6, methionine, S-adenosylmethionine (SAM), s- adenosylhomocysteine (SAH), adenosine, homocysteine, cysteine, and reduced and oxidized glutathione were compared between cases and controls after adjusting for lifestyle and sociodemographic factors. Results Women with NTD-affected pregnancies had significantly higher plasma concentrations of SAH (29.12 vs. 23.13 nmol/L, P = 0.0011), adenosine (0.323 vs. 0.255 μmol/L, P = 0.0269), homocysteine (9.40 vs. 7.56 μmol/L, P < 0.001), and oxidized glutathione (0.379 vs. 0.262μmol/L, P = 0.0001), but lower plasma SAM concentration (78.99 vs. 83.16 nmol/L, P = 0.0172) than controls. This metabolic profile is consistent with reduced methylation capacity and increased oxidative stress in women with affected pregnancies. Conclusions Increased maternal oxidative stress and decreased methylation capacity may contribute to the occurrence of NTDs. Further analysis of relevant genetic and environmental factors is required to define the basis for these observed alterations. PMID:16575882

  12. Association of homocysteine with global DNA methylation in vegetarian Indian pregnant women and neonatal birth anthropometrics.

    PubMed

    Gadgil, Maithili S; Joshi, Kalpana S; Naik, Sadanand S; Pandit, Anand N; Otiv, Suhas R; Patwardhan, Bhushan K

    2014-11-01

    The present study was designed to evaluate if plasma maternal folate, vitamin B-12 and homocysteine levels had an effect on maternal global DNA methylation and neonatal anthropometrics in Indian pregnant women. A total of 49 participants having completed ≥36 weeks of pregnancy were enrolled in the study. Estimation of folate was by Ion capture assay, vitamin B-12 by microparticle enzyme immunoassay, total homocysteine by fluorescence polarization immunoassay and global DNA methylation using Cayman's DNA methylation enzyme immunoassay (EIA) kit. Folate and vitamin B-12 were inversely correlated to homocysteine in pregnant women consuming vegetarian and non-vegetarian diet. No difference in global DNA methylation was found between the vegetarian and non-vegetarian pregnant women. Folate and vitamin B-12 did not show association with global DNA methylation, however plasma total homocysteine of the vegetarian group showed significant correlation to global DNA methylation (r(2 )= 0.49, p = 0.011). Plasma total homocysteine was inversely related to tricep skinfold (r(2 )= -0.484, p = 0.01) and chest circumference (r(2 )= -0.104, p = 0.04) of neonates in vegetarian group. Moderate vitamin B-12 deficiency in vegetarian pregnant women might be the cause of hyperhomocystinemia, hypermethylation when compared to vitamin B-12 sufficient non-vegetarian group.

  13. [Efficacy and safety of heptral, vitamin B6 and folic acid during toxic hepatitis induced by CCL4].

    PubMed

    Antelava, N A; Gogoluari, M I; Gogoluari, L I; Pirtskhalaĭshvili, N N; Okudzhava, M V

    2007-09-01

    The aim of this work was to evaluate of efficacy and safety of complex Heptral, Vitamin B6 and Folic Acid in experimental hepatitis therapy compared with monotherapy. Experiments were carried out on pubertal rats. Eperimental hepatitis models were induced by Tetrachlormethane. The tetrachlormethane intoxication was reproduced by subcutaneous injection of CCL(4) 1ml/kg dissolved in 1ml of olive oil. Cytochrome P450, cytochrome b5, reduced glutation,activity of glutationetranspherase and content of ATP in hepatocytes were measured by the spectrophotometric techniques,but content of homocysteine by chromophtography techniques. Under CCL(4) intoxication disturbance of liver detoxication function, energy deficit and surplus of homocysteine were observed. Treatment of the toxic hepatitis with heptral increased the level of cytochrome P450, cytochrome b5, glutation activity of glutationetranspherase glutathione and reduced content of homocysteine. Complex therapy with Heptral and B6 and folic acid reveal more expressive hepatoprotective effect and safety than monotherapy with Heptral. Complex therapy improves not only the parameters of biotransformation (metabolic and conjugation phase), but also normalizes the level of ATP and homocystein. Vitamins B6 and folic acid increases the efficacy and safety of Heptral. This complex was recomended for treatment of hepatitis.

  14. Tyrosinase inhibition due to interaction of homocyst(e)ine with copper: the mechanism for reversible hypopigmentation in homocystinuria due to cystathionine beta-synthase deficiency.

    PubMed

    Reish, O; Townsend, D; Berry, S A; Tsai, M Y; King, R A

    1995-07-01

    Deficiency of cystathionine beta-synthase (CBS) is a genetic disorder of transsulfuration resulting in elevated plasma homocyst(e)ine and methionine and decreased cysteine. Affected patients have multisystem involvement, which may include light skin and hair. Reversible hypopigmentation in treated homocystinuric patients has been infrequently reported, and the mechanism is undefined. Two CBS-deficient homocystinuric patients manifested darkening of their hypopigmented hair following treatment that decreased plasma homocyst(e)ine. We hypothesized that homocyst(e)ine inhibits tyrosinase, the major pigment enzyme. The activity of tyrosinase extracted from pigmented human melanoma cells (MNT-1) that were grown in the presence of homocysteine was reduced in comparison to that extracted from cells grown without homocysteine. Copper sulfate restored homocyst(e)ine-inhibited tyrosinase activity when added to the culture cell media at a proportion of 1.25 mol of copper sulfate per 1 mol of DL-homocysteine. Holo-tyrosinase activity was inhibited by adding DL-homocysteine to the assay reaction mixture, and the addition of copper sulfate to the reaction mixture prevented this inhibition. Other tested compounds, L-cystine and betaine did not affect tyrosinase activity. Our data suggest that reversible hypopigmentation in homocystinuria is the result of tyrosinase inhibition by homocyst(e)ine and that the probable mechanism of this inhibition is the interaction of homocyst(e)ine with copper at the active site of tyrosinase.

  15. Tyrosinase inhibition due to interaction of homocyst(e)ine with copper: the mechanism for reversible hypopigmentation in homocystinuria due to cystathionine beta-synthase deficiency.

    PubMed Central

    Reish, O; Townsend, D; Berry, S A; Tsai, M Y; King, R A

    1995-01-01

    Deficiency of cystathionine beta-synthase (CBS) is a genetic disorder of transsulfuration resulting in elevated plasma homocyst(e)ine and methionine and decreased cysteine. Affected patients have multisystem involvement, which may include light skin and hair. Reversible hypopigmentation in treated homocystinuric patients has been infrequently reported, and the mechanism is undefined. Two CBS-deficient homocystinuric patients manifested darkening of their hypopigmented hair following treatment that decreased plasma homocyst(e)ine. We hypothesized that homocyst(e)ine inhibits tyrosinase, the major pigment enzyme. The activity of tyrosinase extracted from pigmented human melanoma cells (MNT-1) that were grown in the presence of homocysteine was reduced in comparison to that extracted from cells grown without homocysteine. Copper sulfate restored homocyst(e)ine-inhibited tyrosinase activity when added to the culture cell media at a proportion of 1.25 mol of copper sulfate per 1 mol of DL-homocysteine. Holo-tyrosinase activity was inhibited by adding DL-homocysteine to the assay reaction mixture, and the addition of copper sulfate to the reaction mixture prevented this inhibition. Other tested compounds, L-cystine and betaine did not affect tyrosinase activity. Our data suggest that reversible hypopigmentation in homocystinuria is the result of tyrosinase inhibition by homocyst(e)ine and that the probable mechanism of this inhibition is the interaction of homocyst(e)ine with copper at the active site of tyrosinase. Images Figure 1 PMID:7611281

  16. Effects of zinc deficiency and zinc supplementation on homocysteine levels and related enzyme expression in rats.

    PubMed

    Jing, Mingyan; Rech, Leslie; Wu, Yinghong; Goltz, Douglas; Taylor, Carla G; House, James D

    2015-04-01

    Methionine synthase (MS) and betaine-homocysteine methyltransferase (BHMT) are both zinc (Zn)-dependent methyltransferases and involved in the methylation of homocysteine. The objective of this study was to investigate the effects of dietary Zn supply on homocysteine levels and expression of the two enzymes in growing rats. Male weanling Sprague-Dawley rats were assigned randomly to four dietary groups (n=8/group) for 3 weeks: Zn deficient (ZD; <1mg Zn/kg); Zn control (ZC; 30mg Zn/kg); Zn supplemented (ZS; 300mg Zn/kg); pair fed (PF; 30mg Zn/kg) to the ZD group. Serum and femur Zn concentrations were 83% and 58% lower in ZD, and 49% and 62% higher in ZS compared to ZC (P<0.001), respectively. The ZD rats had lower feed intake (37%), body weight gains (45%), liver (43%) and kidney (31%) weights than those of ZC (P<0.001), but these parameters in ZD were not significantly different from the PF controls. Serum homocysteine concentrations were 65% higher in ZD compared to PF (P<0.05), and there was no significant difference in serum folate levels between ZD and PF groups. The mRNA expression of liver and kidney MS was 57% and 38% lower in ZD than PF (P<0.001), respectively. Hepatic and renal BHMT mRNA levels were not altered in ZD compared to controls. The aforementioned measurements were not significantly different between ZS and ZC groups, except Zn levels. These results demonstrated that homocysteine homeostasis appeared to be disturbed by Zn deficiency but not Zn supplementation, and elevated serum homocysteine might be due to reduced expression of MS during Zn deficiency. Copyright © 2014 Elsevier GmbH. All rights reserved.

  17. Effects of rosuvastatin on the production and activation of matrix metalloproteinase-2 and migration of cultured rat vascular smooth muscle cells induced by homocysteine.

    PubMed

    Shi, Ya-fei; Chi, Ju-fang; Tang, Wei-liang; Xu, Fu-kang; Liu, Long-bin; Ji, Zheng; Lv, Hai-tao; Guo, Hang-yuan

    2013-08-01

    To test the influence of homocysteine on the production and activation of matrix metalloproteinase-2 (MMP-2) and tissue inhibitors of matrix metalloproteinase-2 (TIMP-2) and on cell migration of cultured rat vascular smooth muscle cells (VSMCs). Also, to explore whether rosuvastatin can alter the abnormal secretion and activation of MMP-2 and TIMP-2 and migration of VSMCs induced by homocysteine. Rat VSMCs were incubated with different concentrations of homocysteine (50-5000 μmol/L). Western blotting and gelatin zymography were used to investigate the expressions and activities of MMP-2 and TIMP-2 in VSMCs in culture medium when induced with homocysteine for 24, 48, and 72 h. Transwell chambers were employed to test the migratory ability of VSMCs when incubated with homocysteine for 48 h. Different concentrations of rosuvastatin (10(-9)-10(-5) mol/L) were added when VSMCs were induced with 1000 μmol/L homocysteine. The expressions and activities of MMP-2 and TIMP-2 were examined after incubating for 24, 48, and 72 h, and the migration of VSMCs was also examined after incubating for 48 h. Homocysteine (50-1000 μmol/L) increased the production and activation of MMP-2 and expression of TIMP-2 in a dose-dependent manner. However, when incubated with 5000 μmol/L homocysteine, the expression of MMP-2 was up-regulated, but its activity was down-regulated. Increased homocysteine-induced production and activation of MMP-2 were reduced by rosuvastatin in a dose-dependent manner whereas secretion of TIMP-2 was not significantly altered by rosuvastatin. Homocysteine (50-5000 μmol/L) stimulated the migration of VSMCs in a dose-dependent manner, but this effect was eliminated by rosuvastatin. Homocysteine (50-1000 μmol/L) significantly increased the production and activation of MMP-2, the expression of TIMP-2, and the migration of VSMCs in a dose-dependent manner. Additional extracellular rosuvastatin can decrease the excessive expression and activation of MMP-2 and

  18. A novel NBD-based fluorescent turn-on probe for the detection of cysteine and homocysteine in living cells

    NASA Astrophysics Data System (ADS)

    Wang, Jiamin; Niu, Linqiang; Huang, Jing; Yan, Zhijie; Wang, Jianhong

    2018-03-01

    Biothiols, such as cysteine (Cys), homocysteine (Hcy) and glutathione (GSH), are involved in a number of biological processes and play crucial roles in biological systems. Thus, the detection of biothiols is highly important for early diagnosis of diseases and evaluation of disease progression. Herein, we developed a new turn-on fluorescent probe 1 based on 7-nitro-2,1,3-benzoxadiazole (NBD) with high selectivity and sensitivity for Cys/Hcy on account of nucleophilic substitution and Smiles rearrangement reaction. The probe could sense Cys/Hcy rapidly, the intensity of fluorescence increased immediately within 1 min. Furthermore, the probe is low toxic and has been successfully applied to detect intracellular Cys/Hcy by cell fluorescence imaging in living normal and cancer cells.

  19. Creation of catalytically active particles from enzymes crosslinked with a natural bifunctional agent--homocysteine thiolactone.

    PubMed

    Stroylova, Yulia Y; Semenyuk, Pavel I; Asriyantz, Regina A; Gaillard, Cedric; Haertlé, Thomas; Muronetz, Vladimir I

    2014-09-01

    The current study describes an approach to creation of catalytically active particles with increased stability from enzymes by N-homocysteinylation, a naturally presented protein modification. Enzymatic activities and properties of two globular tetrameric enzymes glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and lactate dehydrogenase (LDH) were studied before and after N-homocysteinylation. Modification of these proteins concerns the accessible lysine residues and introduces an average of 2-2,5 homocysteine residues per protein monomer. Formation of a range of aggregates was observed for both enzymes, which assemble via formation of intermolecular noncovalent bonds and by disulfide bonds. It was demonstrated that both studied enzymes retain their catalytic activities on modification and the subsequent formation of oligomeric forms. At low concentrations of homocysteine thiolactone, modification of GAPDH leads not only to prevention of spontaneous inactivation but also increases thermal stability of this enzyme on heating to 80°C. A moderate reduction of the activity of GAPDH observed in case of its crosslinking with 50-fold excess of homocysteine thiolactone per lysine is probably caused by hindered substrate diffusion. Spherical particles of 100 nm and larger diameters were observed by transmission electron microscopy and atomic force microscope techniques after modification of GAPDH with different homocysteine thiolactone concentrations. In case of LDH, branched fibril-like aggregates were observed under the same conditions. Interestingly, crosslinked samples of both proteins were found to have reversible thermal denaturation profiles, indicating that modification with homocysteine thiolactone stabilizes the spatial structure of these enzymes. © 2014 Wiley Periodicals, Inc.

  20. Correlation between homocysteine and dyslipidemia in ischaemic stroke patients with and without hypertension

    NASA Astrophysics Data System (ADS)

    Aria Arina, Cut; Amir, Darwin; Siregar, Yahwardiah; Sembiring, Rosita J.

    2018-03-01

    Almost 80% of strokes are ischaemic and stroke is the third most common cause of death in developed countries, . The treatment of stroke still limited, the best approach to reduce mortality and morbidity is primary prevention through modification of acquired risk factors. Hypertension and dyslipidemia are one of the major risk factor for stroke while homocysteine is a less well-documented risk factor. The purpose of this study was to know the correlation between homocysteine and dyslipidemia in ischaemic stroke patients with and without hypertension. This study is a cross sectional study; the sample were taken consecutively. All sample matched with inclusion and exclusion criteria, demography data and blood sample were taken. Demography data was analyzed using descriptive statistic, to analyze the relation, we used Chi-Square test. p value <0,05 was significant. Of the 100 patients, were divided into two groups, with hypertension, and without hypertension, hyperhomocysteinemia was found in 62 patients (59 patients had mild hyperhomocysteinemia, three patients had moderate hyperhomocysteinemia) and dyslipidemia was found in 60 patients. There is a significant relation between homocysteine and dyslipidemia in ischaemic stroke patients with hypertension, p value = 0,009. A significant correlation between homocysteine and dyslipidemia might be because both of them have an important role in the acceleration of the atherosclerotic formation by activation platelet and thrombus, but we still need further study to get more explanation about the relation.

  1. A putative role for homocysteine in the pathophysiology of acute bacterial meningitis in children.

    PubMed

    Coimbra, Roney Santos; Calegare, Bruno Frederico Aguilar; Candiani, Talitah Michel Sanchez; D'Almeida, Vânia

    2014-01-01

    Acute bacterial meningitis frequently causes cortical and hippocampal neuron loss leading to permanent neurological sequelae. Neuron death in acute bacterial meningitis involves the excessive activation of NMDA receptors and p53-mediated apoptosis, and the latter is triggered by the depletion of NAD + and ATP cellular stores by the DNA repair enzyme poly(ADP-ribose) polymerase. This enzyme is activated during acute bacterial meningitis in response to DNA damage induced, on its turn, by reactive oxygen and nitrogen species. An excess of homocysteine can also induce this cascade of events in hippocampal neurons. The present work aimed at investigating the possible involvement of homocysteine in the pathophysiology of meningitis by comparing its concentrations in cerebrospinal fluid (CSF) samples from children with viral or acute bacterial meningitis, and control individuals. Homocysteine and cysteine concentrations were assessed by high-performance liquid chromatography in CSF samples from nine patients with acute bacterial meningitis, 13 patients with viral meningitis and 18 controls (median age: 4 years-old; range: <1 to 13) collected by lumbar puncture at admission at the Children's Hospital Joao Paulo II - FHEMIG, from January 2010 to November 2011. We found that homocysteine accumulates up to neurotoxic levels within the central nervous system of patients with acute bacterial meningitis, but not in those with viral meningitis or control individuals. No correlation was found between homocysteine and cysteine concentrations and the cerebrospinal fluid standard cytochemical parameters. Our results suggest that HCY is produced intrathecally in response to acute bacterial meningitis and accumulates within the central nervous system reaching potentially neurotoxic levels. This is the first work to propose a role for HCY in the pathophysiology of brain damage associated with acute bacterial meningitis.

  2. MTHFR C677T polymorphism, homocysteine and B-vitamins status in a sample of Chinese and Malay subjects in Universiti Putra Malaysia.

    PubMed

    Choo, S C; Loh, S P; Khor, G L; Sabariah, M N; Rozita, R

    2011-08-01

    Methylenetetrahydrofolate reductase (MTHFR) C677T is involved in folate and homocysteine metabolism. Disruption in the activity of this enzyme will alter their levels in the body. This study assessed MTHFR C677T polymorphism and its relationship with serum homocysteine and B-vitamins levels in a sample of Chinese and Malays subjects in UPM, Serdang. One hundred subjects were randomly selected from among the university population. Folate, vitamin B12, B6, and homocysteine levels were determined using MBA, ECLIA, and HPLC, respectively. PCR coupled with HinfI digestion was used for detection of MTHFR C677T polymorphism. The frequency of T allele was higher in the Chinese subjects (0.40) compared to the Malay (0.14). Folate, vitamin B12 and B6 levels were highest in the wild genotype in both ethnic groups. Subjects with heterozygous and homozygous genotype showed the highest homocysteine levels. The serum folate and homocysteine were mainly affected by homozygous genotype. MTHFR C677T polymorphism plays an important role in influencing the folate and homocysteine metabolism.

  3. Dissecting the Catalytic Mechanism of Betaine-Homocysteine S-Methyltransferase Using Intrinsic Tryptophan Fluorescence and Site-Directed Mutagenesis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Castro, C.; Gratson, A.A.; Evans, J.C.

    2010-03-05

    Betaine-homocysteine S-methyltransferase (BHMT) is a zinc-dependent enzyme that catalyzes the transfer of a methyl group from glycine betaine (Bet) to homocysteine (Hcy) to form dimethylglycine (DMG) and methionine (Met). Previous studies in other laboratories have indicated that catalysis proceeds through the formation of a ternary complex, with a transition state mimicked by the inhibitor S-({delta}-carboxybutyl)-l-homocysteine (CBHcy). Using changes in intrinsic tryptophan fluorescence to determine the affinity of human BHMT for substrates, products, or CBHcy, we now demonstrate that the enzyme-substrate complex reaches its transition state through an ordered bi-bi mechanism in which Hcy is the first substrate to bind andmore » Met is the last product released. Hcy, Met, and CBHcy bind to the enzyme to form binary complexes with K{sub d} values of 7.9, 6.9, and 0.28 {micro}M, respectively. Binary complexes with Bet and DMG cannot be detected with fluorescence as a probe, but Bet and DMG bind tightly to BHMT-Hcy to form ternary complexes with K{sub d} values of 1.1 and 0.73 {micro}M, respectively. Mutation of each of the seven tryptophan residues in human BHMT provides evidence that the enzyme undergoes two distinct conformational changes that are reflected in the fluorescence of the enzyme. The first is induced when Hcy binds, and the second, when Bet binds. As predicted by the crystal structure of BHMT, the amino acids Trp44 and Tyr160 are involved in binding Bet, and Glu159 in binding Hcy. Replacing these residues by site-directed mutagenesis significantly reduces the catalytic efficiency (V{sub max}/K{sub m}) of the enzyme. Replacing Tyr77 with Phe abolishes enzyme activity.« less

  4. Total Homocysteine Is Associated With White Matter Hyperintensity Volume

    PubMed Central

    Wright, Clinton B.; Paik, Myunghee C.; Brown, Truman R.; Stabler, Sally P.; Allen, Robert H.; Sacco, Ralph L.; DeCarli, Charles

    2005-01-01

    Background Total homocysteine (tHcy) has been implicated as a risk factor for stroke and dementia, but the mechanism is unclear. White matter hyperintensities may be a risk factor for both, but studies of the relationship between tHcy and quantitative measures of white matter hyperintensity volume (WMHV) are lacking, especially in minority populations. Methods A community-based sample of 259 subjects with baseline tHcy levels underwent pixel-based quantitative measurement of WMHV. We examined the relationship between tHcy and WMHV adjusting for age, sociodemographics, vascular risk factors, and B12 deficiency. Results Higher levels of tHcy were associated with WMHV adjusting for sociodemographics and vascular risk factors. Conclusions These cross-sectional data provide evidence that tHcy is a risk factor for white matter damage. PMID:15879345

  5. Non-standard amino acid recognition by Escherichia coli leucyl-tRNA synthetase

    NASA Technical Reports Server (NTRS)

    Martinis, S. A.; Fox, G. E.

    1997-01-01

    Recombinant E. coli leucyl-tRNA synthetase was screened for amino acid-dependent pyrophosphate exchange activity using noncognate aliphatic amino acids including norvaline, homocysteine, norleucine, methionine, and homoserine. [32P]-labeled reaction products were separated by thin layer chromatography using a novel solvent system and then quantified by phosphorimaging. Norvaline which differs from leucine by only one methyl group stimulated pyrophosphate exchange activity as did both homocysteine and norleucine to a lesser extent. The KM parameters for leucine and norvaline were measured to be 10 micromoles and 1.5 mM, respectively. Experiments are in progress to determine if norvaline is transferred to tRNA(Leu) and/or edited by a pre- or post-transfer mechanism.

  6. Associations of blood homocysteine concentrations in Arab schizophrenic patients.

    PubMed

    Akanji, A O; Ohaeri, J U; Al-Shammri, S A; Fatania, H R

    2007-09-01

    This study aimed to evaluate the blood homocysteine concentration in Arab patients with schizophrenia and assess its associations with clinical phenotypes of the disease. Two age-matched groups of subjects were studied: (1) Healthy Controls, HC, n=165; (2) patients with schizophrenia, SZ: n=207. Each subject was evaluated with a standard questionnaire for age at disease onset, family history, disease severity and outcome. Plasma homocysteine levels (Hcys) were measured by immunoassay and serum levels of other biochemical parameters were measured by routine Autoanalyzer techniques. Group HC was heavier (body mass index, BMI) while SZ had greater waist-hip ratio (WHR) and plasma Hcys levels. In SZ, there were significant correlations between Hcys and BMI, triglycerides and HDL. Hcys levels in SZ were highest in the younger male patients. Schizophrenic patients have increased blood Hcys levels which correlate with components of the metabolic syndrome. Hcys levels were highest in the younger male patients and were not influenced by prognostic features of the disease.

  7. Handling of the homocysteine S-conjugate of methylmercury by renal epithelial cells: role of organic anion transporter 1 and amino acid transporters.

    PubMed

    Zalups, Rudolfs K; Ahmad, Sarfaraz

    2005-11-01

    Recently, the activity of the organic anion transporter 1 (OAT1) protein has been implicated in the basolateral uptake of inorganic mercuric species in renal proximal tubular cells. Unfortunately, very little is known about the role of OAT1 in the renal epithelial transport of organic forms of mercury, such as methylmercury (CH(3)Hg(+)). Homocysteine (Hcy) S-conjugates of methylmercury [(S)-(3-amino-3-carboxypropylthio)(methyl)mercury (CH(3)Hg-Hcy)] have been identified recently as being potentially important biologically relevant forms of mercury. Thus, the present study was designed to characterize the transport of CH(3)Hg-Hcy in Madin-Darby canine kidney (MDCK) cells (which are derived from the distal nephron) that were transfected stably with the human isoform of OAT1 (hOAT1). Data on saturation kinetics, time dependence, substrate specificity, and temperature dependence demonstrated that CH(3)Hg-Hcy is a transportable substrate of hOAT1. However, substrate-specificity data from the control MDCK cells also showed that CH(3)Hg-Hcy is a substrate of one or more transporter(s) that is/are not hOAT1. Additional findings indicated that at least one amino acid transport system was probably responsible for this transport. It is noteworthy that the activity of amino acid transporters accounted for the greatest level of uptake of CH(3)Hg-Hcy in the hOAT1-expressing cells. Furthermore, rates of survival of the hOAT1-transfected MDCK cells were significantly lower than those of corresponding control MDCK cells when they were exposed to cytotoxic concentrations of CH(3)Hg-Hcy. Collectively, the present data indicate that CH(3)Hg-Hcy is a transportable substrate of OAT1 and amino acid transporters and, thus, is probably a transportable mercuric species taken up in vivo by proximal tubular epithelial cells.

  8. Plasma homocysteine and cerebral small vessel disease as possible mediators between kidney and cognitive functions in patients with diabetes mellitus.

    PubMed

    Sonoda, Mika; Shoji, Tetsuo; Kuwamura, Yukinobu; Okute, Yujiro; Naganuma, Toshihide; Shima, Hideaki; Motoyama, Koka; Morioka, Tomoaki; Mori, Katsuhito; Fukumoto, Shinya; Shioi, Atsushi; Shimono, Taro; Fujii, Hisako; Kabata, Daijiro; Shintani, Ayumi; Emoto, Masanori; Inaba, Masaaki

    2017-06-29

    Cognitive impairment is more prevalent in those with decreased kidney function. We tested a hypothesis that an increased homocysteine and/or cerebral small vessel diseases (SVDs) mediate the link between kidney and cognitive functions in a cross-sectional study in 143 type 2 diabetes patients without diagnosis of dementia or prior stroke. The exposure and outcome variables were estimated glomerular filtration rate (eGFR) and cognitive performance evaluated with Modified Mini-Mental State (3 MS) examination, respectively. The candidate mediators were plasma homocysteine concentration, and SVDs including silent cerebral infarction, cerebral microbleed, periventricular hyperintensity, and deep and subcortical white matter hyperintensity by magnetic resonance imaging. In multiple regression models adjusted for 12 potential confounders, eGFR was positively associated with 3 MS score, inversely with homocysteine, but not significantly with the presence of any type of SVD. The association of eGFR with 3 MS remained significant when each of the SVDs was added to the model, whereas it disappeared when homocysteine was included in place of SVD. Mediation analysis indicated nearly significant mediation of homocysteine (P = 0.062) but no meaningful mediations of SVDs (P = 0.842-0.930). Thus, homocysteine, not SVDs, was shown to be the possible mediator between kidney and cognitive functions in patients with type 2 diabetes mellitus.

  9. Influence of Combined Methionine Synthase (MTR 2756A > G) and Methylenetetrahydrofolate Reductase (MTHFR 677C > T) Polymorphisms to Plasma Homocysteine Levels in Korean Patients with Ischemic Stroke

    PubMed Central

    Kim, Ok Joon; Hong, Sun Pyo; Ahn, Jung Yong; Hong, Seung Ho; Hwang, Tae Sun; Kim, Soo Ok; Yoo, Wangdon; Oh, Doyeun

    2007-01-01

    Purpose Methionine synthase (MTR) and 5,10-methylenetetrahydrofolate reductase (MTHFR) are the main regulatory enzymes for homocysteine metabolism. The present case-control study was conducted to determine whether there is an association between the MTR 2756A > G or MTHFR 677C > T polymorphism and plasma homocysteine concentration in Korean subjects with ischemic stroke. Materials and Methods DNA samples of 237 patients who had an ischemic stroke and 223 age and sex-matched controls were studied. MTR 2756A > G and MTHFR 677C > T genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results Frequencies of mutant alleles for MTR and MTHFR polymorphisms were not significantly different between the controls and cases. The patient group, however, had significantly higher homocysteine concentrations of the MTR 2756AA and MTHFR 677TT genotypes than the control group (p = 0.04 for MTR, p = 0.01 for MTHFR). The combined MTR 2756AA and MTHFR 677TT genotype (p = 0.04) and the homocysteine concentrations of the patient group were also higher than those of the controls. In addition, the genotype distribution was significant in the MTHFR 677TT genotype (p = 0.008) and combined MTR 2756AA and MTHFR 677TT genotype (p = 0.03), which divided the groups into the top 20% and bottom 20% based on their homocysteine levels. Conclusion The results of the present study demonstrate that the MTR 2756A > G and MTHFR 677C > T polymorphisms interact with elevated total homocysteine (tHcy) levels, leading to an increased risk of ischemic stroke. PMID:17461517

  10. Homocysteine lowering interventions for preventing cardiovascular events

    PubMed Central

    Martí-Carvajal, Arturo J; Solà, Ivan; Lathyris, Dimitrios; Salanti, Georgia

    2014-01-01

    Background Cardiovascular disease such as coronary artery disease, stroke and congestive heart failure, is a leading cause of death worldwide. A postulated risk factor is elevated circulating total homocysteine (tHcy) levels which is influenced mainly by blood levels of cyanocobalamin (vitamin B12), folic acid (vitamin B9) and pyridoxine (vitamin B6). There is uncertainty regarding the strength of association between tHcy and the risk of cardiovascular disease. Objectives To assess the clinical effectiveness of homocysteine-lowering interventions (HLI) in people with or without pre-existing cardiovascular disease. Search methods We searched The Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library (issue 3 2008), MEDLINE (1950 to August 2008), EMBASE (1988 to August 2008), and LILACS (1982 to September 2, 2008). We also searched in Allied and Complementary Medicine (AMED; 1985 to August 2008), ISI Web of Science (1993 to August 2008), and the Cochrane Stroke Group Specialised Register (April 2007). We hand searched pertinent journals and the reference lists of included papers. We also contacted researchers in the field. There was no language restriction in the search. Selection criteria We included randomised clinical trials (RCTs) assessing the effects of HLI for preventing cardiovascular events with a follow-up period of 1 year or longer. We considered myocardial infarction and stroke as the primary outcomes. We excluded studies in patients with end-stage renal disease. Data collection and analysis We independently performed study selection, risk of bias assessment and data extraction. We estimated relative risks (RR) for dichotomous outcomes. We measured statistical heterogeneity using I2. We used a random-effects model to synthesise the findings. Main results We included eight RCTs involving 24,210 participants with a low risk of bias in general terms. HLI did not reduce the risk of non-fatal or fatal myocardial infarction, stroke, or

  11. Effects of homocysteine lowering with B vitamins on cognitive aging: meta-analysis of 11 trials with cognitive data on 22,000 individuals12345

    PubMed Central

    Clarke, Robert; Bennett, Derrick; Parish, Sarah; Lewington, Sarah; Skeaff, Murray; Eussen, Simone JPM; Lewerin, Catharina; Stott, David J; Armitage, Jane; Hankey, Graeme J; Lonn, Eva; Spence, J David; Galan, Pilar; de Groot, Lisette C; Halsey, Jim; Dangour, Alan D; Collins, Rory; Grodstein, Francine

    2014-01-01

    Background: Elevated plasma homocysteine is a risk factor for Alzheimer disease, but the relevance of homocysteine lowering to slow the rate of cognitive aging is uncertain. Objective: The aim was to assess the effects of treatment with B vitamins compared with placebo, when administered for several years, on composite domains of cognitive function, global cognitive function, and cognitive aging. Design: A meta-analysis was conducted by using data combined from 11 large trials in 22,000 participants. Domain-based z scores (for memory, speed, and executive function and a domain-composite score for global cognitive function) were available before and after treatment (mean duration: 2.3 y) in the 4 cognitive-domain trials (1340 individuals); Mini-Mental State Examination (MMSE)–type tests were available at the end of treatment (mean duration: 5 y) in the 7 global cognition trials (20,431 individuals). Results: The domain-composite and MMSE-type global cognitive function z scores both decreased with age (mean ± SE: −0.054 ± 0.004 and −0.036 ± 0.001/y, respectively). Allocation to B vitamins lowered homocysteine concentrations by 28% in the cognitive-domain trials but had no significant effects on the z score differences from baseline for individual domains or for global cognitive function (z score difference: 0.00; 95% CI: −0.05, 0.06). Likewise, allocation to B vitamins lowered homocysteine by 26% in the global cognition trials but also had no significant effect on end-treatment MMSE-type global cognitive function (z score difference: −0.01; 95% CI: −0.03, 0.02). Overall, the effect of a 25% reduction in homocysteine equated to 0.02 y (95% CI: −0.10, 0.13 y) of cognitive aging per year and excluded reductions of >1 mo per year of treatment. Conclusion: Homocysteine lowering by using B vitamins had no significant effect on individual cognitive domains or global cognitive function or on cognitive aging. PMID:24965307

  12. Reconsidering the relation between serum homocysteine and red blood cell distribution width: a cross-sectional study of a large cohort.

    PubMed

    Margalit, Ili; Cohen, Eytan; Goldberg, Elad; Krause, Ilan

    2018-07-01

    In a recent small sample study, red blood cell distribution width (RDW) was suggested as a predictor of homocysteine levels. The current study was aimed to reexamine this association in a large scale sample. A retrospective cross-sectional study of healthy adults, conducted at Rabin Medical Center, during 2000-2014. Data were retrieved from the medical charts and a logistic regression controlling for interfering factors was carried out. Sensitivity analysis was implemented by exclusion of individuals with anaemia. Five thousand, five hundred fifty-four healthy individuals were included. Mean serum homocysteine level was 10.10 (SD 2.72) μmol/L. 34.4% of the study population had a homocysteine level higher than the upper limit of normal (10.8 μmol/L). Homocysteine showed no association with RDW (OR 1.00; 95% CI 0.97-1.03), but increased with age (OR 1.05; 95% CI 1.04-1.06) and decreased with a rise in haemoglobin (OR 0.77; 95% CI 0.71-0.83), and in the mean corpuscular volume (OR 0.86; 95% CI 0.85-0.88). Exclusion of individuals with anaemia did not reveal an association between homocysteine and RDW but found a somewhat smaller association between haemoglobin and RDW [OR 0.82; 95% CI 0.73-0.91]. In our large scale sample we did not find an association between RDW and serum homocysteine.

  13. N-acetylcysteine neither lowers plasma homocysteine concentrations nor improves brachial artery endothelial function in cardiac transplant recipients.

    PubMed

    Miner, S E S; Cole, D E C; Evrovski, J; Forrest, Q; Hutchison, S J; Holmes, K; Ross, H J

    2002-05-01

    N-acetylcysteine is a novel antioxidant that has been reported to reduce plasma homocysteine concentrations and improve endothelial function. Cardiac transplant recipients have a high incidence of coronary endothelial dysfunction and hyperhomocysteinemia, both of which may lead to the development of transplantation coronary artery disease. It was hypothesized that N-acetylcysteine would reduce plasma homocysteine concentrations and improve brachial endothelial function in cardiac transplant recipients. A cohort of stable cardiac transplant recipients was recruited from the outpatient clinic at the Toronto General Hospital, Toronto, Ontario. Brachial artery endothelial functions were studied according to standard techniques to determine flow-mediated dilation of the brachial artery. Plasma homocysteine concentrations were assayed using high performance liquid chromatography with electrochemical detection and pulsed integrated amperometry. After baseline testing, patients were treated in an unblinded fashion with N-acetylcysteine 500 mg/day. After 10 weeks of therapy, patients returned for follow-up endothelial function and homocysteine testing. Thirty-one patients were initially enrolled. Two patients withdrew due to excessive gastrointestinal upset. Two patients did not return for follow-up testing. The remaining 27 patients tolerated the treatment well. At baseline, 85% of the patients had hyperhomocysteinemia (greater than 15 mol/L) with a mean plasma concentration of 18.6 4.7 mol/L. No changes in homocysteine concentrations were seen at follow-up. At baseline, the average flow-mediated dilation was only 4.7 6.3%. No changes were seen at follow-up. Hyperhomocysteinemia and brachial endothelial dysfunction are common in stable cardiac transplant recipients and are unaffected by supplementation with N-acetylcysteine.

  14. Improved Sp1 and Betaine Homocysteine-S-Methyltransferase Expression and Homocysteine Clearance Are Involved in the Effects of Zinc on Oxidative Stress in High-Fat-Diet-Pretreated Mice.

    PubMed

    Wu, Li; Zhou, Xihong; Li, Tiejun; He, Juyun; Huang, Linli; Ouyang, Zicheng; He, Liuqin; Wei, Tao; He, Qinghua

    2017-12-04

    Zinc plays a role in alleviating oxidative stress. However, the related mechanisms remain to be further elucidated. The present study was conducted to investigate whether the recovery of oxidative stress in high-fat-diet (HFD)-pretreated mice was affected by zinc. Male mice received either an HFD or a low-fat-diet (LFD) for 8 weeks. Then, the mice fed with HFD and LFD were both assigned to either a control diet (30 mg zinc, ZD) or a no-added zinc diet (NZD) for an additional 4 weeks. The results showed that after feeding with NZD for 4 weeks, the HFD-pretreated mice had the highest plasma glucose and insulin concentrations, while had the lowest CuZn-SOD and glutathione concentrations. Moreover, after feeding with NZD for 4 weeks, the HFD-pretreated mice had the highest hepatic ROS and homocysteine concentrations, while had the lowest glutathione and methionine concentrations. Furthermore, the HFD-pretreated mice fed with NZD for 4 weeks had the lowest gene and protein expression of betaine homocysteine-S-methyltransferase (BHMT), cystathionine β-synthase, and Sp1. The results suggested that zinc was critical for oxidative stress alleviation and homocysteine clearance in HFD-pretreated mice. It was further elucidated that improved Sp1 and BHMT expression are involved in the effects of zinc on oxidative stress.

  15. The Contrasting Relationships between Betaine and Homocysteine in Two Clinical Cohorts are Associated with Plasma Lipids and Drug Treatments

    PubMed Central

    Lever, Michael; George, Peter M.; Atkinson, Wendy; Elmslie, Jane L.; Slow, Sandy; Molyneux, Sarah L.; Troughton, Richard W.; Richards, A. Mark; Frampton, Christopher M.; Chambers, Stephen T.

    2012-01-01

    Background Urinary betaine excretion positively correlated with plasma homocysteine in outpatients attending a lipid disorders clinic (lipid clinic study). We aimed to confirm this in subjects with established vascular disease. Methods The correlation between betaine excretion and homocysteine was compared in samples collected from subjects 4 months after hospitalization for an acute coronary episode (ACS study, 415 urine samples) and from 158 sequential patients visiting a lipid disorders clinic. Principal findings In contrast to the lipid clinic study, betaine excretion and plasma homocysteine did not correlate in the total ACS cohort. Differences between the patient groups included age, non-HDL cholesterol and medication. In ACS subjects with below median betaine excretion, excretion correlated (using log transformed data) negatively with plasma homocysteine (r = −0.17, p = 0.019, n = 199), with no correlation in the corresponding subset of the lipid clinic subjects. In ACS subjects with above median betaine excretion a positive trend (r = +0.10) between betaine excretion and homocysteine was not significant; the corresponding correlation in lipid clinic subjects was r = +0.42 (p = 0.0001). In ACS subjects, correlations were stronger when plasma non-HDL cholesterol and betaine excretion were above the median, r = +0.20 (p = 0.045); in subjects above median non-HDL cholesterol and below median betaine excretion, r = −0.26 (p = 0.012). ACS subjects taking diuretics or proton pump inhibitors had stronger correlations, negative with lower betaine excretion and positive with higher betaine excretion. Conclusions Betaine excretion correlates with homocysteine in subjects with elevated blood lipids. PMID:22396767

  16. A quantile regression approach can reveal the effect of fruit and vegetable consumption on plasma homocysteine levels.

    PubMed

    Verly, Eliseu; Steluti, Josiane; Fisberg, Regina Mara; Marchioni, Dirce Maria Lobo

    2014-01-01

    A reduction in homocysteine concentration due to the use of supplemental folic acid is well recognized, although evidence of the same effect for natural folate sources, such as fruits and vegetables (FV), is lacking. The traditional statistical analysis approaches do not provide further information. As an alternative, quantile regression allows for the exploration of the effects of covariates through percentiles of the conditional distribution of the dependent variable. To investigate how the associations of FV intake with plasma total homocysteine (tHcy) differ through percentiles in the distribution using quantile regression. A cross-sectional population-based survey was conducted among 499 residents of Sao Paulo City, Brazil. The participants provided food intake and fasting blood samples. Fruit and vegetable intake was predicted by adjusting for day-to-day variation using a proper measurement error model. We performed a quantile regression to verify the association between tHcy and the predicted FV intake. The predicted values of tHcy for each percentile model were calculated considering an increase of 200 g in the FV intake for each percentile. The results showed that tHcy was inversely associated with FV intake when assessed by linear regression whereas, the association was different when using quantile regression. The relationship with FV consumption was inverse and significant for almost all percentiles of tHcy. The coefficients increased as the percentile of tHcy increased. A simulated increase of 200 g in the FV intake could decrease the tHcy levels in the overall percentiles, but the higher percentiles of tHcy benefited more. This study confirms that the effect of FV intake on lowering the tHcy levels is dependent on the level of tHcy using an innovative statistical approach. From a public health point of view, encouraging people to increase FV intake would benefit people with high levels of tHcy.

  17. Homocysteine Lowering by Folate-Rich Diet or Pharmacological Supplementations in Subjects with Moderate Hyperhomocysteinemia

    PubMed Central

    Zappacosta, Bruno; Mastroiacovo, Pierpaolo; Persichilli, Silvia; Pounis, George; Ruggeri, Stefania; Minucci, Angelo; Carnovale, Emilia; Andria, Generoso; Ricci, Roberta; Scala, Iris; Genovese, Orazio; Turrini, Aida; Mistura, Lorenza; Giardina, Bruno; Iacoviello, Licia

    2013-01-01

    Background/Objectives: To compare the efficacy of a diet rich in natural folate and of two different folic acid supplementation protocols in subjects with “moderate” hyperhomocysteinemia, also taking into account C677T polymorphism of 5,10-methylenetetrahydrofolate reductase (MTHFR) gene. Subjects/Methods: We performed a 13 week open, randomized, double blind clinical trial on 149 free living persons with mild hyperhomocyteinemia, with daily 200 μg from a natural folate-rich diet, 200 μg [6S]5-methyltetrahydrofolate (5-MTHF), 200 μg folic acid or placebo. Participants were stratified according to their MTHFR genotype. Results: Homocysteine (Hcy) levels were reduced after folate enriched diet, 5-MTHF or folic acid supplementation respectively by 20.1% (p < 0.002), 19.4% (p < 0.001) and 21.9% (p < 0.001), as compared to baseline levels and significantly as compared to placebo (p < 0.001, p < 0.002 and p < 0.001, respectively for enriched diet, 5-MTHF and folic acid). After this enriched diet and the folic acid supplementation, Hcy in both genotype groups decreased approximately to the same level, with higher percentage decreases observed for the TT group because of their higher pre-treatment value. Similar results were not seen by genotype for 5-MTHF. A significant increase in RBC folate concentration was observed after folic acid and natural folate-rich food supplementations, as compared to placebo. Conclusions: Supplementation with natural folate-rich foods, folic acid and 5-MTHF reached a similar reduction in Hcy concentrations. PMID:23698160

  18. Role of vitamin B6 status on antioxidant defenses, glutathione, and related enzyme activities in mice with homocysteine-induced oxidative stress.

    PubMed

    Hsu, Cheng-Chin; Cheng, Chien-Hsiang; Hsu, Chin-Lin; Lee, Wan-Ju; Huang, Shih-Chien; Huang, Yi-Chia

    2015-01-01

    Vitamin B6 may directly or indirectly play a role in oxidative stress and the antioxidant defense system. The purpose of this study was to examine the associations of vitamin B6 status with cysteine, glutathione, and its related enzyme activities in mice with homocysteine-induced oxidative stress. Four-week-old male BALB/c mice were weighed and divided into one of four dietary treatment groups fed either a normal diet (as a control group and a homocysteine group), a vitamin B6-deficient diet (as a B6-deficient group), or a B6-supplemented diet (a pyridoxine-HCl-free diet supplemented with 14 mg/kg of pyridoxine-HCl, as a B6 supplement group) for 28 days. Homocysteine thiolactone was then added to drinking water in three groups for 21 days to induce oxidative stress. At the end of the study, mice were sacrificed by decapitation and blood and liver samples were obtained. Mice with vitamin B6-deficient diet had the highest homocysteine concentration in plasma and liver among groups. Significantly increased hepatic malondialdehyde levels were observed in the vitamin B6-deficient group. Among homocysteine-treated groups, mice with vitamin B6-deficient diet had the highest plasma glutathione concentration and relatively lower hepatic glutathione concentration. The glutathione peroxidase activities remained relatively stable in plasma and liver whether vitamin B6 was adequate, deficient, or supplemented. Mice with deficient vitamin B6 intakes had an aggravate effect under homocysteine-induced oxidative stress. The vitamin B6-deficient status seems to mediate the oxidative stress in connection with the redistribution of glutathione from liver to plasma, but not further affect glutathione-related enzyme activities in mice with homocysteine-induced oxidative stress.

  19. Homocysteine and Coronary Heart Disease: Meta-analysis of MTHFR Case-Control Studies, Avoiding Publication Bias

    PubMed Central

    Verhoef, Petra; Dötsch-Klerk, Mariska; Lathrop, Mark; Xu, Peng; Nordestgaard, Børge G.; Holm, Hilma; Hopewell, Jemma C.; Saleheen, Danish; Tanaka, Toshihiro; Anand, Sonia S.; Chambers, John C.; Kleber, Marcus E.; Ouwehand, Willem H.; Yamada, Yoshiji; Elbers, Clara; Peters, Bas; Stewart, Alexandre F. R.; Reilly, Muredach M.; Thorand, Barbara; Yusuf, Salim; Engert, James C.; Assimes, Themistocles L.; Kooner, Jaspal; Danesh, John; Watkins, Hugh; Samani, Nilesh J.

    2012-01-01

    Background Moderately elevated blood levels of homocysteine are weakly correlated with coronary heart disease (CHD) risk, but causality remains uncertain. When folate levels are low, the TT genotype of the common C677T polymorphism (rs1801133) of the methylene tetrahydrofolate reductase gene (MTHFR) appreciably increases homocysteine levels, so “Mendelian randomization” studies using this variant as an instrumental variable could help test causality. Methods and Findings Nineteen unpublished datasets were obtained (total 48,175 CHD cases and 67,961 controls) in which multiple genetic variants had been measured, including MTHFR C677T. These datasets did not include measurements of blood homocysteine, but homocysteine levels would be expected to be about 20% higher with TT than with CC genotype in the populations studied. In meta-analyses of these unpublished datasets, the case-control CHD odds ratio (OR) and 95% CI comparing TT versus CC homozygotes was 1.02 (0.98–1.07; p = 0.28) overall, and 1.01 (0.95–1.07) in unsupplemented low-folate populations. By contrast, in a slightly updated meta-analysis of the 86 published studies (28,617 CHD cases and 41,857 controls), the OR was 1.15 (1.09–1.21), significantly discrepant (p = 0.001) with the OR in the unpublished datasets. Within the meta-analysis of published studies, the OR was 1.12 (1.04–1.21) in the 14 larger studies (those with variance of log OR<0.05; total 13,119 cases) and 1.18 (1.09–1.28) in the 72 smaller ones (total 15,498 cases). Conclusions The CI for the overall result from large unpublished datasets shows lifelong moderate homocysteine elevation has little or no effect on CHD. The discrepant overall result from previously published studies reflects publication bias or methodological problems. Please see later in the article for the Editors' Summary PMID:22363213

  20. The association between high plasma homocysteine levels and lower bone mineral density in Slovak women: the impact of vegetarian diet.

    PubMed

    Krivosíková, Zora; Krajcovicová-Kudlácková, Marica; Spustová, Viera; Stefíková, Kornélia; Valachovicová, Martina; Blazícek, Pavel; Nĕmcová, Tatiana

    2010-04-01

    A long-term vegetarian diet is generally poor in vitamin B group. The lack of vitamin B(12) together with vitamin B(6) and folate deficiency is closely related to homocysteine metabolism. Hyperhomocysteinemia was found to be associated with increased bone turnover markers and increased fracture risk. Thus, hyperhomocysteinemia, vitamin B(12) and folate deficiency may be regarded as novel risk factors for micronutrient deficiency-related osteoporosis. To assess the possible impact of a vegetarian diet on bone mineral density in cohort of Slovak vegetarian women. Fasting serum glucose, albumin, calcium, phosphorous and creatinine as well as bone markers, serum vitamin B(12), folate and plasma levels of total homocysteine were assessed in two nutritional groups (vegetarians vs. nonvegetarians) of apparently healthy women (age range 20-70 years). Bone mineral density of the femoral neck, trochanter, total femur and lumbar spine was measured in all subjects. Vegetarians had a significantly lower weight (p < 0.05), higher PTH (p < 0.01) and homocysteine (p < 0.001). Vitamin B(12) was significantly higher in nonvegetarians (p < 0.001). No differences were observed in folate levels. Univariate analysis showed significant association between homocysteine and B(12) (p < 0.01), folate (p < 0.001), creatinine (p < 0.001), total proteins (p < 0.049), age (p < 0.001) and vegetarian food intake (p < 0.001). Vegetarians had a significantly lower TrFBMD (p < 0.05) and ToFBMD (p < 0.05). Age and CTx were significant predictors in all sites of measured BMD and PTH. A strong correlation between homocysteine and FNBMD (r = -0.2009, p < 0.002), TrFBMD (r = -0.1810, p < 0.004) and ToFBMD (r = -0.2225, p < 0.001) was found in all subjects. Homocysteine is one of the predictors of bone mineral density, and hyperhomocysteinemia is associated with lower bone mineral density. In healthy adults, homocysteine levels are dependent on age as well as on nutritional habits. Thus, elderly women on a

  1. Vitamin B-12 status is not associated with plasma homocysteine in parents and their preschool children: lacto-ovo, lacto, and ovo vegetarians and omnivores.

    PubMed

    Yen, Chin-En; Yen, Chi-Hua; Cheng, Chien-Hsiang; Huang, Yi-Chia

    2010-02-01

    Vegetarians may be at risk of certain nutrient deficiencies, particularly vitamin B-12. Vitamin B-12 deficiency may increase plasma homocysteine concentration and thus may potentially increase the risk of cardiovascular disease in vegetarians. The purpose of this study was to assess and compare plasma homocysteine and vitamin B-12 status in vegetarian and omnivorous preschool children and their parents. In addition, the association between parents' and children's homocysteine and vitamin B-12 concentration was also examined. Fifty-six omnivores (28 preschool children and one of their parents), 34 lacto-ovo vegetarians (16 parents and 18 children), 5 ovo vegetarians (2 parents and 3 children), 1 lacto vegetarian parent, and 2 vegan parents were enrolled in this study. The mean age of preschool children was 5.1 +/- 1.3 years and that of their parent was 35.4 +/- 4.2 years. Nutrient intakes were recorded using 3-day dietary records. Fasting venous blood samples were obtained to measure serum creatinine, high-sensitivity C-reactive protein, hematological parameters, plasma homocysteine, serum folate, and vitamin B-12 concentrations. There was no significant difference in dietary folate intake between vegetarian and omnivores within parent and child groups. The mean plasma homocysteine level of vegetarian parents and their children was in the physiological range, and they had slightly but not significantly higher plasma homocysteine levels than omnivores. Omnivorous parents and their children had significantly higher vitamin B-12 intake than vegetarian participants but similar serum vitamin B-12 concentrations. Plasma homocysteine concentration was significantly and negatively associated with only serum folate levels (beta = -0.15) and dietary vitamin B-12 intake (beta = -0.05) in the omnivorous parents after adjusting for age, gender, body mass index, and serum creatinine. Vegetarian parents and their preschool children had a lower vitamin B-12 intake than omnivorous

  2. Methylenetetrahydrofolate reductase gene, homocysteine and coronary artery disease: the A1298C polymorphism does matter. Inferences from a case study (Madeira, Portugal).

    PubMed

    Freitas, Ana I; Mendonça, Isabel; Guerra, Graça; Brión, Maria; Reis, Roberto P; Carracedo, Angel; Brehm, António

    2008-01-01

    Elevated levels of plasma homocysteine, an independent risk factor and a strong predictor of mortality in patients with coronary artery disease (CAD), can result from nutritional deficiencies or genetic errors, including methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms. The contribution of these polymorphisms in the development of CAD remains controversial. We analysed the impact of MTHFR C677T and A1298C on fasting homocysteine and CAD in 298 CAD patients proved by angiography and 510 control subjects from the Island of Madeira (Portugal). After adjustment for other risk factors, plasma homocysteine remained independently correlated with CAD. Serum homocysteine was significantly higher in individuals with 677TT and 1298AA genotypes. There was no difference in the distribution of MTHFR677 genotypes between cases and controls but a significant increase in 1298AA prevalence was found in CAD patients. In spite of the clear effect of C677T mutation on elevated homocysteine levels we only found an association between 1298AA genotype and CAD in this population. The simultaneous presence of 677CT and 1298AA genotypes provides a significant risk of developing the disease, while the 1298AC genotype, combined with 677CC, shows a significant trend towards a decrease in CAD occurrence. The data shows an independent association between elevated levels of homocysteine and CAD. Both MTHFR polymorphisms are associated with increased fasting homocysteine (677TT and 1298AA genotypes), but only the 1298AA variant shows an increased prevalence in CAD group. Odds ratio seem to indicate that individuals with the MTHFR 1298AA genotype and the 677CT/1298AA compound genotype had a 1.6-fold increased risk for developing CAD suggesting a possible association of MTHFR polymorphisms with the risk of CAD in Madeira population.

  3. Vitamin B-6 Supplementation Could Mediate Antioxidant Capacity by Reducing Plasma Homocysteine Concentration in Patients with Hepatocellular Carcinoma after Tumor Resection

    PubMed Central

    Cheng, Shao-Bin; Lin, Ping-Ting; Liu, Hsiao-Tien; Peng, Yi-Shan; Huang, Shih-Chien

    2016-01-01

    Vitamin B-6 has a strong antioxidative effect. It would be useful to determine whether vitamin B-6 supplementation had effects on antioxidant capacities in patients with hepatocellular carcinoma (HCC) who had recently undergone tumor resection. Thirty-three HCC patients were randomly assigned to either the placebo (n = 16) group or the vitamin B-6 50 mg/d (n = 17) group for 12 weeks. Plasma pyridoxal 5′-phosphate, homocysteine, indicators of oxidative stress, and antioxidant capacities were measured. Plasma homocysteine in the vitamin B-6 group was significantly decreased at week 12, while the level of trolox equivalent antioxidant capacity (TEAC) was significantly increased at the end of the intervention period. Vitamin B-6 supplementation had a significant reducing effect on the change of plasma homocysteine (β = −2.4, p = 0.02) but not on the change of TEAC level after adjusting for potential confounders. The change of plasma homocysteine was significantly associated with the change of TEAC after adjusting for potential confounders (β = −162.0, p = 0.03). Vitamin B-6 supplementation seemed to mediate antioxidant capacity via reducing plasma homocysteine rather than having a direct antioxidative effect in HCC patients who had recently undergone tumor resection. The clinical trial number is NCT01964001, ClinicalTrials.gov. PMID:27051670

  4. Homocysteine in renovascular complications: hydrogen sulfide is a modulator and plausible anaerobic ATP generator.

    PubMed

    Sen, Utpal; Pushpakumar, Sathnur B; Amin, Matthew A; Tyagi, Suresh C

    2014-09-15

    Homocysteine (Hcy) is a non-protein amino acid derived from dietary methionine. High levels of Hcy, known as hyperhomocysteinemia (HHcy) is known to cause vascular complications. In the mammalian tissue, Hcy is metabolized by transsulfuration enzymes to produce hydrogen sulfide (H2S). H2S, a pungent smelling gas was previously known for its toxic effects in the central nervous system, recent studies however has revealed protective effects in a variety of diseases including hypertension, diabetes, inflammation, atherosclerosis, and renal disease progression and failure. Interestingly, under stress conditions including hypoxia, H2S can reduce metabolic demand and also act as a substrate for ATP production. This review highlights some of the recent advances in H2S research as a potential therapeutic agent targeting renovascular diseases associated with HHcy. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. [Total homocysteine levels in children with diabetes type 1. Conditional factors].

    PubMed

    Martínez Laborda, S; Salazar García-Blanco, M I; Rodríguez Rigual, M; Baldellou Vázquez, A

    2008-03-01

    To measure the plasma levels of total homocysteine (tHcy) in children with type I diabetes mellitus and their relationship with the control of the disease. We studied a total of 46 patients with ages between 4 and 19 years. The analyzed variables were: sex, age, puberty stage by Tanner, BMI, years of evolution of the illness, self-monitoring, associated diseases, tHcy, folic acid, vitamin B12, glycosylated haemoglobin (HbA1c), lipid profile and renal function. The mean tHcy was of 5.48 +/- 1,64 microm/l, similar to that in our control population. There was a positive correlation with tHcy when analyzing the puberty stage by the Tanner scale. The years of evolution of diabetes varied between 0.4 and 15, with a mean of 5.77 +/- 3.69, with no correlation with tHcy. The glycosylated haemoglobin mean was 7.35 %, with no correlation with tHcy. The levels of folic acid and vitamin B12 were similar to the control population. The lipid profile of our patients was normal, with no association with tHcy levels. There was no correlation between GFR and tHcy. A clinically correct control of children with diabetes mellitus type 1, appears to ensure a normal total homocysteinemia, with no significant differences with the healthy individuals of the same age and social environment.

  6. Vitamin D, Homocysteine, and Folate in Subcortical Vascular Dementia and Alzheimer Dementia.

    PubMed

    Moretti, Rita; Caruso, Paola; Dal Ben, Matteo; Conti, Corrado; Gazzin, Silvia; Tiribelli, Claudio

    2017-01-01

    Dementia is a worldwide health problem which affects millions of patients; Alzheimer's disease (AD) and subcortical vascular dementia (sVAD) are the two most frequent forms of its presentation. As no definite therapeutic options have been discovered, different risk factors for cognitive impairment have been searched for potential therapies. This report focuses on the possible evidence that vitamin D deficiency and hyper-homocysteinemia can be considered as two important factors for the development or the progression of neurodegenerative or vascular pathologies. To this end, we assessed: the difference in vascular risk factors and vitamin D-OH25 levels among groups of sVAD, AD, and healthy age-matched controls; the association of folate, B12, homocysteine, and vitamin D with sVAD/AD and whether a deficiency of vitamin D and an increment in homocysteine levels may be related to neurodegenerative or vessel damages. The commonly-considered vascular risk factors were collected in 543 patients and compared with those obtained from a healthy old volunteer population. ANOVA group comparison showed that vitamin D deficiency was present in demented cases, as well as low levels of folate and high levels of homocysteine, more pronounced in sVAD cases. The statistical models we employed, with regression models built, and adjustments for biochemical, demographic and neuropsychiatric scores, confirmed the association between the three measures (folate decrease, hyperhomocysteinemia and vitamin D decrease) and dementia, more pronounced in sVAD than in AD.

  7. Homocysteine, folate, and vitamin B12 levels and vertebral fracture risk in postmenopausal women.

    PubMed

    El Maghraoui, Abdellah; Ghozlani, Imad; Mounach, Aziza; Rezqi, Asmaa; Oumghar, Khalid; Achemlal, Lahsen; Bezza, Ahmed; Ouzzif, Zhor

    2012-01-01

    The objective of this study was to examine the influence of homocysteine, vitamin B(12), and folate on the prevalence of asymptomatic osteoporotic vertebral fractures (VFs) using vertebral fracture assessment (VFA) in postmenopausal women. The study cohort consisted of 188 consecutive postmenopausal women (mean age, weight, and body mass index of 57.9 ± 8.5 [41-91]yr, 74.4 ± 13.5 [38-150]kg, and 30.4 ± 5.2 [17.1-50.7]kg/m(2), respectively). Lateral VFA images and scans of the lumbar spine and proximal femur were obtained using a Lunar Prodigy Vision densitometer (GE Healthcare Inc., Waukesha, WI). VFs were defined using a combination of Genant's semiquantitative approach and morphometry. Fifty-eight (30.9%) patients had densitometric osteoporosis. VFs were identified using VFA in 76 (40.4%) patients: 61 women had grade 1 VFs and 15 had grade 2 or 3 VFs. No statistical difference was shown between the 3 groups (absence of VFs, VFs grade 1, and VFs grade 2/3) concerning the biological parameters. Comparison of patients according to quartiles of homocysteine levels showed that women in the highest quartile were older and had a lower bone mineral density (BMD); however, the prevalence of VFs was not statistically different from that of women in the other quartile groups. Stepwise regression analysis showed that homocysteine was not independently associated with the presence of VFs, which was mainly related to the osteoporotic status. Although a weak association was observed between hyperhomocysteinemia and low BMD and a trend to higher prevalence of grade 2/3 VFs was observed, our study did not confirm that homocysteine, vitamin B(12), and folate status are important determinants of prevalent asymptomatic VFs in postmenopausal women. Copyright © 2012 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.

  8. Treatment of depression: time to consider folic acid and vitamin B12.

    PubMed

    Coppen, Alec; Bolander-Gouaille, Christina

    2005-01-01

    We review the findings in major depression of a low plasma and particularly red cell folate, but also of low vitamin B12 status. Both low folate and low vitamin B12 status have been found in studies of depressive patients, and an association between depression and low levels of the two vitamins is found in studies of the general population. Low plasma or serum folate has also been found in patients with recurrent mood disorders treated by lithium. A link between depression and low folate has similarly been found in patients with alcoholism. It is interesting to note that Hong Kong and Taiwan populations with traditional Chinese diets (rich in folate), including patients with major depression, have high serum folate concentrations. However, these countries have very low life time rates of major depression. Low folate levels are furthermore linked to a poor response to antidepressants, and treatment with folic acid is shown to improve response to antidepressants. A recent study also suggests that high vitamin B12 status may be associated with better treatment outcome. Folate and vitamin B12 are major determinants of one-carbon metabolism, in which S-adenosylmethionine (SAM) is formed. SAM donates methyl groups that are crucial for neurological function. Increased plasma homocysteine is a functional marker of both folate and vitamin B12 deficiency. Increased homocysteine levels are found in depressive patients. In a large population study from Norway increased plasma homocysteine was associated with increased risk of depression but not anxiety. There is now substantial evidence of a common decrease in serum/red blood cell folate, serum vitamin B12 and an increase in plasma homocysteine in depression. Furthermore, the MTHFR C677T polymorphism that impairs the homocysteine metabolism is shown to be overrepresented among depressive patients, which strengthens the association. On the basis of current data, we suggest that oral doses of both folic acid (800 microg daily

  9. Effect of Combination Folic Acid, Vitamin B6 , and Vitamin B12 Supplementation on Fracture Risk in Women: A Randomized, Controlled Trial.

    PubMed

    Stone, Katie L; Lui, Li-Yung; Christen, William G; Troen, Aron M; Bauer, Douglas C; Kado, Deborah; Schambach, Christopher; Cummings, Steven R; Manson, JoAnn E

    2017-12-01

    Epidemiologic studies have demonstrated an association of elevated plasma homocysteine levels with greater bone resorption and fracture risk. Vitamins B 12 , B 6 , and folic acid are cofactors in homocysteine metabolism, and supplementation with B vitamins is effective in lowering homocysteine levels in humans. However, randomized trials of supplemental B vitamins for reduction of fracture risk have been limited. Therefore, we performed an ancillary study to the Women's Antioxidant and Folic Acid Cardiovascular Study (WAFACS), a large randomized trial of women with preexisting cardiovascular disease or three or more coronary risk factors, to test whether a daily B vitamin intervention including folic acid (2.5 mg/day), vitamin B 6 (50 mg/day), and vitamin B 12 (1 mg/day) reduces nonspine fracture risk over 7.3 years of treatment and follow-up. Among 4810 women, we confirmed 349 nonspine fracture cases by centralized review of medical records. In a substudy of 300 women (150 in treatment group and 150 controls) with paired plasma samples at randomization and follow-up (7.3 years later), we measured two bone turnover markers, including C-terminal cross-linking telopeptide of type I collagen (CTX) and intact type I procollagen N-propeptide (P1NP). In Cox proportional hazards models based on intention-to-treat, we found no significant effects of B vitamin supplementation on nonspine fracture risk (relative hazard = 1.08; 95% confidence interval, 0.88 to 1.34). In a nested case-cohort analysis, there were no significant effects of B vitamins on fracture risk among women with elevated plasma homocysteine levels, or low levels of vitamins B 12 or B 6 , or folate at baseline. Furthermore, treatment with B vitamins had no effect on change in markers of bone turnover. We found no evidence that daily supplementation with B vitamins reduces fracture risk or rates of bone metabolism in middle-aged and older women at high risk of cardiovascular disease. © 2017

  10. A coupled photometric assay for characterization of S-adenosyl-l-homocysteine hydrolases in the physiological hydrolytic direction.

    PubMed

    Kailing, Lyn L; Bertinetti, Daniela; Herberg, Friedrich W; Pavlidis, Ioannis V

    2017-10-25

    S-Adenosyl-l-homocysteine hydrolases (SAHases) are important metabolic enzymes and their dysregulation is associated with some severe diseases. In vivo they catalyze the hydrolysis of S-adenosyl-l-homocysteine (SAH), the by-product of methylation reactions in various organisms. SAH is a potent inhibitor of methyltransferases, thus its removal from the equilibrium is an important requirement for methylation reactions. SAH hydrolysis is also the first step in the cellular regeneration process of the methyl donor S-adenosyl-l-methionine (SAM). However, in vitro the equilibrium lies towards the synthetic direction. To enable characterization of SAHases in the physiologically relevant direction, we have developed a coupled photometric assay that shifts the equilibrium towards hydrolysis by removing the product adenosine, using a high affinity adenosine kinase (AK). This converts adenosine to AMP and thereby forms equimolar amounts of ADP, which is phosphorylated by a pyruvate kinase (PK), in turn releasing pyruvate. The readout of the assay is the consumption of NADH during the lactate dehydrogenase (LDH) catalyzed reduction of pyruvate to lactic acid. The applicability of the assay is showcased for the determination of the kinetic constants of an SAHase from Bradyrhizobium elkanii (K M,SAH 41±5μM, v max,SAH 25±1μM/min with 0.13mg/mL enzyme). This assay is a valuable tool for in vitro characterization of SAHases with biotechnological potential, and for monitoring SAHase activity in diagnostics. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Folic acid fortification: why not vitamin B12 also?

    PubMed

    Selhub, Jacob; Paul, Ligi

    2011-01-01

    Folic acid fortification of cereal grains was introduced in many countries to prevent neural tube defect occurrence. The metabolism of folic acid and vitamin B12 intersect during the transfer of the methyl group from 5-methyltetrahydrofolate to homocysteine catalyzed by B12-dependent methioine synthase. Regeneration of tetrahydrofolate via this reaction makes it available for synthesis of nucleotide precursors. Thus either folate or vitamin B12 deficiency can result in impaired cell division and anemia. Exposure to extra folic acid through fortification may be detrimental to those with vitamin B12 deficiency. Among participants of National Health And Nutrition Examination Survey with low vitamin B12 status, high serum folate (>59 nmol/L) was associated with higher prevalence of anemia and cognitive impairment when compared with normal serum folate. We also observed an increase in the plasma concentrations of total homocysteine and methylmalonic acid (MMA), two functional indicators of vitamin B12 status, with increase in plasma folate under low vitamin B12 status. These data strongly imply that high plasma folate is associated with the exacerbation of both the biochemical and clinical status of vitamin B12 deficiency. Hence any food fortification policy that includes folic acid should also include vitamin B12. Copyright © 2011 International Union of Biochemistry and Molecular Biology, Inc.

  12. A molecular model for the active site of S-adenosyl- l-homocysteine hydrolase

    NASA Astrophysics Data System (ADS)

    Yeh, Jerry C.; Borchardt, Ronald T.; Vedani, Angelo

    1991-06-01

    S-adenosyl- l-homocysteine hydrolase (AdoHcy hydrolase, EC 3.3.1.1.), a specific target for antiviral drug design, catalyzes the hydrolysis of AdoHcy to adenosine (Ado) and homocysteine (Hcy) as well as the synthesis of AdoHcy from Ado and Hcy. The enzyme isolated from different sources has been shown to contain tightly bound NAD+. Based on the 2.0 Å-resolution X-ray crystal structure of dogfish lactate dehydrogenase (LDH), which is functionally homologous to AdoHcy hydrolase, and the primary sequence of rat liver AdoHcy hydrolase, we have derived a molecular model of an extended active site for AdoHcy hydrolase. The computational mutation was performed using the software MUTAR (Yeh et al., University of Kansas, Lawrence), followed by molecular mechanics optimizations using the programs AMBER (Singh et al., University of California, San Francisco) and YETI (Vedani, University of Kansas). Solvation of the model structure was achieved by use of the program SOLVGEN (Jacober, University of Kansas); 56 water molecules were explicitly included in all refinements. Some of these may be involved in the catalytic reaction. We also studied a model of the complex of AdoHcy hydrolase with NAD+, as well as the ternary complexes of the redox reaction catalyzed by AdoHcy hydrolase and has been used to differentiate the relative binding strength of inhibitors.

  13. Effects of homocysteine and its related compounds on oxygen consumption of the rat heart tissue homogenate: the role of different gasotransmitters.

    PubMed

    Uzelac, Jovana Jakovljević; Stanić, Marina; Krstić, Danijela; Čolović, Mirjana; Djurić, Dragan

    2017-11-29

    The objective of this study was to investigate in vitro effects of 10 µM DL-homocysteine (DL-Hcy), DL-homocysteine thiolactone-hydrochloride (DL-Hcy TLHC), and L-homocysteine thiolactone-hydrochloride (L-Hcy TLHC) on the oxygen consumption of rat heart tissue homogenate, as well as the involvement of the gasotransmitters NO, H 2 S and CO in the effects of the most toxic homocysteine compound, DL-Hcy TLHC. The possible contribution of the gasotransmitters in these effects was estimated by using the appropriate inhibitors of their synthesis (N ω -nitro-L-arginine methyl ester (L-NAME), DL-propargylglycine (DL-PAG), and zinc protoporphyrin IX (ZnPPR IX), respectively). The oxygen consumption of rat heart tissue homogenate was measured by Clark/type oxygen electrode in the absence and presence of the investigated compounds. All three homocysteine-based compounds caused a similar decrease in the oxygen consumption rate compared to control: 15.19 ± 4.01%, 12.42 ± 1.01%, and 16.43 ± 4.52% for DL-Hcy, DL-Hcy TLHC, or L-Hcy TLHC, respectively. All applied inhibitors of gasotransmitter synthesis also decreased the oxygen consumption rate of tissue homogenate related to control: 13.53 ± 1.35% for L-NAME (30 µM), 5.32 ± 1.23% for DL-PAG (10 µM), and 5.56 ± 1.39% for ZnPPR IX (10 µM). Simultaneous effect of L-NAME (30 µM) or ZnPPR IX (10 µM) with DL-Hcy TLHC (10 µM) caused a larger decrease of oxygen consumption compared to each of the substances individually. However, when DL-PAG (10 µM) was applied together with DL-Hcy TLHC (10 µM), it attenuated the effect of DL-Hcy TLHC from 12.42 ± 1.01 to 9.22 ± 1.58%. In conclusion, cardiotoxicity induced by Hcy-related compounds, which was shown in our previous research, could result from the inhibition of the oxygen consumption, and might be mediated by the certain gasotransmitters.

  14. Homocysteine and the C677T Gene Polymorphism of Its Key Metabolic Enzyme MTHFR Are Risk Factors of Early Renal Damage in Hypertension in a Chinese Han Population

    PubMed Central

    Yun, Lin; Xu, Rui; Li, Guohua; Yao, Yucai; Li, Jiamin; Cong, Dehong; Xu, Xingshun; Zhang, Lihua

    2015-01-01

    Abstract The combined hyperhomocysteinemia condition is a feature of the Chinese hypertensive population. This study used the case-control method to investigate the association between plasma homocysteine and the C677T gene polymorphism of its key metabolic enzyme, 5, 10-methylenetetrahydrofolate reductase (MTHFR), and early renal damage in a hypertensive Chinese Han population. A total of 379 adult essential hypertensive patients were selected as the study subjects. The personal information, clinical indicators, and the C677T gene polymorphism of MTHFR were texted. This study used the urine microalbumin/urine creatinine ratio (UACR) as a grouping basis: the hypertension without renal damage group (NRD group) and the hypertension combined with early renal damage group (ERD group). Early renal damage in the Chinese hypertensive population was associated with body weight, systolic pressure, diastolic pressure, urea nitrogen, serum creatinine, cystatin C, uric acid, aldosterone, and glomerular filtration rate. The homocysteine level and the UACR in the TT genotype group were higher than those in the CC genotype group. The binary logistic regression analysis results showed that after sex and age were adjusted, the MTHFR C677T gene polymorphism was correlated with early renal damage in hypertension in both the recessive model and in the additive model. Plasma homocysteine and the C677T gene polymorphism of its key metabolic enzyme MTHFR might be independent risk factors of early renal damage in the hypertensive Chinese Han population. PMID:26717388

  15. Homocysteine and the C677T Gene Polymorphism of Its Key Metabolic Enzyme MTHFR Are Risk Factors of Early Renal Damage in Hypertension in a Chinese Han Population.

    PubMed

    Yun, Lin; Xu, Rui; Li, Guohua; Yao, Yucai; Li, Jiamin; Cong, Dehong; Xu, Xingshun; Zhang, Lihua

    2015-12-01

    The combined hyperhomocysteinemia condition is a feature of the Chinese hypertensive population. This study used the case-control method to investigate the association between plasma homocysteine and the C677T gene polymorphism of its key metabolic enzyme, 5, 10-methylenetetrahydrofolate reductase (MTHFR), and early renal damage in a hypertensive Chinese Han population.A total of 379 adult essential hypertensive patients were selected as the study subjects. The personal information, clinical indicators, and the C677T gene polymorphism of MTHFR were texted. This study used the urine microalbumin/urine creatinine ratio (UACR) as a grouping basis: the hypertension without renal damage group (NRD group) and the hypertension combined with early renal damage group (ERD group).Early renal damage in the Chinese hypertensive population was associated with body weight, systolic pressure, diastolic pressure, urea nitrogen, serum creatinine, cystatin C, uric acid, aldosterone, and glomerular filtration rate. The homocysteine level and the UACR in the TT genotype group were higher than those in the CC genotype group. The binary logistic regression analysis results showed that after sex and age were adjusted, the MTHFR C677T gene polymorphism was correlated with early renal damage in hypertension in both the recessive model and in the additive model.Plasma homocysteine and the C677T gene polymorphism of its key metabolic enzyme MTHFR might be independent risk factors of early renal damage in the hypertensive Chinese Han population.

  16. [Influence of vegetarian diet on serum values of homocysteine and total antioxidant status in children].

    PubMed

    Chełchowska, Magdalena; Ambroszkiewicz, Jadwiga; Klemarczyk, Witold; Gajewska, Joanna; Ołtarzewski, Mariusz; Laskowska-Klita, Teresa

    2010-09-01

    The vegetarian diet may play a preventive role in the development of chronic diseases such as coronary heart and cardiovascular disease. However increase of homocysteine (Hcy) concentration in peoples avoiding animal products may contribute to an increased atherosclerotic risk in these subjects. Recent evidence has suggested that role of hyperhomocysteinemia in atherogenesis is associated with process of autooxidation, which can promote the production of hydroxyl radicals, resulting in oxidative modification of low density lipoprotein and endothelium injury. The oxidant-antioxidant imbalance depends not only on the amount of enhanced free oxygen species but also insufficiency of antioxidant defence system. Total antioxidant status (TAS) expresses capacity for scavenging of free radicals minimizes oxidative damage. The aim of this study was to asses concentrations of homocysteine and total antioxidant status in serum of children on vegetarian and omnivorous diet. We also studied levels of vitamin A (retinol) and vitamin E (alpha-tocopherol) particular components of TAS. The study included 35 children, aged 5-16 who had been referred to Institute of Mother and Child for dietary consultation. From those, 17 were lacto-ovo-vegetarians and 18 omnivores. Dietary constituents were analyzed using the nutritional programme Dietetyk2 and completed with supplementation data. Concentration of homocysteine was estimated in serum with fluorescence polarization immunoassay and TAS by colorimetric method. Levels of vitamin A and E were determined using high-pressure liquid chromatography (HPLC). The mean concentration of homocysteine was similar in both studied groups (vegetarians: 6.13 +/- 1.01 micromol/l vs. omnivores: 5.45 +/- 0.98 micromol/l). In vegetarian children serum level of TAS was significantly lower (1.21 +/- 0.06 mmol/I) as compared to those in non-vegetarian ones (1.30 +/- 0.05 mmol/l, p < 0.0001), but remained within the physiological range (1.16-1.40 mmol/l). The

  17. Synthesis of betaine-homocysteine S-methyltransferase is continuously enhanced in fatty livers of thyroidectomized chickens.

    PubMed

    Shibata, T; Akamine, T; Nikki, T; Yamashita, H; Nobukuni, K

    2003-02-01

    We examined thyroidectomized chickens in terms of plasma lipid concentration and protein expression within the liver. Although the body weight of thyroidectomized chickens was remarkably low due to growth retardation, the livers were enlarged and fatty compared to those of sham-operated chickens. An increase in phospholipid, triglyceride, and total cholesterol levels within the blood plasma of thyroidectomized chickens was observed, clearly reflecting increased lipid synthesis within the liver. Overexpression of some proteins, for example, 29- and 45-kDa proteins, was observed in thyroidectomized chicken livers by means of electrophoresis. A peptide map was made for the protein that exhibited the greatest degree of overexpression. One of them demonstrated a molecular mass of 45 kDa and an isoelectric point (pI) between 7.5 and 8.0, depending on its form. Partial N-terminal amino acid sequences were determined from three random peptides of this protein. The amino acid sequence of this protein showed a high degree of homology with the betaine-homocysteine S-methyltransferase (BHMT, EC 2.1.1.5) of some mammalian species. We identified this protein as chicken BHMT because, in addition to its sequence homology with mammalian BHMT, there were similarities were also observed between this 45-kDa protein and mammalian BHMT with respect to molecular mass and isoelectric behavior. In the liver, 10 d after thyroidectomy, the synthesis of hepatic BHMT had already been enhanced, and the high expression was maintained at 50 d of age. Generally, BHMT catalyzes the transfer of a methyl group from betaine to L-homocysteine. In addition, it seems that this enzyme is also closely related to lipid metabolism in the liver; in this study expression of BHMT in the liver corresponded to plasma lipid levels. Moreover, hypothyroidism may be directly or indirectly related to overexpression of BHMT. Due to similarities between the BHMT of chickens and mammalian species, the chicken model might

  18. Hyperhomocysteinemia induced by guanidinoacetic acid is effectively suppressed by choline and betaine in rats.

    PubMed

    Setoue, Minoru; Ohuchi, Seiya; Morita, Tatsuya; Sugiyama, Kimio

    2008-07-01

    Rats were fed 25% casein (25C) diets differing in choline levels (0-0.5%) with and without 0.5% guanidinoacetic acid (GAA) or 0.75% L-methionine for 7 d to determine the effects of dietary choline level on experimental hyperhomocysteinemia. The effects of dietary choline (0.30%) and betaine (0.34%) on GAA- and methionine-induced hyperhomocysteinemia were also compared. Dietary choline suppressed hyperhomocysteinemia induced by GAA, but not by methionine, in a dose-dependent manner. GAA-induced enhancement of the plasma homocysteine concentration was suppressed by choline and betaine to the same degree, but the effects of these compounds were relatively small on methionine-induced hyperhomocysteinemia. Dietary supplementation with choline and betaine significantly increased the hepatic betaine concentration in rats fed a GAA diet, but not in rats fed a methionine diet. These results indicate that choline and betaine are effective at relatively low levels in reducing plasma homocysteine, especially under the condition of betaine deficiency without a loading of homocysteine precursor.

  19. Direct correlation between serum homocysteine level and insulin resistance index in patients with subclinical hypothyroidism: Does subclinical hypothyroidism increase the risk of diabetes and cardio vascular disease together?

    PubMed

    Ebrahimpour, Anahita; Vaghari-Tabari, Mostafa; Qujeq, Durdi; Moein, Soheila; Moazezi, Zoleikha

    2018-05-05

    Subclinical hypothyroidism known as mild thyroid disorder without significant sign and symptoms. The correlation between subclinical hypothyroidism and some of cardiovascular disease risk factors such as serum lipids, homocysteine levels and also insulin resistance index is not well established and the current study was conducted to clarify this issue. Seventy four patients with mild elevation in levels of thyroid stimulating hormone (TSH) along with normal levels of T3 and T4 were selected as patients group and 74 age and sex matched individuals were selected as healthy control group. Serum insulin, triglyceride, glucose, total cholesterol, LDL-cholesterol, HDL-cholesterol and homocysteine levels were measured. Obtained data compared between groups with independent sample t-test. For evaluation of the correlation between mentioned parameters Pearson correlation coefficient method was used. Serum levels of LDL-C and total cholesterol significantly increased in SCH group compared to healthy control group. Homeostatic Model Assessment of Insulin Resistance (HOM-IR) and serum homocysteine level significantly elevated in patients with SCH compared to control group. There was a significant direct correlation between HOM-IR and serum homocysteine levels in SCH patients. Subclinical hypothyroidism likely have significant effect on insulin resistance as major diabetes risk factors and also cardiovascular disease risk factors such as homocysteine. The direct correlation between HOM-IR with serum homocysteine level indicate the possible role of insulin resistance in elevation of serum homocysteine in SCH patient group. Copyright © 2018 Diabetes India. Published by Elsevier Ltd. All rights reserved.

  20. Association of homocysteine level and vascular burden and cognitive function in middle-aged and older adults with chronic kidney disease.

    PubMed

    Yeh, Yi-Chun; Huang, Mei-Feng; Hwang, Shang-Jyh; Tsai, Jer-Chia; Liu, Tai-Ling; Hsiao, Shih-Ming; Yang, Yi-Hsin; Kuo, Mei-Chuan; Chen, Cheng-Sheng

    2016-07-01

    Patients with chronic kidney disease (CKD) have been found to have cognitive impairment. However, the core features and clinical correlates of cognitive impairment are still unclear. Elevated homocysteine levels are present in CKD, and this is a risk factor for cognitive impairment and vascular diseases in the general population. Thus, this study investigated the core domains of cognitive impairment and investigated the associations of homocysteine level and vascular burden with cognitive function in patients with CKD. Patients with CKD aged ≥ 50 years and age- and sex-matched normal comparisons were enrolled. The total fasting serum homocysteine level was measured. Vascular burden was assessed using the Framingham Cardiovascular Risk Scale. Cognitive function was evaluated using comprehensive neuropsychological tests. A total of 230 patients with CKD and 92 comparisons completed the study. Memory impairment and executive dysfunction were identified as core features of cognitive impairment in the CKD patients. Among the patients with CKD, higher serum homocysteine levels (β = -0.17, p = 0.035) and higher Framingham Cardiovascular Risk Scale scores (β = -0.18, p = 0.013) were correlated with poor executive function independently. However, an association with memory function was not noted. Our results showed that an elevated homocysteine level and an increased vascular burden were independently associated with executive function, but not memory, in CKD patients. This findings suggested the co-existence of vascular and non-vascular hypotheses regarding executive dysfunction in CKD patients. Meanwhile, other risk factors related to CKD itself should be investigated in the future. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  1. Plasma Homocysteine and Asymmetrical Dimethyl-l-Arginine (ADMA) and Whole Blood DNA Methylation in Early and Neovascular Age-Related Macular Degeneration: A Pilot Study.

    PubMed

    Pinna, Antonio; Zinellu, Angelo; Tendas, Donatella; Blasetti, Francesco; Carru, Ciriaco; Castiglia, Paolo

    2016-01-01

    To compare the plasma levels of homocysteine and asymmetrical dimethyl-l-arginine (ADMA) and the degree of whole blood DNA methylation in patients with early and neovascular age-related macular degeneration (AMD) and in controls without maculopathy of any sort. This observational case-control pilot study included 39 early AMD patients, 27 neovascular AMD patients and 132 sex- and age-matched controls without maculopathy. Plasma homocysteine and ADMA concentrations and the degree of whole blood DNA methylation were measured. Quantitative variables were compared by Student's t-test or Mann-Whitney test. Logistic regression models were used to investigate the significance of the association between early or wet AMD and some variables. There were no significant differences in mean plasma homocysteine and ADMA concentrations and in the degree of whole blood DNA methylation between patients with early or neovascular AMD and their controls. Similarly, logistic regression analysis disclosed that plasma homocysteine and ADMA levels were not associated with an increased risk for early or neovascular AMD. We failed to demonstrate an association between early or neovascular AMD and increased plasma homocysteine and/or ADMA. Results also suggest that the degree of whole blood DNA methylation is not a marker of AMD.

  2. The importance of folate, vitamins B6 and B12 for the lowering of homocysteine concentrations for patients with recurrent pregnancy loss and MTHFR mutations.

    PubMed

    Serapinas, Danielius; Boreikaite, Evelina; Bartkeviciute, Agne; Bandzeviciene, Rita; Silkunas, Mindaugas; Bartkeviciene, Daiva

    2017-09-01

    In patients with MTHFR (methylenetetrahydrofolate reductase) mutations and hyperhomocysteinemia, recurrent pregnancy loss is a frequent feature. The aim of the study was to evaluate the impact of folic acid, vitamins B6 and B12 supplementation for the lowering of total homocysteine concentrations and pregnancy. 16 patients who had had 3 or more miscarriages and MTHFR mutations were used in the study. They received methylfolate (5mg/day), vitamin B6 (50mg/day) and vitamin B12 (1mg/week). Supplementation induced a decrease in homocysteine from 19.4±5.3μmol/L to 6.9±2.2μmol/L after folate supplementation (p<0.05). During one year 7 women became pregnant and delivered. Two women delivered from the homozygous C677T mutations group (7 patients) and combined heterozygous C677T/A1298C mutations group (5 patients), while 3 deliveries were in A1298C homozygous mutations group (4 patients). In conclusion, supraphysiologic methylfolate, vitamins B6 and B12 supplementation in woman with MTHFR mutations has a beneficial effect on pregnancy outcome. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Folinic acid treatment for schizophrenia associated with folate receptor autoantibodies.

    PubMed

    Ramaekers, V T; Thöny, B; Sequeira, J M; Ansseau, M; Philippe, P; Boemer, F; Bours, V; Quadros, E V

    2014-12-01

    Auto-antibodies against folate receptor alpha (FRα) at the choroid plexus that block N(5)-methyltetrahydrofolate (MTHF) transfer to the brain were identified in catatonic schizophrenia. Acoustic hallucinations disappeared following folinic acid treatment. Folate transport to the CNS prevents homocysteine accumulation and delivers one-carbon units for methyl-transfer reactions and synthesis of purines. The guanosine derivative tetrahydrobiopterin acts as common co-factor for the enzymes producing dopamine, serotonin and nitric oxide. Our study selected patients with schizophrenia unresponsive to conventional treatment. Serum from these patients with normal plasma homocysteine, folate and vitamin B12 was tested for FR autoantibodies of the blocking type on serial samples each week. Spinal fluid was analyzed for MTHF and the metabolites of pterins, dopamine and serotonin. The clinical response to folinic acid treatment was evaluated. Fifteen of 18 patients (83.3%) had positive serum FR auto-antibodies compared to only 1 in 30 controls (3.3%) (χ(2)=21.6; p<0.0001). FRα antibody titers in patients fluctuated over time varying between negative and high titers, modulating folate flux to the CNS, which explained low CSF folate values in 6 and normal values in 7 patients. The mean±SD for CSF MTHF was diminished compared to previously established controls (t-test: 3.90; p=0.0002). A positive linear correlation existed between CSF MTHF and biopterin levels. CSF dopamine and serotonin metabolites were low or in the lower normal range. Administration of folinic acid (0.3-1mg/kg/day) to 7 participating patients during at least six months resulted in clinical improvement. Assessment of FR auto-antibodies in serum is recommended for schizophrenic patients. Clinical negative or positive symptoms are speculated to be influenced by the level and evolution of FRα antibody titers which determine folate flux to the brain with up- or down-regulation of brain folate intermediates

  4. [Acute physical exercise increases homocysteine concentrations in young trained male subjects].

    PubMed

    Maroto-Sánchez, Beatriz; Valtueña, Jara; Albers, Ulrike; Benito, Pedro J; González-Gross, Marcela

    2013-01-01

    High levels of homocysteine (Hcy) have been identified as a cardiovascular risk factor. Regarding physical exercise, the results are contradictory. The aim of this study was to determine the influence of maximal intensity exercise and submaximal constant exercise on total serum homocysteine concentrations (tHcy) and other related parameters. Ten physically active male subjects (mean age: 23.51 ± 1.84), performed two treadmill tests, a maximal test and a stable submaximal test at an intensity of 65% of maximal oxygen uptake (VO2max). Serum concentrations of tHcy, Folate, Vitamin B12 and creatinine were analysed before and after each test. Significant increase in serum tHcy concentrations after the maximal (p < 0.05) and submaximal (p < 0.01) tests were observed. Folate and vitamin B12 concentrations also increased significantly after both tests (p < 0.05). Creatinine levels increased only after the maximal test (p < 0.001). A statistically significant inverse relationship was found between folate and tHcy concentrations (p < 0.05) at all the measurement points. THcy levels increased significantly after acute exercise in both maximum and submaximal intensity exercises. Copyright © AULA MEDICA EDICIONES 2013. Published by AULA MEDICA. All rights reserved.

  5. [Plasma homocysteine, Lp(a), and oxidative stress markers in peripheral macroangiopathy in patients with type 2 diabetes mellitus].

    PubMed

    Real, Jose T; Folgado, José; Molina Mendez, Mercedes; Martinez-Hervás, Sergio; Peiro, Marta; Ascaso, Juan F

    2016-01-01

    To study new risk factors for peripheral macroangiopathy (PM) in patients with diabetes, as oxidative stress (OS) and its interaction with classical risk factors: age, Lp(a), plasma homocysteine values and HbA1c. We studied 204 type2 diabetic (T2DM) patients, consecutive selected form a reference hospital and a secondary hospital form our Community (2009-2010). Design was a case (ABI<0.89) control (ABI0.9-1.2) study. PM was defined using ankle brachial index (ABI). Thirty nine T2DM subjects presented ABI>1.2 and were excluded. Clinical and biological parameters were determined using standard methods. Comparing clinical and biological parameters obtained in both studied groups (T2DM+ABI<0.9 vs T2DM+ABI0.9-1.2), we found statistical significant differences in age, evolution time of diabetes, Lp(a) and plasma homocysteine values. No differences were found in OS parameters: reduced glutathione, oxidized glutathione and maloldialdehide between studied groups. Plasma homocysteine values were an independent risk factor for the presence of PM and were related to evolution time of diabetes and reduced glutathione. We have confirmed that Lp(a) and independently plasma homocysteine values were related to PM in T2DM subjects. No association with PM and OS markers (GSH, GSSG and MDA) were found in T2DM with more than 10years of evolution time of their disease and high prevalence of chronic complications. Copyright © 2016 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

  6. One-carbon metabolism, cognitive impairment and CSF measures of Alzheimer pathology: homocysteine and beyond.

    PubMed

    Dayon, Loïc; Guiraud, Seu Ping; Corthésy, John; Da Silva, Laeticia; Migliavacca, Eugenia; Tautvydaitė, Domilė; Oikonomidi, Aikaterini; Moullet, Barbara; Henry, Hugues; Métairon, Sylviane; Marquis, Julien; Descombes, Patrick; Collino, Sebastiano; Martin, François-Pierre J; Montoliu, Ivan; Kussmann, Martin; Wojcik, Jérôme; Bowman, Gene L; Popp, Julius

    2017-06-17

    Hyperhomocysteinemia is a risk factor for cognitive decline and dementia, including Alzheimer disease (AD). Homocysteine (Hcy) is a sulfur-containing amino acid and metabolite of the methionine pathway. The interrelated methionine, purine, and thymidylate cycles constitute the one-carbon metabolism that plays a critical role in the synthesis of DNA, neurotransmitters, phospholipids, and myelin. In this study, we tested the hypothesis that one-carbon metabolites beyond Hcy are relevant to cognitive function and cerebrospinal fluid (CSF) measures of AD pathology in older adults. Cross-sectional analysis was performed on matched CSF and plasma collected from 120 older community-dwelling adults with (n = 72) or without (n = 48) cognitive impairment. Liquid chromatography-mass spectrometry was performed to quantify one-carbon metabolites and their cofactors. Least absolute shrinkage and selection operator (LASSO) regression was initially applied to clinical and biomarker measures that generate the highest diagnostic accuracy of a priori-defined cognitive impairment (Clinical Dementia Rating-based) and AD pathology (i.e., CSF tau phosphorylated at threonine 181 [p-tau181]/β-Amyloid 1-42 peptide chain [Aβ 1-42 ] >0.0779) to establish a reference benchmark. Two other LASSO-determined models were generated that included the one-carbon metabolites in CSF and then plasma. Correlations of CSF and plasma one-carbon metabolites with CSF amyloid and tau were explored. LASSO-determined models were stratified by apolipoprotein E (APOE) ε4 carrier status. The diagnostic accuracy of cognitive impairment for the reference model was 80.8% and included age, years of education, Aβ 1-42 , tau, and p-tau181. A model including CSF cystathionine, methionine, S-adenosyl-L-homocysteine (SAH), S-adenosylmethionine (SAM), serine, cysteine, and 5-methyltetrahydrofolate (5-MTHF) improved the diagnostic accuracy to 87.4%. A second model derived from plasma included cystathionine

  7. Efficacy of Folic Acid Supplementation in Autistic Children Participating in Structured Teaching: An Open-Label Trial

    PubMed Central

    Sun, Caihong; Zou, Mingyang; Zhao, Dong; Xia, Wei; Wu, Lijie

    2016-01-01

    Autism spectrum disorders (ASD) are recognized as a major public health issue. Here, we evaluated the effects of folic acid intervention on methylation cycles and oxidative stress in autistic children enrolled in structured teaching. Sixty-six autistic children enrolled in this open-label trial and participated in three months of structured teaching. Forty-four children were treated with 400 μg folic acid (two times/daily) for a period of three months during their structured teaching (intervention group), while the remaining 22 children were not given any supplement for the duration of the study (control group). The Autism Treatment Evaluation Checklist (ATEC) and Psychoeducational Profile-third edition (PEP-3) were measured at the beginning and end of the treatment period. Folic acid, homocysteine, and glutathione metabolism in plasma were measured before and after treatment in 29 autistic children randomly selected from the intervention group and were compared with 29 age-matched unaffected children (typical developmental group). The results illustrated folic acid intervention improved autism symptoms towards sociability, cognitive verbal/preverbal, receptive language, and affective expression and communication. Furthermore, this treatment also improved the concentrations of folic acid, homocysteine, and normalized glutathione redox metabolism. Folic acid supplementation may have a certain role in the treatment of children with autism. PMID:27338456

  8. Efficacy of Folic Acid Supplementation in Autistic Children Participating in Structured Teaching: An Open-Label Trial.

    PubMed

    Sun, Caihong; Zou, Mingyang; Zhao, Dong; Xia, Wei; Wu, Lijie

    2016-06-07

    Autism spectrum disorders (ASD) are recognized as a major public health issue. Here, we evaluated the effects of folic acid intervention on methylation cycles and oxidative stress in autistic children enrolled in structured teaching. Sixty-six autistic children enrolled in this open-label trial and participated in three months of structured teaching. Forty-four children were treated with 400 μg folic acid (two times/daily) for a period of three months during their structured teaching (intervention group), while the remaining 22 children were not given any supplement for the duration of the study (control group). The Autism Treatment Evaluation Checklist (ATEC) and Psychoeducational Profile-third edition (PEP-3) were measured at the beginning and end of the treatment period. Folic acid, homocysteine, and glutathione metabolism in plasma were measured before and after treatment in 29 autistic children randomly selected from the intervention group and were compared with 29 age-matched unaffected children (typical developmental group). The results illustrated folic acid intervention improved autism symptoms towards sociability, cognitive verbal/preverbal, receptive language, and affective expression and communication. Furthermore, this treatment also improved the concentrations of folic acid, homocysteine, and normalized glutathione redox metabolism. Folic acid supplementation may have a certain role in the treatment of children with autism.

  9. Obstructive heart defects associated with candidate genes, maternal obesity, and folic acid supplementation.

    PubMed

    Tang, Xinyu; Cleves, Mario A; Nick, Todd G; Li, Ming; MacLeod, Stewart L; Erickson, Stephen W; Li, Jingyun; Shaw, Gary M; Mosley, Bridget S; Hobbs, Charlotte A

    2015-06-01

    Right-sided and left-sided obstructive heart defects (OHDs) are subtypes of congenital heart defects, in which the heart valves, arteries, or veins are abnormally narrow or blocked. Previous studies have suggested that the development of OHDs involved a complex interplay between genetic variants and maternal factors. Using the data from 569 OHD case families and 1,644 control families enrolled in the National Birth Defects Prevention Study (NBDPS) between 1997 and 2008, we conducted an analysis to investigate the genetic effects of 877 single nucleotide polymorphisms (SNPs) in 60 candidate genes for association with the risk of OHDs, and their interactions with maternal use of folic acid supplements, and pre-pregnancy obesity. Applying log-linear models based on the hybrid design, we identified a SNP in methylenetetrahydrofolate reductase (MTHFR) gene (C677T polymorphism) with a main genetic effect on the occurrence of OHDs. In addition, multiple SNPs in betaine-homocysteine methyltransferase (BHMT and BHMT2) were also identified to be associated with the occurrence of OHDs through significant main infant genetic effects and interaction effects with maternal use of folic acid supplements. We also identified multiple SNPs in glutamate-cysteine ligase, catalytic subunit (GCLC) and DNA (cytosine-5-)-methyltransferase 3 beta (DNMT3B) that were associated with elevated risk of OHDs among obese women. Our findings suggested that the risk of OHDs was closely related to a combined effect of variations in genes in the folate, homocysteine, or glutathione/transsulfuration pathways, maternal use of folic acid supplements and pre-pregnancy obesity. © 2015 Wiley Periodicals, Inc.

  10. Vitamin B6 and homocysteine levels in carbamazepine treated epilepsy of Khyber Pakhtunkhwa.

    PubMed

    Shakir, Shakirullah; Ali, Niaz; Udin, Zia; Nazish, Haleema; Nabi, Muhammad

    2017-06-01

    The study focused on the plasma levels of vitamin B 6 and homocysteine in different genotypes of MTHFR (C677T, A1298C) and GABRG2 (C588T, C315T) genes in carbamazepine resistant epilepsy in the population of Khyber Pakhtunkhwa. Patients who were possible candidates for carbamazepine therapy were followed for six months for their seizure control. Plasma levels of vitamin B 6 and homocysteine were determined using immunoassay based techniques at baseline and after six months. MTHFR (C677T, A1298C) and GABRG2 (C588T, C315T) genes were genotyped using restriction fragment length polymorphisms. Seizure control during therapy was recorded on a standardized proforma. Low vitamin B 6 levels and hyperhomocysteinemia were found in 61.7% of resistant patients (n=34). Resistant patients had the following frequencies of variant genotypes (677CT=38.1% and 677TT=24.4%; 1298AC=42.2% and 1298CC=26.1%; 588CT= 47.6% and 315TT= 33.3%) of MTHFR (C677T and A1298C) and GABRG2 (C588T and C315T) genes. A significant decline in vitamin B 6 (P<0.0001) and hyperhomocysteinemia were found in variant genotypes of MTHFR (C677T, A1298C) and GABRG2 (C588T, C315T) genes. Following six months of carbamazepine of therapy in heterozygous variant genotypes of MTHFR (677CT and 1298AC) and GABRG2 (588CT and 315CT) genes, we observed a significant fall in vitamin B 6 levels and hyperhomocysteinemia.

  11. A Combined Supplementation of Omega-3 Fatty Acids and Micronutrients (Folic Acid, Vitamin B12) Reduces Oxidative Stress Markers in a Rat Model of Pregnancy Induced Hypertension

    PubMed Central

    Kemse, Nisha G.; Kale, Anvita A.; Joshi, Sadhana R.

    2014-01-01

    Objectives Our earlier studies have highlighted that an altered one carbon metabolism (vitamin B12, folic acid, and docosahexaenoic acid) is associated with preeclampsia. Preeclampsia is also known to be associated with oxidative stress and inflammation. The current study examines whether maternal folic acid, vitamin B12 and omega-3 fatty acid supplementation given either individually or in combination can ameliorate the oxidative stress markers in a rat model of pregnancy induced hypertension (PIH). Materials and Methods Pregnant Wistar rats were assigned to control and five treatment groups: PIH; PIH + vitamin B12; PIH + folic acid; PIH + Omega-3 fatty acids and PIH + combined micronutrient supplementation (vitamin B12 + folic acid + omega-3 fatty acids). L-Nitroarginine methylester (L-NAME; 50 mg/kg body weight/day) was used to induce hypertension during pregnancy. Blood Pressure (BP) was recorded during pregnancy and dams were dissected at d20 of gestation. Results Animals from the PIH group demonstrated higher (p<0.01 for both) systolic and diastolic BP; lower (p<0.01) pup weight; higher dam plasma homocysteine (p<0.05) and dam and offspring malondialdehyde (MDA) (p<0.01), lower (p<0.05) placental and offspring liver DHA and higher (p<0.01) tumor necrosis factor–alpha (TNF–ά) levels as compared to control. Individual micronutrient supplementation did not offer much benefit. In contrast, combined supplementation lowered systolic BP, homocysteine, MDA and placental TNF-ά levels in dams and liver MDA and protein carbonyl in the offspring as compared to PIH group. Conclusion Key constituents of one carbon cycle (folic acid, vitamin B12 and DHA) may play a role in reducing oxidative stress and inflammation in preeclampsia. PMID:25405347

  12. Turkish propolis protects human endothelial cells in vitro from homocysteine-induced apoptosis.

    PubMed

    Darendelioglu, Ekrem; Aykutoglu, Gurkan; Tartik, Musa; Baydas, Giyasettin

    2016-05-01

    Chronic cardiovascular and neurodegenerative complications induced by hyperhomocysteinemia have been most relatively associated with endothelial cell injury. Elevated homocysteine (Hcy) generates reactive oxygen species (ROS) accompanying with oxidative stress which is hallmarks of the molecular mechanisms responsible for cardiovascular disease. Propolis is a natural product, obtained by honeybee from various oils, pollens, special resins and wax materials, conventionally used with the purpose of treatment by folks Propolis has various biological activities and powerful antioxidant capacity. The flavonoids and phenolic acids, most bioactive components of propolis, have superior antioxidant ability to defend cell from free radicals. This study was designed to examine the protective effects of Turkish propolis (from east of country) on Hcy induced ROS production and apoptosis in human vascular endothelial cells (HUVECs). According to results, co-treatment of HUVECs with propolis decreased Hcy-induced ROS overproduction and lipid peroxidation (LPO) levels. Furthermore, overproductions of Bax, caspase-9 and caspase-3 protein, elevation of cytochrome c release in Hcy-treated HUVECs were significantly reduced by propolis. It was concluded that propolis has cytoprotective ability against cytotoxic effects of high Hcy in HUVECs. Copyright © 2016 Elsevier GmbH. All rights reserved.

  13. Differences in the association between maternal serum homocysteine and ADMA levels in women with pregnancies complicated by preeclampsia and/or intrauterine growth restriction.

    PubMed

    Laskowska, Marzena; Laskowska, Katarzyna; Oleszczuk, Jan

    2013-01-01

    The aim of our study was to investigate the association between homocysteine and asymmetric dimethylarginine in preeclamptic women with and without intrauterine growth restriction compared with normal healthy uncomplicated pregnancies and normotensive pregnancies complicated by idiopathic isolated intrauterine fetal growth restriction. The maternal serum homocysteine and asymmetric dimethylarginine concentrations were determined using a sandwich enzyme-linked immunosorbent assays. A statistically significant positive correlation of maternal serum homocysteine levels with the serum asymmetric dimethylarginine levels was observed in healthy normotensive uncomplicated pregnant women from the control group and in preeclamptic patients with appropriate-for-gestational-age fetuses (R = 0.380079, p-value = 0.002311* and R = 0.455797, p-value = 0.004030* for the control and the P groups, respectively). However, this correlation was not significant in women with pregnancy complicated by intrauterine growth restriction, both isolated and in the course of severe preeclampsia. These findings provide support for the hypothesis that elevated levels of asymmetric dimethylarginine in pregnancy complicated by preeclampsia are associated with elevated homocysteine levels. But our results also demonstrate that in pregnancies complicated by intrauterine growth restriction, this mechanism is important, although not the only one.

  14. Acid-Base Homeostasis

    PubMed Central

    Nakhoul, Nazih; Hering-Smith, Kathleen S.

    2015-01-01

    Acid-base homeostasis and pH regulation are critical for both normal physiology and cell metabolism and function. The importance of this regulation is evidenced by a variety of physiologic derangements that occur when plasma pH is either high or low. The kidneys have the predominant role in regulating the systemic bicarbonate concentration and hence, the metabolic component of acid-base balance. This function of the kidneys has two components: reabsorption of virtually all of the filtered HCO3− and production of new bicarbonate to replace that consumed by normal or pathologic acids. This production or generation of new HCO3− is done by net acid excretion. Under normal conditions, approximately one-third to one-half of net acid excretion by the kidneys is in the form of titratable acid. The other one-half to two-thirds is the excretion of ammonium. The capacity to excrete ammonium under conditions of acid loads is quantitatively much greater than the capacity to increase titratable acid. Multiple, often redundant pathways and processes exist to regulate these renal functions. Derangements in acid-base homeostasis, however, are common in clinical medicine and can often be related to the systems involved in acid-base transport in the kidneys. PMID:26597304

  15. Plasma choline and betaine correlate with serum folate, plasma S-adenosyl-methionine and S-adenosyl-homocysteine in healthy volunteers.

    PubMed

    Imbard, Apolline; Smulders, Yvo M; Barto, Rob; Smith, Desiree E C; Kok, Robert M; Jakobs, Cornelis; Blom, Henk J

    2013-03-01

    Choline is essential for mammalian cell function. It plays a critical role in cell membrane integrity, neurotransmission, cell signaling and lipid metabolism. Moreover, choline is involved in methylation in two ways: a) its synthesis requires methyl groups donated by S-adenosyl-methionine (AdoMet); and b) choline oxidation product betaine methylates homocysteine (Hcy) to methionine (Met) and produces dimethylglycine. This later donates one carbon units to tetrahydrofolate (THF). To evaluate the correlations of choline and betaine with folate, AdoMet, S-anenosyl-homocysteine (AdoHcy), total homocysteine (tHcy), and DNA methylation, choline, betaine and dimethylglycine were measured by LC-MS/MS in plasma of 109 healthy volunteers, in whom folate, AdoMet, AdoHcy, tHcy, and DNA methylation have previously been reported. Using a bivariate model, choline and betaine showed strong positive correlations with folate (r = 0.346 and r = 0.226), AdoHcy (r = 0.468 and r = 0.296), and correlated negatively with AdoMet/AdoHcy ratio (r = – 0.246 and r = – 0.379). Only choline was positively correlated with AdoMet (r = 0.453). Using a multivariate linear regression model, choline correlated strongly with folate ( β = 17.416), AdoMet ( β = 61.272), and AdoHcy ( β = 9.215). Betaine correlated positively with folate ( β = 0.133) and negatively with tHcy ( β = – 0.194) ratio. Choline is an integral part of folate and methylation pathways. Our data highlight the importance of integrating choline in studies concerning addressing pathological conditions related to folate, homocysteine and methylation metabolism.

  16. S-Adenosyl-S-carboxymethyl-l-homocysteine: a novel cofactor found in the putative tRNA-modifying enzyme CmoA

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Byrne, Robert T.; Whelan, Fiona; Aller, Pierre

    2013-06-01

    The putative methyltransferase CmoA is involved in the nucleoside modification of transfer RNA. X-ray crystallography and mass spectrometry are used to show that it contains a novel SAM derivative, S-adenosyl-S-carboxymethyl-l-homocysteine, in which the donor methyl group is replaced by a carboxymethyl group. Uridine at position 34 of bacterial transfer RNAs is commonly modified to uridine-5-oxyacetic acid (cmo{sup 5}U) to increase the decoding capacity. The protein CmoA is involved in the formation of cmo{sup 5}U and was annotated as an S-adenosyl-l-methionine-dependent (SAM-dependent) methyltransferase on the basis of its sequence homology to other SAM-containing enzymes. However, both the crystal structure of Escherichiamore » coli CmoA at 1.73 Å resolution and mass spectrometry demonstrate that it contains a novel cofactor, S-adenosyl-S-carboxymethyl-l-homocysteine (SCM-SAH), in which the donor methyl group is substituted by a carboxymethyl group. The carboxyl moiety forms a salt-bridge interaction with Arg199 that is conserved in a large group of CmoA-related proteins but is not conserved in other SAM-containing enzymes. This raises the possibility that a number of enzymes that have previously been annotated as SAM-dependent are in fact SCM-SAH-dependent. Indeed, inspection of electron density for one such enzyme with known X-ray structure, PDB entry http://scripts.iucr.org/cgi-bin/cr.cgi?rm, suggests that the active site contains SCM-SAH and not SAM.« less

  17. Homocysteine activates T cells by enhancing endoplasmic reticulum-mitochondria coupling and increasing mitochondrial respiration.

    PubMed

    Feng, Juan; Lü, Silin; Ding, Yanhong; Zheng, Ming; Wang, Xian

    2016-06-01

    Hyperhomocysteinemia (HHcy) accelerates atherosclerosis by increasing proliferation and stimulating cytokine secretion in T cells. However, whether homocysteine (Hcy)-mediated T cell activation is associated with metabolic reprogramming is unclear. Here, our in vivo and in vitro studies showed that Hcy-stimulated splenic T-cell activation in mice was accompanied by increased levels of mitochondrial reactive oxygen species (ROS) and calcium, mitochondrial mass and respiration. Inhibiting mitochondrial ROS production and calcium signals or blocking mitochondrial respiration largely blunted Hcy-induced T-cell interferon γ (IFN-γ) secretion and proliferation. Hcy also enhanced endoplasmic reticulum (ER) stress in T cells, and inhibition of ER stress with 4-phenylbutyric acid blocked Hcy-induced T-cell activation. Mechanistically, Hcy increased ER-mitochondria coupling, and uncoupling ER-mitochondria by the microtubule inhibitor nocodazole attenuated Hcy-stimulated mitochondrial reprogramming, IFN-γ secretion and proliferation in T cells, suggesting that juxtaposition of ER and mitochondria is required for Hcy-promoted mitochondrial function and T-cell activation. In conclusion, Hcy promotes T-cell activation by increasing ER-mitochondria coupling and regulating metabolic reprogramming.

  18. Folic acid: influence on the outcome of pregnancy.

    PubMed

    Scholl, T O; Johnson, W G

    2000-05-01

    The periconceptional use of folic acid-containing supplements reduces the first occurrence, as well as the recurrence, of neural tube defects. Women of populations in which adverse pregnancy outcomes are prevalent often consume diets that contain a low density of vitamins and minerals, including folate. Folate intake may need to be sustained after complete closure of the neural tube to decrease the risk of other poor pregnancy outcomes. A central feature of embryonic and fetal development is widespread cell division; folate is central because of its role in nucleic acid synthesis. During gestation, marginal folate nutriture can impair cellular growth and replication in the fetus or placenta. Folate deficiency can occur because dietary folate intake is low or because the metabolic requirement for folate is increased by a particular genetic defect or defects. During pregnancy, low concentrations of dietary and circulating folate are associated with increased risks of preterm delivery, infant low birth weight, and fetal growth retardation. A metabolic effect of folate deficiency is an elevation of blood homocysteine. Likewise, the presence of maternal homocysteine concentrations have been associated both with increased habitual spontaneous abortion and pregnancy complications (eg, placental abruption and preeclampsia), which increase the risk of poor pregnancy outcome and of decreased birth weight and gestation duration.

  19. Considerations for automated machine learning in clinical metabolic profiling: Altered homocysteine plasma concentration associated with metformin exposure.

    PubMed

    Orlenko, Alena; Moore, Jason H; Orzechowski, Patryk; Olson, Randal S; Cairns, Junmei; Caraballo, Pedro J; Weinshilboum, Richard M; Wang, Liewei; Breitenstein, Matthew K

    2018-01-01

    With the maturation of metabolomics science and proliferation of biobanks, clinical metabolic profiling is an increasingly opportunistic frontier for advancing translational clinical research. Automated Machine Learning (AutoML) approaches provide exciting opportunity to guide feature selection in agnostic metabolic profiling endeavors, where potentially thousands of independent data points must be evaluated. In previous research, AutoML using high-dimensional data of varying types has been demonstrably robust, outperforming traditional approaches. However, considerations for application in clinical metabolic profiling remain to be evaluated. Particularly, regarding the robustness of AutoML to identify and adjust for common clinical confounders. In this study, we present a focused case study regarding AutoML considerations for using the Tree-Based Optimization Tool (TPOT) in metabolic profiling of exposure to metformin in a biobank cohort. First, we propose a tandem rank-accuracy measure to guide agnostic feature selection and corresponding threshold determination in clinical metabolic profiling endeavors. Second, while AutoML, using default parameters, demonstrated potential to lack sensitivity to low-effect confounding clinical covariates, we demonstrated residual training and adjustment of metabolite features as an easily applicable approach to ensure AutoML adjustment for potential confounding characteristics. Finally, we present increased homocysteine with long-term exposure to metformin as a potentially novel, non-replicated metabolite association suggested by TPOT; an association not identified in parallel clinical metabolic profiling endeavors. While warranting independent replication, our tandem rank-accuracy measure suggests homocysteine to be the metabolite feature with largest effect, and corresponding priority for further translational clinical research. Residual training and adjustment for a potential confounding effect by BMI only slightly modified

  20. Mouse Betaine-Homocysteine S-Methyltransferase Deficiency Reduces Body Fat via Increasing Energy Expenditure and Impairing Lipid Synthesis and Enhancing Glucose Oxidation in White Adipose Tissue*

    PubMed Central

    Teng, Ya-Wen; Ellis, Jessica M.; Coleman, Rosalind A.; Zeisel, Steven H.

    2012-01-01

    Betaine-homocysteine S-methyltransferase (BHMT) catalyzes the synthesis of methionine from homocysteine. In our initial report, we observed a reduced body weight in Bhmt−/− mice. We initiated this study to investigate the potential role of BHMT in energy metabolism. Compared with the controls (Bhmt+/+), Bhmt−/− mice had less fat mass, smaller adipocytes, and better glucose and insulin sensitivities. Compared with the controls, Bhmt−/− mice had increased energy expenditure, with no changes in food intake, fat uptake or absorption, or in locomotor activity. The reduced adiposity in Bhmt−/− mice was not due to hyperthermogenesis. Bhmt−/− mice failed to maintain a normal body temperature upon cold exposure because of limited fuel supplies. In vivo and ex vivo tests showed that Bhmt−/− mice had normal lipolytic function. The rate of 14C-labeled fatty acid incorporated into [14C]triacylglycerol was the same in Bhmt+/+ and Bhmt−/− gonadal fat depots (GWAT), but it was 62% lower in Bhmt−/− inguinal fat depots (IWAT) compared with that of Bhmt+/+ mice. The rate of 14C-labeled fatty acid oxidation was the same in both GWAT and IWAT from Bhmt+/+ and Bhmt−/− mice. At basal level, Bhmt−/− GWAT had the same [14C]glucose oxidation as did the controls. When stimulated with insulin, Bhmt−/− GWAT oxidized 2.4-fold more glucose than did the controls. Compared with the controls, the rate of [14C]glucose oxidation was 2.4- and 1.8-fold higher, respectively, in Bhmt−/− IWAT without or with insulin stimulus. Our results show for the first time a role for BHMT in energy homeostasis. PMID:22362777

  1. The Acid-Base Titration of a Very Weak Acid: Boric Acid

    ERIC Educational Resources Information Center

    Celeste, M.; Azevedo, C.; Cavaleiro, Ana M. V.

    2012-01-01

    A laboratory experiment based on the titration of boric acid with strong base in the presence of d-mannitol is described. Boric acid is a very weak acid and direct titration with NaOH is not possible. An auxiliary reagent that contributes to the release of protons in a known stoichiometry facilitates the acid-base titration. Students obtain the…

  2. Clinical course in Parkinson's disease with elevated homocysteine.

    PubMed

    O'Suilleabhain, Padraig E; Oberle, Robert; Bartis, Cristina; Dewey, Richard B; Bottiglieri, Teodoro; Diaz-Arrastia, Ramon

    2006-03-01

    Elevated homocysteine (Hcy), prevalent in Parkinson's disease (PD), is potentially a modifiable risk factor for neurologic deterioration. We measured cognitive, affective and motor changes over 2 years in a cohort of people with early PD. Subjects whose Hcy had been elevated (>14 micromol/L, n = 31) at baseline were compared with the rest (n = 66). Overall progression in 2 years did not significantly differ (p = 0.20). Four subjects with elevated and one with normal Hcy had died (p = 0.03). We conclude that hyperhomocysteinemia does not predict significantly worse progression over 2 years in early PD. The data raised the possibility of higher mortality, but the number of deaths was small.

  3. Homocysteine, hyperhomocysteinemia and vascular contributions to cognitive impairment and dementia (VCID)

    PubMed Central

    Hainsworth, Atticus H; Yeo, Natalie E; Weekman, Erica M; Wilcock, Donna M

    2016-01-01

    Homocysteine is produced physiologically in all cells, and is present in plasma of healthy individuals (plasma [HCy]: 3–10µM). While rare genetic mutations (CBS, MTHFR) cause severe hyperhomocysteinemia ([HCy]: 100–200µM), mild-moderate hyperhomocysteinemia ([HCy]: 10–100µM) is common in older people, and is an independent risk factor for stroke and cognitive impairment. As B-vitamin supplementation (B6, B12 and folate) has well-validated homocysteine-lowering efficacy, this may be a readily-modifiable risk factor in vascular contributions to cognitive impairment and dementia (VCID). Here we review the biochemical and cellular actions of HCy related to VCID. Neuronal actions of HCy were at concentrations above the clinically-relevant range. Effects of HCy <100 µM were primarily vascular, including myocyte proliferation, vessel wall fibrosis, impaired nitric oxide signalling, superoxide generation and pro-coagulant actions. HCy-lowering clinical trials relevant to VCID are discussed. Extensive clinical and preclinical data support Hcy as a mediator for VCID. In our view further trails of combined B-vitamin supplementation are called for, incorporating lessons from previous trails and from recent experimental work. To maximise likelihood of treatment effect, a future trial should: supply a high-dose, combination supplement (B6, B12 and folate); target the at-risk age range; target cohorts with low baseline B-vitamin status. PMID:26689889

  4. Gender and single nucleotide polymorphisms in MTHFR, BHMT, SPTLC1, CRBP2R, and SCARB1 are significant predictors of plasma homocysteine normalized by RBC folate in healthy adults.

    USDA-ARS?s Scientific Manuscript database

    Using linear regression models, we studied the main and two-way interaction effects of the predictor variables gender, age, BMI, and 64 folate/vitamin B-12/homocysteine/lipid/cholesterol-related single nucleotide polymorphisms (SNP) on log-transformed plasma homocysteine normalized by red blood cell...

  5. Hydrogen sulfide production from cysteine and homocysteine by periodontal and oral bacteria.

    PubMed

    Yoshida, Akihiro; Yoshimura, Mamiko; Ohara, Naoya; Yoshimura, Shigeru; Nagashima, Shiori; Takehara, Tadamichi; Nakayama, Koji

    2009-11-01

    Hydrogen sulfide is one of the predominant volatile sulfur compounds (VSCs) produced by oral bacteria. This study developed and evaluated a system for detecting hydrogen sulfide production by oral bacteria. L-methionine-alpha-deamino-gamma-mercaptomethane-lyase (METase) and beta carbon-sulfur (beta C-S) lyase were used to degrade homocysteine and cysteine, respectively, to produce hydrogen sulfide. Enzymatic reactions resulting in hydrogen sulfide production were assayed by reaction with bismuth trichloride, which forms a black precipitate when mixed with hydrogen sulfide. The enzymatic activities of various oral bacteria that result in hydrogen sulfide production and the capacity of bacteria from periodontal sites to form hydrogen sulfide in reaction mixtures containing L-cysteine or DL-homocysteine were assayed. With L-cysteine as the substrate, Streptococcus anginosus FW73 produced the most hydrogen sulfide, whereas Porphyromonas gingivalis American Type Culture Collection (ATCC) 33277 and W83 and Fusobacterium nucleatum ATCC 10953 produced approximately 35% of the amount produced by the P. gingivalis strains. Finally, the hydrogen sulfide found in subgingival plaque was analyzed. Using bismuth trichloride, the hydrogen sulfide produced by oral bacteria was visually detectable as a black precipitate. Hydrogen sulfide production by oral bacteria was easily analyzed using bismuth trichloride. However, further innovation is required for practical use.

  6. [Homocysteine and von Willebrand factor in chronic alcoholism].

    PubMed

    Koriakin, A M; Epifantseva, N N; Dadyka, I V; Gorbatovskiĭ, Ia A

    2010-04-01

    The levels of homocysteine (HC) and von Willebrand factor (VWF) as cardiovascular risk factors were studied in patients with Stage II chronic alcoholism. Forty-one men with Stage II chronic alcoholism without clinical signs of somatic and infectious diseases were examined. Their median age was 37 (range 32-40) years; the alcoholization period was 12 (range 8-17) years. Plasma HC and VWF (amount and activity) levels were determined. In 63.4% of chronic alcoholic patients, HC levels was twice as high as in the controls; in 80.6%, both the content and activity of VWF were increased. There was no correlation between the levels of HC and VWF. Vascular endothelial damage concurrent with hyperhomocysteinemia increases a cardiovascular risk in patients with Stage II chronic alcoholism.

  7. Comparison of the effects of nicotinic acid and nicotinamide degradation on plasma betaine and choline levels.

    PubMed

    Sun, Wu-Ping; Zhai, Ming-Zhu; Li, Da; Zhou, Yiming; Chen, Na-Na; Guo, Ming; Zhou, Shi-Sheng

    2017-08-01

    The present study was to compare the effects of nicotinic acid and nicotinamide on the plasma methyl donors, choline and betaine. Thirty adult subjects were randomly divided into three groups of equal size, and orally received purified water (C group), nicotinic acid (300 mg, NA group) or nicotinamide (300 mg, NM group). Plasma nicotinamide, N 1 -methylnicotinamide, homocysteine, betaine and choline levels before and 1.5-h and 3-h post-dosing, plasma normetanephrine and metanephrine concentrations at 3-h post-dosing, and the urinary excretion of N 1 -methyl-2-pyridone-5-carboxamide during the test period were examined. The level of 3-h plasma nicotinamide, N 1 -methylnicotinamide, homocysteine, the urinary excretion of N 1 -methyl-2-pyridone-5-carboxamide and pulse pressure (PP) in the NM group was 221%, 3972%, 61%, 1728% and 21.2% higher than that of the control group (P < 0.01, except homocysteine and PP P < 0.05), while the 3-h plasma betaine, normetanephrine and metanephrine level in the NM group was 24.4%, 9.4% and 11.7% lower (P < 0.05, except betaine P < 0.01), without significant difference in choline levels. Similar but less pronounced changes were observed in the NA group, with a lower level of 3-h plasma N 1 -methylnicotinamide (1.90 ± 0.20 μmol/l vs. 3.62 ± 0.27 μmol/l, P < 0.01) and homocysteine (12.85 ± 1.39 μmol/l vs. 18.08 ± 1.02 μmol/l, P < 0.05) but a higher level of betaine (27.44 ± 0.71 μmol/l vs. 23.52 ± 0.61 μmol/l, P < 0.05) than that of the NM group. The degradation of nicotinamide consumes more betaine than that of nicotinic acid at identical doses. This difference should be taken into consideration in niacin fortification. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  8. Effect of genetic polymorphisms involved in folate metabolism on the concentration of serum folate and plasma total homocysteine (p-tHcy) in healthy subjects after short-term folic acid supplementation: a randomized, double blind, crossover study.

    PubMed

    Cabo, Rona; Hernes, Sigrunn; Slettan, Audun; Haugen, Margaretha; Ye, Shu; Blomhoff, Rune; Mansoor, M Azam

    2015-05-01

    Data on the effect of combined genetic polymorphisms, involved in folate metabolism, on the concentration of serum folate after folic acid supplementation are scarce. Therefore, we investigated the impact of seven gene polymorphisms on the concentration of serum folate and p-tHcy in healthy subjects after short-term folic acid supplementation. In a randomized, double blind, crossover study, apparently healthy subjects were given either 0.8 mg folic acid per day (n = 46) or placebo (n = 45) for 14 days. The washout period was 14 days. Fasting blood samples were collected on day 1, 15, 30 and 45. Data on subjects on folic acid supplementation (n = 91) and on placebo (n = 45) were used for the statistical analysis. The concentration of serum folate increased higher in subjects with higher age (53.5 ± 7.0 years) than in subjects with lower age (24.3 ± 3.2 years) after folic acid supplementation (p = 0.006). The baseline concentration of serum folate in subjects with polymorphism combination, reduced folate carrier protein, RFC1-80 GA and methylenetetrahydrofolate reductase, MTHFR677 CT+TT, was lower than RFC1-80 AA and MTHFR677 CT+TT (p = 0.002). After folic acid supplementation, a higher increase in the concentration of serum folate was detected in subjects with polymorphism combination RFC1-80 GA and MTHFR677 CC than RFC1-80 GG and MTHFR CT+TT combination (p < 0.0001). The baseline concentration of plasma total homocysteine (p-tHcy) was altered by combined polymorphisms in genes associated with folate metabolism. After folic acid supplementation, in subjects with combined polymorphisms in methylenetetrahydrofolate dehydrogenase, MTHFD1-1958 and MTHFR-677 genes, the concentration of p-tHcy was changed (p = 0.002). The combination of RFC1-80 and MTHFR-677 polymorphisms had a profound affect on the concentration of serum folate in healthy subjects before and after folic acid supplementation.

  9. Differences in betaine-homocysteine methyltransferase expression, ER stress response and liver injury between alcohol-fed mice and rats

    PubMed Central

    Shinohara, Masao; Ji, Cheng; Kaplowitz, Neil

    2009-01-01

    Chronic ethanol infusion resulted in greater serum ALT elevation, lipid accumulation, necroinflammation, and focal hepatic cell death in mice than rats. Mice exhibited a remarkable hyperhomocysteinemia but no increase was seen in rats. Similarly, a high methionine low folate diet (HMLF) induced less steatosis, serum ALT increase, and hyperhomocysteinemia in rats than in mice. Western blot analysis of betaine homocysteine methyltransferase (BHMT) expression showed that rats fed either ethanol or HMLF had significantly increased BHMT expression which did not occur in mice. Nuclear NFκB p65 was increased in mouse in response to alcohol feeding. The human BHMT promoter was repressed by homocysteine in mouse hepatocytes but not rat hepatocytes. BHMT induction was faster and greater in primary rat hepatocytes than mouse hepatocytes in response to exogenous homocysteine exposure. Mice fed ethanol i.g. exhibited an increase in GRP78 and IRE1 which was not seen in the rat and SREBP-1 was increased to a greater extent in mice than rats. Thus, rats are more resistant to ethanol induced steatosis, ER stress and hyperhomocysteinemia and this correlates with induction of BHMT in rats. These findings support the hypothesis that a critical factor in the pathogenesis of alcoholic liver injury is the enhanced ability of rat or impaired ability of mouse to up-regulate BHMT which prevents hyperhomocysteinemia, ER stress and liver injury. PMID:20069651

  10. Saffron improved depression and reduced homocysteine level in patients with major depression: A Randomized, double-blind study

    PubMed Central

    Jelodar, Gholamali; Javid, Zahra; Sahraian, Ali; Jelodar, Sina

    2018-01-01

    Objectives: A correlation between hyperhomocysteinemia, and depression has been reported. Saffron (Crocus sativus) is recommended for treatment of depression; hence, in this study the effect of co-administration of saffron and fluoxetine on plasma homocysteine and depression was evaluated. Material and methods: This was a 4-week randomized and double-blind clinical trial which was conducted from March 2013 to February 2014. In this trial, 40 male and females (20-55 years old) diagnosed with severe depression were selected and following filing the Beck form, were randomly divided into two groups. Experimental group was treated with fluoxetine 20 mg/day and saffron 30 mg /day and the control group received placebo and fluoxetine 20 mg/day for four weeks. Before treatment and at the end of the study, fasting blood samples were collected. For females, blood samples were collected on the third day of their menstrual cycle. Results: A significant reduction of homocysteine levels was observed in both sex in the experimental group compared to before treatment (p<0.04), while no such significant change was observed in the control group. A Beck questionnaire value showed lower level in both groups on the last day of treatment as compared to before treatment. There was no significant difference between the two groups in Beck value neither before nor after treatment. Conclusion: Saffron has beneficial effects on depression and homocysteine level in patients with major depression. PMID:29387573

  11. Homocysteine, visceral adiposity-related novel cardiometabolic risk factors, and exaggerated blood pressure response to the exercise treadmill test.

    PubMed

    Türker Duyuler, Pinar; Duyuler, Serkan; Demir, Mevlüt; Uçar Elalmiş, Özgül; Güray, Ümit; İleri, Mehmet

    2017-12-01

    Exaggerated blood pressure response to exercise is a risk factor for the development of future hypertension. In this study, we aimed to investigate the association between homocysteine, epicardial fat thickness, nonalcoholic hepatic steatosis, and exaggerated blood pressure response to exercise. We included 44 normotensive and 40 patients with exaggerated blood pressure response to exercise who have normal resting blood pressure and without a previous diagnosis of hypertension. All patients underwent treadmill exercise test and clinical, ultrasonographic, and echocardiographic evaluation. Exaggerated blood pressure response to exercise is defined as peak exercise systolic blood pressure of at least 210 mmHg in men and at least 190 mmHg in women. Homocysteine and other biochemical parameters were determined with standardized automated laboratory tests. Mean age of all participants is 47.9±8.5 years, and 36 of 84 participants were female. The frequency of diabetes mellitus in both groups was similar (P=0.250). Homeostasis model assessment index-insulin resistance had a statistically insignificant trend to be higher in a patient with exercise hypertension (P=0.058). The nonalcoholic fatty liver was more frequent in patients with exercise hypertension (13.6 vs. 47.5%, P=0.002). Epicardial fat thickness was increased in patients with exercise hypertension (5.5±1.5 vs. 7.3±1.1 mm; P=0.001). However, homocysteine levels did not significantly differ between normotensive and exercise hypertensive patients [12.3 μmol/l (5.7-16.9 μmol/l) vs. 13 μmol/l (5.9-28.3 μmol/l); P=0.883]. In our study, homocysteine levels were not associated with exaggerated blood pressure response to exercise; however, fatty liver and epicardial fat thickness as visceral adiposity-related cardiometabolic risk factors were significantly related with exaggerated blood pressure response to exercise in patients without a previous diagnosis of hypertension.

  12. Prenatal folate, homocysteine and vitamin B12 levels and child brain volumes, cognitive development and psychological functioning: the Generation R Study.

    PubMed

    Ars, Charlotte L; Nijs, Ilse M; Marroun, Hanan E; Muetzel, Ryan; Schmidt, Marcus; Steenweg-de Graaff, Jolien; van der Lugt, Aad; Jaddoe, Vincent W; Hofman, Albert; Steegers, Eric A; Verhulst, Frank C; Tiemeier, Henning; White, Tonya

    2016-01-22

    Previous studies have suggested that prenatal maternal folate deficiency is associated with reduced prenatal brain growth and psychological problems in offspring. However, little is known about the longer-term impact. The aims of this study were to investigate whether prenatal maternal folate insufficiency, high total homocysteine levels and low vitamin B12 levels are associated with altered brain morphology, cognitive and/or psychological problems in school-aged children. This study was embedded in Generation R, a prospective population-based cohort study. The study sample consisted of 256 Dutch children aged between 6 and 8 years from whom structural brain scans were collected using MRI. The mothers of sixty-two children had insufficient (9·1 µmol/l) predicted poorer performance on the language (B -0·31; 95 % CI -0·56, -0·06; P=0·014) and visuo-spatial domains (B -0·36; 95 % CI -0·60, -0·11; P=0·004). No associations with psychological problems were found. Our findings suggest that folate insufficiency in early pregnancy has a long-lasting, global effect on brain development and is, together with homocysteine levels, associated with poorer cognitive performance.

  13. Homocysteine and reactive oxygen species in metabolic syndrome, type 2 diabetes mellitus, and atheroscleropathy: The pleiotropic effects of folate supplementation

    PubMed Central

    Hayden, Melvin R; Tyagi, Suresh C

    2004-01-01

    Homocysteine has emerged as a novel independent marker of risk for the development of cardiovascular disease over the past three decades. Additionally, there is a graded mortality risk associated with an elevated fasting plasma total homocysteine (tHcy). Metabolic syndrome (MS) and type 2 diabetes mellitus (T2DM) are now considered to be a strong coronary heart disease (CHD) risk enhancer and a CHD risk equivalent respectively. Hyperhomocysteinemia (HHcy) in patients with MS and T2DM would be expected to share a similar prevalence to the general population of five to seven percent and of even greater importance is: Declining glomerular filtration and overt diabetic nephropathy is a major determinant of tHcy elevation in MS and T2DM. There are multiple metabolic toxicities resulting in an excess of reactive oxygen species associated with MS, T2DM, and the accelerated atherosclerosis (atheroscleropathy). HHcy is associated with an increased risk of cardiovascular disease, and its individual role and how it interacts with the other multiple toxicities are presented. The water-soluble B vitamins (especially folate and cobalamin-vitamin B12) have been shown to lower HHcy. The absence of the cystathionine beta synthase enzyme in human vascular cells contributes to the importance of a dual role of folic acid in lowering tHcy through remethylation, as well as, its action of being an electron and hydrogen donor to the essential cofactor tetrahydrobiopterin. This folate shuttle facilitates the important recoupling of the uncoupled endothelial nitric oxide synthase enzyme reaction and may restore the synthesis of the omnipotent endothelial nitric oxide to the vasculature. PMID:15134582

  14. A potential fluorescent probe: Maillard reaction product from glutathione and ascorbic acid for rapid and label-free dual detection of Hg(2+) and biothiols.

    PubMed

    Dong, Jiang Xue; Song, Xiao Fang; Shi, Yan; Gao, Zhong Feng; Li, Bang Lin; Li, Nian Bing; Luo, Hong Qun

    2016-07-15

    Maillard reactions and their fluorescent products have drawn much attention in the fields of food and life science, however, the application of fluorescent products separated from the reaction as an indicator for detection of certain substances in sensor field has not been mentioned. In this article, we report on an easy-to-synthesize and water-soluble fluorescent probe separated from the typical Maillard reaction products of glutathione and ascorbic acid, with excellent stability and high quantum yield (18.2%). The further application of the probe has been explored for dual detection of Hg(2+) and biothiols including cysteine, homocysteine, and glutathione, which is based on Hg(2+)-induced fluorescence quenching of the Maillard reaction fluorescent products (MRFPs) and the fluorescence recovery as the introduction of biothiols. This sensing system exhibits a good selectivity and sensitivity, and the linear ranges for Hg(2+), cysteine, homocysteine, and glutathione are 0.05-12, 0.5-10, 0.3-20, and 0.3-20μM, respectively. The detection limits for Hg(2+), cysteine, homocysteine, and glutathione are 22, 47, 96, and 30nM at a signal-to-noise ratio of 3, respectively. Furthermore, the practical applications of this sensor for Hg(2+) and biothiols determination in water samples and human plasma sample have been demonstrated with satisfactory results. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Preconception B-vitamin and homocysteine status, conception, and early pregnancy loss.

    PubMed

    Ronnenberg, Alayne G; Venners, Scott A; Xu, Xiping; Chen, Changzhong; Wang, Lihua; Guang, Wenwei; Huang, Aiqun; Wang, Xiaobin

    2007-08-01

    Maternal vitamin status contributes to clinical spontaneous abortion, but the role of B-vitamin and homocysteine status in subclinical early pregnancy loss is unknown. Three-hundred sixty-four textile workers from Anqing, China, who conceived at least once during prospective observation (1996-1998), provided daily urine specimens for up to 1 year, and urinary human chorionic gonadotropin was assayed to detect conception and early pregnancy loss. Homocysteine, folate, and vitamins B6 and B12 were measured in preconception plasma. Relative to women in the lowest quartile of vitamin B6, those in the third and fourth quartiles had higher adjusted proportional hazard ratios of conception (hazard ratio (HR)=2.2, 95% confidence interval (CI): 1.3, 3.4; HR=1.6, 95% CI: 1.1, 2.3, respectively), and the adjusted odds ratio for early pregnancy loss in conceptive cycles was lower in the fourth quartile (odds ratio=0.5, 95% CI: 0.3, 1.0). Women with sufficient vitamin B6 had a higher adjusted hazard ratio of conception (HR=1.4, 95% CI: 1.1, 1.9) and a lower adjusted odds ratio of early pregnancy loss in conceptive cycles (odds ratio=0.7, 95% CI: 0.4, 1.1) than did women with vitamin B6 deficiency. Poor vitamin B6 status appears to decrease the probability of conception and to contribute to the risk of early pregnancy loss in this population.

  16. Folic Acid Supplementation Delays Atherosclerotic Lesion Development by Modulating MCP1 and VEGF DNA Methylation Levels In Vivo and In Vitro

    PubMed Central

    Cui, Shanshan; Li, Wen; Lv, Xin; Wang, Pengyan; Gao, Yuxia; Huang, Guowei

    2017-01-01

    The pathogenesis of atherosclerosis has been partly acknowledged to result from aberrant epigenetic mechanisms. Accordingly, low folate levels are considered to be a contributing factor to promoting vascular disease because of deregulation of DNA methylation. We hypothesized that increasing the levels of folic acid may act via an epigenetic gene silencing mechanism to ameliorate atherosclerosis. Here, we investigated the atheroprotective effects of folic acid and the resultant methylation status in high-fat diet-fed ApoE knockout mice and in oxidized low-density lipoprotein-treated human umbilical vein endothelial cells. We analyzed atherosclerotic lesion histology, folate concentration, homocysteine concentration, S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH), and DNA methyltransferase activity, as well as monocyte chemotactic protein-1 (MCP1) and vascular endothelial growth factor (VEGF) expression and promoter methylation. Folic acid reduced atherosclerotic lesion size in ApoE knockout mice. The underlying folic acid protective mechanism appears to operate through regulating the normal homocysteine state, upregulating the SAM: SAH ratio, elevating DNA methyltransferase activity and expression, altering MCP1 and VEGF promoter methylation, and inhibiting MCP1 and VEGF expression. We conclude that folic acid supplementation effectively prevented atherosclerosis by modifying DNA methylation through the methionine cycle, improving DNA methyltransferase activity and expression, and thus changing the expression of atherosclerosis-related genes. PMID:28475147

  17. Effect of Combined Treatment With Folic Acid, Vitamin B6, and Vitamin B12 on Plasma Biomarkers of Inflammation and Endothelial Dysfunction in Women.

    PubMed

    Christen, William G; Cook, Nancy R; Van Denburgh, Martin; Zaharris, Elaine; Albert, Christine M; Manson, JoAnn E

    2018-05-18

    The aim of this study was to determine whether reducing plasma homocysteine concentrations with long-term, combined treatment with folic acid, vitamin B 6 , and vitamin B 12 alters plasma biomarkers of inflammation and endothelial dysfunction in women at increased risk of cardiovascular disease. We conducted a blood substudy of 300 treatment-adherent participants (150 in the active treatment group, 150 in the placebo group) in the WAFACS (Women's Antioxidant and Folic Acid Cardiovascular Study), a randomized, double-blind, placebo-controlled trial testing a daily combination of folic acid (2.5 mg), vitamin B 6 (50 mg), vitamin B 12 (1 mg), or matching placebo, in cardiovascular disease prevention among women at increased risk of cardiovascular disease. Plasma concentration of 3 biomarkers of inflammation (C-reactive protein, interleukin-6, and fibrinogen) and a biomarker of endothelial dysfunction (intercellular adhesion molecule 1) were measured at baseline and at the end of treatment and follow-up. After 7.3 years of combined treatment with folic acid, vitamin B 6 , and vitamin B 12 , homocysteine concentrations were reduced by 18% in the active treatment group as compared with the placebo group ( P <0.001). However, there was no difference between treatment groups in change in blood concentration from baseline to follow-up for C-reactive protein ( P =0.77), interleukin-6 ( P =0.91), intercellular adhesion molecule 1 ( P =0.38), or fibrinogen ( P =0.68). These findings indicate that long-term, combined treatment with folic acid, vitamin B 6 , and vitamin B 12 lowers homocysteine concentrations, but does not alter major biomarkers of vascular inflammation, consistent with the lack of clinical cardiovascular disease benefit in the trial. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000541. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  18. The effects and potential mechanisms of folic acid on cognitive function: a comprehensive review.

    PubMed

    Enderami, Athena; Zarghami, Mehran; Darvishi-Khezri, Hadi

    2018-06-23

    Cognitive impairment and dementia are major neurocognitive disorders that cause a noticeable decline in cognitive abilities, including memory and thinking skills. The effectiveness of using folic acid as an adjuvant for management of neurocognitive disorders is not well-known. This paper explains the role of folic acid, including its usefulness, effectiveness, adverse side effects, and active mechanisms on cognitive functions of the elderly. In the current study, we reviewed clinical and experimental studies investigating the use of folic acid prior to November 2017, using PubMed, ISI Web of Knowledge, Science Direct, Scopus, Ovid, and Cochrane Library databases. A total of 142 articles were retrieved by electronic search. Based on the preset inclusion and exclusion criteria, a total of 36 articles were retrieved for full text analysis. According to data obtained from the review, it seems that folic acid supplementation may improve cognitive function by decreasing homocysteine (Hcy), vascular care, attenuating inflammatory status, modification of cerebral folic acid deficiency, and antioxidant responses. Specifically, people with high levels of Hcy have a better response to folic acid supplementation, which may arise from low serum folate concentration.

  19. Low folate status enhances pregnancy changes in plasma betaine and dimethylglycine concentrations and the association between betaine and homocysteine.

    PubMed

    Fernàndez-Roig, Sílvia; Cavallé-Busquets, Pere; Fernandez-Ballart, Joan D; Ballesteros, Monica; Berrocal-Zaragoza, Maria Isabel; Salat-Batlle, Judith; Ueland, Per M; Murphy, Michelle M

    2013-06-01

    Folate, choline, and betaine participate in homocysteine metabolism. It is not known whether they interact during pregnancy. The objective was to investigate how folate status affects choline, betaine, and dimethylglycine during pregnancy. Fasting plasma folate, cobalamin, free choline, betaine, dimethylglycine, and total homocysteine (tHcy) were measured longitudinally at <12, 15, 24-27, and 34 gestational weeks (GW); at labor (nonfasting); and in the cord in participants (n = 522) from the Reus-Tarragona Birth Cohort (NUTrició i Creixement Intrauterí Retardat phase). Timing, dose, and duration of folic acid supplement use were recorded. Folate status was classified as below (low) or above (high) median plasma folate at baseline (27.6 nmol/L) and at 24-27 GW (11.4 nmol/L). Associations between folate or betaine with tHcy were investigated by using multiple linear regression analysis. Plasma betaine decreased by 34.8% (1.0%) throughout pregnancy, and dimethylglycine increased by 39.7% (2.7%) between 24-27 GW and labor (all P < 0.001). Compared with high folate status, low status was associated with a higher dimethylglycine/betaine ratio from 15 GW and with lower plasma betaine and higher dimethylglycine from 24 to 27 GW, for the rest of pregnancy. Regression analysis showed that by 24-27 GW, both plasma folate and betaine were inversely associated with tHcy when folate status was low and that the association between betaine and tHcy depended on folate status at 24-27 and 34 GW (interaction terms: P < 0.001 and P < 0.01). Betaine was inversely associated with tHcy at labor regardless of folate status. Low folate status enhances the reduction in betaine and the increase in dimethylglycine during pregnancy and strengthens the association between betaine and tHcy. This trial was registered at clinicaltrials.gov as NCT01778205.

  20. On the acid-base properties of humic acid in soil.

    PubMed

    Cooke, James D; Hamilton-Taylor, John; Tipping, Edward

    2007-01-15

    Humic acid was isolated from three contrasting organic-rich soils and acid-base titrations performed over a range of ionic strengths. Results obtained were unlike most humic acid data sets; they showed a greater ionic strength dependency at low pH than at high pH. Forward- and back-titrations with the base and acid revealed hysteresis, particularly at low pH. Previous authors attributed this type of hysteresis to humic acid aggregates-created during the isolation procedure-being redissolved during titration as the pH increased and regarded the results as artificial. However, forward- and back-titrations with organic-rich soils also demonstrated a similar hysteretic behavior. These observations indicate (i) that titrations of humic acid in aggregated form (as opposed to the more usual dissolved form) are more representative of the acid-base properties of humic acid in soil and (ii) that the ionic strength dependency of proton binding in humic acid is related to its degree of aggregation. Thus, the current use of models based on data from dissolved humic substances to predictthe acid-base properties of humic acid in soil under environmental conditions may be flawed and could substantially overestimate their acid buffering capacity.

  1. The first proton sponge-based amino acids: synthesis, acid-base properties and some reactivity.

    PubMed

    Ozeryanskii, Valery A; Gorbacheva, Anastasia Yu; Pozharskii, Alexander F; Vlasenko, Marina P; Tereznikov, Alexander Yu; Chernov'yants, Margarita S

    2015-08-21

    The first hybrid base constructed from 1,8-bis(dimethylamino)naphthalene (proton sponge or DMAN) and glycine, N-methyl-N-(8-dimethylamino-1-naphthyl)aminoacetic acid, was synthesised in high yield and its hydrobromide was structurally characterised and used to determine the acid-base properties via potentiometric titration. It was found that the basic strength of the DMAN-glycine base (pKa = 11.57, H2O) is on the level of amidine amino acids like arginine and creatine and its structure, zwitterionic vs. neutral, based on the spectroscopic (IR, NMR, mass) and theoretical (DFT) approaches has a strong preference to the zwitterionic form. Unlike glycine, the DMAN-glycine zwitterion is N-chiral and is hydrolytically cleaved with the loss of glycolic acid on heating in DMSO. This reaction together with the mild decarboxylative conversion of proton sponge-based amino acids into 2,3-dihydroperimidinium salts under air-oxygen was monitored with the help of the DMAN-alanine amino acid. The newly devised amino acids are unique as they combine fluorescence, strongly basic and redox-active properties.

  2. Targeted metabolomics analysis reveals the association between maternal folic acid supplementation and fatty acids and amino acids profiles in rat pups.

    PubMed

    Liu, Zhipeng; Liu, Rui; Chou, Jing; Yu, Jiaying; Liu, Xiaowei; Sun, Changhao; Li, Ying; Liu, Liyan

    2018-07-15

    Maternal diet during pregnancy can influence offspring's health by affecting development and metabolism. This study aimed to analyze the influence of maternal folic acid (FA) supplementation on the metabolism of rat pups using targeted metabolomics. Twenty female rats were randomly assigned to a FA supplementation (FAS group, n = 10) or control group (n = 10), which were fed AIN93G diet with 2 or 10 mg/kg FA, respectively. We then measured amino acids and their derivatives, biogenic amines, and fatty acids in the female rats and their pups by ultra-high performance liquid chromatography-triple quadrupole mass spectrometry (UHPLC/MS-MS) and gas chromatography-mass spectrometry (GC/MS-MS). In maternal rats, the significant changes of three metabolites (proline, γ-aminobutyric acid and esterified octadecatetraenoic acid, P < 0.05) were observed in FAS group. For the rat pups, FAS pups had significantly lower homocysteine and higher FA levels than control pups. The lower levels of amino acids (leucine, isoleucine, serine, proline) were obtained in FAS pups. Furthermore, there were the decreased esterified fatty acids (arachidonic acid, eicosapentaenoic acid, and docosatetraenoic acid) and free fatty acids (oleic acid, linoleic acid, γ-linolenic acid, octadecatetraenoic acid, arachidonic acid, eicosapentaenoic acid and selacholeic acid) in FAS pups. Metabolic changes in the FAS pups were characterized by changes in fatty acids and amino acids. These results suggested that FA supplementation during pregnancy influenced amino acids and fatty acids metabolism in rat pups. This study provides new insights into the regulation of amino acids and fatty acids metabolism during early life. Copyright © 2018 Elsevier B.V. All rights reserved.

  3. Endothelial function and its relationship to leptin, homocysteine, and insulin resistance in lean and overweight eumenorrheic women and PCOS patients: a pilot study.

    PubMed

    Mancini, Fulvia; Cianciosi, Arianna; Reggiani, Giulio Marchesini; Facchinetti, Fabio; Battaglia, Cesare; de Aloysio, Domenico

    2009-06-01

    To verify if patients with polycystic ovarian syndrome (PCOS), have an increased cardiovascular risk compared with healthy controls. Prospective case-control study. University-based practice. Twenty eumenorrheic controls (ten lean [group A] and ten overweight [group B]) and 24 PCOS women (14 lean [group C] and ten overweight [group D]). Cardiovascular risk markers and hormonal parameters were assessed. Androgens, fasting glucose, insulin, leptin, fibrinogen, homocysteine, endothelin-1 and flow-mediated dilatation of the brachial artery were measured to investigate their relationship to weight and to PCOS. The brachial artery diameter and the pulsatility index, after the reactive hyperemia, showed in group A the most intense vasodilatation compared with the other groups. Homocysteine levels did not differ among the groups. Endothelin-1 was significantly higher in group A compared with groups B and D. Leptin was significantly lower in groups A and C compared with groups B and D. Insulin resistance was higher in groups B and D. Group A had significantly higher glucose-insulin ratio compared with all of the other groups; group C had significantly higher glucose-insulin ratio only compared with group D. Weight and PCOS are two independent variables affecting the endothelial function.

  4. The effects of L-cysteine and N-acetyl-L-cysteine on homocysteine metabolism and haemostatic markers, and on cardiac and aortic histology in subchronically methionine-treated Wistar male rats.

    PubMed

    Kostić, Sanja; Mićovic, Žarko; Andrejević, Lazar; Cvetković, Saša; Stamenković, Aleksandra; Stanković, Sanja; Obrenović, Radmila; Labudović-Borović, Milica; Hrnčić, Dragan; Jakovljević, Vladimir; Djurić, Dragan

    2018-06-23

    Methionine is the precursor of homocysteine, a sulfur amino acid intermediate in the methylation and transsulfuration pathways; methionine-rich diets were used to induce hyperhomocysteinemia, and cardiovascular pathology was often observed. Other sulfur amino acids interfere with this metabolism, i.e., L-cysteine (Cys) and N-aceyl-L-cysteine (NAC), and probably also affect cardiovascular system. Their effects are controversial due to their ability to act both as anti- or pro-oxidant. Thus, this study aimed to elucidate their influence on levels of homocysteine, folate and vitamin B12, levels of different haemostatic parameters (fibrinogen, D-dimer, vWF Ag, vWF Ac) in rat serum or plasma as well as their effects on cardiac and aortic tissue histology in subchronically methionine-treated rats. Wistar albino rats were divided into 4 experimental groups: (a) control group (0.9% sodium chloride 0.1-0.2 mL/day) (n = 10) (K); (b) DL-methionine (0.8 mmol/kg/bw/day) (n = 10) (M); (c) DL-methionine (0.8 mmol/kg/bw/day) + L-cysteine (7 mg/kg/bw/day) (n = 8) (C); (d) DL-methionine (0.8 mmol/ kg/bw/day) + N-acetyl-L-cysteine (50 mg/kg/bw/day) (n = 8) (N). All substances were applied i.p., treatment duration 3 weeks. Lower levels of vitamin B12 in all the groups were found. Folate was reduced only in N group. Decreased fibrinogen was noted in C and N groups and increased D-dimer only in C. VWF activity was reduced in M and C groups. Deleterious effects in heart were observed, especially after Cys and NAC application. Aortic tissue remained unchanged. In conclusion, it could be said that sulfur amino acids have the significant impact on cardiovascular system in subchronically methionine-treated rats. This study points out the relevance of their complex interactions and deleterious effects mediated by either direct influence or procoagulant properties.

  5. Physiological Characteristics and Production of Folic Acid of Lactobacillus plantarum JA71 Isolated from Jeotgal, a Traditional Korean Fermented Seafood

    PubMed Central

    Lim, Sang-Dong

    2014-01-01

    Folic acid, one of the B group of vitamins, is an essential substance for maintaining the functions of the nervous system, and is also known to decrease the level of homocysteine in plasma. Homocysteine influences the lowering of the cognitive function in humans, and especially in elderly people. In order to determine the strains with a strong capacity to produce folic acid, 190 bacteria were isolated from various kinds of jeotgal and chungkuk-jang. In our test experiment, JA71 was found to contain 9.03μg/mL of folic acid after 24 h of incubation in an MRS broth. This showed that JA71 has the highest folic acid production ability compared to the other lactic acid bacteria that were isolated. JA71 was identified as Lactobacillus plantarum by the result of API carbohydrate fermentation pattern and 16s rDNA sequence. JA71 was investigated for its physiological characteristics. The optimum growth temperature of JA71 was 37℃, and the cultures took 12 h to reach pH 4.4. JA71 proved more sensitive to bacitracin when compared with fifteen different antibiotics, and showed most resistance to neomycin and vancomycin. Moreover, it was comparatively tolerant of bile juice and acid, and displayed resistance to Escherichia coli, Salmonella Typhimurium, and Staphylococcus aureus with restraint rates of 60.4%, 96.7%, and 76.2%, respectively. These results demonstrate that JA71 could be an excellent strain for application to functional products. PMID:26760752

  6. Complexity in Acid-Base Titrations: Multimer Formation Between Phosphoric Acids and Imines.

    PubMed

    Malm, Christian; Kim, Heejae; Wagner, Manfred; Hunger, Johannes

    2017-08-10

    Solutions of Brønsted acids with bases in aprotic solvents are not only common model systems to study the fundamentals of proton transfer pathways but are also highly relevant to Brønsted acid catalysis. Despite their importance the light nature of the proton makes characterization of acid-base aggregates challenging. Here, we track such acid-base interactions over a broad range of relative compositions between diphenyl phosphoric acid and the base quinaldine in dichloromethane, by using a combination of dielectric relaxation and NMR spectroscopy. In contrast to what one would expect for an acid-base titration, we find strong deviations from quantitative proton transfer from the acid to the base. Even for an excess of the base, multimers consisting of one base and at least two acid molecules are formed, in addition to the occurrence of proton transfer from the acid to the base and simultaneous formation of ion pairs. For equimolar mixtures such multimers constitute about one third of all intermolecular aggregates. Quantitative analysis of our results shows that the acid-base association constant is only around six times larger than that for the acid binding to an acid-base dimer, that is, to an already protonated base. Our findings have implications for the interpretation of previous studies of reactive intermediates in organocatalysis and provide a rationale for previously observed nonlinear effects in phosphoric acid catalysis. © 2017 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

  7. Multimodal switching of conformation and solubility in homocysteine derived polypeptides.

    PubMed

    Kramer, Jessica R; Deming, Timothy J

    2014-04-16

    We report the design and synthesis of poly(S-alkyl-L-homocysteine)s, which were found to be a new class of readily prepared, multiresponsive polymers that possess the unprecedented ability to respond in different ways to different stimuli, either through a change in chain conformation or in water solubility. The responsive properties of these materials are also effected under mild conditions and are completely reversible for all pathways. The key components of these polymers are the incorporation of water solubilizing alkyl functional groups that are integrated with precisely positioned, multiresponsive thioether linkages. This promising system allows multimodal switching of polypeptide properties to obtain desirable features, such as coupled responses to multiple external inputs.

  8. Association of obstructive sleep apnea with homocystein, nitric oxide and total antioxidant capacity levels in patients with or without coronary artery disease.

    PubMed

    Ortaç Ersoy, Ebru; Fırat, Hikmet; Akaydın, Sevgi; Özkan, Yeşim; Durusu, Mine; Darılmaz Yüce, Gülbahar; Ergün, Recai; Topeli, Arzu; Ardıç, Sadık

    2014-01-01

    Obstructive sleep apnea (OSA) is associated with cardiovascular morbidity and mortality. Deficiency of nitric oxide (NO) and plasma levels of homocystein have been implicated in the pathogenesis of cardiovascular disease. OSA results in oxygen desaturation and arousal from sleep. Free oxygen radicals can be produced by hypoxia-reoxygenation. To test for the hypothesis that OSA is associated with cardiovascular morbidity, we investigated levels of homocystein, NO and total antioxidant capacity in OSA patients with and without coronary artery disease (CAD) in comparison with normal subjects and patients with CAD without OSA. Polysomnography was performed in 27 patients who had a myocardial infarction and in 25 patients without evidence of CAD. Patients were grouped according their polysomnography results as OSA with CAD (group 1), OSA without CAD (group 2), CAD (group 3), and normal (group 4) . Levels of homocystein, NO and total antioxidant capacity were determined after an overnight fasting. Data were analysed with parametric and non parametric statistical tests. According to apnea-hypopnea index (AHI) 44.4% of CAD patients were OSA. After polysomnographic evaluation, the patients were re-distributed as follows: OSA with CAD (n= 12), OSA without CAD (n= 14), CAD (n= 15), and normal (n= 11). Homocystein levels were higher in 3 groups compared to controls. AHI, MDI and desaturation time was higher in three -vessel disease compared to one and two- vessel diseases (p< 0.05). NO levels were correlated with the period of oxygen desaturation (r: -0.45, p= 0.031). The antioxidant capacity did not differ between OSA and healthy groups. OSA is frequent in CAD. AHI, MDI and desaturation time are higher in patients with severe CAD. It is important to evaluate OSA patients for CAD.

  9. Synthesis of new kojic acid based unnatural α-amino acid derivatives.

    PubMed

    Balakrishna, C; Payili, Nagaraju; Yennam, Satyanarayana; Uma Devi, P; Behera, Manoranjan

    2015-11-01

    An efficient method for the preparation of kojic acid based α-amino acid derivatives by alkylation of glycinate schiff base with bromokojic acids have been described. Using this method, mono as well as di alkylated kojic acid-amino acid conjugates have been prepared. This is the first synthesis of C-linked kojic acid-amino acid conjugate where kojic acid is directly linked to amino acid through a C-C bond. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Choline and vitamin B12 deficiencies are interrelated in folate-replete long-term total parenteral nutrition patients.

    PubMed

    Compher, Charlene W; Kinosian, Bruce P; Stoner, Nancy E; Lentine, Deborah C; Buzby, Gordon P

    2002-01-01

    Choline has recently been recognized as an essential nutrient, in part based on deficiency data in long-term home total parenteral nutrition (TPN) patients. Choline, a methyl donor in the metabolism of homocysteine, is intricately related to folate status, but little is known about choline and vitamin B12 status. Long-term TPN patients are also subject to vitamin B12 deficiency. The objective of the study was to evaluate any interaction between choline, vitamin B12, and folate in patients with severe malabsorption syndromes, requiring long-term TPN. Plasma free choline, serum and red blood cell (RBC) folate, serum vitamin B12 methylmalonic acid, B6, and plasma total homocysteine concentrations were assayed by standard methods. Low choline was defined as values that fall 1 to < or =3 and marked low choline concentration as >3 SD below the control mean. Both low choline concentrations (52% were marked low, 33% low, 14% normal) and elevated methylmalonic acid concentrations (47%) were prevalent. Choline concentration was significantly lower and RBC folate higher in patients with elevated methylmalonic acid. Total homocysteine elevations were rare (3 of 21) and mild. These data suggest a strong interaction between vitamin B12 and choline deficiencies and folate status in this population, which may be due in part to variations in vitamin and choline delivery by TPN. Folate adequacy may increase B12 use for homocysteine metabolism, thus limiting B12 availability for methylmaIonic acid metabolism. Choline use may also increase, and choline deficiency may worsen if choline substitutes when the vitamin B12 side of the homocysteine metabolic pathway cannot be used.

  11. Hyperhomocysteinaemia in children receiving phenytoin and carbamazepine monotherapy: a cross-sectional observational study.

    PubMed

    Chandrasekaran, Saravanan; Patil, Sooraj; Suthar, Renu; Attri, Savita Verma; Sahu, Jitendra Kumar; Sankhyan, Naveen; Tageja, Mini; Singhi, Pratibha

    2017-04-01

    Long-term therapy with phenytoin and carbamazepine is known to cause hyperhomocysteinaemia. We evaluated the prevalence of hyperhomocysteinaemia in North Indian children receiving phenytoin or carbamazepine monotherapy for >6 months duration and the effect of folic acid supplementation on plasma homocysteine. In this cross-sectional observational study we enrolled consecutive children aged 2-12 years with epilepsy who had received phenytoin or carbamazepine monotherapy for >6 months. Plasma total homocysteine, folic acid, vitamin B12 and antiepileptic drug concentrations were measured. Healthy age- and sex-matched controls were recruited. Children with homocysteine >10.4 µmol/L received folic acid supplementation for 1 month and homocysteine and folic acid concentrations were measured after 1 month follow-up. A total of 112 children receiving antiepileptic monotherapy for >6 months were enrolled. Hyperhomocysteinaemia was present in 54 children (90%) receiving phenytoin, 45 children (90%) receiving carbamazepine therapy and 17 (34%) controls (p<0.05). Mean plasma homocysteine concentrations were significantly higher (18.9±10.2 vs 9.1±3 µmol/L) and serum folic acid concentrations (10.04±8.5 ng/ml vs 12.6±4.8 p<0.001) and vitamin B12 concentrations (365±155 pg/mL vs 474±332 pg/mL, p=0.02) were significantly lower in the study group compared with the control group. Duration of antiepileptic drug therapy correlated significantly with elevated homocysteine and reduced folic acid concentrations (p<0.05). Supplementation with folic acid for 1 month led to a reduction in plasma homocysteine concentrations in the study group (from 20.9±10.3 µmol/L to 14.2±8.2 µmol/L, p<0.05). Phenytoin or carbamazepine monotherapy for >6 months duration is associated with hyperhomocysteinaemia in 90% of North Indian children. Elevated homocysteine concentrations were normalised in these children with folic acid supplementation. Published by the BMJ

  12. Study of wheat breakfast rolls fortified with folic acid. The effect on folate status in women during a 3-month intervention.

    PubMed

    Johansson, Madelene; Witthöft, Cornelia M; Bruce, Ake; Jägerstad, Margaretha

    2002-12-01

    Folate has come into focus due to its protective role against child birth defects such as neural tube defects (NTD). Swedish authorities recommend all fertile women to increase their folate intake to 400 microg/day by eating folate-rich foods. Because not all women follow these recommendations, there is a discussion today about whether Sweden should introduce folic acid fortification in wheat flour and sifted rye flour. This decision needs knowledge about the bioavailability of folic acid from fortified foods. To investigate effects of two folic acid fortification levels on folate status in healthy female volunteers and to study the folic acid stability during the baking procedure and storage of the fortified breakfast rolls. Twenty-nine healthy women were recruited. Folic acid-fortified wheat breakfast rolls were baked with the purpose to contain 200 microg folic acid/roll (roll L) and 400 microg folic acid/roll (roll H). Fourteen women were given one roll/day of roll L (group L) and 15 one roll/day of roll H (group H) during 12 weeks of intervention. Fasting venous blood samples were collected on days 0, 30, 60 and 90. Serum homocysteine concentrations were determined using an immunoassay. Serum and erythrocyte folate concentrations were analysed using a protein-binding assay with fluorescent quantification. The folic acid concentration in the breakfast rolls was analysed by HPLC on days 0, 30, 60 and 90. Total folate concentration was measured with microbiological assay on day 45. Group L Group L had initially an average erythrocyte folate concentration of 577 +/- 93 nmol/L. After 90 days of intervention, an increase of 20 % (p < 0.05) was observed. At day 0, mean serum folate concentrations were 16.9 +/- 4.3 nmol/L. The mean serum folate concentrations increased by 30 % (p < 0.001) after 90 days. At day 0, mean serum homocysteine concentrations were 9.1 +/- 2.0 micromol/L, which decreased by 20 % (p < 0.01) after 30 days. Group H Group H had an initial

  13. Cognitive impairment in folate-deficient rats corresponds to depleted brain phosphatidylcholine and is prevented by methionine without lowering homocysteine

    USDA-ARS?s Scientific Manuscript database

    Poor folate status is associated with cognitive decline and dementia in older adults. Although impaired brain methylation activity and homocysteine toxicity are widely believed to account for this association, how folate deficiency impairs cognition is uncertain. To better define the role of folate ...

  14. Suppression Effects of Betaine-Enriched Spinach on Hyperhomocysteinemia Induced by Guanidinoacetic Acid and Choline Deficiency in Rats

    PubMed Central

    Liu, Yi-Qun; Jia, Zheng; Han, Feng; Inakuma, Takahiro; Miyashita, Tatsuya; Sugiyama, Kimio; Sun, Li-Cui; Xiang, Xue-Song; Huang, Zhen-Wu

    2014-01-01

    Betaine is an important natural component of rich food sources, especially spinach. Rats were fed diets with betaine or spinach powder at the same level of betaine for 10 days to investigate the dose-dependent effects of spinach powder supplementation on hyperhomocysteinemia induced by guanidinoacetic acid (GAA) addition and choline deprivation. The GAA-induced hyperhomocysteinemia in rats fed 25% casein diet (25C) was significantly suppressed by supplementation with betaine or spinach, and it was completely suppressed by taking 11.0% spinach supplementation. The choline deprivation-induced enhancement of plasma homocysteine concentration in rats fed 25% soybean protein diet (25S) was markedly suppressed by 3.82% spinach. Supplementation with betaine or spinach partially prevented the effects of GAA on hepatic concentrations of methionine metabolites. The decrease in activity of betaine-homocysteine S-methyltransferase (BHMT) and cystathionine β-synthase (CBS) in GAA-induced hyperhomocysteinemia was recovered by supplementation with betaine or spinach. Supplementation with betaine or spinach did not affect BHMT activity, whereas it partially restored CBS activity in choline-deprived 25S. The results indicated that betaine or spinach could completely suppress the hyperhomocysteinemia induced by choline deficiency resulting from stimulating the homocysteine removal by both remethylation and cystathionine formation. PMID:25250392

  15. Suppression effects of betaine-enriched spinach on hyperhomocysteinemia induced by guanidinoacetic acid and choline deficiency in rats.

    PubMed

    Liu, Yi-Qun; Jia, Zheng; Han, Feng; Inakuma, Takahiro; Miyashita, Tatsuya; Sugiyama, Kimio; Sun, Li-Cui; Xiang, Xue-Song; Huang, Zhen-Wu

    2014-01-01

    Betaine is an important natural component of rich food sources, especially spinach. Rats were fed diets with betaine or spinach powder at the same level of betaine for 10 days to investigate the dose-dependent effects of spinach powder supplementation on hyperhomocysteinemia induced by guanidinoacetic acid (GAA) addition and choline deprivation. The GAA-induced hyperhomocysteinemia in rats fed 25% casein diet (25 C) was significantly suppressed by supplementation with betaine or spinach, and it was completely suppressed by taking 11.0% spinach supplementation. The choline deprivation-induced enhancement of plasma homocysteine concentration in rats fed 25% soybean protein diet (25S) was markedly suppressed by 3.82% spinach. Supplementation with betaine or spinach partially prevented the effects of GAA on hepatic concentrations of methionine metabolites. The decrease in activity of betaine-homocysteine S-methyltransferase (BHMT) and cystathionine β-synthase (CBS) in GAA-induced hyperhomocysteinemia was recovered by supplementation with betaine or spinach. Supplementation with betaine or spinach did not affect BHMT activity, whereas it partially restored CBS activity in choline-deprived 25S. The results indicated that betaine or spinach could completely suppress the hyperhomocysteinemia induced by choline deficiency resulting from stimulating the homocysteine removal by both remethylation and cystathionine formation.

  16. HYPERHOMOCYSTEINEMIA AND ITS TREATMENT IN PATIENTS WITH PARKINSON’S DISEASE

    PubMed Central

    Ibrahimagic, Omer C.; Smajlovic, Dzevdet; Dostovic, Zikrija; Pasic, Zejneba; Kunic, Suljo; Iljazovic, Amra; Hajdarevic, Denisa Salihovic

    2016-01-01

    Introduction: Homocysteine is process-product of methionine demethylation. It has proatherogenic, prothrombotic, prooxidative, proapoptotic, osteoporotic, neurotoxic, neuroinflamatory, and neurodegenerative effects. Hyperhomocysteinemia correlates with C667T MTHFR mutation, decrease of folic acid and vitamin B, as well as prolonged use of certain medications. Materials and Methods: We measured levels of homocysteine in thirty patients (15::15) with “de novo” Parkinson’s disease, with average age 64.17 ± 13.19 (28-82) years (Department of Neurology, University Clinical Center Tuzla). Normal level of homocysteine for women was 3.36-20.44 micromole/l and 5.9-16 micromole/l for men. We followed the effects of medicament approach (folic acid) every six months for next five years. Results: 20% of patients with “de novo” Parkinson’s disease exhibited hyperhomocysteinemia. An average level of homocysteine was 13.85 ± 5.82 micromole/l. Differences due to age and homocysteine levels, regardless of sex, were not concluded. For the next five years intake of folic acid (periodically, 1-2 months, 5 mg per day, orally) was effective to normalized levels of homocysteine in all. Conclusion: Hyperhomocysteinemia is present in every fifth patient with “de novo” Parkinson’s disease. Folic acid is medication of choice in treatment of hyperhomocysteinemia coexisting with Parkinson’s disease. PMID:27698607

  17. The Metabolic Burden of Methyl Donor Deficiency with Focus on the Betaine Homocysteine Methyltransferase Pathway

    PubMed Central

    Obeid, Rima

    2013-01-01

    Methyl groups are important for numerous cellular functions such as DNA methylation, phosphatidylcholine synthesis, and protein synthesis. The methyl group can directly be delivered by dietary methyl donors, including methionine, folate, betaine, and choline. The liver and the muscles appear to be the major organs for methyl group metabolism. Choline can be synthesized from phosphatidylcholine via the cytidine-diphosphate (CDP) pathway. Low dietary choline loweres methionine formation and causes a marked increase in S-adenosylmethionine utilization in the liver. The link between choline, betaine, and energy metabolism in humans indicates novel functions for these nutrients. This function appears to goes beyond the role of the nutrients in gene methylation and epigenetic control. Studies that simulated methyl-deficient diets reported disturbances in energy metabolism and protein synthesis in the liver, fatty liver, or muscle disorders. Changes in plasma concentrations of total homocysteine (tHcy) reflect one aspect of the metabolic consequences of methyl group deficiency or nutrient supplementations. Folic acid supplementation spares betaine as a methyl donor. Betaine is a significant determinant of plasma tHcy, particularly in case of folate deficiency, methionine load, or alcohol consumption. Betaine supplementation has a lowering effect on post-methionine load tHcy. Hypomethylation and tHcy elevation can be attenuated when choline or betaine is available. PMID:24022817

  18. Combined assessment of DYRK1A, BDNF and homocysteine levels as diagnostic marker for Alzheimer's disease.

    PubMed

    Janel, N; Alexopoulos, P; Badel, A; Lamari, F; Camproux, A C; Lagarde, J; Simon, S; Feraudet-Tarisse, C; Lamourette, P; Arbones, M; Paul, J L; Dubois, B; Potier, M C; Sarazin, M; Delabar, J M

    2017-06-20

    Early identification of Alzheimer's disease (AD) risk factors would aid development of interventions to delay the onset of dementia, but current biomarkers are invasive and/or costly to assess. Validated plasma biomarkers would circumvent these challenges. We previously identified the kinase DYRK1A in plasma. To validate DYRK1A as a biomarker for AD diagnosis, we assessed the levels of DYRK1A and the related markers brain-derived neurotrophic factor (BDNF) and homocysteine in two unrelated AD patient cohorts with age-matched controls. Receiver-operating characteristic curves and logistic regression analyses showed that combined assessment of DYRK1A, BDNF and homocysteine has a sensitivity of 0.952, a specificity of 0.889 and an accuracy of 0.933 in testing for AD. The blood levels of these markers provide a diagnosis assessment profile. Combined assessment of these three markers outperforms most of the previous markers and could become a useful substitute to the current panel of AD biomarkers. These results associate a decreased level of DYRK1A with AD and challenge the use of DYRK1A inhibitors in peripheral tissues as treatment. These measures will be useful for diagnosis purposes.

  19. Defective remethylation of homocysteine is related to decreased synthesis of coenzymes B2 in thyroidectomized rats.

    PubMed

    Ayav, A; Alberto, J M; Barbe, F; Brunaud, L; Gerard, P; Merten, M; Gueant, J L

    2005-02-01

    We investigated the influence of hypothyroidism on homocysteine metabolism in rats, focusing on a hypothetical deficient synthesis of FAD by riboflavin kinases. Animals were allocated in control group (n = 7), thyroidectomized rats (n = 6), rats with diet deficient in vitamin B2, B9, B12, choline and methionine (n = 7), thyroidectomized rats with deficient diet (n = 9). Homocysteine was decreased in operated rats (2.6 +/- 1.01 vs. 4.05 +/- 1.0 mumol/L, P = 0.02) and increased in deficient diet rats (29.56 +/- 4.52 vs. 4.05 +/- 1.0 micromol/L, P = 0.001), when compared to control group. Erythrocyte-Glutathione-Reductase-Activation-Coefficient (index of FAD deficiency) was increased in thyroidectomized or deficient diet rats (P = 0.004 for both). Methylenetetrahydrofolate-reductase and methionine-synthase activities were decreased in thyroidectomized rats but not in those subjected to deficient diet. Cystathionine-beta-synthase was increased only in operated rats. Taken together, these results showed a defective re-methylation in surgical hypothyroidism, which was due in part to a defective synthesis of vitamin B2 coenzymes. This defective pathway was overcompensated by the increased Cystathionine-beta-synthase activity.

  20. Neural Tube Defects, Folic Acid and Methylation

    PubMed Central

    Imbard, Apolline; Benoist, Jean-François; Blom, Henk J.

    2013-01-01

    Neural tube defects (NTDs) are common complex congenital malformations resulting from failure of the neural tube closure during embryogenesis. It is established that folic acid supplementation decreases the prevalence of NTDs, which has led to national public health policies regarding folic acid. To date, animal studies have not provided sufficient information to establish the metabolic and/or genomic mechanism(s) underlying human folic acid responsiveness in NTDs. However, several lines of evidence suggest that not only folates but also choline, B12 and methylation metabolisms are involved in NTDs. Decreased B12 vitamin and increased total choline or homocysteine in maternal blood have been shown to be associated with increased NTDs risk. Several polymorphisms of genes involved in these pathways have also been implicated in risk of development of NTDs. This raises the question whether supplementation with B12 vitamin, betaine or other methylation donors in addition to folic acid periconceptional supplementation will further reduce NTD risk. The objective of this article is to review the role of methylation metabolism in the onset of neural tube defects. PMID:24048206

  1. Sequential injection redox or acid-base titration for determination of ascorbic acid or acetic acid.

    PubMed

    Lenghor, Narong; Jakmunee, Jaroon; Vilen, Michael; Sara, Rolf; Christian, Gary D; Grudpan, Kate

    2002-12-06

    Two sequential injection titration systems with spectrophotometric detection have been developed. The first system for determination of ascorbic acid was based on redox reaction between ascorbic acid and permanganate in an acidic medium and lead to a decrease in color intensity of permanganate, monitored at 525 nm. A linear dependence of peak area obtained with ascorbic acid concentration up to 1200 mg l(-1) was achieved. The relative standard deviation for 11 replicate determinations of 400 mg l(-1) ascorbic acid was 2.9%. The second system, for acetic acid determination, was based on acid-base titration of acetic acid with sodium hydroxide using phenolphthalein as an indicator. The decrease in color intensity of the indicator was proportional to the acid content. A linear calibration graph in the range of 2-8% w v(-1) of acetic acid with a relative standard deviation of 4.8% (5.0% w v(-1) acetic acid, n=11) was obtained. Sample throughputs of 60 h(-1) were achieved for both systems. The systems were successfully applied for the assays of ascorbic acid in vitamin C tablets and acetic acid content in vinegars, respectively.

  2. A comparison of the effects of 2 doses of soy protein or casein on serum lipids, serum lipoproteins, and plasma total homocysteine in hypercholesterolemic subjects.

    PubMed

    Tonstad, Serena; Smerud, Knut; Høie, Lars

    2002-07-01

    Studies have shown that soy protein reduces some atherogenic lipid and lipoprotein concentrations, although lipoprotein(a) concentrations may be increased. The dose response of soy protein has not been established; neither has its effect on plasma total homocysteine. Our objective was to evaluate the effect of 2 doses of soy protein on lipid, lipoprotein, and homocysteine concentrations. Four to 24 wk after being instructed to consume a lipid-lowering diet, 130 men and women with LDL-cholesterol concentrations > or = 4 mmol/L were studied during a parallel group trial in which 4 interventions were assigned randomly. Thirty grams isolated soy protein (ISP) and 10 g cotyledon fiber or 50 g ISP and 16.6 g cotyledon fiber or equivalent doses of casein and cellulose were consumed daily as a beverage for 16 wk. When the 2 groups who consumed ISP were compared with the 2 groups who consumed casein, the differences in the net changes from baseline to week 16 in the concentrations of LDL cholesterol and plasma total homocysteine were -0.26 mmol/L (95% CI: -0.43, -0.09 mmol/L; P = 0.01) and -0.8 micromol/L (-1.4, -0.2 micromol/L; P = 0.005), respectively. The effect of the ISP dose was not significant. There were no significant differences between the 2 ISP and the 2 casein groups in changes in lipoprotein(a), HDL-cholesterol, or triacylglycerol concentrations. Adding 30-50 g soy protein/d to a lipid-lowering diet significantly reduced LDL-cholesterol concentrations without increasing lipoprotein(a) concentrations. Plasma total homocysteine concentrations also decreased, suggesting a novel, possibly antiatherosclerotic effect.

  3. Prevalence and correlates of folic acid supplement use in Canada.

    PubMed

    Colapinto, Cynthia K; O'Connor, Deborah L; Dubois, Lise; Tremblay, Mark S

    2012-06-01

    Dietary supplements are an important source of folic acid, a nutrient that is vital in reducing the risk of neural tube defects. As part of the 2007 to 2009 Canadian Health Measures Survey, data were collected on supplement use, and biomarkers were directly measured. Use of supplements that contain folic acid was reported by 25% of Canadians aged 6 to 79. Females were more likely than males to report taking folic acid supplements. People who ate fruit and vegetables less than once a day had significantly lower odds of taking folic acid-containing supplements than did those who ate fruit and vegetables at least three times a day. Of those who consumed a folic acid supplement, 91% reported also taking a supplement that contained vitamin B12. Red blood cell folate concentrations below the median (less than 1,248 nmol/L), low-to-marginal serum vitamin B12 concentrations (221 pmol/L or less), and high concentrations of plasma homocysteine were negatively correlated with folic acid-containing supplement use.

  4. Hepatic very-low-density lipoprotein and apolipoprotein B production are increased following in vivo induction of betaine–homocysteine S-methyltransferase

    PubMed Central

    Sparks, Janet D.; Collins, Heidi L.; Chirieac, Doru V.; Cianci, Joanne; Jokinen, Jenny; Sowden, Mark P.; Galloway, Chad A.; Sparks, Charles E.

    2006-01-01

    We have previously reported a positive correlation between the expression of BHMT (betaine–homocysteine S-methyltransferase) and ApoB (apolipoprotein B) in rat hepatoma McA (McArdle RH-7777) cells [Sowden, Collins, Smith, Garrow, Sparks and Sparks (1999) Biochem. J. 341, 639–645]. To examine whether a similar relationship occurs in vivo, hepatic BHMT expression was induced by feeding rats a Met (L-methionine)-restricted betaine-containing diet, and parameters of ApoB metabolism were evaluated. There were no generalized metabolic abnormalities associated with Met restriction for 7 days, as evidenced by control levels of serum glucose, ketones, alanine aminotransferase and L-homocysteine levels. Betaine plus the Met restriction resulted in lower serum insulin and non-esterified fatty acid levels. Betaine plus Met restriction induced hepatic BHMT 4-fold and ApoB mRNA 3-fold compared with Met restriction alone. No changes in percentage of edited ApoB mRNA were observed on the test diets. An increase in liver ApoB mRNA correlated with an 82% and 46% increase in ApoB and triacylglycerol production respectively using in vivo Triton WR 1339. Increased secretion of VLDL (very-low-density lipoprotein) with Met restriction plus betaine was associated with a 45% reduction in liver triacylglycerol compared with control. Nuclear run-off assays established that transcription of both bhmt and apob genes was also increased in Met-restricted plus betaine diets. No change in ApoB mRNA stability was detected in BHMT-transfected McA cells. Hepatic ApoB and BHMT mRNA levels were also increased by 1.8- and 3-fold respectively by betaine supplementation of Met-replete diets. Since dietary betaine increased ApoB mRNA, VLDL ApoB and triacylglycerol production and decreased hepatic triacylglycerol, results suggest that induction of apob transcription may provide a potential mechanism for mobilizing hepatic triacylglycerol by increasing ApoB available for VLDL assembly and secretion

  5. Combined assessment of DYRK1A, BDNF and homocysteine levels as diagnostic marker for Alzheimer’s disease

    PubMed Central

    Janel, N; Alexopoulos, P; Badel, A; Lamari, F; Camproux, A C; Lagarde, J; Simon, S; Feraudet-Tarisse, C; Lamourette, P; Arbones, M; Paul, J L; Dubois, B; Potier, M C; Sarazin, M; Delabar, J M

    2017-01-01

    Early identification of Alzheimer’s disease (AD) risk factors would aid development of interventions to delay the onset of dementia, but current biomarkers are invasive and/or costly to assess. Validated plasma biomarkers would circumvent these challenges. We previously identified the kinase DYRK1A in plasma. To validate DYRK1A as a biomarker for AD diagnosis, we assessed the levels of DYRK1A and the related markers brain-derived neurotrophic factor (BDNF) and homocysteine in two unrelated AD patient cohorts with age-matched controls. Receiver-operating characteristic curves and logistic regression analyses showed that combined assessment of DYRK1A, BDNF and homocysteine has a sensitivity of 0.952, a specificity of 0.889 and an accuracy of 0.933 in testing for AD. The blood levels of these markers provide a diagnosis assessment profile. Combined assessment of these three markers outperforms most of the previous markers and could become a useful substitute to the current panel of AD biomarkers. These results associate a decreased level of DYRK1A with AD and challenge the use of DYRK1A inhibitors in peripheral tissues as treatment. These measures will be useful for diagnosis purposes. PMID:28632203

  6. S phase entry causes homocysteine-induced death while ataxia telangiectasia and Rad3 related protein functions anti-apoptotically to protect neurons.

    PubMed

    Ye, Weizhen; Blain, Stacy W

    2010-08-01

    A major phenotype seen in neurodegenerative disorders is the selective loss of neurons due to apoptotic death and evidence suggests that inappropriate re-activation of cell cycle proteins in post-mitotic neurons may be responsible. To investigate whether reactivation of the G1 cell cycle proteins and S phase entry was linked with apoptosis, we examined homocysteine-induced neuronal cell death in a rat cortical neuron tissue culture system. Hyperhomocysteinaemia is a physiological risk factor for a variety of neurodegenerative diseases, including Alzheimer's disease. We found that in response to homocysteine treatment, cyclin D1, and cyclin-dependent kinases 4 and 2 translocated to the nucleus, and p27 levels decreased. Both cyclin-dependent kinases 4 and 2 regained catalytic activity, the G1 gatekeeper retinoblastoma protein was phosphorylated and DNA synthesis was detected, suggesting transit into S phase. Double-labelling immunofluorescence showed a 95% co-localization of anti-bromodeoxyuridine labelling with apoptotic markers, demonstrating that those cells that entered S phase eventually died. Neurons could be protected from homocysteine-induced death by methods that inhibited G1 phase progression, including down-regulation of cyclin D1 expression, inhibition of cyclin-dependent kinases 4 or 2 activity by small molecule inhibitors, or use of the c-Abl kinase inhibitor, Gleevec, which blocked cyclin D and cyclin-dependent kinase 4 nuclear translocation. However, blocking cell cycle progression post G1, using DNA replication inhibitors, did not prevent apoptosis, suggesting that death was not preventable post the G1-S phase checkpoint. While homocysteine treatment caused DNA damage and activated the DNA damage response, its mechanism of action was distinct from that of more traditional DNA damaging agents, such as camptothecin, as it was p53-independent. Likewise, inhibition of the DNA damage sensors, ataxia-telangiectasia mutant and ataxia telangiectasia and Rad

  7. The Conjugate Acid-Base Chart.

    ERIC Educational Resources Information Center

    Treptow, Richard S.

    1986-01-01

    Discusses the difficulties that beginning chemistry students have in understanding acid-base chemistry. Describes the use of conjugate acid-base charts in helping students visualize the conjugate relationship. Addresses chart construction, metal ions, buffers and pH titrations, and the organic functional groups and nonaqueous solvents. (TW)

  8. Inhibition of hydrogen sulfide on the proliferation of vascular smooth muscle cells involved in the modulation of calcium sensing receptor in high homocysteine

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wang, Yuwen; Wang, Xiyao; Liang, Xiaohui

    Hyperhomocysteinemia induces the proliferation of vascular smooth muscle cells (VSMCs). Hydrogen sulfide (H{sub 2}S) inhibits the phenotype switch of VSMCs and calcium-sensing receptor (CaSR) regulated the production of endogenous H{sub 2}S. However, whether CaSR inhibits the proliferation of VSMCs by regulating the endogenous cystathionine-gamma-lyase (CSE, a major enzyme that produces H{sub 2}S) pathway in high homocysteine (HHcy) has not been previously investigated. The intracellular calcium concentration, the concentration of H{sub 2}S, the cell viability, the proliferation and the expression of proteins of cultured VSMCs from rat thoracic aortas were measured, respectively. The results showed that the [Ca{sup 2+}]{sub i} andmore » the expression of p-CaMK and CSE increased upon treatment with CaSR agonist. In HHcy, the H{sub 2}S concentration decrease, the proliferation and migration rate increased, the expression of Cyclin D1, PCNA, Osteopontin and p-Erk1/2 increased while the α-SM actin, P21{sup Cip/WAK−1} and Calponin decreased. The CaSR agonist or exogenous H{sub 2}S significantly reversed the changes of VSMCs caused by HHcy. In conclusion, our results demonstrated that CaSR regulate the endogenous CSE/H{sub 2}S is related to the PLC-IP{sub 3} receptor and CaM signal pathways which inhibit the proliferation of VSMCs, and the latter is involved in the Erk1/2 dependent signal pathway in high homocysteine. - Highlights: • CaSR activation increased the production of endogenous H{sub 2}S in high homocysteine VSMCs. • CaSR modulated the CSE/H{sub 2}S are related to the PLC-IP{sub 3}R and Ca{sup 2+}-CaM signal pathways. • Inhibition of H{sub 2}S on the proliferation of VSMCs is involved in the Erk1/2 pathway. • Explore the potential roles of CaSR in regulating VSMCs proliferation in high homocysteine.« less

  9. Common genetic loci influencing plasma homocysteine concentrations and their effect on risk of coronary artery disease12345

    PubMed Central

    van Meurs, Joyce BJ; Pare, Guillaume; Schwartz, Stephen M; Hazra, Aditi; Tanaka, Toshiko; Vermeulen, Sita H; Cotlarciuc, Ioana; Yuan, Xin; Mälarstig, Anders; Bandinelli, Stefania; Bis, Joshua C; Blom, Henk; Brown, Morris J; Chen, Constance; Chen, Yii-Der; Clarke, Robert J; Dehghan, Abbas; Erdmann, Jeanette; Ferrucci, Luigi; Hamsten, Anders; Hofman, Albert; Hunter, David J; Goel, Anuj; Johnson, Andrew D; Kathiresan, Sekar; Kampman, Ellen; Kiel, Douglas P; Kiemeney, Lambertus ALM; Chambers, John C; Kraft, Peter; Lindemans, Jan; McKnight, Barbara; Nelson, Christopher P; O'Donnell, Christopher J; Psaty, Bruce M; Ridker, Paul M; Rivadeneira, Fernando; Rose, Lynda M; Seedorf, Udo; Siscovick, David S; Schunkert, Heribert; Selhub, Jacob; Ueland, Per M; Vollenweider, Peter; Waeber, Gérard; Waterworth, Dawn M; Watkins, Hugh; Witteman, Jacqueline CM; den Heijer, Martin; Jacques, Paul; Uitterlinden, Andre G; Kooner, Jaspal S; Rader, Dan J; Reilly, Muredach P; Mooser, Vincent; Chasman, Daniel I; Samani, Nilesh J; Ahmadi, Kourosh R

    2013-01-01

    Background: The strong observational association between total homocysteine (tHcy) concentrations and risk of coronary artery disease (CAD) and the null associations in the homocysteine-lowering trials have prompted the need to identify genetic variants associated with homocysteine concentrations and risk of CAD. Objective: We tested whether common genetic polymorphisms associated with variation in tHcy are also associated with CAD. Design: We conducted a meta-analysis of genome-wide association studies (GWAS) on tHcy concentrations in 44,147 individuals of European descent. Polymorphisms associated with tHcy (P < 10−8) were tested for association with CAD in 31,400 cases and 92,927 controls. Results: Common variants at 13 loci, explaining 5.9% of the variation in tHcy, were associated with tHcy concentrations, including 6 novel loci in or near MMACHC (2.1 × 10−9), SLC17A3 (1.0 × 10−8), GTPB10 (1.7 × 10−8), CUBN (7.5 × 10−10), HNF1A (1.2 × 10−12), and FUT2 (6.6 × 10−9), and variants previously reported at or near the MTHFR, MTR, CPS1, MUT, NOX4, DPEP1, and CBS genes. Individuals within the highest 10% of the genotype risk score (GRS) had 3-μmol/L higher mean tHcy concentrations than did those within the lowest 10% of the GRS (P = 1 × 10−36). The GRS was not associated with risk of CAD (OR: 1.01; 95% CI: 0.98, 1.04; P = 0.49). Conclusions: We identified several novel loci that influence plasma tHcy concentrations. Overall, common genetic variants that influence plasma tHcy concentrations are not associated with risk of CAD in white populations, which further refutes the causal relevance of moderately elevated tHcy concentrations and tHcy-related pathways for CAD. PMID:23824729

  10. Disorders of Acid-Base Balance: New Perspectives

    PubMed Central

    Seifter, Julian L.; Chang, Hsin-Yun

    2017-01-01

    Background Disorders of acid-base involve the complex interplay of many organ systems including brain, lungs, kidney, and liver. Compensations for acid-base disturbances within the brain are more complete, while limitations of compensations are more apparent for most systemic disorders. However, some of the limitations on compensations are necessary to survival, in that preservation of oxygenation, energy balance, cognition, electrolyte, and fluid balance are connected mechanistically. Summary This review aims to give new and comprehensive perspective on understanding acid-base balance and identifying associated disorders. All metabolic acid-base disorders can be approached in the context of the relative losses or gains of electrolytes or a change in the anion gap in body fluids. Acid-base and electrolyte balance are connected not only at the cellular level but also in daily clinical practice. Urine chemistry is essential to understanding electrolyte excretion and renal compensations. Key Messages Many constructs are helpful to understand acid-base, but these models are not mutually exclusive. Electroneutrality and the close interconnection between electrolyte and acid-base balance are important concepts to apply in acid-base diagnoses. All models have complexity and shortcuts that can help in practice. There is no reason to dismiss any of the present constructs, and there is benefit in a combined approach. PMID:28232934

  11. The impact of intratracheally instilled carbon black on the cardiovascular system of rats: elevation of blood homocysteine and hyperactivity of platelets.

    PubMed

    Kim, Hwa; Oh, Seok-Jeong; Kwak, Hui-Chan; Kim, Jong-Kyu; Lim, Cheol-Hong; Yang, Jeong-Sun; Park, Kwangsik; Kim, Sang-Kyum; Lee, Moo-Yeol

    2012-01-01

    Carbon black (CB) is an industrial chemical with high potential for human exposure. Although the relationship between exposure to particulate matter (PM) and cardiovascular disease is well documented, the risk of adverse cardiovascular effects attributed to CB particles has not been clearly characterized. This study was performed to (1) investigate the effects of CB on cardiovascular system and (2) identify the target tissue or potential biomarkers. Carbon black with a distinct particle size, N330 (ultrafine particle) and N990 (fine particle), was intratracheally instilled into rats at a doses of 1, 3, or 10 mg/kg. Measurements of thrombotic activity and determination of plasma homocysteine levels, cardiac functionality, and inflammatory responses were conducted at 24-h and 1-wk time points. Exposure to N330 accelerated platelet-dependent blood clotting at 10 mg/kg, the highest exposure tested. Unexpectedly, both N330 and N990 led to prolongation of activated partial thromboplastin time (aPTT), whereas these CB particles failed to affect prothrombin time (PT). N990 produced a significant elevation in the level of plasma homocysteine, a well-established etiological factor in cardiovascular diseases. Both N330 and N990 induced apparent inflammation in the lungs; however, both particles failed to initiate systemic inflammation. Neither CB particle produced observable cardiac symptoms as detected by electrocardiography. Taken together, data show CB exposure enhanced the cardiovascular risk by inducing hyperhomocysteinemia and platelet hyperactivity, although these effects may be variable depending on particle size and exposure duration. Homocysteine may be a potential biomarker for cardiovascular toxicity following CB exposure.

  12. B-vitamin therapy for kidney transplant recipients lowers homocysteine and improves selective cognitive outcomes in the randomized FAVORIT ancillary cognitive trial

    USDA-ARS?s Scientific Manuscript database

    BACKGROUND: Objectives: Elevated plasma total homocysteine (tHcy) is associated with increased risk of cardiovascular disease, stroke and dementia. Results of clinical trials using B-vitamins to reduce the cognitive risks attributed to tHcy have been inconsistent. The high prevalence of both hyperho...

  13. Relation of parity and homocysteine to bone mineral density of postmenopausal women.

    PubMed

    Yilmaz, Necat; Kepkep, Necip; Ciçek, Hülya Kanbur; Celik, Ahmet; Meram, Iclal

    2006-01-01

    Osteoporosis is a major problem in contemporary society. However, there is not enough data on multiparity and osteoporosis from developing and/or undeveloped countries on a large scale. Selection of participants in this study was aimed at the detection of bone status in healthy (normal bone mineral density) postmenopausal (n = 46, 55.3 +/- 6.7 years) and osteoporotic postmenopausal women (n: 33) of similar age. Bone mineral density (BMD) was evaluated using dual energy X-ray absorptiometry. At the DEXA evaluation, 33 women had osteoporotic (T score below -2.5) and 46 had normal BMD values. The number of pregnancies was found to range from 3 to 12 (with an overall mean of 6.7 +/- 2.5), while 2.6 +/- 1.9 (range, 1-7) were miscarriages in all of the 33 postmenopausal osteoporotic women. Serum homocysteine (t-Hcy) and urinary deoxypyridinoline (DPD) levels were significantly higher in osteoporotic postmenopausal women (11.96 +/- 3.84 micromol/L, 15.4 +/- 7.0 nM/mM cr) than in non-osteoporotic postmenopausal women (10.93 +/- 3.6 micromol/L, 10.6 +/- 9.1 nM/mM cr), p < 0.05, p < 0.01, respectively. Surprisingly, in postmenopausal osteoporotic women the homocysteine (t-Hcy) levels were positively associated with the number of deliveries (multiparity; 6.7 +/- 2.5), and positively associated with the number of curettages (2.6 +/- 1.9), r = 0.401, p < 0.038 and r = 0.520, p < 0.029, respectively. The mechanism linking serum t-Hcy to the number of pregnancies is unclear, and the relationship may only be by chance. In conclusion, the present study firstly suggests that the number of pregnancies has an effect on the t-Hcy levels. In addition, our study indicates that there is a significant negative correlation between the number of pregnancies and the lumbar spine BMD.

  14. [Meta-analysis on effect of combined supplementation of folic acid, vitamin B12 and B6 on risk of cardio-cerebrovascular diseases in randomized control trials].

    PubMed

    Lan, X; Dang, S N; Zhao, Y L; Yan, H; Yan, H

    2016-07-01

    To evaluate the effect of the combined supplementation of folic acid, vitamin B12 and B6 on the risk of cardio-cerebrovascular diseases. The literatures of randomized control trials about the relationship between the combined supplementation of folic acid, vitamin B12 and B6 and risk of cardio-cerebrovascular diseases from 1980 to 2014 were retrieved, and the eligible studies were screened for a Meta-analysis. The study indicators were the incidences of cardiovascular disease events, myocardial infarction and stroke. The cffect indicators were relative risk(RR)and 95% confidence interval(CI). Jadad score was used for the quality evaluation of the trials used in the study. The literatures of 11 randomized control trials, involving 26 395 patients, were used in the Meta-analysis. The combined supplementation of B vitamins had no effect on the incidence of cardiovascular disease events(RR=1.00, 95% CI: 0.94-1.07)based on 8 studies. The combined supplementation of B vitamins had no effect on the incidence of myocardial infarction(RR= 1.03, 95% CI: 0.94-1.13)based on 9 studies. The combined supplementation of B vitamins could reduce the incidence of stroke by 14%(RR=0.86, 95%CI: 0.78-0.95)based on 9 studies. Compared with the control group, Taking folic acid combined with vitamin B12 and B6 could reduce the level of homocysteine by 2.53 μmol/L(95%CI:-3.93--1.12). Subgroup analysis indicated that the follow-up time, the dosage of folic acid and vitamin B12 and B6, the history of diseases had no confounding effect on the incidence of cardio-cerebrovascular disease events. But the subgroup analysis for stroke showed that with the extension of follow-up time, the supplementation of B vitamins could reduce the risk of stroke. The effect of folic acid and B12 in small dosage seemed more significant in the prevention of stroke, while the preventive effect of B6 increased with increasing dosage. The preventive effect of combined supplementation of B vitamins was more

  15. Capillary electrophoresis coupled with chloroform-acetonitrile extraction for rapid and highly selective determination of cysteine and homocysteine levels in human blood plasma and urine.

    PubMed

    Ivanov, Alexander Vladimirovich; Bulgakova, Polina Olegovna; Virus, Edward Danielevich; Kruglova, Maria Petrovna; Alexandrin, Valery Vasil'evich; Gadieva, Viktoriya Aleksandrovna; Luzyanin, Boris Petrovich; Kushlinskii, Nikolai Evgen'evich; Fedoseev, Anatolij Nikolaevich; Kubatiev, Aslan Amirkhanovich

    2017-10-01

    A rapid and selective method has been developed for highly sensitive determination of total cysteine and homocysteine levels in human blood plasma and urine by capillary electrophoresis (CE) coupled with liquid-liquid extraction. Analytes were first derivatized with 1,1'-thiocarbonyldiimidazole and then samples were purified by chloroform-ACN extraction. Electrophoretic separation was performed using 0.1 M phosphate with 30 mM triethanolamine, pH 2, containing 25 μM CTAB, 2.5 μM SDS, and 2.5% polyethylene glycol 600. Samples were injected into the capillary (with total length 32 cm and 50 μm id) at 2250 mbar*s and subsequent injection was performed for 30 s with 0.5 M KОН. The total analysis time was less than 9 min, accuracy was 98%, and precision was <2.6%. The LOD was 0.2 μM for homocysteine and 0.5 μM for cysteine. The use of liquid-liquid extraction allowed the precision and sensitivity of the CE method to be significantly increased. The validated method was applied to determine total cysteine and homocysteine content in human blood plasma and urine samples obtained from healthy volunteers and patients with kidney disorders. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. A Computer-Based Simulation of an Acid-Base Titration

    ERIC Educational Resources Information Center

    Boblick, John M.

    1971-01-01

    Reviews the advantages of computer simulated environments for experiments, referring in particular to acid-base titrations. Includes pre-lab instructions and a sample computer printout of a student's use of an acid-base simulation. Ten references. (PR)

  17. Effects of myo-inositol, gymnemic acid, and L-methylfolate in polycystic ovary syndrome patients.

    PubMed

    Stracquadanio, M; Ciotta, L; Palumbo, M A

    2018-06-01

    Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine and metabolic disorder, characterized by chronic anovulation/oligomenorrhea, hyperandrogenism, and insulin-resistance. Moreover, some studies propose a possible association between insulin resistance and hyperhomocysteinemia, which is a significant long-term risk for factor for atherogenesis and chronic vascular damage, especially in situations where insulin levels are increased. Insulin-sensitizing agents are used in the treatment of PCOS: in fact, inositols were shown to have insulin-mimetic properties. Synergic action to myo-inositol is that of gymnemic acids that have antidiabetic, anti-sweetener, and anti-inflammatory activities. Gymnemic acid formulations have also been found useful against obesity due to their ability to delay the glucose absorption in the blood. L-methyl-folate increases peripheral sensitivity to insulin, maintaining folatemia stable, and thus restoring normal homocysteine levels. Unlike folic acid, L-methyl folate has a higher bioavailability, no drug/food interferences, high absorption, and it is stable to UV-A exposure. The aim of our study is to compare the clinical, endocrine, and metabolic parameters in 100 PCOS women treated with myo-inositol, gymnemic acid, and l-methylfolate (Group A) or myo inositol and folic acid only (Group B), continuously for 6 months. From a clinical point of view, it was noticed a more significant improvement of the menstrual cycle regularity and a more significant reduction of BMI in Group A. Moreover, a more significant decrease of total testosterone and increase of SHBG serum levels were noticed in Group A. The metabolic assessment found a more significant decrease of total cholesterol and homocysteine levels; OGTT glycemia and insulinemia values were significantly more improved after treatment with myo-inositol + gymnemic acid. In conclusion, we can state that a good option for the treatment of PCOS is the combined administration of myo

  18. Nucleic acid-based electrochemical nanobiosensors.

    PubMed

    Abi, Alireza; Mohammadpour, Zahra; Zuo, Xiaolei; Safavi, Afsaneh

    2018-04-15

    The detection of biomarkers using sensitive and selective analytical devices is critically important for the early stage diagnosis and treatment of diseases. The synergy between the high specificity of nucleic acid recognition units and the great sensitivity of electrochemical signal transductions has already shown promise for the development of efficient biosensing platforms. Yet nucleic-acid based electrochemical biosensors often rely on target amplification strategies (e.g., polymerase chain reactions) to detect analytes at clinically relevant concentration ranges. The complexity and time-consuming nature of these amplification methods impede moving nucleic acid-based electrochemical biosensors from laboratory-based to point-of-care test settings. Fortunately, advancements in nanotechnology have provided growing evidence that the recruitment of nanoscaled materials and structures can enhance the biosensing performance (particularly in terms of sensitivity and response time) to the level suitable for use in point-of-care diagnostic tools. This Review highlights the significant progress in the field of nucleic acid-based electrochemical nanobiosensing with the focus on the works published during the last five years. Copyright © 2017. Published by Elsevier B.V.

  19. Investigating Students' Reasoning about Acid-Base Reactions

    ERIC Educational Resources Information Center

    Cooper, Melanie M.; Kouyoumdjian, Hovig; Underwood, Sonia M.

    2016-01-01

    Acid-base chemistry is central to a wide range of reactions. If students are able to understand how and why acid-base reactions occur, it should provide a basis for reasoning about a host of other reactions. Here, we report the development of a method to characterize student reasoning about acid-base reactions based on their description of…

  20. Fluorescent sensors based on boronic acids

    NASA Astrophysics Data System (ADS)

    Cooper, Christopher R.; James, Tony D.

    1999-05-01

    Sensor systems have long been needed for detecting the presence in solution of certain chemically or biologically important species. Sensors are used in a wide range of applications from simple litmus paper that shows a single color change in acidic or basic environments to complex biological assays that use enzymes, antibodies and antigens to display binding events. With this work the use of boronic acids in the design and synthesis of sensors for saccharides (diols) will be presented. The fluorescent sensory systems rely on photoinduced electron transfer (PET) to modulate the observed fluorescence. When saccharides form cyclic boronate esters with boronic acids, the Lewis acidity of the boronic acid is enhanced and therefore the Lewis acid-base interaction between the boronic acid and a neighboring amine is strengthened. The strength of this acid-base interaction modulates the PET from the amine (acting as a quencher) to anthracene (acting as a fluorophore). These compounds show increased fluorescence at neutral pH through suppression of the PET from nitrogen to anthracene on saccharide binding. The general strategy for the development of saccharide selective systems will be discussed. The potential of the boronic acid based systems will be illustrated using the development of glucose and glucosamine selective fluorescent sensors as examples.

  1. Factors contributing to the resistivity of a higher casein diet against choline deficiency-induced hyperhomocysteinemia in rats.

    PubMed

    Liu, Yi-qun; Liu, Ying; Morita, Tatsuya; Mori, Makoto; Sugiyama, Kimio

    2012-01-01

    The mechanism by which feeding a higher casein diet results in resistance to choline deprivation-induced hyperhomocysteinemia was investigated in rats. Plasma homocysteine concentration was significantly lower in rats fed a 30% casein diet (30C) than in rats fed a 10% casein diet (10C). Choline deprivation did not enhance plasma homocysteine concentration in rats fed 30C, while it significantly enhanced plasma homocysteine concentration in rats fed 10C. The choline deprivation-induced enhancement of plasma homocysteine concentration in rats fed 10C was significantly suppressed by methionine supplementation in a dose-dependent manner in the range of 0.1 to 0.3%, but the suppressive effect of methionine became smaller with an increase in supplementation level in the range of 0.3 to 0.5%. At a 0.5% supplementation level, methionine did not exhibit any suppressive effect on choline deprivation-induced hyperhomocysteinemia. The higher plasma homocysteine concentration in rats fed choline-deprived 10C+0.5% methionine was significantly decreased by concurrent supplementation with 0.32% glycine+0.94% serine to the level of rats fed 10C. Raising dietary total amino acid level by adding 3.61% branched-chain amino acids (BCAA)+4.5% acidic amino acids (AAA) to choline-deprived 10C+0.5% methionine+0.32% glycine+0.94% serine resulted in a further decrease in plasma homocysteine concentration to a level lower than the level in rats fed 10C. Choline deprivation-induced increases in hepatic S-adenosylhomocysteine and homocysteine concentrations were significantly suppressed by supplementation with glycine+serine and further suppressed by BCAA+AAA. Hepatic cystathionine β-synthase activity and its gene expression were significantly increased by BCAA+AAA. Hepatic triglyceride concentration changed in a manner similar to that of plasma homocysteine concentration. The results indicate that there are at least three factors contributing to the resistivity of rats fed a higher casein

  2. Ultrastructural observation of the acid-base resistant zone of all-in-one adhesives using three different acid-base challenges.

    PubMed

    Tsujimoto, Miho; Nikaido, Toru; Inoue, Go; Sadr, Alireza; Tagami, Junji

    2010-11-01

    The aim of this study was to analyze the ultrastructure of the dentin-adhesive interface using two all-in-one adhesive systems (Clearfil Tri-S Bond, TB; Tokuyama Bond Force, BF) after different acid-base challenges. Three solutions were used as acidic solutions for the acid-base challenges: a demineralizing solution (DS), a phosphoric acid solution (PA), and a hydrochloric acid solution (HCl). After the acid-base challenges, the bonded interfaces were examined by scanning electron microscopy. Thickness of the acid-base resistant zone (ABRZ) created in PA and HCl was thinner than in DS for both adhesive systems. For BF adhesive, an eroded area was observed beneath the ABRZ after immersion in PA and HCl, but not in DS. Conversely for TB adhesive, the eroded area was observed only after immersion in PA. In conclusion, although the ABRZ was observed for both all-in-one adhesive systems, its morphological features were influenced by the ingredients of both the adhesive material and acidic solution.

  3. Primer on clinical acid-base problem solving.

    PubMed

    Whittier, William L; Rutecki, Gregory W

    2004-03-01

    Acid-base problem solving has been an integral part of medical practice in recent generations. Diseases discovered in the last 30-plus years, for example, Bartter syndrome and Gitelman syndrome, D-lactic acidosis, and bulimia nervosa, can be diagnosed according to characteristic acid-base findings. Accuracy in acid-base problem solving is a direct result of a reproducible, systematic approach to arterial pH, partial pressure of carbon dioxide, bicarbonate concentration, and electrolytes. The 'Rules of Five' is one tool that enables clinicians to determine the cause of simple and complex disorders, even triple acid-base disturbances, with consistency. In addition, other electrolyte abnormalities that accompany acid-base disorders, such as hypokalemia, can be incorporated into algorithms that complement the Rules and contribute to efficient problem solving in a wide variety of diseases. Recently urine electrolytes have also assisted clinicians in further characterizing select disturbances. Acid-base patterns, in many ways, can serve as a 'common diagnostic pathway' shared by all subspecialties in medicine. From infectious disease (eg, lactic acidemia with highly active antiviral therapy therapy) through endocrinology (eg, Conn's syndrome, high urine chloride alkalemia) to the interface between primary care and psychiatry (eg, bulimia nervosa with multiple potential acid-base disturbances), acid-base problem solving is the key to unlocking otherwise unrelated diagnoses. Inasmuch as the Rules are clinical tools, they are applied throughout this monograph to diverse pathologic conditions typical in contemporary practice.

  4. Maternal serum homocysteine and uterine artery Doppler as predictors of preeclampsia and poor placentation.

    PubMed

    Maged, Ahmed M; Saad, Hany; Meshaal, Hadeer; Salah, Emad; Abdelaziz, Suzy; Omran, Eman; Deeb, Wesam S; Katta, Maha

    2017-09-01

    The aim of this study was to evaluate the role of maternal serum total Homocysteine (tHcy) and uterine artery (Ut-A) Doppler as predictors of preeclampsia (PE), intrauterine growth restriction (IUGR), and other complications related to poor placentation. A prospective cohort study was conducted on 500 women with spontaneous pregnancies. tHcy was measured at 15-19 weeks, and then, Ut-A Doppler was performed at 18-22 weeks of pregnancy. 453 pregnant women completed the follow-up of the study. The tHcy and Ut-A resistance index were significantly higher in women who developed PE, IUGR, and other complications when compared to controls (tHcy: 7.033 ± 2.744, 6.321 ± 3.645, and 6.602 ± 2.469 vs 4.701 ± 2.082 μmol/L, respectively, p value <0.001 and Ut-A resistance index: 0.587 ± 0.072, 0.587 ± 0.053, and 0.597 ± 0.069 vs 0.524 ± 0.025, respectively, p value <0.001). The use of both tHcy assessment and Ut-A Doppler improved the sensitivity of prediction of PE relative to the use of each one alone (85.2 relative to 73.33 and 60%, respectively). The use of elevated homocysteine and uterine artery Doppler screening are valuable in prediction of preeclampsia, IUGR, and poor placentation disorders. CLINCALTRIAL. NCT02854501.

  5. Teaching Acid/Base Physiology in the Laboratory

    ERIC Educational Resources Information Center

    Friis, Ulla G.; Plovsing, Ronni; Hansen, Klaus; Laursen, Bent G.; Wallstedt, Birgitta

    2010-01-01

    Acid/base homeostasis is one of the most difficult subdisciplines of physiology for medical students to master. A different approach, where theory and practice are linked, might help students develop a deeper understanding of acid/base homeostasis. We therefore set out to develop a laboratory exercise in acid/base physiology that would provide…

  6. Choline metabolic pathway gene polymorphisms and risk for Down syndrome: An association study in a population with folate-homocysteine metabolic impairment.

    PubMed

    Jaiswal, S K; Sukla, K K; Chauhan, A; Lakhotia, A R; Kumar, A; Rai, A K

    2017-01-01

    Choline is an essential nutrient involved in one-carbon metabolism, but its role in mechanisms underlying meiotic non-disjunction is poorly known. The relationship between folate-homocysteine metabolic pathway gene polymorphism and Down syndrome (DS) risk has been widely analyzed, but there are limited reports on its correlation with choline metabolism. In the present case-control association study, we investigated the relationship of three single-nucleotide polymorphisms (SNPs) (phosphatidylethanolamine N-methyltransferase (PEMT) rs12325817, choline dehydrogenase (CHDH) rs12676 and homocysteine methyltransferase (BHMT) rs3733890) of choline metabolism with risk for DS. Genotyping of 228 mothers of a down syndrome child (DSM) and 200 control mothers (CMs) for all SNPs was performed by PCR coupled with restriction fragment length polymorphism method. A significantly increased risk for BHMT +742AA genotype with an odds ratio of 4.96 (95% confidence interval (CI): 1.66-14.88, P=0.0036) was observed. For PEMT rs12325817 and CHDH rs12676, no significant difference in allelic and genotypic frequencies was observed. In genotypic combination analysis considering PEMT -744GG/CHDH +432GG/BHMT +742GG as the reference combination, PEMT -744GC/CHDH +432GG/BHMT +742GG genotypic combination was significantly higher in DSM compared with that in CMs with an odds ratio of 2.061 (95% CI: 1.10-3.86, P=0.0342). We also observed an epistatic interaction between methylenetetrahydrofolate reductase (MTHFR) rs1801133 and choline metabolic pathway gene variants. Our findings indicate impaired choline metabolism showing a greater risk for DS, especially in a population associated with homocysteine-folate impairment. Further studies are required to confirm our findings.

  7. Relationship between homocysteine and coronary artery disease. Results from a large prospective cohort study.

    PubMed

    Schaffer, Alon; Verdoia, Monica; Cassetti, Ettore; Marino, Paolo; Suryapranata, Harry; De Luca, Giuseppe

    2014-08-01

    Coronary artery disease (CAD) still represents the major cause of mortality in developed countries. Large research programs have been focused on the identification of new risk factors to prevent CAD, with special attention to homocysteine (Hcy), due to the known associated increased thrombogenicity, oxidative stress status and endothelial dysfunction. However, controversy still exists on the association between Hcy and CAD. Therefore, aim of the current study was to investigate the association of Hcy with the prevalence and extent of CAD in a large consecutive cohort of patients undergoing coronary angiography. Our population is represented by a total of 3056 consecutive patients undergoing coronary angiography between at the Azienda Ospedaliera "Maggiore della Carità", Novara, Italy. Fasting samples were collected for homocysteine levels assessment. Coronary disease was defined for at least 1 vessel stenosis>50% as evaluated by QCA. Study population was divided according to Hcy tertiles (<13,3, 13,3-18.2, >18.2nmol/ml). High plasmatic level of homocysteine was related with age (p<0.001), male gender (p<0.001), hypertension (p<0.001) renal failure (p<0.001), family history of CAD (p<0.001), previous cerebrovascular accident (p<0.001), previous MI (p=0.002), previous CABG (p=0.003), ejection fraction (p<0.001), higher baseline creatinine (p<0.001), in treatment with nitrates (p<0.001), calcium antagonists (p<0.001), diuretics (p<0.001), Ace inhibitors (ACE-I) (p=0.006), Clopidogrel (p=0.05), haemoglobin (p=0.001), white blood cells (WBC) count (p=0.008), total cholesterol (p=0.04), Low-Density Lipoproteins (LDL) (p=0.01). A significant relationship was found between Hcy levels and the extent of coronary artery disease (71.8% vs 77.8% vs 77.4%, OR[95%CI]=1.18[1.11-1.252.], p<0.001 and severe CAD (23.6% vs 29.5% vs 32.1%, OR [95%CI]=1.275 [1.209-1.344], p<0.001). Elevated Hcy was significantly associated with increased risk of CAD (adjusted OR[95%CI]=1

  8. Altered maternal micronutrients (folic acid, vitamin B(12)) and omega 3 fatty acids through oxidative stress may reduce neurotrophic factors in preterm pregnancy.

    PubMed

    Dhobale, Madhavi; Joshi, Sadhana

    2012-04-01

    Preterm pregnancies account for approximately 10% of the total pregnancies and are associated with low birth weight (LBW) babies. Recent studies have shown that LBW babies are at an increased risk of developing brain disorders such as cognitive dysfunction and psychiatric disorders. Maternal nutrition, particularly, micronutrients involved in one-carbon metabolism (folic acid, vitamin B(12), and docosahexaenoic acid (DHA)) have a major role during pregnancy for developing fetus and are important determinants of epigenesis. A series of our studies in pregnancy complications have well established the importance of omega 3 fatty acids especially DHA. DHA regulates levels of neurotrophins like brain-derived neurotrophic factor and nerve growth factor, which are required for normal neurological development. We have recently described that in one carbon metabolic pathway, membrane phospholipids are major methyl group acceptors and reduced DHA levels may result in diversion of methyl groups toward deoxyribonucleic acid (DNA) ultimately resulting in DNA methylation. In this review, we propose that altered maternal micronutrients (folic acid, vitamin B(12)), increased homocysteine, and oxidative stress levels that cause epigenetic modifications may be one of the mechanisms that contribute to preterm birth and poor fetal outcome, increasing risk for behavioural disorders in children.

  9. [Kidney, Fluid, and Acid-Base Balance].

    PubMed

    Shioji, Naohiro; Hayashi, Masao; Morimatsu, Hiroshi

    2016-05-01

    Kidneys play an important role to maintain human homeostasis. They contribute to maintain body fluid, electrolytes, and acid-base balance. Especially in fluid control, we, physicians can intervene body fluid balance using fluid resuscitation and diuretics. In recent years, one type of fluid resuscitation, hydroxyl ethyl starch has been extensively studied in the field of intensive care. Although their effects on fluid resuscitation are reasonable, serious complications such as kidney injury requiring renal replacement therapy occur frequently. Now we have to pay more attention to this important complication. Another topic of fluid management is tolvaptan, a selective vasopressin-2 receptor antagonist Recent randomized trial suggested that tolvaptan has a similar supportive effect for fluid control and more cost effective compared to carperitide. In recent years, Stewart approach is recognized as one important tool to assess acid-base balance in critically ill patients. This approach has great value, especially to understand metabolic components in acid-base balance. Even for assessing the effects of kidneys on acid-base balance, this approach gives us interesting insight. We should appropriately use this new approach to treat acid-base abnormality in critically ill patients.

  10. Association of cardiometabolic risk profile with prehypertension accompany hyperhomocysteinaemia.

    PubMed

    Chen, Huili; Sun, Yuemin; Wang, Xuechun; Si, Quan; Yao, Wei; Wan, Zheng

    2015-01-01

    Study suggested that elevated homocysteine showed a multiplicative effect on cardiovascular diseases in hypertensive subjects. It was reported that elevated homocysteine level was independently associated with increased arterial stiffness in prehypertensives. It remains unclear whether prehypertensives combined with elevated homocysteine have adverse cardiovascular risk factors. We aimed to compare cardiometabolic risk profile between prehypertensives with hyperhomocysteinaemia and those without either condition. Plasma total homocysteine and risk profile were determined among 874 Chinese non-hypertension individuals in Tianjin. They were subdivided into four groups: prehypertension with hyperhomocysteinaemia (≥10 μmol/L), prehypertension with normal homocysteine (<10 μmol/L), normotension with hyperhomocysteinaemia, normotension with normol homocysteine, respectively. In 874 participants, 22.5% of them were male, mean age was 56.8 years. In multiple comparisons, after adjustment for age, gender, smoking, alcohol, exercise, education prehypertensives had higher body mass index (BMI) and high sensitive C reactive protein (hs-CRP) than normotensives (p < 0.05, respectively); Only prehypertensive subjects with hyperhomocysteinaemia had higher triglyceride and serum uric acid compared to normotensive subjects, and lower HDL cholesterol than normotensives with normal homocysteine (p < 0.05, respectively). However, the significance of higher hs-CRP, uric acid and lower HDL cholesterol were abolished when further adjustment was made for BMI. The combination of prehypertension and hyperhomocusteinaemia increases the likelihood of having adverse cardiometabolic risk profile. Strict lipid management and weigh control may be needed in prehypertensives with elevated homocysteine.

  11. Stable Isotope Dilution Assays for Clinical Analyses of Folates and Other One-Carbon Metabolites: Application to Folate-Deficiency Studies

    PubMed Central

    Kopp, Markus; Morisset, Rosalie; Koehler, Peter

    2016-01-01

    Folate deficiency is generally accepted as a potential direct or indirect risk factor for diseases including spina bifida, coronary heart diseases, malfunctions of the central nervous system, and cancer. The direct inclusion of folates in the methylation cycle, including the remethylation of homocysteine and regeneration of S-adenosylmethionine, underlines the importance of these vitamins and other components of one-carbon metabolism. Therefore, the aim of the present study was to develop a multiple stable isotope dilution assay (SIDA) for the respective analytes in plasma and tissue samples to allow for a closer look at the interaction between a severe folate deficiency and local folate status, as well as further interactions with circulating S-adenosylmethionine, S-adenosylhomocysteine, and homocysteine. The analytical methods were based on SIDAs coupled with liquid chromatography—tandem mass spectrometry (LC-MS/MS) analysis using the deuterated folates [2H4]-5-methyltetrahydrofolic acid, [2H4]-5-formyltetrahydrofolic acid, [2H4]-tetrahydrofolic acid, [2H4]-10-formylfolic acid, and [2H4]-folic acid and the deuterated one-carbon metabolites [2H4]-homocysteine, [2H4]-S-adenosylhomocysteine, and [2H3]-S-adenosylmethionine as internal standards. Three analytical methods have been developed for the analysis of homocysteine, S-adenosylmethionine, S-adenosylhomocysteine, and six folate vitamers. Validation data for the analysis of C1-metabolites in plasma and tissue samples or folate analysis in tissue samples revealed excellent sensitivity, precision, and recovery for all analytes studied. The miniaturized methods using sample volumes as low as 50 μL and weighed portions of 5–25 mg will allow the assessment of the status of folates and additional biomarkers of impaired one-carbon metabolism during folate deficiency. PMID:27276031

  12. Colorimetric detection of biothiols based on aggregation of chitosan-stabilized silver nanoparticles

    NASA Astrophysics Data System (ADS)

    Mohammadi, Somayeh; Khayatian, Gholamreza

    2017-10-01

    We have described a simple and reliable colorimetric method for the sensing of biothiols such as cysteine, homocysteine, and glutathione in biological samples. The selective binding of chitosan capped silver nanoparticles to biothiols induced aggregation of the chitosan-Ag NPs. But the other amino acids that do not have thiol group cannot aggregate the chitosan-Ag NPs. Aggregation of chitosan-Ag NPs has been confirmed with UV-vis absorption spectra, zeta potential and transmission electron microscopy images. Under optimum conditions, good linear relationships existed between the absorption ratios (at A500/A415) and the concentrations of cysteine, homocysteine, and glutathione in the range of 0.1-10.0 μM with detection limits of 15.0, 84.6 and 40.0 nM, respectively. This probe was successfully applied to detect these biothiols in biological samples (urine and plasma).

  13. Whole body acid-base modeling revisited.

    PubMed

    Ring, Troels; Nielsen, Søren

    2017-04-01

    The textbook account of whole body acid-base balance in terms of endogenous acid production, renal net acid excretion, and gastrointestinal alkali absorption, which is the only comprehensive model around, has never been applied in clinical practice or been formally validated. To improve understanding of acid-base modeling, we managed to write up this conventional model as an expression solely on urine chemistry. Renal net acid excretion and endogenous acid production were already formulated in terms of urine chemistry, and we could from the literature also see gastrointestinal alkali absorption in terms of urine excretions. With a few assumptions it was possible to see that this expression of net acid balance was arithmetically identical to minus urine charge, whereby under the development of acidosis, urine was predicted to acquire a net negative charge. The literature already mentions unexplained negative urine charges so we scrutinized a series of seminal papers and confirmed empirically the theoretical prediction that observed urine charge did acquire negative charge as acidosis developed. Hence, we can conclude that the conventional model is problematic since it predicts what is physiologically impossible. Therefore, we need a new model for whole body acid-base balance, which does not have impossible implications. Furthermore, new experimental studies are needed to account for charge imbalance in urine under development of acidosis. Copyright © 2017 the American Physiological Society.

  14. Filling gaps in bacterial amino acid biosynthesis pathways with high-throughput genetics.

    PubMed

    Price, Morgan N; Zane, Grant M; Kuehl, Jennifer V; Melnyk, Ryan A; Wall, Judy D; Deutschbauer, Adam M; Arkin, Adam P

    2018-01-01

    For many bacteria with sequenced genomes, we do not understand how they synthesize some amino acids. This makes it challenging to reconstruct their metabolism, and has led to speculation that bacteria might be cross-feeding amino acids. We studied heterotrophic bacteria from 10 different genera that grow without added amino acids even though an automated tool predicts that the bacteria have gaps in their amino acid synthesis pathways. Across these bacteria, there were 11 gaps in their amino acid biosynthesis pathways that we could not fill using current knowledge. Using genome-wide mutant fitness data, we identified novel enzymes that fill 9 of the 11 gaps and hence explain the biosynthesis of methionine, threonine, serine, or histidine by bacteria from six genera. We also found that the sulfate-reducing bacterium Desulfovibrio vulgaris synthesizes homocysteine (which is a precursor to methionine) by using DUF39, NIL/ferredoxin, and COG2122 proteins, and that homoserine is not an intermediate in this pathway. Our results suggest that most free-living bacteria can likely make all 20 amino acids and illustrate how high-throughput genetics can uncover previously-unknown amino acid biosynthesis genes.

  15. Filling gaps in bacterial amino acid biosynthesis pathways with high-throughput genetics

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Price, Morgan N.; Zane, Grant M.; Kuehl, Jennifer V.

    For many bacteria with sequenced genomes, we do not understand how they synthesize some amino acids. This makes it challenging to reconstruct their metabolism, and has led to speculation that bacteria might be cross-feeding amino acids. Here, we studied heterotrophic bacteria from 10 different genera that grow without added amino acids even though an automated tool predicts that the bacteria have gaps in their amino acid synthesis pathways. Across these bacteria, there were 11 gaps in their amino acid biosynthesis pathways that we could not fill using current knowledge. Using genome-wide mutant fitness data, we identified novel enzymes that fillmore » 9 of the 11 gaps and hence explain the biosynthesis of methionine, threonine, serine, or histidine by bacteria from six genera. We also found that the sulfate-reducing bacterium Desulfovibrio vulgaris synthesizes homocysteine (which is a precursor to methionine) by using DUF39, NIL/ferredoxin, and COG2122 proteins, and that homoserine is not an intermediate in this pathway. Our results suggest that most free-living bacteria can likely make all 20 amino acids and illustrate how high-throughput genetics can uncover previously-unknown amino acid biosynthesis genes.« less

  16. Filling gaps in bacterial amino acid biosynthesis pathways with high-throughput genetics

    DOE PAGES

    Price, Morgan N.; Zane, Grant M.; Kuehl, Jennifer V.; ...

    2018-01-11

    For many bacteria with sequenced genomes, we do not understand how they synthesize some amino acids. This makes it challenging to reconstruct their metabolism, and has led to speculation that bacteria might be cross-feeding amino acids. Here, we studied heterotrophic bacteria from 10 different genera that grow without added amino acids even though an automated tool predicts that the bacteria have gaps in their amino acid synthesis pathways. Across these bacteria, there were 11 gaps in their amino acid biosynthesis pathways that we could not fill using current knowledge. Using genome-wide mutant fitness data, we identified novel enzymes that fillmore » 9 of the 11 gaps and hence explain the biosynthesis of methionine, threonine, serine, or histidine by bacteria from six genera. We also found that the sulfate-reducing bacterium Desulfovibrio vulgaris synthesizes homocysteine (which is a precursor to methionine) by using DUF39, NIL/ferredoxin, and COG2122 proteins, and that homoserine is not an intermediate in this pathway. Our results suggest that most free-living bacteria can likely make all 20 amino acids and illustrate how high-throughput genetics can uncover previously-unknown amino acid biosynthesis genes.« less

  17. Filling gaps in bacterial amino acid biosynthesis pathways with high-throughput genetics

    PubMed Central

    Kuehl, Jennifer V.; Melnyk, Ryan A.; Deutschbauer, Adam M.; Arkin, Adam P.

    2018-01-01

    For many bacteria with sequenced genomes, we do not understand how they synthesize some amino acids. This makes it challenging to reconstruct their metabolism, and has led to speculation that bacteria might be cross-feeding amino acids. We studied heterotrophic bacteria from 10 different genera that grow without added amino acids even though an automated tool predicts that the bacteria have gaps in their amino acid synthesis pathways. Across these bacteria, there were 11 gaps in their amino acid biosynthesis pathways that we could not fill using current knowledge. Using genome-wide mutant fitness data, we identified novel enzymes that fill 9 of the 11 gaps and hence explain the biosynthesis of methionine, threonine, serine, or histidine by bacteria from six genera. We also found that the sulfate-reducing bacterium Desulfovibrio vulgaris synthesizes homocysteine (which is a precursor to methionine) by using DUF39, NIL/ferredoxin, and COG2122 proteins, and that homoserine is not an intermediate in this pathway. Our results suggest that most free-living bacteria can likely make all 20 amino acids and illustrate how high-throughput genetics can uncover previously-unknown amino acid biosynthesis genes. PMID:29324779

  18. Quantification of Lewis acid induced Brønsted acidity of protogenic Lewis bases.

    PubMed

    Lathem, A Paige; Heiden, Zachariah M

    2017-05-09

    Proton transfer promoted by the coordination of protogenic Lewis bases to a Lewis acid is a critical step in catalytic transformations. Although the acidification of water upon coordination to a Lewis acid has been known for decades, no attempts have been made to correlate the Brønsted acidity of the coordinated water molecule with Lewis acid strength. To probe this effect, the pK a 's (estimated error of 1.3 pK a units) in acetonitrile of ten protogenic Lewis bases coordinated to seven Lewis acids containing Lewis acidities varying 70 kcal mol -1 , were computed. To quantify Lewis acid strength, the ability to transfer a hydride (hydride donor ability) from the respective main group hydride was used. Coordination of a Lewis acid to water increased the acidity of the bound water molecule between 20 and 50 pK a units. A linear correlation exhibiting a 2.6 pK a unit change of the Lewis acid-water adduct per ten kcal mol -1 change in hydride donor ability of the respective main group hydride was obtained. For the ten protogenic Lewis bases studied, the coordinated protogenic Lewis bases were acidified between 10 and 50 pK a units. On average, a ten kcal mol -1 change in hydride donor ability of the respective main group hydride resulted in about a 2.8 pK a unit change in the Brønsted acidity of the Lewis acid-Lewis base adducts. Since attempts to computationally investigate the pK a of main group dihydrogen complexes were unsuccessful, experimental determination of the first reported pK a of a main group dihydrogen complex is described. The pK a of H 2 -B(C 6 F 5 ) 3 was determined to be 5.8 ± 0.2 in acetonitrile.

  19. Association of Methylenetetrahydrofolate Reductase (MTHFR 677C>T and 1298A>C) Polymorphisms and Haplotypes with Silent Brain Infarction and Homocysteine Levels in a Korean Population

    PubMed Central

    Han, In Bo; Kim, Ok Joon; Ahn, Jung Yong; Oh, Doyeun; Hong, Sun Pyo; Huh, Ryoong; Chung, Sang Sup

    2010-01-01

    Purpose Methylenetetrahydrofolate reductase (MTHFR) is the main regulatory enzyme for homocysteine metabolism. In the present study, we evaluated whether the MTHFR 677C>T and 1298A>C gene polymorphisms are associated with SBI and plasma homocysteine concentration in a Korean population. Materials and Methods We enrolled 264 patients with SBI and 234 healthy controls in South Korea. Fasting plasma total homocysteine (tHcy) concentrations were measured, and genotype analysis of the MTHFR gene was carried out. Results The plasma tHcy levels were significantly higher in patients with SBI than in healthy controls. Despite a significant association between the MTHFR 677TT genotype and hyperhomocysteinemia, the MTHFR 677C>T genotypes did not appear to influence susceptibility to SBI. However, odds ratios of the 1298AC and 1298AC + CC genotypes for the 1298AA genotype were significantly different between SBI patients and normal controls. The frequencies of 677C-1298A and 677C-1298C haplotypes were significantly higher in the SBI group than in the control group. Conclusion This study demonstrates that the MTHFR 1298A>C polymorphism is a risk factor for SBI in a Korean population. The genotypes of 677C>T and 1298A>C polymorphisms interact additively, and increase the risk of SBI in Korean subjects. PMID:20191019

  20. Association between Serum Unmetabolized Folic Acid Concentrations and Folic Acid from Fortified Foods.

    PubMed

    Palchetti, Cecília Zanin; Paniz, Clóvis; de Carli, Eduardo; Marchioni, Dirce M; Colli, Célia; Steluti, Josiane; Pfeiffer, Christine M; Fazili, Zia; Guerra-Shinohara, Elvira Maria

    2017-01-01

    To investigate the association between serum unmetabolized folic acid (UMFA) concentrations and folic acid from fortified foods and nutrients known as dietary methyl-group donors (folate, methionine, choline, betaine and vitamins B2, B6 and B12) in participants exposed to mandatory fortification of wheat and maize flours with folic acid. Cross-sectional study carried out with 144 healthy Brazilian participants, both sexes, supplement nonusers. Serum folate, UMFA, vitamin B12 and total plasma homocysteine (tHcy) were biochemically measured. Dietary intake was assessed by 2 non-consecutive 24-hour dietary recalls (24-HRs) and deattenuated energy-adjusted nutrient data were used for statistical analysis. Ninety eight (68.1%) participants were women. Median (interquartile range) age was 35.5 (28.0-52.0) years. Elevated serum folate concentrations (>45 nmol/L) were found in 17 (11.8%), while folate deficiency (<7 nmol/L) in 10 (6.9%) participants. No one had vitamin B12 deficiency (<148 pmol/L). An elevated serum UMFA concentration was defined as > 1 nmol/L (90th percentile). UMFA concentrations were positively correlated with folic acid intake and negatively correlated to choline, methionine and vitamin B6 intakes. Participants in the lowest quartile of UMFA concentrations had lower dietary intake of total folate (DFEs) and folic acid, and higher dietary intake of methionine, choline and vitamin B6 than participants in the highest quartile of UMFA. Folic acid intake (OR [95% CI] = 1.02 [1.01-1.04)] and being a male (OR [95% CI] = 0.40 [0.19-0.87) were associated with increased and reduced odds for UMFA concentrations > 0.55 nmol/L (median values), respectively. UMFA concentrations were directly influenced by folic acid intake from fortified foods in a healthy convenience sample of adult Brazilians exposed to mandatory flour fortification with folic acid.

  1. Dose- and Glucose-Dependent Effects of Amino Acids on Insulin Secretion from Isolated Mouse Islets and Clonal INS-1E Beta-Cells

    PubMed Central

    Liu, Zhenping; Jeppesen, Per B.; Gregersen, Søren; Chen, Xiaoping; Hermansen, Kjeld

    2008-01-01

    BACKGROUND: The influence of glucose and fatty acids on beta-cell function is well established whereas little is known about the role of amino acids (AAs). METHODS: Islets isolated from NMRI mice were incubated overnight. After preincubation, isolated islets as well as clonal INS-1E beta-cells were incubated for 60 min in a modified Krebs Ringer buffer containing glucose and AAs. RESULTS: At 16.7 mmol/l (mM) glucose, L-arginine, L-lysine, L-alanine, L-proline, L-leucine, and L-glutamine potentiated glucose-stimulated insulin secretion dose-dependently, while DL-homocysteine inhibited insulin secretion. Maximal insulin stimulation was obtained at 20 mM L-proline, L-lysine, L-alanine, L-arginine (islets: 2.5 to 6.7 fold increase; INS-1E cells: 1.6 to 2.2 fold increase). L-glutamine and L-leucine only increased glucose-stimulated (16.7 mM) insulin secretion (INS-1E cells: 1.5 and 1.3 fold, respectively) at an AA concentration of 20 mM. Homocysteine inhibited insulin secretion both at 5.6 mM and 16.7 mM glucose. At glucose levels ranging from 1.1 to 25 mM, the equimolar concentration of 10 mM, L-proline, L-lysine, L-arginine increased insulin secretion from mouse islets and INS-1E cells at all glucose levels applied, with a maximal effect obtained at 25 mM glucose. At a concentration of 10 mM, L-arginine and L-lysine had the highest insulinotropic potency among the AAs investigated. CONCLUSION: L-arginine, L-lysine, L-alanine, L-proline, L-leucine and L-glutamine acutely stimulate insulin secretion from mouse islets and INS-1E cells in a dose- and glucose-dependent manner, whereas DL-homocysteine inhibits insulin release. PMID:19290384

  2. Activation of NMDA receptor by elevated homocysteine in chronic liver disease contributes to encephalopathy.

    PubMed

    Choudhury, Sabanum; Borah, Anupom

    2015-07-01

    Liver diseases lead to a complex syndrome characterized by neurological, neuro-psychiatric and motor complications, called hepatic encephalopathy, which is prevalent in patients and animal models of acute, sub-chronic and chronic liver failure. Although alterations in GABAergic, glutamatergic, cholinergic and serotonergic neuronal functions have been implicated in HE, the molecular mechanisms that lead to HE in chronic liver disease (CLD) is least illustrated. Due to hepatocellular failure, levels of ammonia and homocysteine (Hcy), in addition to others, are found to increase in the brain as well as plasma. Hcy, a non-protein forming amino acid and an excitotoxin, activates ionotropic glutamate (n-methyl-d-aspartate; NMDA) receptors, and thereby leads to influx of Ca(2+) into neurons, which in turn activates several pathways that trigger oxidative stress, inflammation and apoptosis, collectively called excitotoxicity. Elevated levels of Hcy in the plasma and brain, a condition called Hyperhomocysteinemia (HHcy), and the resultant NMDA receptor-mediated excitotoxicity has been implicated in several diseases, including Parkinson's disease and Alzheimer's disease. Although, hyperammonemia has been shown to cause excitotoxicity, the role of HHcy in the development of behavioral and neurochemical alterations that occur in HE has not been illustrated yet. It is hypothesized that CLD-induced HHcy plays a major role in the development of HE through activation of NMDA receptors. It is further hypothesized that HHcy synergizes with hyperammonemia to activate NMDA receptor in the brain, and thereby cause oxidative stress, inflammation and apoptosis, and neuronal loss that leads to HE. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Role of Homocysteine in the Ischemic Stroke and Development of Ischemic Tolerance

    PubMed Central

    Lehotský, Ján; Tothová, Barbara; Kovalská, Maria; Dobrota, Dušan; Beňová, Anna; Kalenská, Dagmar; Kaplán, Peter

    2016-01-01

    Homocysteine (Hcy) is a toxic, sulfur-containing intermediate of methionine metabolism. Hyperhomocysteinemia (hHcy), as a consequence of impaired Hcy metabolism or defects in crucial co-factors that participate in its recycling, is assumed as an independent human stroke risk factor. Neural cells are sensitive to prolonged hHcy treatment, because Hcy cannot be metabolized either by the transsulfuration pathway or by the folate/vitamin B12 independent remethylation pathway. Its detrimental effect after ischemia-induced damage includes accumulation of reactive oxygen species (ROS) and posttranslational modifications of proteins via homocysteinylation and thiolation. Ischemic preconditioning (IPC) is an adaptive response of the CNS to sub-lethal ischemia, which elevates tissues tolerance to subsequent ischemia. The main focus of this review is on the recent data on homocysteine metabolism and mechanisms of its neurotoxicity. In this context, the review documents an increased oxidative stress and functional modification of enzymes involved in redox balance in experimentally induced hyperhomocysteinemia. It also gives an interpretation whether hyperhomocysteinemia alone or in combination with IPC affects the ischemia-induced neurodegenerative changes as well as intracellular signaling. Studies document that hHcy alone significantly increased Fluoro-Jade C- and TUNEL-positive cell neurodegeneration in the rat hippocampus as well as in the cortex. IPC, even if combined with hHcy, could still preserve the neuronal tissue from the lethal ischemic effects. This review also describes the changes in the mitogen-activated protein kinase (MAPK) protein pathways following ischemic injury and IPC. These studies provide evidence for the interplay and tight integration between ERK and p38 MAPK signaling mechanisms in response to the hHcy and also in association of hHcy with ischemia/IPC challenge in the rat brain. Further investigations of the protective factors leading to ischemic

  4. Homocysteine alters cerebral microvascular integrity and causes remodeling by antagonizing GABA-A receptor*

    PubMed Central

    Lominadze, David; Tyagi, Neetu; Sen, Utpal; Ovechkin, Alexander; Tyagi, Suresh C.

    2012-01-01

    High levels of homocysteine (Hcy), known as hyperhomocysteinemia (HHcy), are associated with cerebrovascular diseases, such as vascualr dementia, stroke, and Alzheimer's disease. The -amino butyric acid (GABA) is a inhibitory neurotransmitter and a ligand of GABA-A receptor. By inhibiting excitatory response it may decrease complications associated with vascular dementia and stroke. Hcy specifically competes with the GABA-A receptors and acts as an excitotoxic neurotransmitter. Previously we have shown that Hcy increases levels of NADPH oxidase and reactive oxygen species (ROS), and decreases levels of thioredoxin and peroxiredoxin by antagonizing the GABA-A receptor. Hcy treatment leads to activation of matrix metalloproteinases (MMPs) in cerebral circualtion by inducing redox stress and ROS. The hypothesis is that Hcy induces MMPs and suppresses tissue inhibitors of metalloproteinase (TIMPs), in part, by inhibiting the GABA-A receptor. This leads to degradation of the matrix and disruption of the blood brain barrier. The brain cortex of transgenic mouse model of HHcy (cystathionine -synthase, CBS −/+) and GABA-A receptor null mice treated with and without muscimol (GABA-A receptor agonist) was analysed. The mRNA levels were measured by Q-RT-PCR. Levels of MMP-2, -9, -13, and TIMP-1, -2, -3, and -4 were evaluated by in situ labeling and PCR-gene arrays. Pial venular permeability to fluorescence-labeled albumin was assessed with intravital fluorescence microscopy. We found that Hcy increases metalloproteinase activity and decreases TIMP-4 by antagonizing the GABA-A receptor. The results demonstrate a novel mechanism in which brain microvascular permeability changes during HHcy and vascular dementias, and have therapeutic ramifications for microvascular disease in Alzheimer's patients. PMID:22886392

  5. Plasma choline and betaine and their relation to plasma homocysteine in normal pregnancy.

    PubMed

    Velzing-Aarts, Francien V; Holm, Pål I; Fokkema, M Rebecca; van der Dijs, Fey P; Ueland, Per M; Muskiet, Frits A

    2005-06-01

    Plasma concentrations of total homocysteine (tHcy) decrease during pregnancy. This reduction has been investigated in relation to folate status, but no study has addressed the possible role of betaine and its precursor choline. We investigated the courses of plasma choline and betaine during normal human pregnancy and their relations to plasma tHcy. Blood samples were obtained monthly; the initial samples were taken at gestational week (GW) 9, and the last samples were taken approximately 3 mo postpartum. The study population comprised 50 women of West African descent. Most of the subjects took folic acid irregularly. Plasma choline (geometric x; 95% reference interval) increased continuously during pregnancy, from 6.6 (4.5, 9.7) micromol/L at GW 9 to 10.8 (7.4, 15.6) micromol/L at GW 36. Plasma betaine decreased in the first half of pregnancy, from 16.3 (8.6, 30.8) micromol/L at GW 9 to 10.3 (6.6, 16.2) micromol/L at GW 20 and remained constant thereafter. We confirmed a reduction in plasma tHcy, and the lowest concentration was found in the second trimester. From GW 16 onward, an inverse relation between plasma tHcy and betaine was observed. Multiple regression analysis showed that plasma betaine was a strong predictor of plasma tHcy from GW 20 onward. The steady increase in choline throughout gestation may ensure choline availability for placental transfer with subsequent use by the growing fetus. Betaine becomes a strong predictor of tHcy during the course of pregnancy. Both of these findings emphasize the importance of choline and betaine status during normal human pregnancy.

  6. [Homocysteine after a methionine load in healthy subjects with adequate B-vitamin status].

    PubMed

    López-Alarcón, Mardia; Chávez-Negrete, Adolfo; Montalvo-Velarde, Irene; Maldonado-Hernández, Jorge; Vital-Reyes, Víctor Saúl

    2011-01-01

    Plasma homocysteine (Hcy) determination at 6-8 h after an oral methionine load (OML) allows for identification of some, but not all, individuals at risk to develop cardiovascular disease. It is probable that in some cases the Hcy increases occur later, or it elevates between normal ranges but in a sustained manner. However, the entire Hcy response curve has not been described. We undertook this study to determine Hcy concentrations from baseline to 24- and 48-h after an OML in non-B-vitamin deficient adult subjects with other risk factors for high levels of Hcy such as smoking and overweight. In a cross-over, clinical design, Hcy concentrations were determined at 2-h intervals throughout 12 h and at 24 h and 48 h after an OML (0.1 g/kg). Hcy and vitamin B6 (VB6) concentrations were measured by high-performance liquid chromatography (HPLC). Folic acid (FA) and vitamin B12 (VB12) were measured by radioimmunoassay (RIA). Statistical analysis included delta values and areas under the curve. Student t-test and repeated measurement analyses were conducted to control for confounders. Twenty-nine subjects with adequate Hcy, FA, VB6 and VB12 status were included. The maximum Hcy concentration occurred 8 h after the load and returned to baseline concentrations after 24 h. All subjects presented Hcy after the load within normal ranges, but smoking and overweight synergistically influenced the response to the challenge, producing a sustained elevation after the dose. Hcy concentrations after an OML remained above baseline for at least 24 h. Smoking and overweight affected the response to the methionine challenge.

  7. General base-general acid catalysis by terpenoid cyclases.

    PubMed

    Pemberton, Travis A; Christianson, David W

    2016-07-01

    Terpenoid cyclases catalyze the most complex reactions in biology, in that more than half of the substrate carbon atoms often undergo changes in bonding during the course of a multistep cyclization cascade that proceeds through multiple carbocation intermediates. Many cyclization mechanisms require stereospecific deprotonation and reprotonation steps, and most cyclization cascades are terminated by deprotonation to yield an olefin product. The first bacterial terpenoid cyclase to yield a crystal structure was pentalenene synthase from Streptomyces exfoliatus UC5319. This cyclase generates the hydrocarbon precursor of the pentalenolactone family of antibiotics. The structures of pentalenene synthase and other terpenoid cyclases reveal predominantly nonpolar active sites typically lacking amino acid side chains capable of serving general base-general acid functions. What chemical species, then, enables the Brønsted acid-base chemistry required in the catalytic mechanisms of these enzymes? The most likely candidate for such general base-general acid chemistry is the co-product inorganic pyrophosphate. Here, we briefly review biological and nonbiological systems in which phosphate and its derivatives serve general base and general acid functions in catalysis. These examples highlight the fact that the Brønsted acid-base activities of phosphate derivatives are comparable to the Brønsted acid-base activities of amino acid side chains.

  8. Homocysteine and the risk of ischemic stroke in a triethnic cohort: the NOrthern MAnhattan Study.

    PubMed

    Sacco, Ralph L; Anand, Kishlay; Lee, Hye-Seung; Boden-Albala, Bernadette; Stabler, Sally; Allen, Robert; Paik, Myunghee C

    2004-10-01

    The level of total homocysteine (tHcy) that confers a risk of ischemic stroke is unsettled, and no prospective cohort studies have included sufficient elderly minority subjects. We investigated the association between mild to moderate fasting tHcy level and the incidence of ischemic stroke, myocardial infarction, and vascular death in a multiethnic prospective study. A population-based cohort was followed for vascular events (stroke, myocardial infarction, and vascular death). Baseline values of tHcy and methylmalonic acid were measured among 2939 subjects (mean age, 69+/-10; 61% women, 53% Hispanics, 24% blacks, and 20% whites). Cox proportional models were used to calculate hazard ratios (HRs) and 95% CIs in tHcy categories after adjusting for age, race, education, renal insufficiency, B12 deficiency, and other risk factors. The adjusted HR for a tHcy level > or =15 micromol/L compared with <10 micromol/L was greatest for vascular death (HR=6.04; 95% CI, 3.44 to 10.60), followed by combined vascular events (HR=2.27; 95% CI, 1.51 to 3.43), ischemic stroke (HR=2.01; 95% CI, 1.00 to 4.05), and nonvascular death (HR=2.02; 95% CI, 1.31 to 3.14). Mild to moderate elevations of tHcy of 10 to 15 micromol/L were not significantly predictive of ischemic stroke, but increased the risk of vascular death (2.27; 95% CI, 1.44 to 3.60) and combined vascular events (1.42; 95% CI, 1.06 to 1.88). The effect of tHcy was stronger among whites and Hispanics, but not a significant risk factor for blacks. Total Hcy elevations above 15 micromol/L are an independent risk factor for ischemic stroke, whereas mild elevations of tHcy of 10 to 15 micromol/L are less predictive. The vascular effects of tHcy are greatest among whites and Hispanics, and less among blacks.

  9. An evidence-based approach to globally assess the covariate-dependent effect of the MTHFR single nucleotide polymorphism rs1801133 on blood homocysteine: a systematic review and meta-analysis.

    PubMed

    Jin, Huifeng; Cheng, Haojie; Chen, Wei; Sheng, Xiaoming; Levy, Mark A; Brown, Mark J; Tian, Junqiang

    2018-05-01

    The single nucleotide polymorphism of the gene 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T (or rs1801133) is the most established genetic factor that increases plasma total homocysteine (tHcy) and consequently results in hyperhomocysteinemia. Yet, given the limited penetrance of this genetic variant, it is necessary to individually predict the risk of hyperhomocysteinemia for an rs1801133 carrier. We hypothesized that variability in this genetic risk is largely due to the presence of factors (covariates) that serve as effect modifiers, confounders, or both, such as folic acid (FA) intake, and aimed to assess this risk in the complex context of these covariates. We systematically extracted from published studies the data on tHcy, rs1801133, and any previously reported rs1801133 covariates. The resulting metadata set was first used to analyze the covariates' modifying effect by meta-regression and other statistical means. Subsequently, we controlled for this modifying effect by genotype-stratifying tHcy data and analyzed the variability in the risk resulting from the confounding of covariates. The data set contains data on 36 rs1801133 covariates that were collected from 114,799 participants and 256 qualified studies, among which 6 covariates (sex, age, race, FA intake, smoking, and alcohol consumption) are the most frequently informed and therefore included for statistical analysis. The effect of rs1801133 on tHcy exhibits significant variability that can be attributed to effect modification as well as confounding by these covariates. Via statistical modeling, we predicted the covariate-dependent risk of tHcy elevation and hyperhomocysteinemia in a systematic manner. We showed an evidence-based approach that globally assesses the covariate-dependent effect of rs1801133 on tHcy. The results should assist clinicians in interpreting the rs1801133 data from genetic testing for their patients. Such information is also important for the public, who increasingly

  10. COMMERCIAL EXTRACT FROM ARONIA AS A MODULATOR OF ADHESIVE PROPERTIES OF FIBRINOGEN TREATED WITH HOMOCYSTEINE AND ITS THIOLACTONE IN VITRO.

    PubMed

    Olas, Beata; Kontek, Bogdan; Oleszek, Wieslaw; Stochmal, Anna

    2016-11-01

    Research has confirmed the positive effect of berries of Aivnia melanocarpa on the cardiovascular system. The protective effects of polyphenol-rich extract from berries of A. melanocarpa against changes in biological properties of fibrinogen were studied. In in vino model of hyperhomocysteinemia the capability of fibrinogen to interact with human blood platelets was measured by platelet adhesion in the presence of extract fromA. nelanocapa. We induced hyperhomocystenemia using a reduced form of homocysteine (Hey, at a final concentration of 0.01. 0.1 and 1 μM) and the most reactive form of Hey - its cyclic thioester, homocysteine thiolactone (HTL, at a final concentration of 0.1, 0.5 and I μM). It was observed that Hey or HTL-treated fibrinogen, in comparison with untreated molecule, had a distinct capability to mediate blood platelet adhesion. The experiments also indicate that polyphenol-rich extract from black chokeberries (at final concentrations of 2.5-10 pM/mL) reduced the toxic action of Hey and HTL on the adhesive properties of fibrinogen. The possible protection exerted by black chokeberry extract, through restoring the platelet adhesion of Hey or HTL treated fibrinogen, may be important for vascular diseases.

  11. Effects of diet on titratable acid-base excretion in grasshoppers.

    PubMed

    Frazier, M R; Harrison, J F; Behmer, S T

    2000-01-01

    Despite the potential for diet to affect organismal acid-base status, especially in herbivores, little is known about the effects of diet on acid-base loading and excretion. We tested the effects of diet on acid-base loading and excretion in grasshoppers by (a) comparing the fecal acid-base content of 15 grasshopper species collected from the field and (b) comparing fecal acid-base excretion rates of Schistocerca americana grasshoppers fed vegetable diets that differed in their ashed and raw acid-base contents. The field experiments indicated that grass-feeding species excrete fairly neutral fecal pellets, while forb/mixed-feeding species vary widely in their fecal acid-base contents. In the laboratory experiment, acid-base excretion rates were positively correlated with dietary ashed base intake rates but were not correlated with the acid-base content of raw, unashed diet or feeding rate. These experiments suggest that some diets could strongly challenge the acid-base homeostasis of herbivores; in some grasshoppers, dietary acid-base loads could produce certainly lethal 1-unit changes in average body pH within 6 h if they were not excreted.

  12. The Kidney and Acid-Base Regulation

    ERIC Educational Resources Information Center

    Koeppen, Bruce M.

    2009-01-01

    Since the topic of the role of the kidneys in the regulation of acid base balance was last reviewed from a teaching perspective (Koeppen BM. Renal regulation of acid-base balance. Adv Physiol Educ 20: 132-141, 1998), our understanding of the specific membrane transporters involved in H+, HCO , and NH transport, and especially how these…

  13. Acid-base properties of 2-phenethyldithiocarbamoylacetic acid, an antitumor agent

    NASA Astrophysics Data System (ADS)

    Novozhilova, N. E.; Kutina, N. N.; Petukhova, O. A.; Kharitonov, Yu. Ya.

    2013-07-01

    The acid-base properties of the 2-phenethyldithiocarbamoylacetic acid (PET) substance belonging to the class of isothiocyanates and capable of inhibiting the development of tumors on many experimental models were studied. The acidity and hydrolysis constants of the PET substance in ethanol, acetone, aqueous ethanol, and aqueous acetone solutions were determined from the data of potentiometric (pH-metric) titration of ethanol and acetone solutions of PET with aqueous solidum hydroxide at room temperature.

  14. Acid-base properties of humic and fulvic acids formed during composting.

    PubMed

    Plaza, César; Senesi, Nicola; Polo, Alfredo; Brunetti, Gennaro

    2005-09-15

    The soil acid-base buffering capacity and the biological availability, mobilization, and transport of macro- and micronutrients, toxic metal ions, and xenobiotic organic cations in soil are strongly influenced by the acid-base properties of humic substances, of which humic and fulvic acids are the major fractions. For these reasons, the proton binding behavior of the humic acid-like (HA) and fulvic acid-like (FA) fractions contained in a compost are believed to be instrumental in its successful performance in soil. In this work, the acid-base properties of the HAs and FAs isolated from a mixture of the sludge residue obtained from olive oil mill wastewater (OMW) evaporated in an open-air pond and tree cuttings (TC) at different stages of composting were investigated by a current potentiometric titration method and the nonideal competitive adsorption (NICA)-Donnan model. The NICA-Donnan model provided an excellent description of the acid-base titration data, and pointed out substantial differences in site density and proton-binding affinity between the HAs and FAs examined. With respect to FAs, HAs were characterized by a smaller content of carboxylic- and phenolic-type groups and their larger affinities for proton binding. Further, HAs featured a greater heterogeneity in carboxylic-type groups than FAs. The composting process increased the content and decreased the proton affinity of carboxylic- and phenolic-type groups of HAs and FAs, and increased the heterogeneity of phenolic-type groups of HAs. As a whole, these effects indicated that the composting process could produce HA and FA fractions with greater cation binding capacities. These results suggest that composting of organic materials improves their agronomic and environmental value by increasing their potential to retain and exchange macro- and micronutrients, and to reduce the bioavailability of organic and inorganic pollutants.

  15. Quantitative, high-resolution epigenetic profiling of CpG loci identifies associations with cord blood plasma homocysteine and birth weight in humans

    PubMed Central

    Ismail, Khaled MK; Haworth, Kim E; Mein, Charles; Carroll, William D

    2011-01-01

    Supplementation with folic acid during pregnancy is known to reduce the risk of neural tube defects and low birth weight. It is thought that folate and other one-carbon intermediates might secure these clinical effects via DNA methylation. We examined the effects of folate on the human methylome using quantitative interrogation of 27,578 CpG loci associated with 14,496 genes at single-nucleotide resolution across 12 fetal cord blood samples. Consistent with previous studies, the majority of CpG dinucleotides located within CpG islands exhibited hypomethylation while those outside CpG islands showed mid-high methylation. However, for the first time in human samples, unbiased analysis of methylation across samples revealed a significant correlation of methylation patterns with plasma homocysteine, LINE-1 methylation and birth weight centile. Additionally, CpG methylation significantly correlated with either birth weight or LINE-1 methylation were predominantly located in CpG islands. These data indicate that levels of folate-associated intermediates in cord blood reflect their influence and consequences for the fetal epigenome and potentially on pregnancy outcome. In these cases, their influence might be exerted during late gestation or reflect those present during the peri-conceptual period. PMID:20864804

  16. Homocysteine enhances MMP-9 production in murine macrophages via ERK and Akt signaling pathways

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lee, Seung Jin; Lee, Yi Sle; Seo, Kyo Won

    2012-04-01

    Homocysteine (Hcy) at elevated levels is an independent risk factor of cardiovascular diseases, including atherosclerosis. In the present study, we investigated the effect of Hcy on the production of matrix metalloproteinases (MMP) in murine macrophages. Among the MMP known to regulate the activities of collagenase and gelatinase, Hcy exclusively increased the gelatinolytic activity of MMP-9 in J774A.1 cells as well as in mouse peritoneal macrophages. Furthermore, this activity was found to be correlated with Western blot findings in J774A.1 cells, which showed that MMP-9 expression was concentration- and time-dependently increased by Hcy. Inhibition of the ERK and Akt pathways ledmore » to a significant decrease in Hcy-induced MMP-9 expression, and combined treatment with inhibitors of the ERK and Akt pathways showed an additive effects. Activity assays for ERK and Akt showed that Hcy increased the phosphorylation of both, but these phosphorylation were not affected by inhibitors of the Akt and ERK pathways. In line with these findings, the molecular inhibition of ERK and Akt using siRNA did not affect the Hcy-induced phosphorylation of Akt and ERK, respectively. Taken together, these findings suggest that Hcy enhances MMP-9 production in murine macrophages by separately activating the ERK and Akt signaling pathways. -- Highlights: ► Homocysteine (Hcy) induced MMP-9 production in murine macrophages. ► Hcy induced MMP-9 production through ERK and Akt signaling pathways. ► ERK and Akt signaling pathways were activated by Hcy in murine macrophages. ► ERK and Akt pathways were additively act on Hcy-induced MMP-9 production. ► Hcy enhances MMP-9 production in macrophages via activation of ERK and Akt signaling pathways in an independent manner.« less

  17. Cognitive Impairment in Folate-Deficient Rats Corresponds to Depleted Brain Phosphatidylcholine and Is Prevented by Dietary Methionine without Lowering Plasma Homocysteine12

    PubMed Central

    Troen, Aron M.; Chao, Wei-Hsun; Crivello, Natalia A.; D'Anci, Kristen E.; Shukitt-Hale, Barbara; Smith, Don E.; Selhub, Jacob; Rosenberg, Irwin H.

    2008-01-01

    Poor folate status is associated with cognitive decline and dementia in older adults. Although impaired brain methylation activity and homocysteine toxicity are widely thought to account for this association, how folate deficiency impairs cognition is uncertain. To better define the role of folate deficiency in cognitive dysfunction, we fed rats folate-deficient diets (0 mg FA/kg diet) with or without supplemental L-methionine for 10 wk, followed by cognitive testing and tissue collection for hematological and biochemical analysis. Folate deficiency with normal methionine impaired spatial memory and learning; however, this impairment was prevented when the folate-deficient diet was supplemented with methionine. Under conditions of folate deficiency, brain membrane content of the methylated phospholipid phosphatidylcholine was significantly depleted, which was reversed with supplemental methionine. In contrast, neither elevated plasma homocysteine nor brain S-adenosylmethionine and S-adenosylhomocysteine concentrations predicted cognitive impairment and its prevention by methionine. The correspondence of cognitive outcomes to changes in brain membrane phosphatidylcholine content suggests that altered phosphatidylcholine and possibly choline metabolism might contribute to the manifestation of folate deficiency-related cognitive dysfunction. PMID:19022979

  18. Renal acidification responses to respiratory acid-base disorders.

    PubMed

    Madias, Nicolaos E

    2010-01-01

    Respiratory acid-base disorders are those abnormalities in acid-base equilibrium that are expressed as primary changes in the arterial carbon dioxide tension (PaCO2). An increase in PaCO2 (hypercapnia) acidifies body fluids and initiates the acid-base disturbance known as respiratory acidosis. By contrast, a decrease in PaCO2 (hypocapnia) alkalinizes body fluids and initiates the acid-base disturbance known as respiratory alkalosis. The impact on systemic acidity of these primary changes in PaCO2 is ameliorated by secondary, directional changes in plasma [HCO3¯] that occur in 2 stages. Acutely, hypercapnia or hypocapnia yields relatively small changes in plasma [HCO3¯] that originate virtually exclusively from titration of the body's nonbicarbonate buffers. During sustained hypercapnia or hypocapnia, much larger changes in plasma [HCO3¯] occur that reflect adjustments in renal acidification mechanisms. Consequently, the deviation of systemic acidity from normal is smaller in the chronic forms of these disorders. Here we provide an overview of the renal acidification responses to respiratory acid-base disorders. We also identify gaps in knowledge that require further research.

  19. Nucleic Acid-Based Nanodevices in Biological Imaging.

    PubMed

    Chakraborty, Kasturi; Veetil, Aneesh T; Jaffrey, Samie R; Krishnan, Yamuna

    2016-06-02

    The nanoscale engineering of nucleic acids has led to exciting molecular technologies for high-end biological imaging. The predictable base pairing, high programmability, and superior new chemical and biological methods used to access nucleic acids with diverse lengths and in high purity, coupled with computational tools for their design, have allowed the creation of a stunning diversity of nucleic acid-based nanodevices. Given their biological origin, such synthetic devices have a tremendous capacity to interface with the biological world, and this capacity lies at the heart of several nucleic acid-based technologies that are finding applications in biological systems. We discuss these diverse applications and emphasize the advantage, in terms of physicochemical properties, that the nucleic acid scaffold brings to these contexts. As our ability to engineer this versatile scaffold increases, its applications in structural, cellular, and organismal biology are clearly poised to massively expand.

  20. Serum homocysteine levels in patients with probable vascular dementia.

    PubMed

    Alajbegović, Salem; Lepara, Orhan; Hadžović-Džuvo, Almira; Mutevelić-Turković, Alma; Alajbegović, Lejla; Zaćiragić, Asija; Avdagić, Nesina; Valjevac, Amina; Babić, Nermina; Dervišević, Amela

    2017-08-01

    Aim To investigate total homocysteine (tHcy) serum concentration in patients with probable vascular dementia (VD) and in agematched controls, as well as to determine an association between tHcy serum concentration and cognitive impairment in patients with probable VD. Methods Serum concentration of tHcy was determined by the Fluorescence Polarization Immunoassay on the AxSYM System. Cognitive impairment was tested by the Mini Mental Status Examination (MMSE) score. Body mass index (BMI) was calculated for each subject included in the study. Results Age, systolic, diastolic blood pressure and BMI did not differ significantly between the two groups. Mean serum tHcy concentration in the control group of subjects was 13.35 µmol/L, while in patients with probable VD it was significantly higher, 19.45 µmol/L (p=0.002). A negative but insignificant association between serum tHcy concentration and cognitive impairment in patients with probable VD was found. Conclusion Increased tHcy concentration in patients with probable VD suggests the possible independent role of Hcy in the pathogenesis of VD. Copyright© by the Medical Assotiation of Zenica-Doboj Canton.

  1. Folic Acid, Vitamin B6, and Vitamin B12 in Combination and Age-related Macular Degeneration in a Randomized Trial of Women

    PubMed Central

    Christen, William G.; Glynn, Robert J.; Chew, Emily Y.; Albert, Christine M.; Manson, JoAnn E.

    2008-01-01

    Context Observational epidemiologic studies indicate a direct association between homocysteine concentration in the blood and risk of age-related macular degeneration (AMD), but randomized trial data to examine the effect of homocysteine-lowering in AMD are lacking. Objective To examine incidence of AMD in a trial of folic acid/vitamin B6/vitamin B12. Design Randomized, double-masked, placebo-controlled trial. Participants 5,442 female health professionals aged 40 years or older with preexisting cardiovascular disease (CVD) or 3 or more CVD risk factors. A total of 5,205 of these women did not have a diagnosis of AMD at baseline and were included in this analysis. Intervention Participants were randomly assigned to receive a combination of folic acid (2.5 mg/d), vitamin B6 (50 mg/d), and vitamin B12 (1 mg/d), or placebo. Main Outcome Measures Total AMD, defined as a self-report documented by medical record evidence of an initial diagnosis after randomization, and visually-significant AMD, defined as confirmed incident AMD with visual acuity of 20/30 or worse attributable to this condition. Results After an average of 7.3 years of treatment and follow-up, there were 55 cases of AMD in the folic acid/B6/B12 group and 82 in the placebo group (relative risk [RR], 0.66; 95% confidence interval [CI], 0.47–0.93; p=0.02). For visually-significant AMD, there were 26 cases in the folic acid/B6/B12 group and 44 in the placebo group (RR, 0.59; 95% CI, 0.36–0.95; p=0.03). Conclusions These randomized trial data from a large cohort of women at high risk of CVD indicate that daily supplementation with folic acid/B6/B12 may reduce the risk of AMD. PMID:19237716

  2. Acid-base titrations using microfluidic paper-based analytical devices.

    PubMed

    Karita, Shingo; Kaneta, Takashi

    2014-12-16

    Rapid and simple acid-base titration was accomplished using a novel microfluidic paper-based analytical device (μPAD). The μPAD was fabricated by wax printing and consisted of ten reservoirs for reaction and detection. The reaction reservoirs contained various amounts of a primary standard substance, potassium hydrogen phthalate (KHPth), whereas a constant amount of phenolphthalein was added to all the detection reservoirs. A sample solution containing NaOH was dropped onto the center of the μPAD and was allowed to spread to the reaction reservoirs where the KHPth neutralized it. When the amount of NaOH exceeded that of the KHPth in the reaction reservoirs, unneutralized hydroxide ion penetrated the detection reservoirs, resulting in a color reaction from the phenolphthalein. Therefore, the number of the detection reservoirs with no color change determined the concentration of the NaOH in the sample solution. The titration was completed within 1 min by visually determining the end point, which required neither instrumentation nor software. The volumes of the KHPth and phenolphthalein solutions added to the corresponding reservoirs were optimized to obtain reproducible and accurate results for the concentration of NaOH. The μPADs determined the concentration of NaOH at orders of magnitude ranging from 0.01 to 1 M. An acid sample, HCl, was also determined using Na2CO3 as a primary standard substance instead of KHPth. Furthermore, the μPAD was applicable to the titrations of nitric acid, sulfuric acid, acetic acid, and ammonia solutions. The μPADs were stable for more than 1 month when stored in darkness at room temperature, although this was reduced to only 5 days under daylight conditions. The analysis of acidic hot spring water was also demonstrated in the field using the μPAD, and the results agreed well with those obtained by classic acid-base titration.

  3. Abdominal aortic aneurysm and the association with serum levels of Homocysteine, vitamins B6, B12 and Folate

    PubMed Central

    Lindqvist, Markus; Hellström, Anders; Henriksson, Anders E

    2012-01-01

    Previous investigations have shown hyperhomocysteinemi in patients with abdominal aortic aneurysm (AAA). In the present study we evaluated the circulating level of homocysteine (Hcy) in relation to renal function, vitamins B6, B12 and folate status in AAA patients with special regard to aneurysm size, and rupture. Hcy, Creatinine, B6, B12 and folate were measured in 119 patients with AAA and 36 controls without aneurysm matched by age, gender and smoking habit. As expected there was a weak correlation between Hcy and vitamins B6, B12 or folate. We found similar levels of Hcy, B6 and folic acid in patients with nonruptured AAA compared to the control group matched by age, gender and smoking habit. There was no correlation between maximum diameter of the nonruptured AAA (n=78) and Hcy, B6 or folate. However, the present study shows a significant inverse correlation between maximum diameter of the nonruptured AAA (n=78) and B12 (r = -0.304, p=0.007) with significant higher levels in small AAA compared to large AAA. In conclusion, Hcy does not seem to be a useful biomarker in AAA disease. The unexpected finding of B12 levels correlating to aneurysm diameter warrants urgent further investigation of B12 supplement to prevent progression of small AAA. PMID:23173106

  4. Abdominal aortic aneurysm and the association with serum levels of Homocysteine, vitamins B6, B12 and Folate.

    PubMed

    Lindqvist, Markus; Hellström, Anders; Henriksson, Anders E

    2012-01-01

    Previous investigations have shown hyperhomocysteinemi in patients with abdominal aortic aneurysm (AAA). In the present study we evaluated the circulating level of homocysteine (Hcy) in relation to renal function, vitamins B6, B12 and folate status in AAA patients with special regard to aneurysm size, and rupture. Hcy, Creatinine, B6, B12 and folate were measured in 119 patients with AAA and 36 controls without aneurysm matched by age, gender and smoking habit. As expected there was a weak correlation between Hcy and vitamins B6, B12 or folate. We found similar levels of Hcy, B6 and folic acid in patients with nonruptured AAA compared to the control group matched by age, gender and smoking habit. There was no correlation between maximum diameter of the nonruptured AAA (n=78) and Hcy, B6 or folate. However, the present study shows a significant inverse correlation between maximum diameter of the nonruptured AAA (n=78) and B12 (r = -0.304, p=0.007) with significant higher levels in small AAA compared to large AAA. In conclusion, Hcy does not seem to be a useful biomarker in AAA disease. The unexpected finding of B12 levels correlating to aneurysm diameter warrants urgent further investigation of B12 supplement to prevent progression of small AAA.

  5. Elevated total plasma homocysteine and 667C{r_arrow}T mutation of the 5,10-methylenetetrahydrofolate reductase gene in thrombotic vascular disease

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    De Franchis, R.; Sebastio, G.; Andria, G.

    1996-07-01

    Moderate elevation of total plasma homocysteine (tHcy) has been reported as an independent risk factor for thrombotic vascular disease, a well-known multifactorial disorder. Possible genetic causes of elevated tHcy include defects of the sulfur-containing amino acids metabolism due to deficiencies of cystathionine {Beta}-synthase, of 5,10-methylenetetrahydrofolate reductase (MTHFR), and of the enzymes of cobalamin metabolism. An impaired activity of MTHFR due to a thermolabile form of the enzyme has been observed in {le}28% of hyperhomocysteinemic patients with premature vascular disease. More recently, the molecular basis of such enzymatic thermolability has been related to a common mutation of the MTHFR gene, causingmore » a C-to-T substitution at nt 677 (677C{r_arrow}T). This mutation was found in 38% of unselected chromosomes from 57 French Canadian individuals. The homozygous state for the mutation was present in 12% of these subjects and correlated with significantly elevated tHcy. Preliminary evidence indicates that the frequency of homozygotes for the 677C{r_arrow}T mutation may vary significantly in populations from different geographic areas. 5 refs., 2 tabs.« less

  6. Associations between homocysteine metabolism related SNPs and carotid intima-media thickness: a Chinese sib pair study.

    PubMed

    Sun, Kexin; Song, Jing; Liu, Kuo; Fang, Kai; Wang, Ling; Wang, Xueyin; Li, Jing; Tang, Xun; Wu, Yiqun; Qin, Xueying; Wu, Tao; Gao, Pei; Chen, Dafang; Hu, Yonghua

    2017-04-01

    Carotid intima-media thickness (CIMT) is a good surrogate for atherosclerosis. Hyperhomocysteinemia is an independent risk factor for cardiovascular diseases. We aim to investigate the relationships between homocysteine (Hcy) related biochemical indexes and CIMT, the associations between Hcy related SNPs and CIMT, as well as the potential gene-gene interactions. The present study recruited full siblings (186 eligible families with 424 individuals) with no history of cardiovascular events from a rural area of Beijing. We examined CIMT, intima-media thickness for common carotid artery (CCA-IMT) and carotid bifurcation, tested plasma levels for Hcy, vitamin B6 (VB6), vitamin B12 (VB12) and folic acid (FA), and genotyped 9 SNPs on MTHFR, MTR, MTRR, BHMT, SHMT1, CBS genes. Associations between SNPs and biochemical indexes and CIMT indexes were analyzed using family-based association test analysis. We used multi-level mixed-effects regression model to verify SNP-CIMT associations and to explore the potential gene-gene interactions. VB6, VB12 and FA were negatively correlated with CIMT indexes (p < 0.05). rs2851391 T allele was associated with decreased plasma VB12 levels (p = 0.036). In FABT, CBS rs2851391 was significantly associated with CCA-IMT (p = 0.021) and CIMT (p = 0.019). In multi-level mixed-effects regression model, CBS rs2851391 was positively significantly associated with CCA-IMT (Coef = 0.032, se = 0.009, raw p < 0.001) after Bonferoni correction (corrected α = 0.0056). Gene-gene interactions were found between CBS rs2851391 and BHMT rs10037045 for CCA-IMT (p = 0.011), as well as between CBS rs2851391 and MTR rs1805087 for CCA-IMT (p = 0.007) and CIMT (p = 0.022). Significant associations are found between Hcy metabolism related genetic polymorphisms, biochemical indexes and CIMT indexes. There are complex interactions between genetic polymorphisms for CCA-IMT and CIMT.

  7. Chem I Supplement: Emphasis on Acids and Bases

    ERIC Educational Resources Information Center

    Journal of Chemical Education Staff

    1977-01-01

    Provides supplementary notes on acids and bases suitable for secondary school chemistry instruction, including acidity in solid and natural waters, acidity balance in body chemistry, acid and basic foods, pH values of common fluids, examples of drugs, and commercial preparation of nitric acid. (SL)

  8. Evaluation of a computer-based approach to teaching acid/base physiology.

    PubMed

    Rawson, Richard E; Quinlan, Kathleen M

    2002-12-01

    Because acid/base physiology is a difficult subject for most medical and veterinary students, the first author designed a software program, Acid/Base Primer, that would help students with this topic. The Acid/Base Primer was designed and evaluated within a conceptual framework of basic educational principles. Seventy-five first-year veterinary students (of 81; 93% response rate) participated in this study. Students took both a pre- and posttest of content understanding. After completing the Acid/Base Primer in pairs, each student filled out a survey evaluating the features of the program and describing his/her use and experience of it. Four pairs of students participated in interviews that elaborated on the surveys. Scores improved from 53 +/- 2% on the pretest to 74 +/- 1% on an immediate posttest. On surveys and in interviews, students reported that the program helped them construct their own understanding of acid/base physiology and prompted discussions in pairs of students when individual understandings differed. The case-based format provided anchors and a high degree of relevance. Repetition of concepts helped students develop a more complex network of understanding. Questions in the program served to scaffold the learning process by providing direction, accentuating the relevant features of the cases, and provoking discussion. Guidelines for software development were generated on the basis of the findings and relevant educational literature.

  9. The acid-base resistant zone in three dentin bonding systems.

    PubMed

    Inoue, Go; Nikaido, Toru; Foxton, Richard M; Tagami, Junji

    2009-11-01

    An acid-base resistant zone has been found to exist after acid-base challenge adjacent to the hybrid layer using SEM. The aim of this study was to examine the acid-base resistant zone using three different bonding systems. Dentin disks were applied with three different bonding systems, and then a resin composite was light-cured to make dentin disk sandwiches. After acid-base challenge, the polished surfaces were observed using SEM. For both one- and two-step self-etching primer systems, an acid-base resistant zone was clearly observed adjacent to the hybrid layer - but with differing appearances. For the wet bonding system, the presence of an acid-base resistant zone was unclear. This was because the self-etching primer systems etched the dentin surface mildly, such that the remaining mineral phase of dentin and the bonding agent yielded clear acid-base resistant zones. In conclusion, the acid-base resistant zone was clearly observed when self-etching primer systems were used, but not so for the wet bonding system.

  10. General Base-General Acid Catalysis by Terpenoid Cyclases§

    PubMed Central

    Pemberton, Travis A.; Christianson, David W.

    2016-01-01

    Terpenoid cyclases catalyze the most complex reactions in biology, in that more than half of the substrate carbon atoms often undergo changes in bonding during the course of a multistep cyclization cascade that proceeds through multiple carbocation intermediates. Many cyclization mechanisms require stereospecific deprotonation and reprotonation steps, and most cyclization cascades are terminated by deprotonation to yield an olefin product. The first bacterial terpenoid cyclase to yield a crystal structure was pentalenene synthase from Streptomyces exfoliatus UC5319. This cyclase generates the hydrocarbon precursor of the pentalenolactone family of antibiotics. The structures of pentalenene synthase and other terpenoid cyclases reveal predominantly nonpolar active sites typically lacking amino acid side chains capable of serving general base-general acid functions. What chemical species, then, enables the Brønsted acid-base chemistry required in the catalytic mechanisms of these enzymes? The most likely candidate for such general base-general acid chemistry is the co-product inorganic pyrophosphate. Here, we briefly review biological and nonbiological systems in which phosphate and its derivatives serve general base and general acid functions in catalysis. These examples highlight the fact that the Brønsted acid-base activities of phosphate derivatives are comparable to the Brønsted acid-base activities of amino acid side chains. PMID:27072285

  11. Ammonia Transporters and Their Role in Acid-Base Balance

    PubMed Central

    2017-01-01

    Acid-base homeostasis is critical to maintenance of normal health. Renal ammonia excretion is the quantitatively predominant component of renal net acid excretion, both under basal conditions and in response to acid-base disturbances. Although titratable acid excretion also contributes to renal net acid excretion, the quantitative contribution of titratable acid excretion is less than that of ammonia under basal conditions and is only a minor component of the adaptive response to acid-base disturbances. In contrast to other urinary solutes, ammonia is produced in the kidney and then is selectively transported either into the urine or the renal vein. The proportion of ammonia that the kidney produces that is excreted in the urine varies dramatically in response to physiological stimuli, and only urinary ammonia excretion contributes to acid-base homeostasis. As a result, selective and regulated renal ammonia transport by renal epithelial cells is central to acid-base homeostasis. Both molecular forms of ammonia, NH3 and NH4+, are transported by specific proteins, and regulation of these transport processes determines the eventual fate of the ammonia produced. In this review, we discuss these issues, and then discuss in detail the specific proteins involved in renal epithelial cell ammonia transport. PMID:28151423

  12. Assessing College Students' Understanding of Acid Base Chemistry Concepts

    ERIC Educational Resources Information Center

    Wan, Yanjun Jean

    2014-01-01

    Typically most college curricula include three acid base models: Arrhenius', Bronsted-Lowry's, and Lewis'. Although Lewis' acid base model is generally thought to be the most sophisticated among these three models, and can be further applied in reaction mechanisms, most general chemistry curricula either do not include Lewis' acid base model, or…

  13. Hepatic and renal betaine-homocysteine methyltransferase activity in pigs as affected by dietary intakes of sulfur amino acids, choline, and betaine.

    PubMed

    Emmert, J L; Webel, D M; Biehl, R R; Griffiths, M A; Garrow, L S; Garrow, T A; Baker, D H

    1998-02-01

    In Exp. 1, young pigs were fed a basal diet containing .17% methionine (Met) (.14% digestible Met), and .48% cystine (.38% digestible cystine) for 14 d (34 to 48 d of age). Treatment additions were .25% DL-Met, .34% betaine, .30% choline, or .25% DL-Met and .34% betaine. Methionine, but not betaine or choline supplementation, increased (P < .05) weight gain and feed efficiency. Hepatic betaine-homocysteine methyltransferase (BHMT) activity was increased (P < .05) by betaine and choline supplementation but was not affected by Met deficiency. Renal BHMT activity was increased (P < .05) by Met deficiency and was further increased (P < .05) by betaine supplementation. In Exp. 2, 10-kg pigs were fed the basal diet from Exp. 1 supplemented with enough DL-Met to bring the total basal Met to .24% (.20% digestible Met). Treatment additions consisted of .20% DL-Met or .34% betaine, and diets were fed for 16 d (34 to 50 d of age). Feed efficiency increased (P < .05) in response to Met, but not to betaine, supplementation. Hepatic BHMT activity increased (P < .05) in response to betaine and Met, but no changes in renal BHMT activity occurred. Although statistically significant changes in hepatic and renal BHMT activity occurred in both experiments, the magnitude of the responses was probably not physiologically important. Therefore, in contrast to previous findings with rats and chicks, it does not seem that hepatic and renal BHMT activity in pigs is influenced substantially by Met deficiency, or by surfeit levels of choline or betaine.

  14. Preparation and Optimization of Amorphous Ursodeoxycholic Acid Nano-suspensions by Nanoprecipitation based on Acid-base Neutralization for Enhanced Dissolution.

    PubMed

    Xie, Yike; Chen, Zhongjian; Su, Rui; Li, Ye; Qi, Jianping; Wu, Wei; Lu, Yi

    2017-01-01

    Ursodeoxycholic acid, usually used to dissolve cholesterol gallstones in clinic, is a typical hydrophobic drug with poor oral bioavailability due to dissolution rate-limited performance. The objective of this study was to increase the dissolution of ursodeoxycholic acid by amorphous nanosuspensions. Nanoprecipitation based on acid-base neutralization was used to prepare the nanosuspensions with central composite design to optimize the formula. The nanosuspensions were characterized by particle size, morphology, crystallology and dissolution. The ursodeoxycholic acid nanosuspensions showed mean particle size around 380 nm with polydispersion index value about 0.25. Scanning electron microscope observed high coverage of HPMC-E50 onto the surface of the nanosuspensions. Differential scanning calorimetry and powder X-ray diffractometry revealed amorphous structure of the ursodeoxycholic acid nanosuspensions. A significant increase of dissolution in acidic media was achieved by the amorphous nanosuspensions compared with the physical mixture. It can be predicted that the amorphous nanosuspensions show great potential in improving the oral bioavailability of ursodeoxycholic acid. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  15. The effect of two different doses comprising the simultaneous administration of intravenous B-complex vitamins and oral folic acid on serum homocysteine levels in hemodialysis patients.

    PubMed

    Sombolos, Kostas; Papaioannou, Anna; Christidou, Fotini; Natse, Taisir; Bamichas, Gerasimos; Gionanlis, Lazaros; Katsaris, George; Progia, Evagelia

    2006-01-01

    Several regimens using different doses of folic acid (FA) alone or supplemented with B-complex vitamins (BCVs) have been tested for their ability to reduce total homocysteine (tHcy) serum levels in hemodialysis (HD) patients. In the present study, we assessed the effect of two different doses comprising the simultaneous administration of intravenous (IV) BCVs and an oral FA supplementation on serum tHCy levels in HD patients. In a cohort of 49 patients (31 male, 18 female) undergoing chronic HD treatment for a mean of 40.0+/-40.7 months, serum concentrations of tHcy, folate and vitamin-B12 (vB12) were determined at the end of three sequential periods as follows: 20 weeks without any BCV and/or FA supplementation (period A), 20 weeks with a dose comprising the simultaneous administration of IV BCVs and an oral supplementation of 5 mg of FA once a week (period B), and 20 weeks with a dose comprising the simultaneous administration of IV BCVs and an oral supplementation of 5 mg of FA thrice a week (period C). An IV dose of BCVs consisting of a 5 mL solution containing vitamin B1 (250 mg), vitamin B6 (250 mg) and vitamin B12 (1.5 mg) was administered at the end of hemodialysis. Mean serum tHcy levels were significantly higher at the end of period A relative to levels at the end of periods B and C (35.8+/-23 micromol/L vs. 22.0+/-17.6 and 15.0+/-4.5 micromol/L, respectively; p<0.000001). Mean serum folate levels and mean serum vB12 levels were significantly lower at the end of period A relative to levels at the end of periods B and C (p<0.000001). Mean serum tHcy levels were lowest at the end of period C (p<0.000001 in comparison to periods A and B), and 26 of the 49 HD patients (67.3%) possessed tHcy levels below 16 micromol/L. In HD patients, high doses consisting of the simultaneous administration of IV BCVs and an oral FA supplementation resulted in the efficient reduction of serum tHcy levels.

  16. An approach to complex acid-base problems

    PubMed Central

    Herd, Anthony M.

    2005-01-01

    OBJECTIVE To review rules and formulas for solving even the most complex acid-base problems. SOURCES OF INFORMATION MEDLINE was searched from January 1966 to December 2003. The search was limited to English-language review articles involving human subjects. Nine relevant review papers were found and provide the background. As this information is well established and widely accepted, it is not judged for strength of evidence, as is standard practice. MAIN MESSAGE An understanding of the body’s responses to acidemia or alkalemia can be gained through a set of four rules and two formulas that can be used to interpret almost any acid-base problems. Physicians should, however, remember the “golden rule” of acid-base interpretation: always look at a patient’s clinical condition. CONCLUSION Physicians practising in acute care settings commonly encounter acid-base disturbances. While some of these are relatively simple and easy to interpret, some are more complex. Even complex cases can be resolved using the four rules and two formulas. PMID:15751566

  17. Homocysteinemia in mice with genetic betaine homocysteine S-methyltransferase deficiency is independent of dietary folate intake.

    PubMed

    Teng, Ya-Wen; Cerdena, Ignacio; Zeisel, Steven H

    2012-11-01

    Elevated homocysteine (Hcy) concentrations are associated with increased risk of several chronic diseases. Hcy can be removed by methylating it to form methionine via either the betaine homocysteine S-methyltransferase (BHMT) or the methionine synthase (MS) pathway. BHMT uses betaine as the methyl donor, whereas MS uses 5-methyltetrahydrofolate. We previously found that mice with the gene encoding Bhmt deleted (Bhmt(-/-)) had altered Hcy metabolites in tissues. This study aimed to determine whether folate supplementation of Bhmt(-/-) mice reverses, and folate deficiency exacerbates, these metabolic changes. Bhmt(-/-) mice and their littermates (Bhmt(+/+) mice) were fed a folate-deficient (FD; 0 mg/kg diet), a folate control (FC; 2 mg/kg diet), or a folate-supplemented (FS; 20 mg/kg diet) diet for 4 wk. Bhmt(-/-) mice had higher plasma Hcy and hepatic S-adenosylhomocysteine (AdoHcy) concentrations and had lower hepatic S-adenosylmethionine (AdoMet) concentrations compared with Bhmt(+/+) mice for all diets. Although the FD diet increased plasma Hcy (P < 0.05) and hepatic AdoHcy (P < 0.001) concentrations in Bhmt(+/+) mice compared with FC and FS mice, the FD diet had no effect on the metabolites measured in Bhmt(-/-) mice. The FS diet did not ameliorate elevated plasma Hcy and elevated hepatic AdoHcy concentrations but did increase hepatic AdoMet concentrations in Bhmt(-/-) mice (P < 0.001) compared with FD and FC mice. We conclude that the BHMT pathway is a major route for the elimination of Hcy in mice and that the MS pathway has little excess capacity to methylate the Hcy that accumulates when the BHMT pathway is blocked.

  18. Nucleic acid duplexes incorporating a dissociable covalent base pair

    NASA Technical Reports Server (NTRS)

    Gao, K.; Orgel, L. E.; Bada, J. L. (Principal Investigator)

    1999-01-01

    We have used molecular modeling techniques to design a dissociable covalently bonded base pair that can replace a Watson-Crick base pair in a nucleic acid with minimal distortion of the structure of the double helix. We introduced this base pair into a potential precursor of a nucleic acid double helix by chemical synthesis and have demonstrated efficient nonenzymatic template-directed ligation of the free hydroxyl groups of the base pair with appropriate short oligonucleotides. The nonenzymatic ligation reactions, which are characteristic of base paired nucleic acid structures, are abolished when the covalent base pair is reduced and becomes noncoplanar. This suggests that the covalent base pair linking the two strands in the duplex is compatible with a minimally distorted nucleic acid double-helical structure.

  19. Nucleic acid duplexes incorporating a dissociable covalent base pair

    PubMed Central

    Gao, Kui; Orgel, Leslie E.

    1999-01-01

    We have used molecular modeling techniques to design a dissociable covalently bonded base pair that can replace a Watson-Crick base pair in a nucleic acid with minimal distortion of the structure of the double helix. We introduced this base pair into a potential precursor of a nucleic acid double helix by chemical synthesis and have demonstrated efficient nonenzymatic template-directed ligation of the free hydroxyl groups of the base pair with appropriate short oligonucleotides. The nonenzymatic ligation reactions, which are characteristic of base paired nucleic acid structures, are abolished when the covalent base pair is reduced and becomes noncoplanar. This suggests that the covalent base pair linking the two strands in the duplex is compatible with a minimally distorted nucleic acid double-helical structure. PMID:10611299

  20. Brain MRI, apoliprotein E genotype, and plasma homocysteine in American Indian Alzheimer disease patients and Indian controls.

    PubMed

    Weiner, Myron F; de la Plata, Carlos Marquez; Fields, B A Julie; Womack, Kyle B; Rosenberg, Roger N; Gong, Yun-Hua; Qu, Bao-Xi; Diaz-Arrastia, Ramon; Hynan, Linda S

    2009-02-01

    We obtained brain MRIs, plasma homocysteine levels and apolipoprotein E genotyping for 11 American Indian Alzheimer disease (AD) subjects and 10 Indian controls. We calculated white matter hyperintensity volume (WMHV), whole brain volume (WBV), and ratio of white matter hyperintensity volume to whole brain volume (WMHV/WBV). There were no significant differences between AD subjects and controls in gender, history of hypertension, diabetes, or history of high cholesterol, but hypertension and diabetes were more common among AD subjects. There was no difference between AD and control groups in age (range for all subjects was 61-89 years), % Indian heritage, waist size or body mass index. Median Indian heritage was 50% or greater in both groups. Range of education was 5-13 years in the AD group and 12-16 years in controls. Median plasma homocysteine concentration was higher in AD subjects (11 micromol/L vs. 9.8 micromol/L), but did not achieve statistical significance. Significantly more AD subjects had apolipoprotein Eepsilon4 alleles than did controls (63% vs.10%). Neuroimaging findings were not significantly different between the 2 groups, but AD subjects had greater WMHV (median 15.64 vs. 5.52 cc) and greater WMHV/WBV ratio (median 1.63 vs. 0.65 %) and a far greater range of WMHV. In combined AD subjects and controls, WBV correlated with BMI and age. WMHV and WMHV/WBV correlated inversely with MMSE scores (p = 0.001, 0.002, respectively). In addition, WMHV correlated positively with % Indian heritage (p = 0.047).

  1. Using Willie's Acid-Base Box for Blood Gas Analysis

    ERIC Educational Resources Information Center

    Dietz, John R.

    2011-01-01

    In this article, the author describes a method developed by Dr. William T. Lipscomb for teaching blood gas analysis of acid-base status and provides three examples using Willie's acid-base box. Willie's acid-base box is constructed using three of the parameters of standard arterial blood gas analysis: (1) pH; (2) bicarbonate; and (3) CO[subscript…

  2. Students' Alternate Conceptions on Acids and Bases

    ERIC Educational Resources Information Center

    Pan, Hanqing; Henriques, Laura

    2015-01-01

    Knowing what students bring to the classroom can and should influence how we teach them. This study is a review of the literature associated with secondary and postsecondary students' ideas about acids and bases. It was found that there are six types of alternate ideas about acids and bases that students hold. These are: macroscopic properties of…

  3. Hydroxamic acids as weak base indicators: protonation in strong acid media.

    PubMed

    García, B; Ibeas, S; Hoyuelos, F J; Leal, J M; Secco, F; Venturini, M

    2001-11-30

    The protonation equilibria of N-phenylbenzohydroxamic, benzohydroxamic, salicylhydroxamic, and N-p-tolylcinnamohydroxamic acids have been studied at 25 degrees C in concentrated sulfuric, hydrochloric, and perchloric acid media; the UV-vis spectral measurements were analyzed using the Hammett equation and the Bunnett-Olsen and excess acidity methods. The medium effects observed in the UV spectral curves were corrected with the Cox-Yates and vector analysis methods. The H(A) acidity function based on benzamides provided the best results. The range of variation of the solvation coefficient m is similar to that of amides, this indicating similar solvation requirements for amides and hydroxamic acids. For the same substrate, the observed variations of pK(BH)(+) with the mineral acid used was justified by formation of solvent-separated ion pairs; for the same mineral acid, the observed changes in pK(BH)(+) can be explained by the solvation of BH(+). The change of the pK(BH)(+) values was in reasonably good agreement with the sequence of the catalytic efficiency of the mineral acids used, HCl > H(2)SO(4) > HClO(4).

  4. Downregulation of hepatic betaine:homocysteine methyltransferase (BHMT) expression in taurine-deficient mice is reversed by taurine supplementation in vivo

    PubMed Central

    Jurkowska, Halina; Niewiadomski, Julie; Hirschberger, Lawrence L.; Roman, Heather B.; Mazor, Kevin M.; Liu, Xiaojing; Locasale, Jason W.; Park, Eunkyue

    2016-01-01

    The cysteine dioxygenase (Cdo1)-null and the cysteine sulfinic acid decarboxylase (Csad)-null mouse are not able to synthesize hypotaurine/taurine by the cysteine/cysteine sulfinate pathway and have very low tissue taurine levels. These mice provide excellent models for studying the effects of taurine on biological processes. Using these mouse models, we identified betaine:homocysteine methyltransferase (BHMT) as a protein whose in vivo expression is robustly regulated by taurine. BHMT levels are low in liver of both Cdo1-null and Csad-null mice, but are restored to wild-type levels by dietary taurine supplementation. A lack of BHMT activity was indicated by an increase in the hepatic betaine level. In contrast to observations in liver of Cdo1-null and Csad-null mice, BHMT was not affected by taurine supplementation of primary hepatocytes from these mice. Likewise, CSAD abundance was not affected by taurine supplementation of primary hepatocytes, although it was robustly upregulated in liver of Cdo1-null and Csad-null mice and lowered to wild-type levels by dietary taurine supplementation. The mechanism by which taurine status affects hepatic CSAD and BHMT expression appears to be complex and to require factors outside of hepatocytes. Within the liver, mRNA abundance for both CSAD and BHMT was upregulated in parallel with protein levels, indicating regulation of BHMT and CSAD mRNA synthesis or degradation. PMID:26481005

  5. Structure-based conformational preferences of amino acids

    PubMed Central

    Koehl, Patrice; Levitt, Michael

    1999-01-01

    Proteins can be very tolerant to amino acid substitution, even within their core. Understanding the factors responsible for this behavior is of critical importance for protein engineering and design. Mutations in proteins have been quantified in terms of the changes in stability they induce. For example, guest residues in specific secondary structures have been used as probes of conformational preferences of amino acids, yielding propensity scales. Predicting these amino acid propensities would be a good test of any new potential energy functions used to mimic protein stability. We have recently developed a protein design procedure that optimizes whole sequences for a given target conformation based on the knowledge of the template backbone and on a semiempirical potential energy function. This energy function is purely physical, including steric interactions based on a Lennard-Jones potential, electrostatics based on a Coulomb potential, and hydrophobicity in the form of an environment free energy based on accessible surface area and interatomic contact areas. Sequences designed by this procedure for 10 different proteins were analyzed to extract conformational preferences for amino acids. The resulting structure-based propensity scales show significant agreements with experimental propensity scale values, both for α-helices and β-sheets. These results indicate that amino acid conformational preferences are a natural consequence of the potential energy we use. This confirms the accuracy of our potential and indicates that such preferences should not be added as a design criterion. PMID:10535955

  6. Anticancer and antiviral effects and inactivation of S-adenosyl-L-homocysteine hydrolase with 5'-carboxaldehydes and oximes synthesized from adenosine and sugar-modified analogues.

    PubMed

    Wnuk, S F; Yuan, C S; Borchardt, R T; Balzarini, J; De Clercq, E; Robins, M J

    1997-05-23

    Selectively protected adenine nucleosides were converted into 5'-carboxaldehyde analogues by Moffatt oxidation (dimethyl sulfoxide/dicyclohexylcarbodiimide/dichloroacetic acid) or with the Dess-Martin periodinane reagent. Hydrolysis of a 5'-fluoro-5'-S-methyl-5'-thio (alpha-fluoro thioether) arabinosyl derivative also gave the 5'-carboxaldehyde. Treatment of 5'-carboxaldehydes with hydroxylamine [or O-(methyl, ethyl, and benzyl)hydroxylamine] hydrochloride gave E/Z oximes. Treatment of purified oximes with aqueous trifluoroacetic acid and acetone effected trans-oximation to provide clean samples of 5'-carboxaldehydes. Adenosine (Ado)-5'-carboxaldehyde and its 4'-epimer are potent inhibitors of S-adenosyl-L-homocysteine (AdoHcy) hydrolase. They bind efficiently to the enzyme and undergo oxidation at C3' to give 3'-keto analogues with concomitant reduction of the NAD+ cofactor to give an inactive, tightly bound NADH-enzyme complex (type I cofactor-depletion inhibition). Potent type I inhibition was observed with 5'-carboxaldehydes that contain a ribo cis-2',3'-glycol. Their oxime derivatives are "proinhibitors" that undergo enzyme-catalyzed hydrolysis to release the inhibitors at the active site. The 2'-deoxy and 2'-epimeric (arabinosyl) analogues were much weaker inhibitors, and the 3'-deoxy compounds bind very weakly. Ado-5'-carboxaldehyde oxime had potent cytotoxicity in tumor cell lines and was toxic to normal human cells. Analogues had weaker cytotoxic and antiviral potencies, and the 3'-deoxy compounds were essentially devoid of cytotoxic and antiviral activity.

  7. Fatty acids rehabilitated long-term neurodegenerative: like symptoms in olfactory bulbectomized rats.

    PubMed

    Yehuda, Shlomo; Rabinovitz, Sharon

    2015-05-01

    Our previous study demonstrated that an olfactory bulbectomy in rats induced short-term, multifaceted, devastating Alzheimer's-like effects, which included cognitive impairment, hyperactivity, hyperthermia, and increased levels of homocysteine and pro-inflammatory cytokines, including IL-17A. In addition, the rats exhibited an increase in the hyperphosphorylation of brain Tau proteins and in the number of neurofibrillary tangles. Here, we examined the long-term effects of the surgery and found that olfactory bulbectomy also rendered the rats to become anemic with brain iron overload. Additionally, a significant reduction in the membrane fluidity index in frontal cortex synaptosomes was found. Treatment with a mixture of n - 3/n - 6 of fatty acids restored the unwanted effect. The beneficial effects of fatty acids are mediated via the effects of fatty acids on the neuronal membrane structure and fluidity. These findings are similar to Alzheimer's symptoms, which suggest this model can be used as an animal model for Alzheimer's disease. We recommend using this model to scan potential new anti-Alzheimer's drugs.

  8. Solid-state acid-base interactions in complexes of heterocyclic bases with dicarboxylic acids: crystallography, hydrogen bond analysis, and 15N NMR spectroscopy.

    PubMed

    Li, Z Jane; Abramov, Yuriy; Bordner, Jon; Leonard, Jason; Medek, Ales; Trask, Andrew V

    2006-06-28

    A cancer candidate, compound 1, is a weak base with two heterocyclic basic nitrogens and five hydrogen-bonding functional groups, and is sparingly soluble in water rendering it unsuitable for pharmaceutical development. The crystalline acid-base pairs of 1, collectively termed solid acid-base complexes, provide significant increases in the solubility and bioavailability compared to the free base, 1. Three dicarboxylic acid-base complexes, sesquisuccinate 2, dimalonate 3, and dimaleate 4, show the most favorable physicochemical profiles and are studied in greater detail. The structural analyses of the three complexes using crystal structure and solid-state NMR reveal that the proton-transfer behavior in these organic acid-base complexes vary successively correlating with Delta pKa. As a result, 2 is a neutral complex, 3 is a mixed ionic and zwitterionic complex and 4 is an ionic salt. The addition of the acidic components leads to maximized hydrogen bond interactions forming extended three-dimensional networks. Although structurally similar, the packing arrangements of the three complexes are considerably different due to the presence of multiple functional groups and the flexible backbone of 1. The findings in this study provide insight into the structural characteristics of complexes involving heterocyclic bases and carboxylic acids, and demonstrate that X-ray crystallography and 15N solid-state NMR are truly complementary in elucidating hydrogen bonding interactions and the degree of proton transfer of these complexes.

  9. Synthesis and characterization of boric acid mediated metal-organic frameworks based on trimesic acid and terephthalic acid

    NASA Astrophysics Data System (ADS)

    Ozer, Demet; Köse, Dursun A.; Şahin, Onur; Oztas, Nursen Altuntas

    2017-08-01

    The new metal-organic framework materials based on boric acid reported herein. Sodium and boron containing metal-organic frameworks were synthesized by one-pot self-assembly reaction in the presence of trimesic acid and terephthalic acid in water/ethanol solution. Boric acid is a relatively cheap boron source and boric acid mediated metal-organic framework prepared mild conditions compared to the other boron source based metal-organic framework. The synthesized compounds were characterized by FT-IR, p-XRD, TGA/DTA, elemental analysis, 13C-MAS NMR, 11B-NMR and single crystal measurements. The molecular formulas of compounds were estimated as C18H33B2Na5O28 and C8H24B2Na2O17 according to the structural analysis. The obtained complexes were thermally stable. Surface properties of inorganic polymer complexes were investigated by BET analyses and hydrogen storage properties of compound were also calculated.

  10. Boronic acid-tethered amphiphilic hyaluronic acid derivative-based nanoassemblies for tumor targeting and penetration.

    PubMed

    Jeong, Jae Young; Hong, Eun-Hye; Lee, Song Yi; Lee, Jae-Young; Song, Jae-Hyoung; Ko, Seung-Hak; Shim, Jae-Seong; Choe, Sunghwa; Kim, Dae-Duk; Ko, Hyun-Jeong; Cho, Hyun-Jong

    2017-04-15

    (3-Aminomethylphenyl)boronic acid (AMPB)-installed hyaluronic acid-ceramide (HACE)-based nanoparticles (NPs), including manassantin B (MB), were fabricated for tumor-targeted delivery. The amine group of AMPB was conjugated to the carboxylic acid group of hyaluronic acid (HA) via amide bond formation, and synthesis was confirmed by spectroscopic methods. HACE-AMPB/MB NPs with a 239-nm mean diameter, narrow size distribution, negative zeta potential, and >90% drug encapsulation efficiency were fabricated. Exposed AMPB in the outer surface of HACE-AMPB NPs (in the aqueous environment) may react with sialic acid of cancer cells. The improved cellular accumulation efficiency, in vitro antitumor efficacy, and tumor penetration efficiency of HACE-AMPB/MB NPs, compared with HACE/MB NPs, in MDA-MB-231 cells (CD44 receptor-positive human breast adenocarcinoma cells) may be based on the CD44 receptor-mediated endocytosis and phenylboronic acid-sialic acid interaction. Enhanced in vivo tumor targetability, infiltration efficiency, and antitumor efficacies of HACE-AMPB NPs, compared with HACE NPs, were observed in a MDA-MB-231 tumor-xenografted mouse model. In addition to passive tumor targeting (based on an enhanced permeability and retention effect) and active tumor targeting (interaction between HA and CD44 receptor), the phenylboronic acid-sialic acid interaction can play important roles in augmented tumor targeting and penetration of HACE-AMPB NPs. STATEMENT OF SIGNIFICANCE: (3-Aminomethylphenyl)boronic acid (AMPB)-tethered hyaluronic acid-ceramide (HACE)-based nanoparticles (NPs), including manassantin B (MB), were fabricated and their tumor targeting and penetration efficiencies were assessed in MDA-MB-231 (CD44 receptor-positive human adenocarcinoma) tumor models. MB, which exhibited antitumor efficacies via the inhibition of angiogenesis and hypoxia inducible factor (HIF)-1, was entrapped in HACE-AMPB NPs in this study. Phenylboronic acid located in the outer surface

  11. Genome-wide meta-analysis of homocysteine and methionine metabolism identifies five one carbon metabolism loci and a novel association of ALDH1L1 with ischemic stroke

    USDA-ARS?s Scientific Manuscript database

    Circulating homocysteine levels (tHcy), a product of the folate one carbon metabolism pathway (FOCM) through the demethylation of methionine, are heritable and are associated with an increased risk of common diseases such as stroke, cardiovascular disease (CVD), cancer and dementia. The FOCM is the ...

  12. Homocysteine and risk of age-related macular degeneration: a systematic review and meta-analysis.

    PubMed

    Pinna, Antonio; Zaccheddu, Francesco; Boscia, Francesco; Carru, Ciriaco; Solinas, Giuliana

    2018-05-01

    There is still no agreement on total plasma homocysteine (tHcy) role in age-related macular degeneration (AMD), the leading cause of new blindness in industrialized countries. We performed a systematic review and meta-analysis of the published data on the correlation between tHcy and AMD. MEDLINE/PubMed and ISI Web of Sciences searches were performed according to MOOSE guidelines. Case-control studies were eligible for inclusion. Participants and controls were AMD patients and subjects without AMD. The main outcome measure was wet AMD. Homocysteine level was the main exposure variable. Data were pooled using a random-effects model. Twelve case-control studies were identified: 10 assessed wet AMD, four dry AMD, one early AMD, one late AMD, and one any AMD. As for wet AMD, there was a total of 453 cases and 514 controls. Mean tHcy was on average 1.1 μmol/l (95% confidence interval [CI] = 0.96-1.25) greater in wet AMD cases, but there was evidence of extreme between-study heterogeneity (p < 0.001, I 2  = 91.8%). In a model homogenous for age, including six wet AMD studies (214 cases, 274 controls), mean tHcy was on average 0.58 μmol/l (95% CI = 0.35-0.73) greater in the case group, a not statistically significant result (p = 0.144) associated with moderate heterogeneity (I 2  = 39.2%). Our meta-analysis indicates that there is some weak evidence that increased tHcy might be associated with wet AMD; however, this result should be interpreted cautiously, because of a marked between-study heterogeneity and the possible effect of publication bias. Future studies, preferably of cohort design, are necessary before any firm conclusions on the putative role of increased tHcy on AMD can be drawn. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  13. Applications of synchrotron-based spectroscopic techniques in studying nucleic acids and nucleic acid-functionalized nanomaterials

    PubMed Central

    Wu, Peiwen; Yu, Yang; McGhee, Claire E.; Tan, Li Huey

    2014-01-01

    In this review, we summarize recent progresses in the application of synchrotron-based spectroscopic techniques for nucleic acid research that takes advantage of high-flux and high-brilliance electromagnetic radiation from synchrotron sources. The first section of the review focuses on the characterization of the structure and folding processes of nucleic acids using different types of synchrotron-based spectroscopies, such as X-ray absorption spectroscopy, X-ray emission spectroscopy, X-ray photoelectron spectroscopy, synchrotron radiation circular dichroism, X-ray footprinting and small-angle X-ray scattering. In the second section, the characterization of nucleic acid-based nanostructures, nucleic acid-functionalized nanomaterials and nucleic acid-lipid interactions using these spectroscopic techniques is summarized. Insights gained from these studies are described and future directions of this field are also discussed. PMID:25205057

  14. Applications of synchrotron-based spectroscopic techniques in studying nucleic acids and nucleic acid-functionalized nanomaterials

    DOE PAGES

    Wu, Peiwen; Yu, Yang; McGhee, Claire E.; ...

    2014-09-10

    In this paper, we summarize recent progress in the application of synchrotron-based spectroscopic techniques for nucleic acid research that takes advantage of high-flux and high-brilliance electromagnetic radiation from synchrotron sources. The first section of the review focuses on the characterization of the structure and folding processes of nucleic acids using different types of synchrotron-based spectroscopies, such as X-ray absorption spectroscopy, X-ray emission spectroscopy, X-ray photoelectron spectroscopy, synchrotron radiation circular dichroism, X-ray footprinting and small-angle X-ray scattering. In the second section, the characterization of nucleic acid-based nanostructures, nucleic acid-functionalized nanomaterials and nucleic acid-lipid interactions using these spectroscopic techniques is summarized. Insightsmore » gained from these studies are described and future directions of this field are also discussed.« less

  15. Broadly Applicable Strategy for the Fluorescence Based Detection and Differentiation of Glutathione and Cysteine/Homocysteine: Demonstration in Vitro and in Vivo.

    PubMed

    Chen, Wenqiang; Luo, Hongchen; Liu, Xingjiang; Foley, James W; Song, Xiangzhi

    2016-04-05

    Glutathione (GSH), cysteine (Cys), and homocysteine (Hcy) are small biomolecular thiols that are present in all cells and extracellular fluids of healthy mammals. It is well-known that each plays a separate, critically important role in human physiology and that abnormal levels of each are predictive of a variety of different disease states. Although a number of fluorescence-based methods have been developed that can detect biomolecules that contain sulfhydryl moieties, few are able to differentiate between GSH and Cys/Hcy. In this report, we demonstrate a broadly applicable approach for the design of fluorescent probes that can achieve this goal. The strategy we employ is to conjugate a fluorescence-quenching 7-nitro-2,1,3-benzoxadiazole (NBD) moiety to a selected fluorophore (Dye) through a sulfhydryl-labile ether linkage to afford nonfluorescent NBD-O-Dye. In the presence of GSH or Cys/Hcy, the ether bond is cleaved with the concomitant generation of both a nonfluorescent NBD-S-R derivative and a fluorescent dye having a characteristic intense emission band (B1). In the special case of Cys/Hcy, the NBD-S-Cys/Hcy cleavage product can undergo a further, rapid, intramolecular Smiles rearrangement to form a new, highly fluorescent NBD-N-Cys/Hcy compound (band B2); because of geometrical constraints, the GSH derived NBD-S-GSH derivative cannot undergo a Smiles rearrangement. Thus, the presence of a single B1 or double B1 + B2 signature can be used to detect and differentiate GSH from Cys/Hcy, respectively. We demonstrate the broad applicability of our approach by including in our studies members of the Flavone, Bodipy, and Coumarin dye families. Particularly, single excitation wavelength could be applied for the probe NBD-OF in the detection of GSH over Cys/Hcy in both aqueous solution and living cells.

  16. Acid-base chemistry and aluminum transport in an acidic watershed and pond in New Hampshire

    Treesearch

    Scott W. Bailey; Charles T. Driscoll; James W. Hornbeck

    1995-01-01

    Cone Pond is one of the few acidic, clear-water ponds in the White Mountains of New Hampshire, a region dominated by high inputs of strong acids from atmospheric deposition and low base content of bedrock. Monitoring was conducted for 13 months to compare and contrast the acid-base chemistry of the terrestrial and aquatic portions of the watershed. Variations in Al...

  17. A Closer Look at Acid-Base Olfactory Titrations

    ERIC Educational Resources Information Center

    Neppel, Kerry; Oliver-Hoyo, Maria T.; Queen, Connie; Reed, Nicole

    2005-01-01

    Olfactory titrations using raw onions and eugenol as acid-base indicators are reported. An in-depth investigation on olfactory titrations is presented to include requirements for potential olfactory indicators and protocols for using garlic, onions, and vanillin as acid-base olfactory indicators are tested.

  18. [Nutrition, acid-base metabolism, cation-anion difference and total base balance in humans].

    PubMed

    Mioni, R; Sala, P; Mioni, G

    2008-01-01

    The relationship between dietary intake and acid-base metabolism has been investigated in the past by means of the inorganic cation-anion difference (C(+)(nm)-A(-)(nm)) method based on dietary ash-acidity titration after the oxidative combustion of food samples. Besides the inorganic components of TA (A(-)(nm)-C(+)(nm)), which are under renal control, there are also metabolizable components (A(-)(nm)-C(+)(nm)) of TA, which are under the control of the intermediate metabolism. The whole body base balance, NBb(W), is obtained only by the application of C(+)(nm)-A(-)(nm) to food, feces and urine, while the metabolizable component (A(-)(nm)-C(+)(nm)) is disregarded. A novel method has been subsequently suggested to calculate the net balance of fixed acid, made up by the difference between the input of net endogenous acid production: NEAP = SO(4)(2-)+A(-)(m)-(C(+)(nm)-A(-)(nm)), and the output of net acid excretion: NAE = TA + NH(4)(+) - HCO(3)(-). This approach has been criticized because 1) it includes metabolizable acids, whose production cannot be measured independently; 2) the specific control of metabolizable acid and base has been incorrectly attributed to the kidney; 3) the inclusion of A-m in the balance input generates an acid overload; 4) the object of measurement in making up a balance has to be the same, a condition not fulfilled as NEAP is different from NAE. Lastly, by rearranging the net balance of the acid equation, the balance of nonmetabolizable acid equation is obtained. Therefore, any discrepancy between these two equations is due to the inaccuracy in the urine measurement of metabolizable cations and/or anions.

  19. Tetra primer ARMS-PCR relates folate/homocysteine pathway genes and ACE gene polymorphism with coronary artery disease.

    PubMed

    Masud, Rizwan; Qureshi, Irfan Zia

    2011-09-01

    Cardiovascular disorders and coronary artery disease (CAD) are significant contributors to morbidity and mortality in heart patients. As genes of the folate/homocysteine pathway have been linked with the vascular disease, we investigated association of these gene polymorphisms with CAD/myocardial infarction (MI) using the novel approach of tetraprimer ARMS-PCR. A total of 230 participants (129 MI cases, 101 normal subjects) were recruited. We genotyped rs1801133 and rs1801131 SNPs in 5'10' methylenetetrahydrofolate reductase (MTHFR), rs1805087 SNP in 5' methyltetrahydrofolate homocysteine methyltransferase (MTR), rs662 SNP in paroxanse1 (PON1), and rs5742905 polymorphism in cystathionine beta synthase (CBS). Angiotensin converting enzyme (ACE) insertion/deletion polymorphism was detected through conventional PCR. Covariates included blood pressure, fasting blood sugar, serum cholesterol, and creatinine concentrations. Our results showed allele frequencies at rs1801133, rs1801131, rs1805087 and the ACE insertion/deletion (I/D) polymorphism varied between cases and controls. Logistic regression, after adjusting for covariates, demonstrated significant associations of rs1801133 and rs1805087 with CAD in the additive, dominant, and genotype model. In contrast, ACE I/D polymorphism was significantly related with CAD where recessive model was applied. Gene-gene interaction against the disease status revealed two polymorphism groups: rs1801133, rs662, and rs1805087; and rs1801131, rs662, and ACE I/D. Only the latter interaction maintained significance after adjusted for covariates. Our study concludes that folate pathway variants exert contributory influence on susceptibility to CAD. We further suggest that tetraprimer ARMS-PCR successfully resolves the genotypes in selected samples and might prove to be a superior technique compared to the conventional approach.

  20. Salmon diet in patients with active ulcerative colitis reduced the simple clinical colitis activity index and increased the anti-inflammatory fatty acid index--a pilot study.

    PubMed

    Grimstad, Tore; Berge, Rolf K; Bohov, Pavol; Skorve, Jon; Gøransson, Lasse; Omdal, Roald; Aasprong, Ole G; Haugen, Margaretha; Meltzer, Helle M; Hausken, Trygve

    2011-02-01

    Data concerning the anti-inflammatory effect of dietary n-3 polyunsaturated fatty acids (PUFAs) in patients with ulcerative colitis (UC) are inconsistent. Salmon fillet contains n-3 PUFAs and bioactive peptides that may improve its effects compared to fish oil alone. We assessed the efficacy of a salmon-rich diet in patients with mild ulcerative colitis. An 8-week intervention pilot study was designed to assess the effects of 600 grams Atlantic salmon consumption weekly in 12 UC patients. Simple clinical colitis activity index (SCCAI), a dietary questionnaire, sigmoidoscopy, selected serum inflammatory markers, fecal calprotectin, and plasma and rectal biopsy fatty acid profiles were assessed before and after intervention. The levels of C20:4n-6 arachidonic acid in biopsies after dietary intervention were correlated with histology and endoscopy scores. The concentrations of n-3 PUFAs, C20:5n-3 eicosapentaenoic acid, C22:6n-3 docosahexaenoic acid, and the n-3/n-6 ratio increased in plasma and rectal biopsies. The anti-inflammatory fatty acid index (AIFAI) increased both in biopsies and plasma accompanied with a significantly reduced SCCAI. Based on evidence of SCCAI and AIFAI and a tendency of decreased levels of CRP and homocysteine, intake of Atlantic salmon may have beneficial effects on disease activity in patients with mild ulcerative colitis.

  1. Longitudinal change in plasma total homocysteine during pregnancy and postpartum in Brazilian women and its relation with folate status and other factors.

    PubMed

    Glorimar, R; Pereira, S E A; Trugo, N M F

    2004-03-01

    Fasting plasma total homocysteine (tHcy) concentration was determined in a cohort of pregnant Brazilian women (n = 46) supplemented with folic acid from the second trimester of pregnancy. Blood samples were obtained in the first and third trimesters from all women, and 30-40 days postpartum from seventeen women. Plasma tHcy decreased during pregnancy from 10.3 to 8.7 micromol/L, and was 11.6 micromol/L in the postpartum. Plasma and erythrocyte folate increased, consistent with use of the folate supplement, but decreased slightly in the postpartum, whereas the opposite occurred for plasma vitamin B12. tHcy was inversely correlated with plasma and erythrocyte folate in the third trimester (r = -0.585 and -0.460, respectively). This relationship occurred despite the fact that all women had attained what could be considered adequate levels of folate indices. Furthermore, the change (third trimester minus first trimester levels) of tHcy was inversely correlated (p < 0.01) with the changes in plasma (r = -0.573) and erythrocyte folate (r = -0.525). tHcy had no correlation in any of the periods tested with plasma vitamin B12, plasma albumin, hematocrit, hemoglobin, iron indices, dietary intakes of folate, vitamins B12 and B6, and levels of folate supplement.

  2. Four week supplementation with mixed fruit and vegetable juice concentrates increased protective serum antioxidants and folate and decreased plasma homocysteine in Japanese subjects.

    PubMed

    Kawashima, Akira; Madarame, Takeo; Koike, Hiroto; Komatsu, Yasuhiro; Wise, John A

    2007-01-01

    Fruit and vegetable consumption has been inversely associated with the risk of chronic diseases including cancer and cardiovascular disease, with the beneficial effects attributed to a variety of protective antioxidants, carotenoids and phytonutrients. The objective of the present study was to determine the effect of supplementation with dehydrated concentrates from mixed fruit and vegetable juices (Juice Plus+R) on serum antioxidant and folate status, plasma homocysteine levels and markers for oxidative stress and DNA damage. Japanese subjects (n=60; age 27.8 yrs; BMI 22.1) were recruited to participate in a double-blind placebo controlled study and were randomized into 2 groups of 30, matched for sex, age, BMI and smoking status (39 males, 22 smokers; 21 females, 13 smokers). Subjects were given encapsulated supplements containing mixed fruit and vegetable juice concentrates or a matching placebo for 28 days, with blood and urine samples collected at baseline, day 14 and day 28 for analytical testing. Compared with the placebo, 28 day supplementation significantly increased the concentration of serum beta-carotene 528% (p<0.0001), lycopene 80.2% (p<0.0005), and alpha tocopherol 39.5% (p<0.0001). Serum folate increased 174.3% (p<0.0001) and correlated with a decrease in plasma homocysteine of -19.9% (p<0.03). Compared with baseline, measures of oxidative stress decreased with serum lipid peroxides declining -10.5% (p<0.02) and urine 8OHdG decreasing -21.1% (p<0.02). Evaluation of data from smokers only (n=17) after 28 days of active supplementation showed comparable changes. In the absence of dietary modification, supplementation with the fruit and vegetable juice concentrate capsules proved to be a highly bioavailable source of phytonutrients. Important antioxidants were elevated to desirable levels associated with decreased risk of disease while markers of oxidative stress were reduced, and folate status improved with a concomitant decrease in homocysteine, and

  3. Homocysteine concentration, related B vitamins, and betaine in pregnant women recruited to the Seychelles Child Development Study.

    PubMed

    Wallace, Julie Mw; Bonham, Maxine P; Strain, Jj; Duffy, Emeir M; Robson, Paula J; Ward, Mary; McNulty, Helene; Davidson, Philip W; Myers, Gary J; Shamlaye, Conrad F; Clarkson, Tom W; Molloy, Anne M; Scott, John M; Ueland, Per M

    2008-02-01

    Both folate and betaine are important predictors of total homocysteine (tHcy) during pregnancy. However, studies to date have only been undertaken in populations with Western dietary patterns. We investigated the predictors of tHcy in pregnant women recruited in the Seychelles, a population where access to fortified foods is limited and where women habitually consume diets rich in fish, eggs, rice, and fruit. Pregnant women (n = 226) provided blood samples at enrollment, at week 28 of gestation, and at delivery. Cord blood was obtained from a subset of participants (n = 135). As in other studies, maternal tHcy was lower during pregnancy than at delivery, whereas folate and vitamin B-12 status declined significantly to delivery. Despite low maternal folate status at delivery (median: 9.0 nmol/L), with 35% of women in the deficient range (serum folate: <6.8 nmol/L), cord blood folate status (median: 40.2 nmol/L) was similar to concentrations reported in Western populations. Folate was a significant predictor of tHcy at all time points (P < 0.001). In contrast with previous studies, betaine was only a significant predictor of maternal tHcy (P < 0.001) when the essential amino acid methionine was low. The current study reports 2 important findings. First, fetal requirements for folate are paramount, such that cord blood folate status is maintained, even when maternal status is low. Second, betaine is a significant predictor of tHcy in pregnant women with low serum folate and low serum methionine concentrations.

  4. Thai Grade 11 students' alternative conceptions for acid-base chemistry

    NASA Astrophysics Data System (ADS)

    Artdej, Romklao; Ratanaroutai, Thasaneeya; Coll, Richard Kevin; Thongpanchang, Tienthong

    2010-07-01

    This study involved the development of a two-tier diagnostic instrument to assess Thai high school students' understanding of acid-base chemistry. The acid-base diagnostic test (ABDT) comprising 18 items was administered to 55 Grade 11 students in a science and mathematics programme during the second semester of the 2008 academic year. Analysis of students' responses from this study followed the methodology outlined by Çalik and Ayas. The research findings suggest that the ABDT, the multiple choice diagnostic instrument, enables researchers and teachers to classify students' understanding at different levels. Most students exhibited alternative conceptions for several concepts: acid-base theory, dissociation of strong acids or bases, and dissociation of weak acids/bases. Interestingly, one of the concepts that students appeared to find most difficult, and for which they exhibited the most alternative conceptions, was acid-base theory. Some alternative conceptions revealed in this study differ from earlier reports, such as the concept of electrolyte and non-electrolyte solutions as well as the concentration changes of H3O+and OH- in water. These research findings present valuable information for facilitating better understanding of acid-base chemistry by providing insight into the preventable and correctable alternative conceptions exhibited by students.

  5. Acid-base homeostasis in the human system

    NASA Technical Reports Server (NTRS)

    White, R. J.

    1974-01-01

    Acid-base regulation is a cooperative phenomena in vivo with body fluids, extracellular and intracellular buffers, lungs, and kidneys all playing important roles. The present account is much too brief to be considered a review of present knowledge of these regulatory systems, and should be viewed, instead, as a guide to the elements necessary to construct a simple model of the mutual interactions of the acid-base regulatory systems of the body.

  6. An Acid-Base Chemistry Example: Conversion of Nicotine

    NASA Astrophysics Data System (ADS)

    Summerfield, John H.

    1999-10-01

    The current government interest in nicotine conversion by cigarette companies provides an example of acid-base chemistry that can be explained to students in the second semester of general chemistry. In particular, the conversion by ammonia of the +1 form of nicotine to the easier-to-assimilate free-base form illustrates the effect of pH on acid-base equilibrium. The part played by ammonia in tobacco smoke is analogous to what takes place when cocaine is "free-based".

  7. A computational study of ultrafast acid dissociation and acid-base neutralization reactions. I. The model.

    PubMed

    Maurer, Patrick; Thomas, Vibin; Rivard, Ugo; Iftimie, Radu

    2010-07-28

    Ultrafast, time-resolved investigations of acid-base neutralization reactions have recently been performed using systems containing the photoacid 8-hydroxypyrene-1,3,6-trisulfonic acid trisodium salt (HPTS) and various Bronsted bases. Two conflicting neutralization mechanisms have been formulated by Mohammed et al. [Science 310, 83 (2005)] and Siwick et al. [J. Am. Chem. Soc. 129, 13412 (2007)] for the same acid-base system. Herein an ab initio molecular dynamics based computational model is formulated, which is able to investigate the validity of the proposed mechanisms in the general context of ground-state acid-base neutralization reactions. Our approach consists of using 2,4,6-tricyanophenol (exp. pKa congruent with 1) as a model for excited-state HPTS( *) (pKa congruent with 1.4) and carboxylate ions for the accepting base. We employ our recently proposed dipole-field/quantum mechanics (QM) treatment [P. Maurer and R. Iftimie, J. Chem. Phys. 132, 074112 (2010)] of the proton donor and acceptor molecules. This approach allows one to tune the free energy of neutralization to any desired value as well as model initial nonequilibrium hydration effects caused by a sudden increase in acidity, making it possible to achieve a more realistic comparison with experimental data than could be obtained via a full-QM treatment of the entire system. It is demonstrated that the dipole-field/QM model reproduces correctly key properties of the 2,4,6-tricyanophenol acid molecule including gas-phase proton dissociation energies and dipole moments, and condensed-phase hydration structure and pKa values.

  8. Low-Dose Creatine Supplementation Lowers Plasma Guanidinoacetate, but Not Plasma Homocysteine, in a Double-Blind, Randomized, Placebo-Controlled Trial.

    PubMed

    Peters, Brandilyn A; Hall, Megan N; Liu, Xinhua; Parvez, Faruque; Siddique, Abu B; Shahriar, Hasan; Uddin, Mohammad Nasir; Islam, Tariqul; Ilievski, Vesna; Graziano, Joseph H; Gamble, Mary V

    2015-10-01

    Creatine synthesis from guanidinoacetate consumes ~50% of s-adenosylmethionine (SAM)-derived methyl groups, accounting for an equivalent proportion of s-adenosylhomocysteine (SAH) and total homocysteine (tHcys) synthesis. Dietary creatine inhibits the synthesis of guanidinoacetate, thereby lowering plasma tHcys in rats. We tested the hypotheses that creatine supplementation lowers plasma guanidinoacetate, increases blood SAM, lowers blood SAH, and lowers plasma tHcys. Bangladeshi adults were randomly assigned to receive 1 of 4 treatments for 12 wk: placebo (n = 101), 3 g/d creatine (Cr; n = 101), 400 μg/d folic acid (FA; n = 153), or 3 g/d creatine plus 400 μg/d folic acid (Cr+FA; n = 103). The outcomes of plasma guanidinoacetate and tHcys, as well as whole blood SAM and SAH, were analyzed at baseline and week 12 by HPLC. Treatment effects of creatine supplementation were examined with the use of the group comparisons of Cr vs. placebo and Cr+FA vs. FA. Plasma guanidinoacetate declined by 10.6% (95% CI: 4.9, 15.9) in the Cr group while increasing nonsignificantly in the placebo group (3.7%; 95% CI: -0.8, 8.5) (Pgroup difference = 0.0002). Similarly, plasma guanidinoacetate declined by 9.0% (95% CI: 3.4, 14.2) in the Cr+FA group while increasing in the FA group (7.0%; 95% CI: 2.0, 12.2) (Pgroup difference < 0.0001). Plasma tHcys declined by 23.4% (95% CI: 19.5, 27.1) and 21.0% (95% CI: 16.4, 25.2) in the FA and Cr+FA groups, respectively (Pgroup difference = 0.41), with no significant changes in the placebo or Cr groups (Pgroup difference = 0.35). A decrease in guanidinoacetate over time was associated with a decrease in tHcys over time in the Cr+FA group (β = 0.30; 95% CI: 0.17, 0.43; P < 0.0001). Our findings indicate that whereas creatine supplementation downregulates endogenous creatine synthesis, this may not on average lower plasma tHcys in humans. However, tHcys did decrease in those participants who experienced a decline in plasma guanidinoacetate while

  9. Influence of renal function on the association between homocysteine level and risk of ischemic stroke.

    PubMed

    Cheng, Yao; Kong, Fan-Zhen; Dong, Xiao-Feng; Xu, Qin-Rong; Gui, Qian; Wang, Wei; Feng, Hong-Xuan; Luo, Wei-Feng; Gao, Zong-En; Wu, Guan-Hui

    2017-01-01

    We examined whether the association between total homocysteine (tHCY) and risk of ischemic stroke (IS) varies depending on renal function to gain insight into why tHCY-lowering vitamins do not reduce the incidence of cardiovascular disease in clinical trials. We analyzed data from 542 IS patients with large artery atherosclerosis (LAA) or small artery occlusion (SAO) after stratification by estimated glomerular filtration rate (eGFR) to evaluate renal function. We found that tHCY level was positively associated with the occurrence of IS in both LAA (OR: 1.159, 95% CI: 1.074-1.252, P <0.001) and SAO (OR: 1.143, 95% CI: 1.064-1.228, P <0.001) patients and in LAA (OR: 1.135, 95% CI: 1.047-1.230, P =0.002) and SAO (OR: 1.159, 95% CI: 1.060-1.268, P =0.001) subgroups with normal renal function but not in LAA or SAO subgroups with renal insufficiency. eGFR level was positively associated with IS in LAA (OR: 1.022, 95% CI: 1.010-1.034, P <0.001) and SAO (OR: 1.024, 1.012-1.037, P <0.001) subgroups with normal renal function but was negatively associated with IS in LAA (OR: 0.875, 95% CI: 0.829-0.925, P <0.001) and SAO (OR: 0.890, 95% CI: 0.850-0.932, P <0.001) subgroups with renal insufficiency. Folic acid level was negatively associated with IS in LAA (OR: 0.734, 95% CI: 0.606-0.889, P =0.002) and SAO (OR: 0.861, 95% CI: 0.767-0.967, P =0.012) subgroups with renal insufficiency. Therefore, renal function as evaluated by eGFR exerts a significant influence on the association between tHCY and risk of IS.

  10. Taurine ameliorated homocysteine-induced H9C2 cardiomyocyte apoptosis by modulating endoplasmic reticulum stress.

    PubMed

    Zhang, Zhimin; Zhao, Lianyou; Zhou, Yanfen; Lu, Xuanhao; Wang, Zhengqiang; Wang, Jipeng; Li, Wei

    2017-05-01

    Homocysteine (Hcy)-triggered endoplasmic reticulum (ER) stress-mediated endothelial cell apoptosis has been suggested as a cause of Hcy-dependent vascular injury. However, whether ER stress is the molecular mechanism linking Hcy and cardiomyocytes death is unclear. Taurine has been reported to exert cardioprotective effects via various mechanisms. However, whether taurine protects against Hcy-induced cardiomyocyte death by attenuating ER stress is unknown. This study aimed to evaluate the opposite effects of taurine on Hcy-induced cardiomyocyte apoptosis and their underlying mechanisms. Our results demonstrated that low-dose or short-term Hcy treatment increased the expression of glucose-regulated protein 78 (GRP78) and activated protein kinase RNA-like ER kinase (PERK), inositol-requiring enzyme 1 (IRE1), and activating transcription factor 6 (ATF6), which in turn prevented apoptotic cell death. High-dose Hcy or prolonged Hcy treatment duration significantly up-regulated levels of C/EBP homologous protein (CHOP), cleaved caspase-12, p-c-Jun N-terminal kinase (JNK), and then triggered apoptotic events. High-dose Hcy also resulted in a decrease in mitochondrial membrane potential (Δψm) and an increase in cytoplasmic cytochrome C and the expression of cleaved caspase-9. Pretreatment of cardiomyocytes with sodium 4-phenylbutyric acid (an ER stress inhibitor) significantly inhibited Hcy-induced apoptosis. Furthermore, blocking the PERK pathway partly alleviated Hcy-induced ER stress-modulated cardiomyocyte apoptosis, and down-regulated the levels of Bax and cleaved caspase-3. Experimental taurine pretreatment inhibited the expression of ER stress-related proteins, and protected against apoptotic events triggered by Hcy-induced ER stress. Taken together, our results suggest that Hcy triggered ER stress in cardiomyocytes, which was the crucial molecular mechanism mediating Hcy-induced cardiomyocyte apoptosis, and the adverse effect of Hcy could be prevented by taurine.

  11. Role of Copper and Homocysteine in Pressure Overload Heart Failure

    PubMed Central

    Hughes, William M.; Rodriguez, Walter E.; Rosenberger, Dorothea; Chen, Jing; Sen, Utpal; Tyagi, Neetu; Moshal, Karni S.; Vacek, Thomas; Kang, Y. James

    2009-01-01

    Elevated levels of homocysteine (Hcy) (known as hyperhomocysteinemia HHcy) are involved in dilated cardiomyopathy. Hcy chelates copper and impairs copper-dependent enzymes. Copper deficiency has been linked to cardiovascular disease. We tested the hypothesis that copper supplement regresses left ventricular hypertrophy (LVH), fibrosis and endothelial dysfunction in pressure overload DCM mice hearts. The mice were grouped as sham, sham + Cu, aortic constriction (AC), and AC + Cu. Aortic constriction was performed by transverse aortic constriction. The mice were treated with or without 20 mg/kg copper supplement in the diet for 12 weeks. The cardiac function was assessed by echocardiography and electrocardiography. The matrix remodeling was assessed by measuring matrix metalloproteinase (MMP), tissue inhibitor of metalloproteinases (TIMPs), and lysyl oxidase (LOX) by Western blot analyses. The results suggest that in AC mice, cardiac function was improved with copper supplement. TIMP-1 levels decreased in AC and were normalized in AC + Cu. Although MMP-9, TIMP-3, and LOX activity increased in AC and returned to baseline value in AC + Cu, copper supplement showed no significant effect on TIMP-4 activity after pressure overload. In conclusion, our data suggest that copper supplement helps improve cardiac function in a pressure overload dilated cardiomyopathic heart. PMID:18679830

  12. Saliva/serum ghrelin, obestatin and homocysteine levels in patients with ischaemic heart disease

    PubMed Central

    Kilic, Nermin; Dagli, Necati; Aydin, Suleyman; Erman, Fazilet; Bek, Yuksel; Akin, Okhan; Kilic, SS; Erdemli, Haci Kemal; Alacam, Hasan

    2017-01-01

    Summary Background: We aimed to compare ghrelin, obestatin, homocysteine (Hcy), vitamin B12 and folate levels in the serum and saliva of ischaemic heart disease patients. Methods: Serum and saliva were collected from 33 ischaemic heart disease (IHD) patients and 28 age- and body mass index-matched healthy individuals. Levels of acylated and desacylated ghrelin, obestatin and Hcy were determined using the ELISA method. Results: Acylated ghrelin, desacylated ghrelin and obestatin levels in the saliva were found to be higher than those in the serum of the control group, while acylated and desacylated ghrelin levels in the saliva were significantly lower than those in the serum. Obestatin levels were higher in IHD patients (p = 0.001). Saliva and serum vitamin B12 and folate levels in IHD patients were significantly lower than in the control group (p = 0.001). Conclusions: It was determined that serum ghrelin levels increased in ischaemic heart disease patients, while serum levels of obestatin decreased. PMID:28759087

  13. Risk of Dementia Associated with Elevated Plasma Homocysteine in a Latin American Population

    PubMed Central

    Chacón, Inara J.; Molero, Aldrín E.; Pino-Ramírez, Gloria; Luchsinger, José A.; Lee, Joseph H.; Maestre, Gladys E.

    2009-01-01

    The relationship between total homocysteine (tHcy) and dementia risk remains controversial, as the association varies among populations and dementia subtypes. We studied a Venezuelan population that has high prevalence of both elevated tHcy and dementia. We tested the hypotheses that (1) elevated tHcy is associated with increased dementia risk, (2) the risk is greater for vascular dementia (VaD) than for Alzheimer's disease (AD), and (3) a history of stroke may partly explain this association. 2100 participants (≥55 years old) of the Maracaibo Aging Study underwent standardized neurological, neuropsychiatric, and cardiovascular assessments. Elevated tHcy was significantly associated with dementia, primarily VaD. When history of stroke and other confounding factors were taken into account, elevated tHcy remained a significant risk factor in older (>66 years), but not in younger (55–66 years) subjects. Ongoing studies of this population may provide insight into the mechanism by which tHcy increases risk for dementia. PMID:20798752

  14. Leptin concentrations and SCD-1 indices in classical homocystinuria: Evidence for the role of sulfur amino acids in the regulation of lipid metabolism.

    PubMed

    Poloni, Soraia; Spritzer, Poli Mara; Mendes, Roberta H; D'Almeida, Vânia; Castro, Kamila; Sperb-Ludwig, Fernanda; Kugele, Johanna; Tucci, Sara; Blom, Henk J; Schwartz, Ida V D

    2017-10-01

    We describe body composition, lipid metabolism and Stearoyl-CoA desaturase-1 (SCD-1) indices in patients with classical homocystinuria (HCU). Eleven treated HCU patients and 16 healthy controls were included. Body composition and bone mineral density were assessed by dual X-ray absorptiometry. Sulfur amino acids (SAA) and their derivatives (total homocysteine, cysteine, methionine, S-adenosylmethionine, S-adenosylhomocysteine, and glutathione), lipids (free fatty acids, acylcarnitines, triglycerides and lipoproteins), glucose, insulin, leptin, adiponectin, and isoprostanes were measured in plasma. Insulin resistance was evaluated by HOMA-IR. To estimate liver SCD-1 activity, SCD-16 [16:1(n-7)/16:0] and SCD-18 [18:1(n-9)/18:0] desaturation indices were determined. In HCU patients, SCD-16 index was significantly reduced (p=0.03). A trend of an association of SCD-16 index with cysteine was observed (r=0.624, p=0.054). HCU patients displayed lower lean mass (p<0.05), with no differences in fat mass percentage. Leptin and low-density lipoprotein concentrations were lower in HCU patients (p<0.05). Femur bone mineral density Z-scores were correlated with plasma cysteine (r=0.829; p=0.04) and total homocysteine (r=-0.829; p=0.04) in HCU patients. We report alterations in leptin and SCD-1 in HCU patients. These results agree with previous findings from epidemiologic and animal studies, and support a role for SAA on lipid homeostasis. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. What is the Ultimate Goal in Acid-Base Regulation?

    ERIC Educational Resources Information Center

    Balakrishnan, Selvakumar; Gopalakrishnan, Maya; Alagesan, Murali; Prakash, E. Sankaranarayanan

    2007-01-01

    It is common to see chapters on acid-base physiology state that the goal of acid-base regulatory mechanisms is to maintain the pH of arterial plasma and not arterial PCO [subscript 2] (Pa[subscript CO[subscript 2

  16. Possible ethnic differences in plasma homocysteine levels associated with coronary artery disease between south Asian and east Asian immigrants.

    PubMed

    Senaratne, M P; MacDonald, K; De Silva, D

    2001-11-01

    Hyperhomocysteinemia has been identified as a risk factor for coronary artery disease (CAD). South Asians appear to have a high incidence of CAD, while East Asians have a very low incidence. The present study was undertaken because the relative association of plasma homocysteine levels (PH) with CAD in South Asians (SA = Indian, Pakistani, Sri Lankan) and East Asians (EA = Chinese, Japanese) is not known. Fasting PH were drawn on all patients with CAD of SA (age 62.4+/-1.1 years, 72 men, 14 women) and EA (age 61.8+/-3.0 years, 13 men, 4 women) descent. These were compared with PH available from Caucasian (CA) patients (age 61.1+/-1.1 years, 89 men, 17 women) with CAD. The PH in SA, EA, and CA patients were 11.0+/-0.5, 7.6+/-0.5, and 10.8+/-0.6 micromol/l, respectively (p<0.001 between EA and SA/CA). Percentages of SA, EA, and CA with elevated PH (> 12.0 micromol/l) were 33.7, 5.9, and 28.2%, respectively. There were no significant differences in the lipid subfractions between the SA and EA group. History of smoking was significantly higher in the EA (52.9 vs. 26.2%), while hypertension and diabetes mellitus had similar prevalences. Significant differences in PH of SA versus EA patients with CAD exist. The relative contribution of homocysteine in the development of CAD appears to be less in EA immigrants. In contrast, the association between CAD and PH in SA immigrants appears to be similar to that of Caucasians.

  17. Homocysteine Level and Risk of Abdominal Aortic Aneurysm: A Meta-Analysis

    PubMed Central

    Cao, Hui; Hu, Xinhua; Zhang, Qiang; Li, Jun; Wang, Junpeng; Shao, Yang; Liu, Bing; Xin, Shijie

    2014-01-01

    Objectives Previous studies have reported inconsistent findings regarding the association between elevated plasma homocysteine (Hcy) levels and abdominal aortic aneurysm (AAA). We investigated this association between Hcy levels in patients with AAA and unaffected controls by conducting a meta-analysis and systematic review. Methods We conducted a systematic literature search (up to August 2013) of the PubMed database and Embase. We selected observational studies that evaluated Hcy levels in subjects with AAA compared to unaffected controls. Criteria for inclusion were the assessment of baseline Hcy and risk of AAA as an outcome. The results were presented as odd ratio (OR) and corresponding 95% confidence intervals (CI) comparing AAA patients to the control subjects. Results 7 studies with 6,445 participants were identified and analyzed. Overall, elevated plasma Hcy was associated with an increased risk of AAA (3.29; 95% CI 1.66–6.51). The pooled adjusted OR from a random effect model of only men participants in the AAA compared with the control group was 2.36 (95% CI 0.63–8.82). Conclusion This meta-analysis and systematic review suggested that Hcy significantly increased the risk of AAA. PMID:24465733

  18. Reactive Distillation for Esterification of Bio-based Organic Acids

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Fields, Nathan; Miller, Dennis J.; Asthana, Navinchandra S.

    2008-09-23

    The following is the final report of the three year research program to convert organic acids to their ethyl esters using reactive distillation. This report details the complete technical activities of research completed at Michigan State University for the period of October 1, 2003 to September 30, 2006, covering both reactive distillation research and development and the underlying thermodynamic and kinetic data required for successful and rigorous design of reactive distillation esterification processes. Specifically, this project has led to the development of economical, technically viable processes for ethyl lactate, triethyl citrate and diethyl succinate production, and on a larger scalemore » has added to the overall body of knowledge on applying fermentation based organic acids as platform chemicals in the emerging biorefinery. Organic acid esters constitute an attractive class of biorenewable chemicals that are made from corn or other renewable biomass carbohydrate feedstocks and replace analogous petroleum-based compounds, thus lessening U.S. dependence on foreign petroleum and enhancing overall biorefinery viability through production of value-added chemicals in parallel with biofuels production. Further, many of these ester products are candidates for fuel (particularly biodiesel) components, and thus will serve dual roles as both industrial chemicals and fuel enhancers in the emerging bioeconomy. The technical report from MSU is organized around the ethyl esters of four important biorenewables-based acids: lactic acid, citric acid, succinic acid, and propionic acid. Literature background on esterification and reactive distillation has been provided in Section One. Work on lactic acid is covered in Sections Two through Five, citric acid esterification in Sections Six and Seven, succinic acid in Section Eight, and propionic acid in Section Nine. Section Ten covers modeling of ester and organic acid vapor pressure properties using the SPEAD (Step

  19. Immunoprotective responses of T helper type 1 stimulatory protein‐S‐adenosyl‐L‐homocysteine hydrolase against experimental visceral leishmaniasis

    PubMed Central

    Khare, P.; Jaiswal, A. K.; Tripathi, C. D. P.; Sundar, S.

    2016-01-01

    Summary It is well known that a patient in clinical remission of visceral leishmaniasis (VL) remains immune to reinfection, which provides a rationale for the feasibility of a vaccine against this deadly disease. In earlier studies, observation of significant cellular responses in treated Leishmania patients as well as in hamsters against leishmanial antigens from different fractions led to its further proteomic characterization, wherein S‐adenosyl‐L‐homocysteine hydrolase (AdoHcy) was identified as a helper type 1 (Th1) stimulatory protein. The present study includes immunological characterization of this protein, its cellular responses [lymphoproliferation, nitric oxide (NO) production and cytokine responses] in treated Leishmania‐infected hamsters and patients as well as prophylactic efficacy against Leishmania challenge in hamsters and the immune responses generated thereof. Significantly higher cellular responses were noticed against recombinant L. donovani S‐adenosyl‐L‐homocysteine hydrolase (rLdAdoHcy) compared to soluble L. donovani antigen in treated samples. Moreover, stimulation of peripheral blood mononuclear cells with rLdAdoHcy up‐regulated the levels of interferon (IFN)‐γ, interleukin (IL)−12 and down‐regulated IL‐10. Furthermore, vaccination with rLdAdoHcy generated perceptible delayed‐type hypersensitivity response and exerted considerably good prophylactic efficacy (∼70% inhibition) against L. donovani challenge. The efficacy was confirmed by the increased expression levels of inducible NO synthase and Th1‐type cytokines, IFN‐γ and IL‐12 and down‐regulation of IL‐4, IL‐10 and transforming growth factor (TGF)‐β. The results indicate the potentiality of rLdAdoHcy protein as a suitable vaccine candidate against VL. PMID:26898994

  20. Immunoprotective responses of T helper type 1 stimulatory protein-S-adenosyl-L-homocysteine hydrolase against experimental visceral leishmaniasis.

    PubMed

    Khare, P; Jaiswal, A K; Tripathi, C D P; Sundar, S; Dube, A

    2016-08-01

    It is well known that a patient in clinical remission of visceral leishmaniasis (VL) remains immune to reinfection, which provides a rationale for the feasibility of a vaccine against this deadly disease. In earlier studies, observation of significant cellular responses in treated Leishmania patients as well as in hamsters against leishmanial antigens from different fractions led to its further proteomic characterization, wherein S-adenosyl-L-homocysteine hydrolase (AdoHcy) was identified as a helper type 1 (Th1) stimulatory protein. The present study includes immunological characterization of this protein, its cellular responses [lymphoproliferation, nitric oxide (NO) production and cytokine responses] in treated Leishmania-infected hamsters and patients as well as prophylactic efficacy against Leishmania challenge in hamsters and the immune responses generated thereof. Significantly higher cellular responses were noticed against recombinant L. donovani S-adenosyl-L-homocysteine hydrolase (rLdAdoHcy) compared to soluble L. donovani antigen in treated samples. Moreover, stimulation of peripheral blood mononuclear cells with rLdAdoHcy up-regulated the levels of interferon (IFN)-γ, interleukin (IL)-12 and down-regulated IL-10. Furthermore, vaccination with rLdAdoHcy generated perceptible delayed-type hypersensitivity response and exerted considerably good prophylactic efficacy (∼70% inhibition) against L. donovani challenge. The efficacy was confirmed by the increased expression levels of inducible NO synthase and Th1-type cytokines, IFN-γ and IL-12 and down-regulation of IL-4, IL-10 and transforming growth factor (TGF)-β. The results indicate the potentiality of rLdAdoHcy protein as a suitable vaccine candidate against VL. © 2016 British Society for Immunology.

  1. Helicobacter Pylori Gastritis, a Presequeale to Coronary Plaque

    PubMed Central

    Raut, Shrikant C.; Patil, Vinayak W.; Dalvi, Shubhangi M.; Bakhshi, Girish D.

    2015-01-01

    Helicobacter pylori are considered the most common human pathogen colonizing gastric mucosa. Gastritis with or without H. pylori infection is associated with increase in levels of homocysteine and high-sensitivity C-reactive protein (hs-CRP) but a more pronounced increase is noted in gastritis with H. pylori infection. Increasing level of homocysteine, due to decreased absorption of vitamin B12 and folic acid, together with increased CRP levels in gastritis with H. pylori infection may be the earliest event in the process of atherosclerosis and plaque formation. Retrospective study conducted at tertiary care hospital in Mumbai by Department of Biochemistry in association with Department of Surgery. Eighty patients who underwent gastroscopy in view of gastritis were subjected to rapid urease test for diagnosis of H. pylori infection. Vitamin B12, folic acid, homocysteine and hs-CRP were analyzed using chemiluminescence immuno assay. Student’s t-test, Pearson’s correlation and linear regression used for statistical analysis. Patients with H. pylori gastritis had significantly lower levels of vitamin B12 (271.6±101.3 vs 390.6±176.7 pg/mL; P=0.0005), as well as higher levels of homocysteine (17.4±7.4 vs 13.8±7.8 µmol/L; P=0.037) and hs-CRP (2.5±2.9 vs 1.2±1.1 mg/L; P=0.017), than in patients without H. pylori gastritis. However, folic acid showed (8.9±3.2 vs 10.0±3.6 ng/mL; P=0.171) no significant difference. Elevated homocysteine and hs-CRP in H. pylori gastritis may independently induce endothelial dysfunction, leading to cardiovascular pathology. PMID:25918633

  2. Methionine and serine synergistically suppress hyperhomocysteinemia induced by choline deficiency, but not by guanidinoacetic acid, in rats fed a low casein diet.

    PubMed

    Liu, Yi-qun; Liu, Ying; Morita, Tatsuya; Sugiyama, Kimio

    2011-01-01

    The effects of dietary supplementation with 0.5% methionine, 2.5% serine, or both on hyperhomocysteinemia induced by deprivation of dietary choline or by dietary addition of 0.5% guanidinoacetic acid (GAA) were investigated in rats fed a 10% casein diet. Hyperhomocysteinemia induced by choline deprivation was not suppressed by methionine alone and was only partially suppressed by serine alone, whereas it was completely suppressed by a combination of methionine and serine, suggesting a synergistic effect of methionine and serine. Fatty liver was also completely prevented by the combination of methionine and serine. Compared with methionine alone, the combination of methionine and serine decreased hepatic S-adenosylhomocysteine and homocysteine concentrations and increased hepatic betaine and serine concentrations and betaine-homocysteine S-methyltransferase activity. GAA-induced hyperhomocysteinemia was partially suppressed by methionine alone, but no interacting effect of methionine and serine was detected. In contrast, GAA-induced fatty liver was completely prevented by the combination of methionine and serine. These results indicate that a combination of methionine and serine is effective in suppressing both hyperhomocysteinemia and fatty liver induced by choline deprivation, and that methionine alone is effective in suppressing GAA-induced hyperhomocysteinemia partially.

  3. Paediatric acid-base disorders: A case-based review of procedures and pitfalls

    PubMed Central

    Carmody, J Bryan; Norwood, Victoria F

    2013-01-01

    Acid-base disorders occur frequently in paediatric patients. Despite the perception that their analysis is complex and difficult, a straightforward set of rules is sufficient to interpret even the most complex disorders – provided certain pitfalls are avoided. Using a case-based approach, the present article reviews the fundamental concepts of acid-base analysis and highlights common mistakes and oversights. Specific topics include the proper identification of the primary disorder; distinguishing compensatory changes from additional primary disorders; use of the albumin-corrected anion gap to generate a differential diagnosis for patients with metabolic acidosis; screening for mixed disorders with the delta-delta formula; recognizing the limits of compensation; use of the anion gap to identify ‘hidden’ acidosis; and the importance of using information from the history and physical examination to identify the specific cause of a patient’s acid-base disturbance. PMID:24381489

  4. Prebiotic synthesis of carboxylic acids, amino acids and nucleic acid bases from formamide under photochemical conditions⋆

    NASA Astrophysics Data System (ADS)

    Botta, Lorenzo; Mattia Bizzarri, Bruno; Piccinino, Davide; Fornaro, Teresa; Robert Brucato, John; Saladino, Raffaele

    2017-07-01

    The photochemical transformation of formamide in the presence of a mixture of TiO2 and ZnO metal oxides as catalysts afforded a large panel of molecules of biological relevance, including carboxylic acids, amino acids and nucleic acid bases. The reaction was less effective when performed in the presence of only one mineral, highlighting the role of synergic effects between the photoactive catalysts. Taken together, these results suggest that the synthesis of chemical precursors for both the genetic and the metabolic apparatuses might have occurred in a simple environment, consisting of formamide, photoactive metal oxides and UV-radiation.

  5. The relationship between odd- and branched-chain fatty acids and microbial nucleic acid bases in rumen

    PubMed Central

    Liu, Keyuan; Hao, Xiaoyan; Li, Yang; Luo, Guobin; Zhang, Yonggen; Xin, Hangshu

    2017-01-01

    Objective This study aims to identify the relationship between odd- and branched-chain fatty acids (OBCFAs) and microbial nucleic acid bases in the rumen, and to establish a model to accurately predict microbial protein flow by using OBCFA. Methods To develop the regression equations, data on the rumen contents of individual cows were obtained from 2 feeding experiments. In the first experiment, 3 rumen-fistulated dry dairy cows arranged in a 3×3 Latin square were fed diets of differing forage to concentration ratios (F:C). The second experiment consisted of 9 lactating Holstein dairy cows of similar body weights at the same stage of pregnancy. For each lactation stage, 3 cows with similar milk production were selected. The rumen contents were sampled at 4 time points of every two hours after morning feeding 6 h, and then to analyse the concentrations of OBCFA and microbial nucleic acid bases in the rumen samples. Results The ruminal bacteria nucleic acid bases were significantly influenced by feeding diets of differing forge to concentration ratios and lactation stages of dairy cows (p<0.05). The concentrations of OBCFAs, especially odd-chain fatty acids and C15:0 isomers, strongly correlated with the microbial nucleic acid bases in the rumen (p<0.05). The equations of ruminal microbial nucleic acid bases established by ruminal OBCFAs contents showed a good predictive capacity, as indicated by reasonably low standard errors and high R-squared values. Conclusion This finding suggests that the rumen OBCFA composition could be used as an internal marker of rumen microbial matter. PMID:28728386

  6. The relationship between odd- and branched-chain fatty acids and microbial nucleic acid bases in rumen.

    PubMed

    Liu, Keyuan; Hao, Xiaoyan; Li, Yang; Luo, Guobin; Zhang, Yonggen; Xin, Hangshu

    2017-11-01

    This study aims to identify the relationship between odd- and branched-chain fatty acids (OBCFAs) and microbial nucleic acid bases in the rumen, and to establish a model to accurately predict microbial protein flow by using OBCFA. To develop the regression equations, data on the rumen contents of individual cows were obtained from 2 feeding experiments. In the first experiment, 3 rumen-fistulated dry dairy cows arranged in a 3×3 Latin square were fed diets of differing forage to concentration ratios (F:C). The second experiment consisted of 9 lactating Holstein dairy cows of similar body weights at the same stage of pregnancy. For each lactation stage, 3 cows with similar milk production were selected. The rumen contents were sampled at 4 time points of every two hours after morning feeding 6 h, and then to analyse the concentrations of OBCFA and microbial nucleic acid bases in the rumen samples. The ruminal bacteria nucleic acid bases were significantly influenced by feeding diets of differing forge to concentration ratios and lactation stages of dairy cows (p<0.05). The concentrations of OBCFAs, especially odd-chain fatty acids and C15:0 isomers, strongly correlated with the microbial nucleic acid bases in the rumen (p<0.05). The equations of ruminal microbial nucleic acid bases established by ruminal OBCFAs contents showed a good predictive capacity, as indicated by reasonably low standard errors and high R-squared values. This finding suggests that the rumen OBCFA composition could be used as an internal marker of rumen microbial matter.

  7. Homocysteine concentration, related B vitamins, and betaine in pregnant women recruited to the Seychelles Child Development Study123

    PubMed Central

    Wallace, Julie MW; Bonham, Maxine P; Strain, JJ; Duffy, Emeir M; Robson, Paula J; Ward, Mary; McNulty, Helene; Davidson, Philip W; Myers, Gary J; Shamlaye, Conrad F; Clarkson, Tom W; Molloy, Anne M; Scott, John M; Ueland, Per M

    2008-01-01

    Background Both folate and betaine are important predictors of total homocysteine (tHcy) during pregnancy. However, studies to date have only been undertaken in populations with Western dietary patterns. Objective We investigated the predictors of tHcy in pregnant women recruited in the Seychelles, a population where access to fortified foods is limited and where women habitually consume diets rich in fish, eggs, rice, and fruit. Design Pregnant women (n = 226) provided blood samples at enrollment, at week 28 of gestation, and at delivery. Cord blood was obtained from a subset of participants (n = 135). Results As in other studies, maternal tHcy was lower during pregnancy than at delivery, whereas folate and vitamin B-12 status declined significantly to delivery. Despite low maternal folate status at delivery (median: 9.0 nmol/L), with 35% of women in the deficient range (serum folate: <6.8 nmol/L), cord blood folate status (median: 40.2 nmol/L) was similar to concentrations reported in Western populations. Folate was a significant predictor of tHcy at all time points (P < 0.001). In contrast with previous studies, betaine was only a significant predictor of maternal tHcy (P < 0.001) when the essential amino acid methionine was low. Conclusions The current study reports 2 important findings. First, fetal requirements for folate are paramount, such that cord blood folate status is maintained, even when maternal status is low. Second, betaine is a significant predictor of tHcy in pregnant women with low serum folate and low serum methionine concentrations. PMID:18258630

  8. [Procedural analysis of acid-base balance disorder: case serials in 4 patents].

    PubMed

    Ma, Chunyuan; Wang, Guijie

    2017-05-01

    To establish the standardization process of acid-base balance analysis, analyze cases of acid-base balance disorder with the aid of acid-base balance coordinate graph. The acid-base balance theory were reviewed systematically on recent research progress, and the important concepts, definitions, formulas, parameters, regularity and inference in the analysis of acid-base balance were studied. The analysis of acid-base balance disordered processes and steps were figured. The application of acid-base balance coordinate graph in the cases was introduced. The method of "four parameters-four steps" analysis was put forward to analyze the acid-base balance disorders completely. "Four parameters" included pH, arterial partial pressure of carbon dioxide (PaCO 2 ), HCO 3 - and anion gap (AG). "Four steps" were outlined by following aspects: (1) according to the pH, PaCO 2 and HCO 3 - , the primary or main types of acid-base balance disorder was determined; (2) primary or main types of acid-base disorder were used to choose the appropriate compensation formula and to determine the presence of double mixed acid-base balance disorder; (3) the primary acid-base balance disorders were divided into two parts: respiratory acidosis or respiratory alkalosis, at the same time, the potential HCO 3 - should be calculated, the measured HCO 3 - should be replaced with potential HCO 3 - , to determine whether there were three mixed acid-base disorders; (4) based on the above analysis the data judged as the simple AG increased-metabolic acidosis was needed to be further analyzed. The ratio of ΔAG↑/ΔHCO 3 - ↓ was also needed to be calculated, to determine whether there was normal AG metabolic acidosis or metabolic alkalosis. In the clinical practice, PaCO 2 (as the abscissa) and HCO 3 - (as the ordinate) were used to establish a rectangular coordinate system, through origin (0, 0) and coordinate point (40, 24) could be a straight line, and all points on the straight line pH were equal

  9. Analysis of 26 amino acids in human plasma by HPLC using AQC as derivatizing agent and its application in metabolic laboratory.

    PubMed

    Sharma, Gaurav; Attri, Savita Verma; Behra, Bijaylaxmi; Bhisikar, Swapnil; Kumar, Praveen; Tageja, Minni; Sharda, Sheetal; Singhi, Pratibha; Singhi, Sunit

    2014-05-01

    The present study reports the simultaneous analysis of 26 physiological amino acids in plasma along with total cysteine and homocysteine by high-performance liquid chromatography (HPLC) employing 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC) as precolumn derivatizing reagent. Separations were carried out using Lichrospher 100 RP-18e (5 μm) 250 × 4.0 mm column connected to 100 CN 4.0 × 4.0 mm guard column on a quaternary HPLC system and run time was 53 min. Linearity of the peak areas for different concentrations ranging from 2.5 to 100 pmol/μL of individual amino acids was determined. A good linearity (R (2) > 0.998) was achieved in the standard mixture for each amino acid. Recovery of amino acids incorporated at the time of derivatization ranged from 95 to 106 %. Using this method we have established the normative data of amino acids in plasma, the profile being comparable to the range reported in literature and identified cases of classical homocystinuria, cobalamin defect/deficiency, non-ketotic hyperglycinemia, hyperprolinemia, ketotic hyperglycinemia, urea cycle defect and maple syrup urine disease.

  10. The role of NMDA and mGluR5 receptors in calcium mobilization and neurotoxicity of homocysteine in trigeminal and cortical neurons and glial cells.

    PubMed

    Abushik, Polina A; Niittykoski, Minna; Giniatullina, Raisa; Shakirzyanova, Anastasia; Bart, Genevieve; Fayuk, Dmitriy; Sibarov, Dmitry A; Antonov, Sergei M; Giniatullin, Rashid

    2014-04-01

    Recent studies suggested contribution of homocysteine (HCY) to neurodegenerative disorders and migraine. However, HCY effect in the nociceptive system is essentially unknown. To explore the mechanism of HCY action, we studied short- and long-term effects of this amino acid on rat peripheral and central neurons. HCY induced intracellular Ca²⁺ transients in cultured trigeminal neurons and satellite glial cells (SGC), which were blocked by the NMDA antagonist AP-5 in neurons, but not in SGCs. In contrast, 3-((2-Methyl-4-thiazolyl)ethynyl)pyridine (MTEP), the metabotropic mGluR5 (metabotropic glutamate receptor 5 subtype) antagonist, preferentially inhibited Ca²⁺ transients in SGCs. Prolonged application of HCY induced apoptotic cell death of both kinds of trigeminal cells. The apoptosis was blocked by AP-5 or by the mGluR5 antagonist MTEP. Likewise, in cortical neurons, HCY-induced cell death was inhibited by AP-5 or MTEP. Imaging with 2',7'-dichlorodihydrofluorescein diacetate or mitochondrial dye Rhodamine-123 as well as thiobarbituric acid reactive substances assay did not reveal involvement of oxidative stress in the action of HCY. Thus, elevation of intracellular Ca²⁺ by HCY in neurons is mediated by NMDA and mGluR5 receptors while SGC are activated through the mGluR5 subtype. Long-term neurotoxic effects in peripheral and central neurons involved both receptor types. Our data suggest glutamatergic mechanisms of HCY-induced sensitization and apoptosis of trigeminal nociceptors. © 2013 International Society for Neurochemistry.

  11. Prospects for nucleic acid-based therapeutics against hepatitis C virus.

    PubMed

    Lee, Chang Ho; Kim, Ji Hyun; Lee, Seong-Wook

    2013-12-21

    In this review, we discuss recent advances in nucleic acid-based therapeutic technologies that target hepatitis C virus (HCV) infection. Because the HCV genome is present exclusively in RNA form during replication, various nucleic acid-based therapeutic approaches targeting the HCV genome, such as ribozymes, aptamers, siRNAs, and antisense oligonucleotides, have been suggested as potential tools against HCV. Nucleic acids are potentially immunogenic and typically require a delivery tool to be utilized as therapeutics. These limitations have hampered the clinical development of nucleic acid-based therapeutics. However, despite these limitations, nucleic acid-based therapeutics has clinical value due to their great specificity, easy and large-scale synthesis with chemical methods, and pharmaceutical flexibility. Moreover, nucleic acid therapeutics are expected to broaden the range of targetable molecules essential for the HCV replication cycle, and therefore they may prove to be more effective than existing therapeutics, such as interferon-α and ribavirin combination therapy. This review focuses on the current status and future prospects of ribozymes, aptamers, siRNAs, and antisense oligonucleotides as therapeutic reagents against HCV.

  12. Lewis Acid-Base Chemistry of 7-Azaisoindigo-Based Organic Semiconductors.

    PubMed

    Randell, Nicholas M; Fransishyn, Kyle M; Kelly, Timothy L

    2017-07-26

    Low-band-gap organic semiconductors are important in a variety of organic electronics applications, such as organic photovoltaic devices, photodetectors, and field effect transistors. Building on our previous work, which introduced 7-azaisoindigo as an electron-deficient building block for the synthesis of donor-acceptor organic semiconductors, we demonstrate how Lewis acids can be used to further tune the energies of the frontier molecular orbitals. Coordination of a Lewis acid to the pyridinic nitrogen of 7-azaisoindigo greatly diminishes the electron density in the azaisoindigo π-system, resulting in a substantial reduction in the lowest unoccupied molecular orbital (LUMO) energy. This results in a smaller highest occupied molecular orbital-LUMO gap and shifts the lowest-energy electronic transition well into the near-infrared region. Both H + and BF 3 are shown to coordinate to azaisoindigo and affect the energy of the S 0 → S 1 transition. A combination of time-dependent density functional theory and UV/vis and 1 H NMR spectroscopic titrations reveal that when two azaisoindigo groups are present and high concentrations of acid are used, both pyridinic nitrogens bind Lewis acids. Importantly, we demonstrate that this acid-base chemistry can be carried out at the solid-vapor interface by exposing thin films of aza-substituted organic semiconductors to vapor-phase BF 3 ·Et 2 O. This suggests the possibility of using the BF 3 -bound 7-azaisoindigo-based semiconductors as n-type materials in various organic electronic applications.

  13. The central nervous system in animal models of hyperhomocysteinemia.

    PubMed

    Troen, Aron M

    2005-09-01

    Growing epidemiological evidence of associations between mildly elevated plasma homocysteine with age-related cognitive impairment, neurodegenerative and cerebrovascular disease has stimulated interest in the role of homocysteine in neurological and neuropsychiatric disorders. Homocysteine is an intermediate in the folate, vitamin B12 and B6 dependent pathways of one-carbon and sulfur amino acid metabolism. Impairments of these pathways may cause CNS dysfunction by promoting the intracellular generation of homocysteine, which is postulated to have vasotoxic and neurotoxic properties. It might also inhibit the methylation of myelin basic protein and membrane phospholipids, or disrupt biogenic amine metabolism and many other vital CNS reactions. However, it is unclear which, if any, of these putative mechanisms underlies the epidemiological associations. Genetic mouse models of hyperhomocysteinemia suggest that the primary metabolic disturbances rather than homocysteine per se may be important in determining neurological outcomes. However, severe and early developmental abnormalities in these mice limit their usefulness for understanding the relation of hyperhomocysteinemia to adult CNS disorders. Pharmacologic and dietary studies on homocysteine in rodents have reported heightened neuronal sensitivity to neurotoxic insults, neurochemical abnormalities and cerebrovascular dysfunction. Such studies are consistent with a causal relationship, but they fail to distinguish between effects that might result from a dietary imbalance and those that might be caused by homocysteine per se. Future work should be directed towards refining these models in order to distinguish between the effects of homocysteine and its determinants on neurological and behavioral outcomes that represent different CNS disorders.

  14. Boronic acid-based chemical sensors for saccharides.

    PubMed

    Zhang, Xiao-Tai; Liu, Guang-Jian; Ning, Zhang-Wei; Xing, Guo-Wen

    2017-11-27

    During the past decades, the interaction between boronic acids-functionalized sensors and saccharides is of great interest in the frontier domain of the interdiscipline concerning both biology and chemistry. Various boronic acid-based sensing systems have been developed to detect saccharides and corresponding derivatives in vitro as well as in vivo, which embrace unimolecular sensors, two-component sensing ensembles, functional assemblies, and boronic acid-loaded nanomaterials or surfaces. New sensing strategies emerge in endlessly with excellent selectivity and sensitivity. In this review, several typical sensing systems were introduced and some promising examples were highlighted to enable the deep insight of saccharides sensing on the basis of boronic acids. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Evaluating Interest in Acids-Bases: Development of an Acid-Base Interest Scale (ABIS) and Assessment of Pre-Service Science Teachers' Interest

    ERIC Educational Resources Information Center

    Çiçek, Ö.; Ilhan, N.

    2017-01-01

    Students are more likely to be successful in topics they are interested in than others. This study aims to develop an Acid-Base Interest Scale (ABIS) and subsequently evaluate the interest of pre-service science teachers in acids-bases according to gender, years at the university, type of high school the pre-service science teachers attended, and…

  16. Sequence determination and analysis of S-adenosyl-L-homocysteine hydrolase from yellow lupine (Lupinus luteus).

    PubMed

    Brzeziński, K; Janowski, R; Podkowiński, J; Jaskólski, M

    2001-01-01

    The coding sequences of two S-adenosyl-L-homocysteine hydrolases (SAHases) were identified in yellow lupine by screenig of a cDNA library. One of them, corresponding to the complete protein, was sequenced and compared with 52 other SAHase sequences. Phylogenetic analysis of these proteins identified three groups of the enzymes. Group A comprises only bacterial sequences. Group B is subdivided into two subgroups, one of which (B1) is formed by animal sequences. Subgroup B2 consist of two distinct clusters, B2a and B2b. Cluster B2b comprises all known plant sequences, including the yellow lupine enzyme, which are distinguished by a 50-residue insert. Group C is heterogeneous and contains SAHases from Archaea as well as a new class of animal enzymes, distinctly different from those in group B1.

  17. Soluble adenylyl cyclase is an acid-base sensor in epithelial base-secreting cells.

    PubMed

    Roa, Jinae N; Tresguerres, Martin

    2016-08-01

    Blood acid-base regulation by specialized epithelia, such as gills and kidney, requires the ability to sense blood acid-base status. Here, we developed primary cultures of ray (Urolophus halleri) gill cells to study mechanisms for acid-base sensing without the interference of whole animal hormonal regulation. Ray gills have abundant base-secreting cells, identified by their noticeable expression of vacuolar-type H(+)-ATPase (VHA), and also express the evolutionarily conserved acid-base sensor soluble adenylyl cyclase (sAC). Exposure of cultured cells to extracellular alkalosis (pH 8.0, 40 mM HCO3 (-)) triggered VHA translocation to the cell membrane, similar to previous reports in live animals experiencing blood alkalosis. VHA translocation was dependent on sAC, as it was blocked by the sAC-specific inhibitor KH7. Ray gill base-secreting cells also express transmembrane adenylyl cyclases (tmACs); however, tmAC inhibition by 2',5'-dideoxyadenosine did not prevent alkalosis-dependent VHA translocation, and tmAC activation by forskolin reduced the abundance of VHA at the cell membrane. This study demonstrates that sAC is a necessary and sufficient sensor of extracellular alkalosis in ray gill base-secreting cells. In addition, this study indicates that different sources of cAMP differentially modulate cell biology. Copyright © 2016 the American Physiological Society.

  18. Respiratory Acid-Base Disorders in the Critical Care Unit.

    PubMed

    Hopper, Kate

    2017-03-01

    The incidence of respiratory acid-base abnormalities in the critical care unit (CCU) is unknown, although respiratory alkalosis is suspected to be common in this population. Abnormal carbon dioxide tension can have many physiologic effects, and changes in Pco 2 may have a significant impact on outcome. Monitoring Pco 2 in CCU patients is an important aspect of critical patient assessment, and identification of respiratory acid-base abnormalities can be valuable as a diagnostic tool. Treatment of respiratory acid-base disorders is largely focused on resolution of the primary disease, although mechanical ventilation may be indicated in cases with severe respiratory acidosis. Published by Elsevier Inc.

  19. Reduced folate and serum vitamin metabolites in patients with rectal carcinoma: an open-label feasibility study of pemetrexed with folic acid and vitamin B12 supplementation

    PubMed Central

    Odin, Elisabeth A.; Carlsson, Göran U.; Kurlberg, Göran K.; Björkqvist, Hillevi G.; Tångefjord, Maria T.; Gustavsson, Bengt G.

    2016-01-01

    The objectives of this single-center, open-label, phase II study were to evaluate (a) the feasibility and safety of neoadjuvant administration of pemetrexed with oral folic acid and vitamin B12 (FA/B12) in newly diagnosed patients with resectable rectal cancer and (b) intracellular and systemic vitamin metabolism. Patients were treated with three cycles of pemetrexed (500 mg/m2, every 3 weeks) and FA/B12 before surgery. The reduced folates tetrahydrofolate, 5-methyltetrahydrofolate, and 5,10-methylenetetrahydrofolate were evaluated from biopsies in tumor tissue and in adjacent mucosa. Serum levels of homocysteine, cystathionine, and methylmalonic acid were also measured. All 37 patients received three cycles of pemetrexed; 89.2% completed their planned dosage within a 9-week feasibility time frame. Neither dose reductions nor study drug-related serious adverse events were reported. Reduced folate levels were significantly higher in tumor tissue compared with adjacent mucosa at baseline. After FA/B12 administration, tissue levels of reduced folates increased significantly and remained high during treatment in both tumor and mucosa until surgery. Serum levels of cystathionine increased significantly compared with baseline after FA/B12 administration, but then decreased, fluctuating cyclically during pemetrexed therapy. Homocysteine and methylmalonic acid levels decreased significantly after FA/B12 administration, and remained below baseline levels during the study. These results indicate that administration of three neoadjuvant cycles of single-agent pemetrexed, every 3 weeks, with FA/B12 in patients with resectable rectal cancer is feasible and tolerable. Tissue and serum vitamin metabolism results demonstrate the influence of pemetrexed and FA/B12 on vitamin metabolism and warrant further study. PMID:26825869

  20. The effects of the modulation of NMDA receptors by homocysteine thiolactone and dizocilpine on cardiodynamics and oxidative stress in isolated rat heart.

    PubMed

    Srejovic, Ivan; Jakovljevic, Vladimir; Zivkovic, Vladimir; Barudzic, Nevena; Radovanovic, Ana; Stanojlovic, Olivera; Djuric, Dragan M

    2015-03-01

    In light of the limited data concerning the role of N-methyl-D-aspartate (NMDA) receptors in cardiac function, the aim of the present study was to determine the role of NMDA receptors in cardiac function, as well as the possible role played by the oxidative stress induced by the overstimulation of NMDA receptors in isolated rat heart. The hearts of male, Wistar albino rats (n = 24, 12 in each experimental group, BM 180-200 g) were retrogradely perfused at a constant perfusion pressure (70 cm H₂O₂), using the Langendorff technique, and cardiodynamic parameters were determined during the subsequent administration of DL-homocysteine thiolactone (DL-Hcy TLHC) alone, the combination of DL-Hcy TLHC and dizocilpine (MK-801), and MK-801 alone. In the second experimental group, the order of the administration of each of the substances was reversed. The oxidative stress biomarkers, including thiobarbituric acid reactive substances (TBARS), NO(2)(-), O(2)(-) and H₂O₂, were each determined spectrophotometrically. DL-Hcy TLHC and MK-801 depressed cardiac function. DL-Hcy TLHC decreased oxidative stress, a finding that contrasted with the results of the experiments in which MK-801 was administered first. The findings of this study were suggestive of the likely role played by NMDA receptors in the regulation of cardiac function and coronary circulation in isolated rat heart.

  1. Nitrous Oxide Anesthesia and Plasma Homocysteine in Adolescents

    PubMed Central

    Nagele, Peter; Tallchief, Danielle; Blood, Jane; Sharma, Anshuman; Kharasch, Evan D.

    2011-01-01

    Background Nitrous oxide inactivates vitamin B12, inhibits methionine synthase and consequently increases plasma total homocysteine (tHcy). Prolonged exposure to nitrous oxide can lead to neuropathy, spinal cord degeneration and even death in children. We tested the hypothesis that nitrous oxide anesthesia causes a significant increase in plasma tHcy in children. Methods Twenty-seven children (age 10-18 years) undergoing elective major spine surgery were enrolled and serial plasma samples from 0 – 96 hours after induction were obtained. The anesthetic regimen, including the use of nitrous oxide, was at the discretion of the anesthesiologist. Plasma tHcy was measured using standard enzymatic assays. Results The median baseline plasma tHcy concentration was 5.1 μmol/L (3.9 – 8.0 μmol/L, interquartile range) and increased in all patients exposed to nitrous oxide (n=26) by an average of +9.4 μmol/L (geometric mean; 95% CI 7.1 – 12.5 μmol/L) or +228% (mean; 95% CI 178% - 279%). Plasma tHcy peaked between 6-8 hours after induction of anesthesia. One patient who did not receive nitrous oxide had no increase in plasma tHcy. Several patients experienced a several-fold increase in plasma tHcy (max. +567%). The increase in plasma tHcy was strongly correlated with the duration and average concentration of nitrous oxide anesthesia (r= 0.80; p<0.001). Conclusions Pediatric patients undergoing nitrous oxide anesthesia develop significantly increased plasma tHcy concentrations. The magnitude of this effect appears to be greater compared to adults; however, the clinical relevance is unknown. PMID:21680854

  2. Respiratory Adaptations in Acid-base Disturbances: Role of Cerebral Fluids,

    DTIC Science & Technology

    1979-06-19

    The respiratory and metabolic components of acid-base homeostasis are defined. A quantitative empirical description of the (incomplete) mutual...literature. Respiratory adaptations in steady acid-base disturbances of metabolic origin (hyperventilation with hypocapnia in primary metabolic acidosis, and...hypoventilation with hypercapnia in metabolic alkalosis ) are analyzed as a function of the acidity of the cerebral fluids (cerebrospinal and cerebral interstitial fluid). (Author)

  3. Acid-base equilibria inside amine-functionalized mesoporous silica.

    PubMed

    Yamaguchi, Akira; Namekawa, Manato; Kamijo, Toshio; Itoh, Tetsuji; Teramae, Norio

    2011-04-15

    Acid-base equilibria and effective proton concentration inside a silica mesopore modified with a trimethyl ammonium (TMAP) layer were studied by steady-state fluorescence experiments. The mesoporous silica with a dense TMAP layer (1.4 molecules/nm(2)) was prepared by a post grafting of N-trimethoxysilylpropyl-N,N,N-trimethylammonium at surfactant-templated mesoporous silica (diameter of silica framework =3.1 nm). The resulting TMAP-modified mesoporous silica strongly adsorbed of anionic fluorescence indicator dyes (8-hydroxypyrene-1,3,6-trisulfonate (pyranine), 8-aminopyrene-1,3,6-trisulfonate (APTS), 5,10,15,20-tetraphenyl-21H,23H-porphinetetrasulfonic acid disulfuric acid (TPPS), 2-naphthol-3,6-disulfonate (2NT)) and fluorescence excitation spectra of these dyes within TMAP-modified mesoporous silica were measured by varying the solution pH. The fluorescence experiments revealed that the acid-base equilibrium reactions of all pH indicator dyes within the TMAP-modified silica mesopore were quite different from those in bulk water. From the analysis of the acid-base equilibrium of pyranine, the following relationships between solution pH (pH(bulk)) and the effective proton concentration inside the pore (pH(pore)) were obtained: (1) shift of pH(pore) was 1.8 (ΔpH(pore)=1.8) for the pH(bulk) change from 2.1 to 9.1 (ΔpH(bulk)=7.0); (2) pH(pore) was not simply proportional to pH(bulk); (3) the inside of the TMAP-modified silica mesopore was suggested to be in a weak acidic or neutral condition when pH(bulk) was changed from 2.0 to 9.1. Since these relationships between pH(bulk) and pH(pore) could explain the acid-base equilibria of other pH indicator dyes (APTS, TPPS, 2NT), these relationships were inferred to describe the effective proton concentration inside the TMAP-modified silica mesopore. © 2011 American Chemical Society

  4. Synthesis and antimicrobial activities of new higher amino acid Schiff base derivatives of 6-aminopenicillanic acid and 7-aminocephalosporanic acid

    NASA Astrophysics Data System (ADS)

    Özdemir (nee Güngör), Özlem; Gürkan, Perihan; Özçelik, Berrin; Oyardı, Özlem

    2016-02-01

    Novel β-lactam derivatives (1c-3c) (1d-3d) were produced by using 6-aminopenicillanic acid (6-APA), 7-aminocephalosporanic acid (7-ACA) and the higher amino acid Schiff bases. The synthesized compounds were characterized by elemental analysis, IR, 1H/13C NMR and UV-vis spectra. Antibacterial activities of all the higher amino acid Schiff bases (1a-3a) (1b-3b) and β-lactam derivatives were screened against three gram negative bacteria (Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Acinetobacter baumannii RSKK 02026), three gram positive bacteria (Staphylococcus aureus ATCC 25923, Enterococcus faecalis ATCC 07005, Bacillus subtilis ATCC 6633) and their drug-resistant isolates by using broth microdilution method. Two fungi (Candida albicans and Candida krusei) were used for antifungal activity.

  5. Syntheses, structural, computational, and thermal analysis of acid-base complexes of picric acid with N-heterocyclic bases.

    PubMed

    Goel, Nidhi; Singh, Udai P

    2013-10-10

    Four new acid-base complexes using picric acid [(OH)(NO2)3C6H2] (PA) and N-heterocyclic bases (1,10-phenanthroline (phen)/2,2';6',2"-terpyridine (terpy)/hexamethylenetetramine (hmta)/2,4,6-tri(2-pyridyl)-1,3,5-triazine (tptz)) were prepared and characterized by elemental analysis, IR, NMR and X-ray crystallography. Crystal structures provide detailed information of the noncovalent interactions present in different complexes. The optimized structures of the complexes were calculated in terms of the density functional theory. The thermolysis of these complexes was investigated by TG-DSC and ignition delay measurements. The model-free isoconversional and model-fitting kinetic approaches have been applied to isothermal TG data for kinetics investigation of thermal decomposition of these complexes.

  6. TRANSFUSIONS—Hazardous Acid-Base Changes with Citrated Blood

    PubMed Central

    Pedro, Jovita M. San; Iwai, Seizo; Hattori, Mitsuo; Leigh, M. Digby

    1962-01-01

    In a study of the acid-base changes in the blood of rabbits during and following transfusions of citrated blood and of heparinized blood, it was observed that, with citrated blood, pH decreased and carbon dioxide tensions rose. With heparinized blood, the acid-base balance was maintained within normal limits following transfusions. The potential hazards of rapid massive citrated blood transfusions in the anesthetized patient during operation must be kept in mind. PMID:14496706

  7. Hard and soft acids and bases: atoms and atomic ions.

    PubMed

    Reed, James L

    2008-07-07

    The structural origin of hard-soft behavior in atomic acids and bases has been explored using a simple orbital model. The Pearson principle of hard and soft acids and bases has been taken to be the defining statement about hard-soft behavior and as a definition of chemical hardness. There are a number of conditions that are imposed on any candidate structure and associated property by the Pearson principle, which have been exploited. The Pearson principle itself has been used to generate a thermodynamically based scale of relative hardness and softness for acids and bases (operational chemical hardness), and a modified Slater model has been used to discern the electronic origin of hard-soft behavior. Whereas chemical hardness is a chemical property of an acid or base and the operational chemical hardness is an experimental measure of it, the absolute hardness is a physical property of an atom or molecule. A critical examination of chemical hardness, which has been based on a more rigorous application of the Pearson principle and the availability of quantitative measures of chemical hardness, suggests that the origin of hard-soft behavior for both acids and bases resides in the relaxation of the electrons not undergoing transfer during the acid-base interaction. Furthermore, the results suggest that the absolute hardness should not be taken as synonymous with chemical hardness but that the relationship is somewhat more complex. Finally, this work provides additional groundwork for a better understanding of chemical hardness that will inform the understanding of hardness in molecules.

  8. The Roles of Acids and Bases in Enzyme Catalysis

    ERIC Educational Resources Information Center

    Weiss, Hilton M.

    2007-01-01

    Many organic reactions are catalyzed by strong acids or bases that protonate or deprotonate neutral reactants leading to reactive cations or anions that proceed to products. In enzyme reactions, only weak acids and bases are available to hydrogen bond to reactants and to transfer protons in response to developing charges. Understanding this…

  9. Nucleic acid based fluorescent sensor for mercury detection

    DOEpatents

    Lu, Yi; Liu, Juewen

    2013-02-05

    A nucleic acid enzyme comprises an oligonucleotide containing thymine bases. The nucleic acid enzyme is dependent on both Hg.sup.2+and a second ion as cofactors, to produce a product from a substrate. The substrate comprises a ribonucleotide, a deoxyribonucleotide, or both.

  10. Complexity in Acid–Base Titrations: Multimer Formation Between Phosphoric Acids and Imines

    PubMed Central

    Malm, Christian; Kim, Heejae; Wagner, Manfred

    2017-01-01

    Abstract Solutions of Brønsted acids with bases in aprotic solvents are not only common model systems to study the fundamentals of proton transfer pathways but are also highly relevant to Brønsted acid catalysis. Despite their importance the light nature of the proton makes characterization of acid–base aggregates challenging. Here, we track such acid–base interactions over a broad range of relative compositions between diphenyl phosphoric acid and the base quinaldine in dichloromethane, by using a combination of dielectric relaxation and NMR spectroscopy. In contrast to what one would expect for an acid–base titration, we find strong deviations from quantitative proton transfer from the acid to the base. Even for an excess of the base, multimers consisting of one base and at least two acid molecules are formed, in addition to the occurrence of proton transfer from the acid to the base and simultaneous formation of ion pairs. For equimolar mixtures such multimers constitute about one third of all intermolecular aggregates. Quantitative analysis of our results shows that the acid‐base association constant is only around six times larger than that for the acid binding to an acid‐base dimer, that is, to an already protonated base. Our findings have implications for the interpretation of previous studies of reactive intermediates in organocatalysis and provide a rationale for previously observed nonlinear effects in phosphoric acid catalysis. PMID:28597513

  11. Structure and functioning of the acid-base system in the Baltic Sea

    NASA Astrophysics Data System (ADS)

    Kuliński, Karol; Schneider, Bernd; Szymczycha, Beata; Stokowski, Marcin

    2017-12-01

    The marine acid-base system is relatively well understood for oceanic waters. Its structure and functioning is less obvious for the coastal and shelf seas due to a number of regionally specific anomalies. In this review article we collect and integrate existing knowledge of the acid-base system in the Baltic Sea. Hydrographical and biogeochemical characteristics of the Baltic Sea, as manifested in horizontal and vertical salinity gradients, permanent stratification of the water column, eutrophication, high organic-matter concentrations and high anthropogenic pressure, make the acid-base system complex. In this study, we summarize the general knowledge of the marine acid-base system as well as describe the peculiarities identified and reported for the Baltic Sea specifically. In this context we discuss issues such as dissociation constants in brackish water, different chemical alkalinity models including contributions by organic acid-base systems, long-term changes in total alkalinity, anomalies of borate alkalinity, and the acid-base effects of biomass production and mineralization. Finally, we identify research gaps and specify limitations concerning the Baltic Sea acid-base system.

  12. On the observation of the need for an unusually high concentration of cysteine and homocysteine to induce aggregation of polymer-stabilized gold nano particles

    NASA Astrophysics Data System (ADS)

    Radhakumary, C.; Sreenivasan, K.

    2013-02-01

    This study reports the interaction of chitosan-stabilized gold nanoparticles (CH-AuNPs) with cysteine (Cys) and homocysteine (Hcys) in aqueous media at pH 1.4. Since the polymer precipitates at higher pH, and the amino acids Cys and HCys are soluble at acidic pH, we kept the pH around 1.4 for stabilizing the particles. Zeta potential of CH-AuNPs was found to be positive and it is reasonable to assume that +ve Cys or Hcys at pH 1.4 will experience repulsive force. However, TEM images and absorption spectra indicated formation of aggregates including rod-like assembly. An interesting observation was the need for unusually high concentration of analytes (Cys and Hcys) to induce the assembly of CH-AuNPs. We also found time bound variation of the optical properties probably indicating the interaction is kinetically controlled and only a fraction of the analyte molecules having sufficient energy can bind onto the particles. We observed that at elevated temperature, the reaction was faster with a lower concentration of Cys or Hcys. These observations were supported by the classical Derjaguin-Landau-Verwey-Overbeek (DLVO) theory which describes the interparticle interaction and the colloidal stability in solution. Only molecules possessing enough energy to cross this force barrier can cause the aggregation. We also noted a time lag between Cys and Hcys to influence optical properties reflecting the possibility of using this simple approach to discriminate these two clinically relevant molecules. Our observation shows that simple sensing as well as generation of novel nanostructures could be manipulated by a judicious choice of conditions such as stabilizing agents, pH, etc.

  13. Acid-Base Chemistry of White Wine: Analytical Characterisation and Chemical Modelling

    PubMed Central

    Prenesti, Enrico; Berto, Silvia; Toso, Simona; Daniele, Pier Giuseppe

    2012-01-01

    A chemical model of the acid-base properties is optimized for each white wine under study, together with the calculation of their ionic strength, taking into account the contributions of all significant ionic species (strong electrolytes and weak one sensitive to the chemical equilibria). Coupling the HPLC-IEC and HPLC-RP methods, we are able to quantify up to 12 carboxylic acids, the most relevant substances responsible of the acid-base equilibria of wine. The analytical concentration of carboxylic acids and of other acid-base active substances was used as input, with the total acidity, for the chemical modelling step of the study based on the contemporary treatment of overlapped protonation equilibria. New protonation constants were refined (L-lactic and succinic acids) with respect to our previous investigation on red wines. Attention was paid for mixed solvent (ethanol-water mixture), ionic strength, and temperature to ensure a thermodynamic level to the study. Validation of the chemical model optimized is achieved by way of conductometric measurements and using a synthetic “wine” especially adapted for testing. PMID:22566762

  14. Acid-base chemistry of white wine: analytical characterisation and chemical modelling.

    PubMed

    Prenesti, Enrico; Berto, Silvia; Toso, Simona; Daniele, Pier Giuseppe

    2012-01-01

    A chemical model of the acid-base properties is optimized for each white wine under study, together with the calculation of their ionic strength, taking into account the contributions of all significant ionic species (strong electrolytes and weak one sensitive to the chemical equilibria). Coupling the HPLC-IEC and HPLC-RP methods, we are able to quantify up to 12 carboxylic acids, the most relevant substances responsible of the acid-base equilibria of wine. The analytical concentration of carboxylic acids and of other acid-base active substances was used as input, with the total acidity, for the chemical modelling step of the study based on the contemporary treatment of overlapped protonation equilibria. New protonation constants were refined (L-lactic and succinic acids) with respect to our previous investigation on red wines. Attention was paid for mixed solvent (ethanol-water mixture), ionic strength, and temperature to ensure a thermodynamic level to the study. Validation of the chemical model optimized is achieved by way of conductometric measurements and using a synthetic "wine" especially adapted for testing.

  15. Lewis base activation of Lewis acids: development of a Lewis base catalyzed selenolactonization.

    PubMed

    Denmark, Scott E; Collins, William R

    2007-09-13

    The concept of Lewis base activation of Lewis acids has been applied to the selenolactonization reaction. Through the use of substoichiometric amounts of Lewis bases with "soft" donor atoms (S, Se, P) significant rate enhancements over the background reaction are seen. Preliminary mechanistic investigations have revealed the resting state of the catalyst as well as the significance of a weak Brønsted acid promoter.

  16. Crystal and molecular structure of eight organic acid-base adducts from 2-methylquinoline and different acids

    NASA Astrophysics Data System (ADS)

    Zhang, Jing; Jin, Shouwen; Tao, Lin; Liu, Bin; Wang, Daqi

    2014-08-01

    Eight supramolecular complexes with 2-methylquinoline and acidic components as 4-aminobenzoic acid, 2-aminobenzoic acid, salicylic acid, 5-chlorosalicylic acid, 3,5-dinitrosalicylic acid, malic acid, sebacic acid, and 1,5-naphthalenedisulfonic acid were synthesized and characterized by X-ray crystallography, IR, mp, and elemental analysis. All of the complexes are organic salts except compound 2. All supramolecular architectures of 1-8 involve extensive classical hydrogen bonds as well as other noncovalent interactions. The results presented herein indicate that the strength and directionality of the classical hydrogen bonds (ionic or neutral) between acidic components and 2-methylquinoline are sufficient to bring about the formation of binary organic acid-base adducts. The role of weak and strong noncovalent interactions in the crystal packing is ascertained. These weak interactions combined, the complexes 1-8 displayed 2D-3D framework structure.

  17. Total serum homocysteine as an indicator of vitamin B12 and folate status

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chu, R.C.; Hall, C.A.

    1988-10-01

    Presented is a modification of an assay for total serum homocysteine (Hcy) in which the Hcy plus radioactive adenosine is converted enzymatically to labeled S-adenosylhomocysteine (AdoHcy). The modifications included a commerical source for the AdoHcy hydrolase, adenosine labeled with either /sup 14/C or /sup 3/H, and separation of the AdoHcy by thin layer chromatography. The assay was sensitive to 25 pmol. Hcy levels in sera from 18 controls ranged from 6.9 to 12.1 mumol/L with a mean of 9.1 and a SD of 1.5 mumol/L. The total serum Hcy was increased in vitamin B12 and folate deficiency. The level wasmore » high in congenital defects of vitamin B12 metabolism, blocking the methylation of Hcy regardless of the serum vitamin B12 levels, but was normal in the absence of tissue deficiency even if the serum vitamin B12 levels were low. The procedure has been found practical in two years of use and requires only 0.1 mL of serum.« less

  18. A Clinical Approach to the Diagnosis of Acid-Base Disorders

    PubMed Central

    Bear, Robert A.

    1986-01-01

    The ability to diagnose and manage acid-base disorders rapidly and effectively is essential to the care of critically ill patients. This article presents an approach to the diagnosis of pure and mixed acid-base disorders, metabolic or respiratory. The approach taken is based on using the law of mass-action equation as it applies to the bicarbonate buffer system (Henderson equation), using sub-classifications for diagnostic purposes of causes of metabolic acidosis and metabolic alkalosis, and using a knowledge of the well-defined and predictable compensatory responses that attempt to limit the change in pH in each of the primary acid-base disorders. PMID:21267134

  19. Nucleic acid-based nanoengineering: novel structures for biomedical applications

    PubMed Central

    Li, Hanying; LaBean, Thomas H.; Leong, Kam W.

    2011-01-01

    Nanoengineering exploits the interactions of materials at the nanometre scale to create functional nanostructures. It relies on the precise organization of nanomaterials to achieve unique functionality. There are no interactions more elegant than those governing nucleic acids via Watson–Crick base-pairing rules. The infinite combinations of DNA/RNA base pairs and their remarkable molecular recognition capability can give rise to interesting nanostructures that are only limited by our imagination. Over the past years, creative assembly of nucleic acids has fashioned a plethora of two-dimensional and three-dimensional nanostructures with precisely controlled size, shape and spatial functionalization. These nanostructures have been precisely patterned with molecules, proteins and gold nanoparticles for the observation of chemical reactions at the single molecule level, activation of enzymatic cascade and novel modality of photonic detection, respectively. Recently, they have also been engineered to encapsulate and release bioactive agents in a stimulus-responsive manner for therapeutic applications. The future of nucleic acid-based nanoengineering is bright and exciting. In this review, we will discuss the strategies to control the assembly of nucleic acids and highlight the recent efforts to build functional nucleic acid nanodevices for nanomedicine. PMID:23050076

  20. Zinc and homocysteine levels in polycystic ovarian syndrome patients with insulin resistance.

    PubMed

    Guler, Ismail; Himmetoglu, Ozdemir; Turp, Ahmet; Erdem, Ahmet; Erdem, Mehmet; Onan, M Anıl; Taskiran, Cagatay; Taslipinar, Mine Yavuz; Guner, Haldun

    2014-06-01

    In this study, our objective was to evaluating the value of serum zinc levels as an etiologic and prognostic marker in patients with polycystic ovarian syndrome. We conducted a prospective study, including 53 women with polycystic ovarian syndrome and 33 healthy controls. We compared serum zinc levels, as well as clinical and metabolic features, of the cases. We also compared serum zinc levels between patients with polycystic ovarian syndrome with insulin resistance. Mean zinc levels were found to be significantly lower in patients with polycystic ovarian syndrome than healthy controls. Multiple logistic regression analysis of significant metabolic variables between polycystic ovarian syndrome and control groups (serum zinc level, body mass index, the ratio of triglyceride/high-density lipoprotein cholesterol, and homocysteine) revealed that zinc level was the most significant variable to predict polycystic ovarian syndrome. Mean serum zinc levels tended to be lower in patients with polycystic ovarian syndrome with impaired glucose tolerance than patients with normal glucose tolerance, but the difference was not statistically significant. In conclusion, zinc deficiency may play a role in the pathogenesis of polycystic ovarian syndrome and may be related with its long-term metabolic complications.

  1. Environmental and Chemical Aging of Fatty-Acid-Based Vinyl Ester Composites

    DTIC Science & Technology

    2011-04-01

    Environmental and Chemical Aging of Fatty- Acid -Based Vinyl Ester Composites by Steven E. Boyd and John J. La Scala ARL-TR-5523 April...2011 Environmental and Chemical Aging of Fatty- Acid -Based Vinyl Ester Composites Steven E. Boyd and John J. La Scala Weapons and Materials...COVERED (From - To) October 2009–September 2010 4. TITLE AND SUBTITLE Environmental and Chemical Aging of Fatty- Acid -Based Vinyl Ester Composites

  2. Medium-term methionine supplementation increases plasma homocysteine but not ADMA and improves blood pressure control in rats fed a diet rich in protein and adequate in folate and choline.

    PubMed

    Mariotti, François; Hammiche, Alexia; Blouet, Clémence; Daré, Sophie; Tomé, Daniel; Huneau, Jean François

    2006-10-01

    Hyperhomocysteinemia (HHcy) is associated with cardiovascular risk, possibly because it increases asymmetric dimethyl-arginine (ADMA), but the general association remains unclear and may vary with nutritional and physiological conditions. We aimed to monitor the effect of methionine supplementation, and subsequent HHcy, on plasma ADMA and hemodynamics in the context of a diet rich in protein and adequate in folic acid and choline. For 6 weeks, rats were fed a 29% protein diet supplemented (M) or not (C) with 8 g/kg L: -methionine. Blood pressure and plasma amino acids, including homocysteine and ADMA, were measured throughout the experiment and additional parameters, including in vivo hemodynamic response to acetylcholine, were measured at week 5-6. As compared to the C diet, the M diet induced a marked HHcy during the first 3 weeks, which lessened at week 5. In contrast, plasma ADMA stayed similar in the C and M diet. Paradoxically, M rats had lower mean and diastolic blood pressure values over the experiment, together with a lower left ventricular mass at week 6, when compared with C rats. No difference was observed between groups regarding vascular reactivity and plasma NOx at week 6. In a context of a diet rich in protein and adequate in methyl donors, rats exhibit a complex adaptation to the medium-term methionine supplementation, with improvement in blood pressure control despite marked HHcy. The lack of increase in plasma ADMA may account for the absence of detrimental effects of HHcy on hemodynamics.

  3. Natural Humic-Acid-Based Phototheranostic Agent.

    PubMed

    Miao, Zhao-Hua; Li, Kai; Liu, Pei-Ying; Li, Zhenglin; Yang, Huanjie; Zhao, Qingliang; Chang, Manli; Yang, Qingzhu; Zhen, Liang; Xu, Cheng-Yan

    2018-04-01

    Humic acids, a major constituent of natural organic carbon resources, are naturally formed through the microbial biodegradation of animal and plant residues. Due to numerous physiologically active groups (phenol, carboxyl, and quinone), the biomedical applications of humic acid have been already investigated across different cultures for several centuries or even longer. In this work, sodium humate, the sodium salt of humic acid, is explored as phototheranostic agent for light-induced photoacoustic imaging and photothermal therapy based on intrinsic absorption in the near-infrared region. The purified colloidal sodium humate exhibits a high photothermal conversion efficiency up to 76.3%, much higher than that of the majority of state-of-the-art photothermal agents including gold nanorods, Cu 9 S 5 nanoparticles, antimonene quantum dots, and black phosphorus quantum dots, leading to obvious photoacoustic enhancement in vitro and in vivo. Besides, highly effective photothermal ablation of HeLa tumor is achieved through intratumoral injection. Impressively, sodium humate reveals ultralow toxicity at the cellular and animal levels. This work promises the great potential of humic acids as light-mediated theranostic agents, thus expanding the application scope of traditional humic acids in biomedical field. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. An off-on fluorescence probe targeting mitochondria based on oxidation-reduction response for tumor cell and tissue imaging

    NASA Astrophysics Data System (ADS)

    Yao, Hanchun; Cao, Li; Zhao, Weiwei; Zhang, Suge; Zeng, Man; Du, Bin

    2017-10-01

    In this study, a tumor-targeting poly( d, l-lactic-co-glycolic acid) (PLGA) loaded "off-on" fluorescent probe nanoparticle (PFN) delivery system was developed to evaluate the region of tumor by off-on fluorescence. The biodegradability of the nanosize PFN delivery system readily released the probe under tumor acidic conditions. The probe with good biocompatibility was used to monitor the intracellular glutathione (GSH) of cancer cells and selectively localize to mitochondria for tumor imaging. The incorporated tumor-targeting probe was based on the molecular photoinduced electron transfer (PET) mechanism preventing fluorescence ("off" state) and could be easily released under tumor acidic conditions. However, the released tumor-targeting fluorescence probe molecule was selective towards GSH with high selectivity and an ultra-sensitivity for the mitochondria of cancer cells and tissues significantly increasing the probe molecule fluorescence signal ("on" state). The tumor-targeting fluorescence probe showed sensitivity to GSH avoiding interference from cysteine and homocysteine. The PFNs could enable fluorescence-guided cancer imaging during cancer therapy. This work may expand the biological applications of PFNs as a diagnostic reagent, which will be beneficial for fundamental research in tumor imaging. [Figure not available: see fulltext.

  5. Amino acid-based zwitterionic polymers: antifouling properties and low cytotoxicity.

    PubMed

    Li, Wenchen; Liu, Qingsheng; Liu, Lingyun

    2014-01-01

    A group of five amino acid containing zwitterionic vinyl monomers, based on serine, lysine, ornithine, glutamic acid, and aspartic acid, respectively, were proposed and developed for potential antifouling applications. Their polymer brushes were grafted on gold chips by surface-initiated photoiniferter-mediated polymerization. We then compared their performance in resisting protein adsorption from full human serum and plasma. All five polymers can reduce protein adsorption by more than 90% compared to the unmodified gold. The ornithine-based and aspartic acid-based poly(methacrylamide) can most strongly resist protein adsorption from serum and plasma, compared to the other three. The ability of surfaces to suppress bacterial adhesion is another criterion in evaluating antifouling properties of materials. Our results show that the five polymer-grafted surfaces can significantly suppress Escherichia coli K12 adhesion to 99% compared to the bare gold surface. The zwitterionic structure of amino acids, with homogenously distributed and balanced positive and negative charges, is responsible for the outstanding antifouling properties. Considering multiple potential applications (e.g. medical devices and drug delivery) of the antifouling materials, we further systematically evaluated the cytotoxicity of both monomers and polymer nanogels for all five materials at various concentrations. Very low cytotoxicity was observed for all tested amino acid-based monomers and nanogels, which is comparable or even lower than the traditional and some newly developed antifouling materials, which might be related to the biomimetic nature of amino acids.

  6. Extraction of domoic acid from seawater and urine using a resin based on 2-(trifluoromethyl)acrylic acid.

    PubMed

    Piletska, Elena V; Villoslada, Fernando Navarro; Chianella, Iva; Bossi, Alessandra; Karim, Kal; Whitcombe, Michael J; Piletsky, Sergey A; Doucette, Gregory J; Ramsdell, John S

    2008-03-03

    A new solid-phase extraction (SPE) matrix with high affinity for the neurotoxin domoic acid (DA) was designed and tested. A computational modelling study led to the selection of 2-(trifluoromethyl)acrylic acid (TFMAA) as a functional monomer capable of imparting affinity towards domoic acid. Polymeric adsorbents containing TFMAA were synthesised and tested in high ionic strength solutions such as urine and seawater. The TFMAA-based polymers demonstrated excellent performance in solid-phase extraction of domoic acid, retaining the toxin while salts and other interfering compounds such as aspartic and glutamic acids were removed by washing and selective elution. It was shown that the TFMAA-based polymer provided the level of purification of domoic acid from urine and seawater acceptable for its quantification by high performance liquid chromatography-mass spectrometry (HPLC-MS) and enzyme-linked immunosorbent assay (ELISA) without any additional pre-concentration and purification steps.

  7. Efficient production of free fatty acids from ionic liquid-based acid- or enzyme-catalyzed bamboo hydrolysate.

    PubMed

    Mi, Le; Qin, Dandan; Cheng, Jie; Wang, Dan; Li, Sha; Wei, Xuetuan

    2017-03-01

    Two engineered Escherichia coli strains, DQ101 (MG1655 fadD - )/pDQTES and DQ101 (MG1655 fadD - )/pDQTESZ were constructed to investigate the free fatty acid production using ionic liquid-based acid- or enzyme-catalyzed bamboo hydrolysate as carbon source in this study. The plasmid, pDQTES, carrying an acyl-ACP thioesterase 'TesA of E. coli in pTrc99A was constructed firstly, and then (3R)-hydroxyacyl-ACP dehydratase was ligated after the TesA to give the plasmid pDQTESZ. These two strains exhibited efficient fatty acid production when glucose was used as the sole carbon source, with a final concentration of 2.45 and 3.32 g/L, respectively. The free fatty acid production of the two strains on xylose is not as efficient as that on glucose, which was 2.32 and 2.96 g/L, respectively. For mixed sugars, DQ101 (MG1655 fadD - )-based strains utilized glucose and pentose sequentially under the carbon catabolite repression (CCR) regulation. The highest total FFAs concentration from the mixed sugar culture reached 2.81 g/L by DQ101 (MG1655 fadD - )/pDQTESZ. Furthermore, when ionic liquid-based enzyme-catalyzed bamboo hydrolysate was used as the carbon source, the strain DQ101 (MG1655 fadD - )/pDQTESZ could produce 1.23 g/L FFAs with a yield of 0.13 g/g, and while it just produced 0.65 g/L free fatty acid with the ionic liquid-based acid-catalyzed bamboo hydrolysate as the feedstock. The results suggested that enzymatic catalyzed bamboo hydrolysate with ionic liquid pretreatment could serve as an efficient feedstock for free fatty acid production.

  8. [What is the contribution of Stewart's concept in acid-base disorders analysis?].

    PubMed

    Quintard, H; Hubert, S; Ichai, C

    2007-05-01

    To explain the different approaches for interpreting acid-base disorders; to develop the Stewart model which offers some advantages for the pathophysiological understanding and the clinical interpretation of acid-base imbalances. Record of french and english references from Medline data base. The keywords were: acid-base balance, hyperchloremic acidosis, metabolic acidosis, strong ion difference, strong ion gap. Data were selected including prospective and retrospective studies, reviews, and case reports. Acid-base disorders are commonly analysed by using the traditional Henderson-Hasselbalch approach which attributes the variations in plasma pH to the modifications in plasma bicarbonates or PaCO2. However, this approach seems to be inadequate because bicarbonates and PaCO2 are completely dependent. Moreover, it does not consider the role of weak acids such as albuminate, in the determination of plasma pH value. According to the Stewart concept, plasma pH results from the degree of plasma water dissociation which is determined by 3 independent variables: 1) strong ion difference (SID) which is the difference between all the strong plasma cations and anions; 2) quantity of plasma weak acids; 3) PaCO2. Thus, metabolic acid-base disorders are always induced by a variation in SID (decreased in acidosis) or in weak acids (increased in acidosis), whereas respiratory disorders remains the consequence of a change in PaCO2. These pathophysiological considerations are important to analyse complex acid-base imbalances in critically ill patients. For example, due to a decrease in weak acids, hypoalbuminemia increases SID which may counter-balance a decrease in pH and an elevated anion gap. Thus if using only traditional tools, hypoalbuminemia may mask a metabolic acidosis, because of a normal pH and a normal anion gap. In this case, the association of metabolic acidosis and alkalosis is only expressed by respectively a decreased SID and a decreased weak acids concentration

  9. NPIDB: Nucleic acid-Protein Interaction DataBase.

    PubMed

    Kirsanov, Dmitry D; Zanegina, Olga N; Aksianov, Evgeniy A; Spirin, Sergei A; Karyagina, Anna S; Alexeevski, Andrei V

    2013-01-01

    The Nucleic acid-Protein Interaction DataBase (http://npidb.belozersky.msu.ru/) contains information derived from structures of DNA-protein and RNA-protein complexes extracted from the Protein Data Bank (3846 complexes in October 2012). It provides a web interface and a set of tools for extracting biologically meaningful characteristics of nucleoprotein complexes. The content of the database is updated weekly. The current version of the Nucleic acid-Protein Interaction DataBase is an upgrade of the version published in 2007. The improvements include a new web interface, new tools for calculation of intermolecular interactions, a classification of SCOP families that contains DNA-binding protein domains and data on conserved water molecules on the DNA-protein interface.

  10. Molecular mechanisms of acid-base sensing by the kidney.

    PubMed

    Brown, Dennis; Wagner, Carsten A

    2012-05-01

    A major function of the kidney is to collaborate with the respiratory system to maintain systemic acid-base status within limits compatible with normal cell and organ function. It achieves this by regulating the excretion and recovery of bicarbonate (mainly in the proximal tubule) and the secretion of buffered protons (mainly in the distal tubule and collecting duct). How proximal tubular cells and distal professional proton transporting (intercalated) cells sense and respond to changes in pH, bicarbonate, and CO(2) status is a question that has intrigued many generations of renal physiologists. Over the past few years, however, some candidate molecular pH sensors have been identified, including acid/alkali-sensing receptors (GPR4, InsR-RR), kinases (Pyk2, ErbB1/2), pH-sensitive ion channels (ASICs, TASK, ROMK), and the bicarbonate-stimulated adenylyl cyclase (sAC). Some acid-sensing mechanisms in other tissues, such as CAII-PDK2L1 in taste buds, might also have similar roles to play in the kidney. Finally, the function of a variety of additional membrane channels and transporters is altered by pH variations both within and outside the cell, and the expression of several metabolic enzymes are altered by acid-base status in parts of the nephron. Thus, it is possible that a master pH sensor will never be identified. Rather, the kidney seems equipped with a battery of molecules that scan the epithelial cell environment to mount a coordinated physiologic response that maintains acid-base homeostasis. This review collates current knowledge on renal acid-base sensing in the context of a whole organ sensing and response process.

  11. Nucleic acid aptamer-based methods for diagnosis of infections.

    PubMed

    Park, Ki Soo

    2018-04-15

    Infectious diseases are a serious global problem, which not only take an enormous human toll but also incur tremendous economic losses. In combating infectious diseases, rapid and accurate diagnostic tests are required for pathogen identification at the point of care (POC). In this review, investigations of diagnostic strategies for infectious diseases that are based on aptamers, especially nucleic acid aptamers, oligonucleotides that have high affinities and specificities toward their targets, are described. Owing to their unique features including low cost of production, easy chemical modification, high chemical stability, reproducibility, and low levels of immunogenicity and toxicity, aptamers have been widely utilized as bio-recognition elements (bio-receptors) for the development of infection diagnostic systems. We discuss nucleic acid aptamer-based methods that have been developed for diagnosis of infections using a format that organizes discussion according to the target pathogenic analytes including toxins or proteins, whole cells and nucleic acids. Also included is, a summary of recent advances made in the sensitive detection of pathogenic bacteria utilizing the isothermal nucleic acid amplification method. Lastly, a nucleic acid aptamer-based POC system is described and future directions of studies in this area are discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Improving Pharmacy Students' Understanding and Long-term Retention of Acid-Base Chemistry

    PubMed Central

    2007-01-01

    Despite repeated exposure to the principles underlying the behavior of organic acids and bases in aqueous solution, some pharmacy students remain confused about the topic of acid-base chemistry. Since a majority of organic drug molecules have acid-base character, the ability to predict their reactivity and the extent to which they will ionize in a given medium is paramount to students' understanding of essentially all aspects of drug action in vivo and in vitro. This manuscript presents a medicinal chemistry lesson in the fundamentals of acid-base chemistry that many pharmacy students have found enlightening and clarifying PMID:19503706

  13. How Do Undergraduate Students Conceptualize Acid-Base Chemistry? Measurement of a Concept Progression

    ERIC Educational Resources Information Center

    Romine, William L.; Todd, Amber N.; Clark, Travis B.

    2016-01-01

    We developed and validated a new instrument, called "Measuring Concept progressions in Acid-Base chemistry" (MCAB) and used it to better understand the progression of undergraduate students' understandings about acid-base chemistry. Items were developed based on an existing learning progression for acid-base chemistry. We used the Rasch…

  14. Jigsaw Cooperative Learning: Acid-Base Theories

    ERIC Educational Resources Information Center

    Tarhan, Leman; Sesen, Burcin Acar

    2012-01-01

    This study focused on investigating the effectiveness of jigsaw cooperative learning instruction on first-year undergraduates' understanding of acid-base theories. Undergraduates' opinions about jigsaw cooperative learning instruction were also investigated. The participants of this study were 38 first-year undergraduates in chemistry education…

  15. Novel Cysteine-Centered Sulfur Metabolic Pathway in the Thermotolerant Methylotrophic Yeast Hansenula polymorpha

    PubMed Central

    Oh, Doo-Byoung; Kwon, Ohsuk; Lee, Sang Yup; Sibirny, Andriy A.; Kang, Hyun Ah

    2014-01-01

    In yeast and filamentous fungi, sulfide can be condensed either with O-acetylhomoserine to generate homocysteine, the precursor of methionine, or with O-acetylserine to directly generate cysteine. The resulting homocysteine and cysteine can be interconverted through transsulfuration pathway. Here, we systematically analyzed the sulfur metabolic pathway of the thermotolerant methylotrophic yeast Hansenula polymorpha, which has attracted much attention as an industrial yeast strain for various biotechnological applications. Quite interestingly, the detailed sulfur metabolic pathway of H. polymorpha, which was reconstructed based on combined analyses of the genome sequences and validation by systematic gene deletion experiments, revealed the absence of de novo synthesis of homocysteine from inorganic sulfur in this yeast. Thus, the direct biosynthesis of cysteine from sulfide is the only pathway of synthesizing sulfur amino acids from inorganic sulfur in H. polymorpha, despite the presence of both directions of transsulfuration pathway Moreover, only cysteine, but no other sulfur amino acid, was able to repress the expression of a subset of sulfur genes, suggesting its central and exclusive role in the control of H. polymorpha sulfur metabolism. 35S-Cys was more efficiently incorporated into intracellular sulfur compounds such as glutathione than 35S-Met in H. polymorpha, further supporting the cysteine-centered sulfur pathway. This is the first report on the novel features of H. polymorpha sulfur metabolic pathway, which are noticeably distinct from those of other yeast and filamentous fungal species. PMID:24959887

  16. Fermented probiotic beverages based on acid whey.

    PubMed

    Skryplonek, Katarzyna; Jasińska, Małgorzata

    2015-01-01

    Production of fermented probiotic beverages can be a good method for acid whey usage. The obtained products combine a high nutritional value of whey with health benefits claimed for probiotic bacteria. The aim of the study was to define quality properties of beverages based on fresh acid whey and milk with addition of buttermilk powder or sweet whey powder. Samples were inoculated with two strains of commercial probiotic cultures: Lactobacillus acidophilus La-5 or Bifidobacterium animalis Bb-12. After fermentation, samples were stored at refrigerated conditions. After 1, 4, 7, 14 and 21 days sensory characteristics, hardness, acetaldehyde content, titratable acidity, pH acidity and count of bacteria cells were evaluated. Throughout all storage period, the number of bacteria was higher than 8 log cfu/ml in the all samples. Beverages with La-5 strain had higher hardness and acidity, whilst samples with Bb-12 contained more acetaldehyde. Samples with buttermilk powder had better sensory properties than with sweet whey powder. Obtained products made of acid whey combined with milk and fortified with buttermilk powder or sweet whey powder, are good medium for growth and survival of examined probiotic bacteria strains. The level of bacteria was sufficient to provide health benefits to consumers.

  17. Food composition and acid-base balance: alimentary alkali depletion and acid load in herbivores.

    PubMed

    Kiwull-Schöne, Heidrun; Kiwull, Peter; Manz, Friedrich; Kalhoff, Hermann

    2008-02-01

    Alkali-enriched diets are recommended for humans to diminish the net acid load of their usual diet. In contrast, herbivores have to deal with a high dietary alkali impact on acid-base balance. Here we explore the role of nutritional alkali in experimentally induced chronic metabolic acidosis. Data were collected from healthy male adult rabbits kept in metabolism cages to obtain 24-h urine and arterial blood samples. Randomized groups consumed rabbit diets ad libitum, providing sufficient energy but variable alkali load. One subgroup (n = 10) received high-alkali food and approximately 15 mEq/kg ammonium chloride (NH4Cl) with its drinking water for 5 d. Another group (n = 14) was fed low-alkali food for 5 d and given approximately 4 mEq/kg NH4Cl daily for the last 2 d. The wide range of alimentary acid-base load was significantly reflected by renal base excretion, but normal acid-base conditions were maintained in the arterial blood. In rabbits fed a high-alkali diet, the excreted alkaline urine (pH(u) > 8.0) typically contained a large amount of precipitated carbonate, whereas in rabbits fed a low-alkali diet, both pH(u) and precipitate decreased considerably. During high-alkali feeding, application of NH4Cl likewise decreased pH(u), but arterial pH was still maintained with no indication of metabolic acidosis. During low-alkali feeding, a comparably small amount of added NH4Cl further lowered pH(u) and was accompanied by a significant systemic metabolic acidosis. We conclude that exhausted renal base-saving function by dietary alkali depletion is a prerequisite for growing susceptibility to NH4Cl-induced chronic metabolic acidosis in the herbivore rabbit.

  18. The effect of antiepileptic drugs on vitamin B12 metabolism.

    PubMed

    Aslan, K; Bozdemir, H; Unsal, C; Güvenc, B

    2008-02-01

    The effects of antiepileptic drugs (AED) on the serum concentration of vitamin B12, folic acid and homocysteine (HMC), and erythrocyte folic acid levels were determined in 45 epileptic patients (30 women, 15 men; mean age 31.7 years) and 23 healthy volunteers (control group; 18 women, five men; mean age 33.4 years). All patients were either on carbamazepine (CMZ), oxcarbazepine (OXZ), or valporate (VP) monotherapy. Serum vitamin B12 levels were low in 17.8% of patients and 8.7% of the controls (P = 0.299). Serum homocysteine levels were high in 17.8% of the patients (P = 0.008). Fifty percent of the patients who had hyperhomocysteinemia, and 75% of the patients who had low serum vitamin B12 level were on CMZ monotherapy. Peripheral blood smears showed hypersegmented neutrophils and macrocytosis in 13.3%, hypochromia and microcytosis in 26.7%, acanthocytes in 2.2%, and thrombocytosis in 2.2% of all patients. The control group had normal peripheral blood smears, except in four cases that showed hypocromia and microcytosis. Long-term administration of AED may cause elevation of homocysteine and development of subnormal serum vitamin B12 levels. Peripheral blood smear abnormalities were frequently seen in patients receiving antiepileptic treatment (P = 0.022), particularly in patients on CMZ monotherapy (P = 0.281). However, homocysteine, vitamin B12, folic acid levels and peripheral blood smear findings did not correlate with the drugs used (P = 0.665, 0.336, 0.249 for CMZ, OXZ, VP, respectively).

  19. Biomedical research of novel biodegradable copoly(amino acid)s based on 6-aminocaproic acid and L-proline.

    PubMed

    Zhang, Weipeng; Shao, Jianmin

    2010-08-01

    The biomedical properties of novel biodegradable copoly(amino acid)s based on 6-aminocaproic acid and L-proline were analyzed in this article. The cytotoxicity of the copolymer films was tested in vitro using human embryonic kidney (HEK) 293 cells. The cell proliferation, cell cycle, cell apoptosis, and hemolysis of the polymers were also investigated. No significant cytotoxic response was detected statistically by cytotoxicity assay, and the results of cell apoptosis and cell cycle showed that there were no statistically significant differences in them. Generally, the cells spread and grew well on polymer film. Meanwhile, the extent of hemolysis on the polymers was acceptable. Evaluation of cytotoxicity by cell cycle and apoptosis as a supplementary assay is correspondingly discussed in this article. (c) 2010 Wiley Periodicals, Inc.

  20. Homocysteine remethylation in broilers fed surfeit choline or betaine and varying levels and sources of methionine from eight to twenty-two days of age.

    PubMed

    Pillai, P B; Fanatico, A C; Blair, M E; Emmert, J L

    2006-10-01

    Experiments were conducted to assess the effect of surfeit choline (CHOL) or betaine (BET) on growth performance and homocysteine (HCY) remethylation of young broilers fed graded levels of DL-Met (DLM) or 2-hydroxy-4-(methylthio) butanoic acid (HMB). In Experiment 1, a corn-peanut meal diet deficient in Met (0.25% digestible) and Cys (0.28% digestible) was fed; treatments were formulated to contain graded levels (0, 0.04, or 0.08%) of Met from DLM or 0.04% HMB (adjusted for 88% purity) that were fed in the presence or absence of surfeit isomethyl CHOL (0.25%) or BET (0.28%). In Experiment 2, identical treatments were used, but an additional level of HMB (0.08%) was fed, and the basal diet was adequate in Cys (0.43% digestible). There was no overall effect of CHOL or BET on growth performance in Experiments 1 and 2 (P > 0.05); a significant improvement (P < 0.05) in weight gain and feed efficiency did occur with CHOL and BET addition to the basal diet in Experiment 2. In both experiments, weight gain increased linearly (P < 0.05) with the addition of DLM or HMB. Slope ratio methodology was used to assess HMB efficacy in Experiment 2. In the presence of adequate Cys, HMB efficacy was 81.3%; addition of surfeit BET or CHOL had minimal effect on efficacy. The stable isotope study revealed that CHOL and BET addition to diets deficient in Met and Cys or Met alone increased HCY remethylation. It also showed that CHOL and BET have greater influence on folate-dependent remethylation of HCY (via Met synthase) than on BET-dependent remethylation (via BET-HCY methyltransferase) and that levels of CHOL and BET and type of S amino acid deficiency effect remethylation and HMB efficacy.

  1. Thai Grade 11 Students' Alternative Conceptions for Acid-Base Chemistry

    ERIC Educational Resources Information Center

    Artdej, Romklao; Ratanaroutai, Thasaneeya; Coll, Richard Kevin; Thongpanchang, Tienthong

    2010-01-01

    This study involved the development of a two-tier diagnostic instrument to assess Thai high school students' understanding of acid-base chemistry. The acid-base diagnostic test (ABDT) comprising 18 items was administered to 55 Grade 11 students in a science and mathematics programme during the second semester of the 2008 academic year. Analysis of…

  2. Preconception folic acid use modulates estradiol and follicular responses to ovarian stimulation.

    PubMed

    Twigt, John M; Hammiche, Fatima; Sinclair, Kevin D; Beckers, Nicole G; Visser, Jenny A; Lindemans, Jan; de Jong, Frank H; Laven, Joop S E; Steegers-Theunissen, Régine P

    2011-02-01

    Folate is a methyl donor. Availability of folate affects DNA methylation profiles and thereby gene expression profiles. We investigated the effects of low-dose folic acid use (0.4 mg/d) on the ovarian response to mild and conventional ovarian stimulation in women. In a randomized trial among subfertile women, 24 and 26 subjects received conventional and mild ovarian stimulation, respectively. Blood samples were taken during the early follicular phase of the cycle prior to treatment and on the day of human chorionic gonadotropin administration for determination of serum total homocysteine, anti-Müllerian hormone (AMH), estradiol, and folate. Folic acid use was validated by questionnaire and serum folate levels. Preovulatory follicles were visualized, counted, and diameters recorded using transvaginal ultrasound. The relation between folic acid use and ovarian response was assessed using linear regression analysis. Folic acid use modified the ovarian response to ovarian stimulation treatment. The estradiol response was higher in nonfolic acid users receiving conventional treatment [β(interaction) = 0.52 (0.07-0.97); P = 0.03], and this effect was independent of serum AMH levels and the preovulatory follicle count. In the conventional treatment, the mean follicle number was also greater in nonusers compared with the users group (14.1 vs. 8.9, P = 0.03). Low-dose folic acid use attenuates follicular and endocrine responses to conventional stimulation, independent of AMH and follicle count. The nature of this observation suggests that the effect of folic acid is most prominent during early follicle development, affecting immature follicles. Deleterious effects of folate deficiency, like DNA hypomethylation and oxidative stress, can help to explain our observations.

  3. Sulphur-containing Amino Acids: Protective Role Against Free Radicals and Heavy Metals.

    PubMed

    Colovic, Mirjana B; Vasic, Vesna M; Djuric, Dragan M; Krstic, Danijela Z

    2018-01-30

    Sulphur is an abundant element in biological systems, which plays an important role in processes essential for life as a constituent of proteins, vitamins and other crucial biomolecules. The major source of sulphur for humans is plants being able to use inorganic sulphur in the purpose of sulphur-containing amino acids synthesis. Sulphur-containing amino acids include methionine, cysteine, homocysteine, and taurine. Methionine and cysteine are classified as proteinogenic, canonic amino acids incorporated in protein structure. Sulphur amino acids are involved in the synthesis of intracellular antioxidants such as glutathione and N-acetyl cysteine. Moreover, naturally occurring sulphur-containing ligands are effective and safe detoxifying agents, often used in order to prevent toxic metal ions effects and their accumulation in human body. Literature search for peer-reviewed articles was performed using PubMed and Scopus databases, and utilizing appropriate keywords. This review is focused on sulphur-containing amino acids - methionine, cysteine, taurine, and their derivatives - glutathione and N-acetylcysteine, and their defense effects as antioxidant agents against free radicals. Additionally, the protective effects of sulphur-containing ligands against the toxic effects of heavy and transition metal ions, and their reactivation role towards the enzyme inhibition are described. Sulphur-containing amino acids represent a powerful part of cell antioxidant system. Thus, they are essential in the maintenance of normal cellular functions and health. In addition to their worthy antioxidant action, sulphur-containing amino acids may offer a chelating site for heavy metals. Accordingly, they may be supplemented during chelating therapy, providing beneficial effects in eliminating toxic metals. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  4. Low-Dose Creatine Supplementation Lowers Plasma Guanidinoacetate, but Not Plasma Homocysteine, in a Double-Blind, Randomized, Placebo-Controlled Trial123

    PubMed Central

    Peters, Brandilyn A; Hall, Megan N; Liu, Xinhua; Parvez, Faruque; Siddique, Abu B; Shahriar, Hasan; Uddin, Mohammad Nasir; Islam, Tariqul; Ilievski, Vesna; Graziano, Joseph H; Gamble, Mary V

    2015-01-01

    Background: Creatine synthesis from guanidinoacetate consumes ∼50% of s-adenosylmethionine (SAM)–derived methyl groups, accounting for an equivalent proportion of s-adenosylhomocysteine (SAH) and total homocysteine (tHcys) synthesis. Dietary creatine inhibits the synthesis of guanidinoacetate, thereby lowering plasma tHcys in rats. Objective: We tested the hypotheses that creatine supplementation lowers plasma guanidinoacetate, increases blood SAM, lowers blood SAH, and lowers plasma tHcys. Methods: Bangladeshi adults were randomly assigned to receive 1 of 4 treatments for 12 wk: placebo (n = 101), 3 g/d creatine (Cr; n = 101), 400 μg/d folic acid (FA; n = 153), or 3 g/d creatine plus 400 μg/d folic acid (Cr+FA; n = 103). The outcomes of plasma guanidinoacetate and tHcys, as well as whole blood SAM and SAH, were analyzed at baseline and week 12 by HPLC. Treatment effects of creatine supplementation were examined with the use of the group comparisons of Cr vs. placebo and Cr+FA vs. FA. Results: Plasma guanidinoacetate declined by 10.6% (95% CI: 4.9, 15.9) in the Cr group while increasing nonsignificantly in the placebo group (3.7%; 95% CI: −0.8, 8.5) (Pgroup difference = 0.0002). Similarly, plasma guanidinoacetate declined by 9.0% (95% CI: 3.4, 14.2) in the Cr+FA group while increasing in the FA group (7.0%; 95% CI: 2.0, 12.2) (Pgroup difference < 0.0001). Plasma tHcys declined by 23.4% (95% CI: 19.5, 27.1) and 21.0% (95% CI: 16.4, 25.2) in the FA and Cr+FA groups, respectively (Pgroup difference = 0.41), with no significant changes in the placebo or Cr groups (Pgroup difference = 0.35). A decrease in guanidinoacetate over time was associated with a decrease in tHcys over time in the Cr+FA group (β = 0.30; 95% CI: 0.17, 0.43; P < 0.0001). Conclusions: Our findings indicate that whereas creatine supplementation downregulates endogenous creatine synthesis, this may not on average lower plasma tHcys in humans. However, tHcys did decrease in those participants

  5. High-dose vitamin B6 decreases homocysteine serum levels in patients with schizophrenia and schizoaffective disorders: a preliminary study.

    PubMed

    Miodownik, Chanoch; Lerner, Vladimir; Vishne, Tali; Sela, Ben-Ami; Levine, Joseph

    2007-01-01

    Vitamin B6 plays an essential role in the normal functioning of the central nervous system. Normal homocysteine (Hcy) serum level is maintained by remethylation of Hcy to methionine by enzymes that require folic acid and vitamin B12 and by catabolism to cysteine by a vitamin B6-dependent enzyme. These findings may be consistent with the hypothesis that the vitamin B6 status may influence plasma Hcy levels. The aims of this preliminary study were (1) to determine whether a correlation exists between Hcy and vitamin B6 levels in patients with schizophrenia and schizoaffective disorders and (2) to investigate whether treatment with high-dose vitamin B6 may reduce Hcy levels in these patients. In this preliminary study, we enrolled 11 patients with schizophrenia or schizoaffective disorders (7 men and 4 women; mean age +/- SD, 50 +/- 12 years) receiving high doses of vitamin B6 treatment (1200 mg/d) for 12 weeks. Blood samples for the assessment of pyridoxal-5-phosphate and Hcy serum levels were obtained at baseline and after 12 weeks of treatment. Age was significantly positively correlated with Hcy levels at baseline (r = 0.392, P = 0.004). All other parameters, including diagnosis, disease duration, and pyridoxal-5-phosphate serum level, were not correlated with Hcy serum levels at baseline. After vitamin B6 treatment, Hcy serum levels significantly decreased (14.2 +/- 3.4 vs. 11.8 +/- 2.0 micromol/L, respectively, t = 2.679, P = 0.023); this decrease being statistically significant in men but not in women. High doses of vitamin B6 lead to a decrease in Hcy serum level in male patients with schizophrenia or schizoaffective disorder.

  6. Active-learning versus teacher-centered instruction for learning acids and bases

    NASA Astrophysics Data System (ADS)

    Acar Sesen, Burcin; Tarhan, Leman

    2011-07-01

    Background and purpose: Active-learning as a student-centered learning process has begun to take more interest in constructing scientific knowledge. For this reason, this study aimed to investigate the effectiveness of active-learning implementation on high-school students' understanding of 'acids and bases'. Sample The sample of this study was 45 high-school students (average age 17 years) from two different classes, which were randomly assigned to the experimental (n = 21) and control groups (n = 25), in a high school in Turkey. Design and methods A pre-test consisting of 25 items was applied to both experimental and control groups before the treatment in order to identify student prerequisite knowledge about their proficiency for learning 'acids and bases'. A one-way analysis of variance (ANOVA) was conducted to compare the pre-test scores for groups and no significant difference was found between experimental (ME = 40.14) and control groups (MC = 41.92) in terms of mean scores (F 1,43 = 2.66, p > 0.05). The experimental group was taught using an active-learning curriculum developed by the authors and the control group was taught using traditional course content based on teacher-centered instruction. After the implementation, 'Acids and Bases Achievement Test' scores were collected for both groups. Results ANOVA results showed that students' 'Acids and Bases Achievement Test' post-test scores differed significantly in terms of groups (F 1,43 = 102.53; p < 0.05). Additionally, in this study 54 misconceptions, 14 of them not reported in the literature before, were observed in the following terms: 'acid and base theories'; 'metal and non-metal oxides'; 'acid and base strengths'; 'neutralization'; 'pH and pOH'; 'hydrolysis'; 'acid-base equilibrium'; 'buffers'; 'indicators'; and 'titration'. Based on the achievement test and individual interview results, it was found that high-school students in the experimental group had fewer misconceptions and understood the

  7. Design of cinnamaldehyde amino acid Schiff base compounds based on the quantitative structure–activity relationship

    Treesearch

    Hui Wang; Mingyue Jiang; Shujun Li; Chung-Yun Hse; Chunde Jin; Fangli Sun; Zhuo Li

    2017-01-01

    Cinnamaldehyde amino acid Schiff base (CAAS) is a new class of safe, bioactive compounds which could be developed as potential antifungal agents for fungal infections. To design new cinnamaldehyde amino acid Schiff base compounds with high bioactivity, the quantitative structure–activity relationships (QSARs) for CAAS compounds against Aspergillus niger (A. niger) and...

  8. Syntheses and structure characterization of ten acid-base hybrid crystals based on N-containing aromatic brønsted bases and mineral acids

    NASA Astrophysics Data System (ADS)

    Lin, Zhihao; Jin, Shouwen; Li, Xiaoliang; Xiao, Xiao; Hu, Kaikai; Guo, Ming; Chi, Xinchen; Liu, Hui; Wang, Daqi

    2017-10-01

    Cocrystallization of the aromatic brønsted bases with a series of mineral acids gave a total of ten hybrid salts with the compositions: (2-methylquinoline)2: (hydrochloride acid): 3H2O [(HL1)+. (L1)·· (Cl-) · (H2O)3] (1), (6-bromobenzo[d]thiazol-2-amine): (hydrochloride acid) [(HL2)+. (Cl-)] (2), (6-bromobenzo[d]thiazol-2-amine): (nitric acid) [(HL2)+. (NO3-)] (3), (6-bromobenzo[d]thiazol-2-amine): (sulfuric acid) [(HL2)+ · (HSO4)-] (4), (6-bromobenzo[d]thiazol-2-amine): (phosphoric acid) [(HL2)+ · (H2PO4)-] (5), (5,7-dimethyl-1,8-naphthyridine-2-amine): (hydrochloride acid): 3H2O [(HL3)+ · (Cl-) (H2O)3] (6), (5,7-dimethyl-1,8-naphthyridine-2-amine): (hydrobromic acid): CH3OH [(HL3)+ · (Br)- · CH3OH] (7), (5,7-dimethyl-1,8-naphthyridine-2-amine): (sulfuric acid): H2O [(HL3)+ · (HSO4)- · H2O] (8), (2-aminophenol): (phosphoric acid) [(HL4)+ · (H2PO4)-] (9), and (2-amino-4-chlorophenol): (phosphoric acid) [(HL5)+ · (H2PO4)-] (10). The ten salts have been characterized by X-ray diffraction analysis, IR, and elemental analysis, and the melting points of all the salts were also reported. And their structural and supramolecular aspects are fully analyzed. The result reveals that among the ten investigated crystals the ring N of the heterocycle or the NH2 in the aminophenol are protonated when the acids are deprotonated, and the crystal packing is interpreted in terms of the strong charge-assisted classical hydrogen bonds between the NH+/NH3+ and deprotonated acidic groups. Further analysis of the crystal packing of the salts indicated that a different family of additional CHsbnd O, CHsbnd Cl, CH3sbnd N, CH3sbnd O, CHsbnd Br, CH3sbnd Br, Brsbnd Cl, Clsbnd S, Osbnd S, Osbnd O, Brsbnd S, Hsbnd H, and π-π associations contribute to the stabilization and expansion of the total high-dimensional frameworks. For the coexistence of the various weak nonbonding interactions these structures adopted homo or hetero supramolecular synthons or both. Some classical

  9. Amino acid-based dithiazines: synthesis and photofragmentation of their benzaldehyde adducts.

    PubMed

    Kurchan, Alexei N; Kutateladze, Andrei G

    2002-11-14

    Alpha-amino acids and GABA are functionalized with dithiazine rings via reaction with sodium hydrosulfide in aqueous formaldehyde. The resulting dithiazines are lithiated at -78 degrees C and reacted with benzaldehyde furnishing amino acid-based 2,5-bis-substituted dithiazines. These adducts undergo externally sensitized photofragmentation with quantum efficiency comparable to that of the parent dithiane adducts, thus offering a novel approach to amino acid-based photolabile tethers. [reaction: see text

  10. High Performance Fatty Acid-Based Vinyl Ester Resin for Liquid Molding

    DTIC Science & Technology

    2007-07-01

    High Performance Fatty Acid -Based Vinyl Ester Resin for Liquid Molding by Xing Geng, John J. La Scala, James M. Sands, and Giuseppe R...it to the originator. Army Research Laboratory Aberdeen Proving Ground, MD 21005-5069 ARL-RP-184 July 2007 High Performance Fatty Acid ...CONTRACT NUMBER 5b. GRANT NUMBER 4. TITLE AND SUBTITLE High Performance Fatty Acid -Based Vinyl Ester Resin for Liquid Molding 5c. PROGRAM

  11. Strong ion calculator--a practical bedside application of modern quantitative acid-base physiology.

    PubMed

    Lloyd, P

    2004-12-01

    To review acid-base balance by considering the physical effects of ions in solution and describe the use of a calculator to derive the strong ion difference and Atot and strong ion gap. A review of articles reporting on the use of strong ion difference and Atot in the interpretation of acid base balance. Tremendous progress has been made in the last decade in our understanding of acid-base physiology. We now have a quantitative understanding of the mechanisms underlying the acidity of an aqueous solution. We can now predict the acidity given information about the concentration of the various ion-forming species within it. We can predict changes in acid-base status caused by disturbance of these factors, and finally, we can detect unmeasured anions with greater sensitivity than was previously possible with the anion gap, using either arterial or venous blood sampling. Acid-base interpretation has ceased to be an intuitive and arcane art. Much of it is now an exact computation that can be automated and incorporated into an online hospital laboratory information system. All diseases and all therapies can affect a patient's acid-base status only through the final common pathway of one or more of the three independent factors. With Constable's equations we can now accurately predict the acidity of plasma. When there is a discrepancy between the observed and predicted acidity we can deduce the net concentration of unmeasured ions to account for the difference.

  12. Metal active site elasticity linked to activation of homocysteine in methionine synthases

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Koutmos, Markos; Pejchal, Robert; Bomer, Theresa M.

    2008-04-02

    Enzymes possessing catalytic zinc centers perform a variety of fundamental processes in nature, including methyl transfer to thiols. Cobalamin-independent (MetE) and cobalamin-dependent (MetH) methionine synthases are two such enzyme families. Although they perform the same net reaction, transfer of a methyl group from methyltetrahydrofolate to homocysteine (Hcy) to form methionine, they display markedly different catalytic strategies, modular organization, and active site zinc centers. Here we report crystal structures of zinc-replete MetE and MetH, both in the presence and absence of Hcy. Structural investigation of the catalytic zinc sites of these two methyltransferases reveals an unexpected inversion of zinc geometry uponmore » binding of Hcy and displacement of an endogenous ligand in both enzymes. In both cases a significant movement of the zinc relative to the protein scaffold accompanies inversion. These structures provide new information on the activation of thiols by zinc-containing enzymes and have led us to propose a paradigm for the mechanism of action of the catalytic zinc sites in these and related methyltransferases. Specifically, zinc is mobile in the active sites of MetE and MetH, and its dynamic nature helps facilitate the active site conformational changes necessary for thiol activation and methyl transfer.« less

  13. Plasma homocysteine involved in methylation and expression of thrombomodulin in cerebral infarction.

    PubMed

    Yang, Zhifu; Wang, Lizhen; Zhang, Wei; Wang, Xinxin; Zhou, Shengnian

    2016-05-13

    Homocysteine (Hcy) regulates endothelial injury and methylation status of key genes in cerebral ischemia. Thrombomodulin (TM) may be protective against cerebral ischemia by downregulating coagulation. However, it remains unclear whether Hcy involved in methylation and expression of TM in cerebral infarction (CI). Here, we find patients with cerebral infarction had a higher TM methylation level than controls (74.2% vs 47.5%, X(2) = 14.724, P = 0.00), which are positively correlated with plasma levels of tHcy (r = 0.701, P = 0.00) and negatively related to mRNA expression of TM (r = -0.711, P = 0.00). Plasma levels of tHcy (t = 7.566, P = 0.00) and sTM (t = 17.268, P = 0.00) are significantly higher in cases than in controls. Our data indicate hyperhomocysteine leads to hypermethylation of the TM gene and further induces TM gene silencing, which may play an important role in the occurrence and development of CI. Plasma higher concentrations of sTM in cases are not caused by TM expression and may be only a result of Hcy induced endothelial injury. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. A Comparison of Different Teaching Designs of "Acids and Bases" Subject

    ERIC Educational Resources Information Center

    Ültay, Neslihan; Çalik, Muammer

    2016-01-01

    Inability to link the acid-base concepts with daily life phenomena (as contexts) highlights the need for further research on the context-based acid-base chemistry. In this vein, the aim of this study is to investigate the effects of different teaching designs (REACT strategy, 5Es learning model and traditional (existing) instruction) relevant with…

  15. Low serum vitamin B12 is associated with recurrent pregnancy loss in Syrian women.

    PubMed

    Hübner, Ulrich; Alwan, Ahmad; Jouma, Muhidin; Tabbaa, Mohammad; Schorr, Heike; Herrmann, Wolfgang

    2008-01-01

    Hyperhomocysteinemia and B-vitamin deficiency are associated with recurrent abortion. Recent studies have not investigated functional markers of vitamin B12 deficiency, such as methylmalonic acid. A total of 43 consecutive Syrian women with unexplained recurrent abortion and 32 pregnant controls were enrolled in the study. Serum folate, vitamin B12, methylmalonic acid and plasma homocysteine were determined. Vitamin B12 was significantly decreased in patients with recurrent abortion compared to controls (mean concentrations 197 vs. 300 pg/mL, p=0.004). The lowest mean serum vitamin B12 (172 pg/mL) was observed in primary aborters. Homocysteine was elevated in aborters in comparison to controls (8.3 vs. 7.1 micromol/L, p=0.093). Folate and methylmalonic acid did not differ significantly between the study groups. A highly significant correlation between homocysteine and methylmalonic acid and vitamin B12 was observed only in patients but not in controls (p<0.001 and p=0.002, respectively). In the logistic regression model, only serum vitamin B12 emerged with a significant odds ratio. The results confirm low serum vitamin B12 in recurrent abortion patients. However, methylmalonic acid did not support that functional vitamin B12 plays a role in this group. This unexpected result might be due to a decrease of the metabolically inert vitamin B12 fraction (holohaptocorrin) or confounding factors. Further studies are necessary to investigate the role of vitamin B12 deficiency in recurrent abortion.

  16. Conformational Behaviour of Azasugars Based on Mannuronic Acid.

    PubMed

    van Rijssel, Erwin R; Janssen, Antonius P A; Males, Alexandra; Davies, Gideon J; van der Marel, Gijsbert A; Overkleeft, Herman S; Codée, Jeroen D C

    2017-07-04

    A set of mannuronic-acid-based iminosugars, consisting of the C-5-carboxylic acid, methyl ester and amide analogues of 1deoxymannorjirimicin (DMJ), was synthesised and their pH-dependent conformational behaviour was studied. Under acidic conditions the methyl ester and the carboxylic acid adopted an "inverted" 1 C 4 chair conformation as opposed to the "normal" 4 C 1 chair at basic pH. This conformational change is explained in terms of the stereoelectronic effects of the ring substituents and it parallels the behaviour of the mannuronic acid ester oxocarbenium ion. Because of this solution-phase behaviour, the mannuronic acid ester azasugar was examined as an inhibitor for a Caulobacter GH47 mannosidase that hydrolyses its substrates by way of a reaction itinerary that proceeds through a 3 H 4 transition state. No binding was observed for the mannuronic acid ester azasugar, but sub-atomic resolution data were obtained for the DMJ⋅CkGH47 complex, showing two conformations- 3 S 1 and 1 C 4 -for the DMJ inhibitor. © 2017 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

  17. Characteristics of weak base-induced vacuoles formed around individual acidic organelles.

    PubMed

    Hiruma, Hiromi; Kawakami, Tadashi

    2011-01-01

    We have previously found that the weak base 4-aminopyridine induces Brownian motion of acidic organelles around which vacuoles are formed, causing organelle traffic disorder in neurons. Our present study investigated the characteristics of vacuoles induced by weak bases (NH(4)Cl, aminopyridines, and chloroquine) using mouse cells. Individual vacuoles included acidic organelles identified by fluorescent protein expression. Mitochondria and actin filaments were extruded outside the vacuoles, composing the vacuole rim. Staining with amine-reactive fluorescence showed no protein/amino acid content in vacuoles. Thus, serous vacuolar contents are probably partitioned by viscous cytosol, other organelles, and cytoskeletons, but not membrane. The weak base (chloroquine) was immunochemically detected in intravacuolar organelles, but not in vacuoles. Early vacuolization was reversible, but long-term vacuolization caused cell death. The vacuolization and cell death were blocked by the vacuolar H(+)-ATPase inhibitor and Cl--free medium. Staining with LysoTracker or LysoSensor indicated that intravacuolar organelles were strongly acidic and vacuoles were slightly acidic. This suggests that vacuolization is caused by accumulation of weak base and H(+) in acidic organelles, driven by vacuolar H(+)-ATPase associated with Cl(-) entering, and probably by subsequent extrusion of H(+) and water from organelles to the surrounding cytoplasm.

  18. Surface acid-base behaviors of Chinese loess.

    PubMed

    Chu, Zhaosheng; Liu, Wenxin; Tang, Hongxiao; Qian, Tianwei; Li, Shushen; Li, Zhentang; Wu, Guibin

    2002-08-15

    Acid-base titration was applied to investigate the surface acid-base properties of a Chinese loess sample at different ionic strengths. The acidimetric supernatant was regarded as the system blank of titration to correct the influence of particle dissolution on the estimation of proton consumption. The titration behavior of the system blank could be described by the hydrolysis of Al3+ and Si(OH)4 in aqueous solution as well as the production of hydroxyaluminosilicates. The formation of Al-Si species on homogeneous surface sites by hydrous aluminum and silicic acid, released from solid substrate during the acidic titration, was considered in the model description of the back-titration procedure. A surface reaction model was suggested as follows: >SOH<-->SO(-)+H+, pK(a)(int)=3.48-3.98;>SOH+Al(3+)+H4SiO4<-->SOAl(OSi(OH)3(+)+2H+, pK(SC)=3.48-4.04. Two simple surface complexation models accounted for the interfacial structure, i.e., the constant capacitance model (CCM) and the diffuse layer model (DLM), and gave a satisfactory description of the experimental data. Considering the effect of ionic strength on the electrostatic profile at the solid-aqueous interface, the DLM was appropriate at the low concentrations (0.01 and 0.005 mol/L) of background electrolyte (NaNO3 in this study), while the CCM was preferable in the case of high ionic strength (0.1 mol/L).

  19. [Features of allele polymorphism of genes involved in homocysteine and folate metabolism in patients with atherosclerosis of the lower extremity arteries].

    PubMed

    Klenkova, N A; Kapustin, S I; Saltykova, N B; Shmeleva, V M; Blinov, M N

    2009-01-01

    Under study were features of allele polymorphism of genes of methylenetetrahydrofolate reductase (MTHFR C677T and A1298C), methionine synthase (MS A 2756G), methionine synthase reductase (MTRR A66G) and methylenetetrahydrofolate dehydrogenase (MTHFD G1958A) in patients with atherosclerosis of the lower extremity arteries (ALEA). Patients with hyperhomocysteinemia (HHcy) had statistically significant increase of allele MTHFR 677T and MTRR 66GG as compared both with the control group and with the group of patients without HHcy. It suggests that polymorphism of genes involved in homocystein and folate metabolism might affect the risk of HHcy in patients with ALEA.

  20. Linear Titration Curves of Acids and Bases.

    PubMed

    Joseph, N R

    1959-05-29

    The Henderson-Hasselbalch equation, by a simple transformation, becomes pH - pK = pA - pB, where pA and pB are the negative logarithms of acid and base concentrations. Sigmoid titration curves then reduce to straight lines; titration curves of polyelectrolytes, to families of straight lines. The method is applied to the titration of the dipeptide glycyl aminotricarballylic acid, with four titrable groups. Results are expressed as Cartesian and d'Ocagne nomograms. The latter is of a general form applicable to polyelectrolytes of any degree of complexity.

  1. Acid-Base Disorders--A Computer Simulation.

    ERIC Educational Resources Information Center

    Maude, David L.

    1985-01-01

    Describes and lists a program for Apple Pascal Version 1.1 which investigates the behavior of the bicarbonate-carbon dioxide buffer system in acid-base disorders. Designed specifically for the preclinical medical student, the program has proven easy to use and enables students to use blood gas parameters to arrive at diagnoses. (DH)

  2. [Acid-base equilibrium and the brain].

    PubMed

    Rabary, O; Boussofara, M; Grimaud, D

    1994-01-01

    In physiological conditions, the regulation of acid-base balance in brain maintains a noteworthy stability of cerebral pH. During systemic metabolic acid-base imbalances cerebral pH is well controlled as the blood/brain barrier is slowly and poorly permeable to electrolytes (HCO3- and H+). Cerebral pH is regulated by a modulation of the respiratory drive, triggered by the early alterations of interstitial fluid pH, close to medullary chemoreceptors. As blood/brain barrier is highly permeable to Co2, CSF pH is corrected in a few hours, even in case of severe metabolic acidosis and alkalosis. Conversely, during ventilatory acidosis and alkalosis the cerebral pH varies in the same direction and in the same range than blood pH. Therefore, the brain is better protected against metabolic than ventilatory acid-base imbalances. Ventilatory acidosis and alkalosis are able to impair cerebral blood flow and brain activity through interstitial pH alterations. During respiratory acidosis, [HCO3-] increases in extracellular fluids to control cerebral pH by two main ways: a carbonic anhydrase activation at the blood/brain and blood/CSF barriers level and an increase in chloride shift in glial cells (HCO3- exchanged for Cl-). During respiratory alkalosis, [HCO3-] decreases in extracellular fluids by the opposite changes in HCO3- transport and by an increase in lactic acid synthesis by cerebral cells. The treatment of metabolic acidosis with bicarbonates may induce a cerebral acidosis and worsen a cerebral oedema during ketoacidosis. Moderate hypocapnia carried out to treat intracranial hypertension is mainly effective when cerebral blood flow is high and vascular CO2 reactivity maintained. Hypocapnia may restore an altered cerebral blood flow autoregulation. Instrumental hypocapnia requires a control of cerebral perfusion pressure and cerebral arteriovenous difference for oxygen, to select patients for whom this kind of treatment may be of benefit, to choose the optimal level of

  3. Uric acid levels in patients with schizophrenia on clozapine monotherapy.

    PubMed

    Wysokiński, Adam; Kłoszewska, Iwona

    2015-08-01

    We tested the hypothesis that uric acid levels are higher in subjects with schizophrenia treated with clozapine than in healthy control and they correlate with anthropometric measurements, laboratory tests and results of bioimpedance analysis of body composition. Data for 24 subjects with schizophrenia treated with clozapine and 24 age- and sex-matched healthy volunteers was analyzed. There was no difference of fasting uric acid concentrations between clozapine and control groups (4.5 ± 1.4 vs. 4.3 ± 1.3 mg/dl, P = 0.87). Regarding the whole group, uric acid levels were significantly higher in men (5.2 ± 1.2 vs. 3.6 ± 0.9, P < 0.001). Uric acid levels correlated with weight (R = 0.58, P = 0.003), body mass index (BMI; R = 0.49, P = 0.01), abdominal circumference (R = 0.45, P = 0.03), waist circumference (R = 0.47, P = 0.02), waist-to-hip ratio (R = 0.42, P = 0.04), insulin (R = 0.50, P = 0.01), homoeostasis model assessment of insulin resistance 2 (HOMA2-IR; R = 0.49, P = 0.01), basal metabolic rate (R = 0.56, P = 0.004), lean body mass (R = 0.55, P = 0.005) and body water (R = 0.55, P = 0.005). There were no significant differences of uric acid levels for smoking status, impaired fasting glucose, abdominal obesity, obesity/overweight and dyslipidemia. Uric acid levels did not correlate with age, duration of clozapine treatment, clozapine dose, leg circumference, systolic blood pressure, diastolic blood pressure, total body fat, triglycerides, total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), homocysteine, corrected calcium, glucose and homoeostasis model assessment of insulin resistance 1 (HOMA1-IR). We did not find significant differences in blood uric acid levels between subjects with schizophrenia and controls. Association with weight, BMI, abdominal and waist circumferences, insulin levels and insulin resistance may support uric acid role as an important cardiovascular risk factor. Association with lean weight may explain

  4. Acid base activity of live bacteria: Implications for quantifying cell wall charge

    NASA Astrophysics Data System (ADS)

    Claessens, Jacqueline; van Lith, Yvonne; Laverman, Anniet M.; Van Cappellen, Philippe

    2006-01-01

    To distinguish the buffering capacity associated with functional groups in the cell wall from that resulting from metabolic processes, base or acid consumption by live and dead cells of the Gram-negative bacterium Shewanella putrefaciens was measured in a pH stat system. Live cells exhibited fast consumption of acid (pH 4) or base (pH 7, 8, 9, and 10) during the first few minutes of the experiments. At pH 5.5, no acid or base was required to maintain the initial pH constant. The initial amounts of acid or base consumed by the live cells at pH 4, 8, and 10 were of comparable magnitudes as those neutralized at the same pHs by intact cells killed by exposure to gamma radiation or ethanol. Cells disrupted in a French press required higher amounts of acid or base, due to additional buffering by intracellular constituents. At pH 4, acid neutralization by suspensions of live cells stopped after 50 min, because of loss of viability. In contrast, under neutral and alkaline conditions, base consumption continued for the entire duration of the experiments (5 h). This long-term base neutralization was, at least partly, due to active respiration by the cells, as indicated by the build-up of succinate in solution. Qualitatively, the acid-base activity of live cells of the Gram-positive bacterium Bacillus subtilis resembled that of S. putrefaciens. The pH-dependent charging of ionizable functional groups in the cell walls of the live bacteria was estimated from the initial amounts of acid or base consumed in the pH stat experiments. From pH 4 to 10, the cell wall charge increased from near-zero values to about -4 × 10 -16 mol cell -1 and -6.5 × 10 -16 mol cell -1 for S. putrefaciens and B. subtilis, respectively. The similar cell wall charging of the two bacterial strains is consistent with the inferred low contribution of lipopolysaccharides to the buffering capacity of the Gram-negative cell wall (of the order of 10%).

  5. An Olfactory Indicator for Acid-Base Titrations.

    ERIC Educational Resources Information Center

    Flair, Mark N.; Setzer, William N.

    1990-01-01

    The use of an olfactory acid-base indicator in titrations for visually impaired students is discussed. Potential olfactory indicators include eugenol, thymol, vanillin, and thiophenol. Titrations performed with each indicator with eugenol proved to be successful. (KR)

  6. Biodegradation and Osteosarcoma Cell Cultivation on Poly(aspartic acid) Based Hydrogels.

    PubMed

    Juriga, Dávid; Nagy, Krisztina; Jedlovszky-Hajdú, Angéla; Perczel-Kovách, Katalin; Chen, Yong Mei; Varga, Gábor; Zrínyi, Miklós

    2016-09-14

    Development of novel biodegradable and biocompatible scaffold materials with optimal characteristics is important for both preclinical and clinical applications. The aim of the present study was to analyze the biodegradability of poly(aspartic acid)-based hydrogels, and to test their usability as scaffolds for MG-63 osteoblast-like cells. Poly(aspartic acid) was fabricated from poly(succinimide) and hydrogels were prepared using natural amines as cross-linkers (diaminobutane and cystamine). Disulfide bridges were cleaved to thiol groups and the polymer backbone was further modified with RGD sequence. Biodegradability of the hydrogels was evaluated by experiments on the base of enzymes and cell culture medium. Poly(aspartic acid) hydrogels possessing only disulfide bridges as cross-links proved to be degradable by collagenase I. The MG-63 cells showed healthy, fibroblast-like morphology on the double cross-linked and RGD modified hydrogels. Thiolated poly(aspartic acid) based hydrogels provide ideal conditions for adhesion, survival, proliferation, and migration of osteoblast-like cells. The highest viability was found on the thiolated PASP gels while the RGD motif had influence on compacted cluster formation of the cells. These biodegradable and biocompatible poly(aspartic acid)-based hydrogels are promising scaffolds for cell cultivation.

  7. Hydrogen Sulfide Ameliorates Homocysteine-Induced Alzheimer's Disease-Like Pathology, Blood-Brain Barrier Disruption, and Synaptic Disorder.

    PubMed

    Kamat, Pradip K; Kyles, Philip; Kalani, Anuradha; Tyagi, Neetu

    2016-05-01

    Elevated plasma total homocysteine (Hcy) level is associated with an increased risk of Alzheimer's disease (AD). During transsulfuration pathways, Hcy is metabolized into hydrogen sulfide (H2S), which is a synaptic modulator, as well as a neuro-protective agent. However, the role of hydrogen sulfide, as well as N-methyl-D-aspartate receptor (NMDAR) activation, in hyperhomocysteinemia (HHcy) induced blood-brain barrier (BBB) disruption and synaptic dysfunction, leading to AD pathology is not clear. Therefore, we hypothesized that the inhibition of neuronal NMDA-R by H2S and MK801 mitigate the Hcy-induced BBB disruption and synapse dysfunction, in part by decreasing neuronal matrix degradation. Hcy intracerebral (IC) treatment significantly impaired cerebral blood flow (CBF), and cerebral circulation and memory function. Hcy treatment also decreases the expression of cystathionine-β-synthase (CBS) and cystathionine-γ-lyase (CSE) in the brain along with increased expression of NMDA-R (NR1) and synaptosomal Ca(2+) indicating excitotoxicity. Additionally, we found that Hcy treatment increased protein and mRNA expression of intracellular adhesion molecule 1 (ICAM-1), matrix metalloproteinase (MMP)-2, and MMP-9 and also increased MMP-2 and MMP-9 activity in the brain. The increased expression of ICAM-1, glial fibrillary acidic protein (GFAP), and the decreased expression of vascular endothelial (VE)-cadherin and claudin-5 indicates BBB disruption and vascular inflammation. Moreover, we also found decreased expression of microtubule-associated protein 2 (MAP-2), postsynaptic density protein 95 (PSD-95), synapse-associated protein 97 (SAP-97), synaptosomal-associated protein 25 (SNAP-25), synaptophysin, and brain-derived neurotrophic factor (BDNF) showing synapse dysfunction in the hippocampus. Furthermore, NaHS and MK801 treatment ameliorates BBB disruption, CBF, and synapse functions in the mice brain. These results demonstrate a neuro-protective effect of H2S over Hcy

  8. Intake of fish oil, oleic acid, folic acid, and vitamins B-6 and E for 1 year decreases plasma C-reactive protein and reduces coronary heart disease risk factors in male patients in a cardiac rehabilitation program.

    PubMed

    Carrero, Juan Jesús; Fonollá, Juristo; Marti, José Luis; Jiménez, Jesús; Boza, Julio J; López-Huertas, Eduardo

    2007-02-01

    Certain nutrients have been shown to be effective in preventing coronary heart disease. We hypothesized that a daily intake of low amounts of a number of these nutrients would exert beneficial effects on risk factors and clinical variables in patients that suffered from myocardial infarction (MI) and were following a cardiac rehabilitation program. Forty male MI patients were randomly allocated into 2 groups. The supplemented group consumed 500 mL/d of a fortified dairy product containing eicosapentaenoic acid, docosahexaenoic acid, oleic acid, folic acid, and vitamins A, B-6, D, and E. The control group consumed 500 mL/d of semi-skimmed milk with added vitamins A and D. The patients received supervised exercise training, lifestyle and dietary recommendations, and they were instructed to consume the products in addition to their regular diet. Blood extractions and clinical examinations were performed after 0, 3, 6, 9, and 12 mo. Plasma concentrations of eicosapentaenoic acid, docosahexaenoic acid, oleic acid, folic acid, vitamin B-6, and vitamin E increased after supplementation (P<0.05). Plasma total and LDL-cholesterol, apolipoprotein B, and high-sensitivity C-reactive protein concentrations decreased in the supplemented group (P<0.05), and plasma total homocysteine decreased in both groups. There were no changes in heart rate, blood pressure, or cardiac electrocardiographic parameters in either group. Therapeutic lifestyle changes, effected through a CR program comprising regular exercise and the intake of a combination of dietary nutrients, reduced a variety of risk factors in MI patients, which supports the rationale for nutritional programs in the secondary prevention of coronary heart disease.

  9. Mathematical modeling of acid-base physiology

    PubMed Central

    Occhipinti, Rossana; Boron, Walter F.

    2015-01-01

    pH is one of the most important parameters in life, influencing virtually every biological process at the cellular, tissue, and whole-body level. Thus, for cells, it is critical to regulate intracellular pH (pHi) and, for multicellular organisms, to regulate extracellular pH (pHo). pHi regulation depends on the opposing actions of plasma-membrane transporters that tend to increase pHi, and others that tend to decrease pHi. In addition, passive fluxes of uncharged species (e.g., CO2, NH3) and charged species (e.g., HCO3− , NH4+) perturb pHi. These movements not only influence one another, but also perturb the equilibria of a multitude of intracellular and extracellular buffers. Thus, even at the level of a single cell, perturbations in acid-base reactions, diffusion, and transport are so complex that it is impossible to understand them without a quantitative model. Here we summarize some mathematical models developed to shed light onto the complex interconnected events triggered by acids-base movements. We then describe a mathematical model of a spherical cell–which to our knowledge is the first one capable of handling a multitude of buffer reaction–that our team has recently developed to simulate changes in pHi and pHo caused by movements of acid-base equivalents across the plasma membrane of a Xenopus oocyte. Finally, we extend our work to a consideration of the effects of simultaneous CO2 and HCO3− influx into a cell, and envision how future models might extend to other cell types (e.g., erythrocytes) or tissues (e.g., renal proximal-tubule epithelium) important for whole-body pH homeostasis. PMID:25617697

  10. [Development and practice evaluation of blood acid-base imbalance analysis software].

    PubMed

    Chen, Bo; Huang, Haiying; Zhou, Qiang; Peng, Shan; Jia, Hongyu; Ji, Tianxing

    2014-11-01

    To develop a blood gas, acid-base imbalance analysis computer software to diagnose systematically, rapidly, accurately and automatically determine acid-base imbalance type, and evaluate the clinical application. Using VBA programming language, a computer aided diagnostic software for the judgment of acid-base balance was developed. The clinical data of 220 patients admitted to the Second Affiliated Hospital of Guangzhou Medical University were retrospectively analyzed. The arterial blood gas [pH value, HCO(3)(-), arterial partial pressure of carbon dioxide (PaCO₂)] and electrolytes included data (Na⁺ and Cl⁻) were collected. Data were entered into the software for acid-base imbalances judgment. At the same time the data generation was calculated manually by H-H compensation formula for determining the type of acid-base imbalance. The consistency of judgment results from software and manual calculation was evaluated, and the judgment time of two methods was compared. The clinical diagnosis of the types of acid-base imbalance for the 220 patients: 65 cases were normal, 90 cases with simple type, mixed type in 41 cases, and triplex type in 24 cases. The accuracy of the judgment results of the normal and triplex types from computer software compared with which were calculated manually was 100%, the accuracy of the simple type judgment was 98.9% and 78.0% for the mixed type, and the total accuracy was 95.5%. The Kappa value of judgment result from software and manual judgment was 0.935, P=0.000. It was demonstrated that the consistency was very good. The time for software to determine acid-base imbalances was significantly shorter than the manual judgment (seconds:18.14 ± 3.80 vs. 43.79 ± 23.86, t=7.466, P=0.000), so the method of software was much faster than the manual method. Software judgment can replace manual judgment with the characteristics of rapid, accurate and convenient, can improve work efficiency and quality of clinical doctors and has great

  11. Are plasma homocysteine concentrations in Brazilian adolescents influenced by the intake of the main food sources of natural folate?

    PubMed

    Bigio, Roberta Schein; Verly, Eliseu; de Castro, Michelle Alessandra; Cesar, Chester Luis Galvão; Fisberg, Regina Mara; Marchioni, Dirce Maria Lobo

    2013-01-01

    Folate, a B vitamin, has been associated with a reduced concentration of plasma homocysteine (phcy), a marker of cardiovascular disease. The contribution of fruits and vegetables (FV) and other natural folate-rich foods to folate intake and folate status in Brazilian adolescents has hardly been determined. To investigate the intake of FV and beans and its association with the concentration of phcy in adolescents. This was a cross-sectional population-based study with a complex sample survey, with 198 adolescents who completed two 24-hour dietary recalls, a food frequency questionnaire, and a fasting blood draw. Usual dietary intake estimates were derived applying the Multiple Source Method. Three different generalized linear models with a gamma distribution were developed for each sex to evaluate the relationship between phcy and tertiles of FV intake as well as to evaluate the relationship between phcy and tertiles of FV and bean intake. No association was found between phcy concentration and FV intake or between phcy and FV and beans. Serum folate and female sex were inversely related to phcy. Phcy was not related to FV or FV and beans; this may be attributable to a low intake of these food groups. Copyright © 2013 S. Karger AG, Basel.

  12. Study of the acid-base properties of mineral soil horizons using pK spectroscopy

    NASA Astrophysics Data System (ADS)

    Shamrikova, E. V.; Vanchikova, E. V.; Ryazanov, M. A.

    2007-11-01

    The presence of groups 4 and 5 participating in acid-base equilibria was revealed in samples from mineral horizons of the gley-podzolic soil of the Komi Republic using pK spectroscopy (the mathematical processing of potentiometric titration curves for plotting the distribution of acid groups according to their pK values). The specific quantity of acid-base sites in soil samples was calculated. The contribution of organic and mineral soil components to the groups of acid-base sites was estimated. The pK values of groups determining the potential, exchangeable, and unexchangeable acidities were found. The heterogeneity of acid components determining different types of soil acidity was revealed.

  13. Folic Acid Reduces Tau Phosphorylation by Regulating PP2A Methylation in Streptozotocin-Induced Diabetic Mice

    PubMed Central

    Zheng, Miaoyan; Zou, Chen; Li, Mengyue; Huang, Guowei; Gao, Yuxia; Liu, Huan

    2017-01-01

    High incidence rate of Alzheimer’s disease (AD) is observed in patients with type 2 diabetes. Aggregated β-amyloid (Aβ) and hyperphosphorylated tau are the hallmarks of AD. Hyperphosphorylated tau has been detected in diabetic animals as well as in diabetic patients. Folates mediate the transfer of one carbon unit, required in various biochemical reactions. The effect of folate on tau phosphorylation in diabetic models still remains unknown. In this study, we investigated the effect and mechanism of folic acid on hyperphosphorylation of tau in streptozotocin (STZ)-induced diabetic mice. Diabetic mice induced by STZ, at the age of 10 weeks, were administered with three levels of folic acid: folic acid-deficient diet, diet with normal folic acid content, and 120 μg/kg folic acid diet for 8 weeks. Levels of serum folate and blood glucose were monitored. Tau phosphorylation, protein phosphatase 2A (PP2A) methylation, and Glycogen synthase kinase 3β (GSK-3β) phosphorylation were detected using Western blot. The S-adenosyl methionine:S-adenosyl homocysteine ratio (SAM:SAH) in brain tissues was also determined. DNA methyltransferase (DNMT) mRNA expression levels were detected using real-time PCR. Folic acid reduced tau hyperphosphorylation at Ser396 in the brain of diabetes mellitus (DM) mice. In addition, PP2A methylation and DNMT1 mRNA expression were significantly increased in DM mice post folic acid treatment. GSK-3β phosphorylation was not regulated by folic acid administration. Folic acid can reduce tau phosphorylation by regulating PP2A methylation in diabetic mice. These results support that folic acid can serve as a multitarget neuronal therapeutic agent for treating diabetes-associated cognitive dysfunction. PMID:28422052

  14. Adsorption of nucleic acid bases and amino acids on single-walled carbon and boron nitride nanotubes: a first-principles study.

    PubMed

    Zheng, Jiaxin; Song, Wei; Wang, Lu; Lu, Jing; Luo, Guangfu; Zhou, Jing; Qin, Rui; Li, Hong; Gao, Zhengxiang; Lai, Lin; Li, Guangping; Mei, Wai Ning

    2009-11-01

    We study the adsorptions of nucleic acid bases adenine (A), cytosine (C), guanine (G), thymine (T), and uracil (U) and four amino acids phenylalanine, tyrosine, tryptophan, alanine on the single-walled carbon nanotubes (SWCNTs) and boron nitride nanotubes (SWBNNTs) by using density functional theory. We find that the aromatic content plays a critical role in the adsorption. The adsorptions of nucleic acid bases and amino acids on the (7, 7) SWBNNT are stronger than those on the (7, 7) SWCNT. Oxidative treatment of SWCNTs favors the adsorption of biomolecules on nanotubes.

  15. Homocysteine induces oxidative stress to damage trabecular meshwork cells.

    PubMed

    You, Zhi-Peng; Zhang, Yue-Zhi; Zhang, Yu-Lan; Shi, Lu; Shi, Ke

    2018-05-01

    The aim of the present study was to investigate the effect of homocysteine (Hcy) in on human trabecular meshwork cells (HTMCs). A total of 41 patients with primary open-angle glaucoma (POAG) and 53 patients with senile cataracts (control group) were recruited. Plasma and aqueous humor samples were collected and the Hcy concentrations were determined using enzymatic cycling assays. In cell experiments, normal HTMCs were passaged and randomly divided into a blank control group, a normal HTMC group and experimental groups, which were treated with different concentrations of Hcy. The HTMC activities were detected using the Cell Counting Kit-8 method and the HTMC mitochondrial membrane potential (MMP) was detected using JC-1 staining. Reactive oxygen species (ROS) released by trabecular meshwork cells was detected using flow cytometry and superoxide dismjutase-1 (SOD1) expression was detected using immunoblotting. The results revealed that the concentration of Hcy in the plasma and aqueous humor of the POAG group (14.44±0.86 and 1.60±0.27 µmol/l, respectively) was significantly higher compared with the control group (10.82±0.29 and 0.69±0.39 µmol/l). All tested concentrations (30, 100, 300 and 1,000 µmol/l) of Hcy reduced the MMP in HTMCs and inhibited HTMC proliferation in a dose-dependent manner. ROS production by HTMCs significantly increased with increased concentrations of Hcy, whereas SOD1 expression significantly decreased in a dose-dependent manner. In summary, patients with POAG were demonstrated to have increased concentrations of Hcy in the plasma and aqueous humor. High concentrations of Hcy in HTMCs induced an oxidative stress state, thereby further inhibiting HTMC proliferation. The results of the present study demonstrate that Hcy may be a potential treatment target in patients with POAG.

  16. Elongated and substituted triazine-based tricarboxylic acid linkers for MOFs.

    PubMed

    Klinkebiel, Arne; Beyer, Ole; Malawko, Barbara; Lüning, Ulrich

    2016-01-01

    New triazine-based tricarboxylic acid linkers were prepared as elongated relatives of triazinetribenzoic acid (TATB). Additionally, functional groups (NO 2 , NH 2 , OMe, OH) were introduced for potential post-synthetic modification (PSM) of MOFs. Functionalized tris(4-bromoaryl)triazine "cores" ( 3a , 3b ) were obtained by unsymmetric trimerization mixing one equivalent of an acid chloride (OMe or NO 2 substituted) with two equivalents of an unsubstituted nitrile. Triple Suzuki coupling of the cores 3 with suitable phenyl- and biphenylboronic acid derivatives provided elongated tricarboxylic acid linkers as carboxylic acids 17 and 20 or their esters 16 and 19 . Reduction of the nitro group and cleavage of the methoxy group gave the respective amino and hydroxy-substituted triazine linkers.

  17. A mathematical model of pH, based on the total stoichiometric concentration of acids, bases and ampholytes dissolved in water.

    PubMed

    Mioni, Roberto; Mioni, Giuseppe

    2015-10-01

    In chemistry and in acid-base physiology, the Henderson-Hasselbalch equation plays a pivotal role in studying the behaviour of the buffer solutions. However, it seems that the general function to calculate the valence of acids, bases and ampholytes, N = f(pH), at any pH, has only been provided by Kildeberg. This equation can be applied to strong acids and bases, pluriprotic weak acids, bases and ampholytes, with an arbitrary number of acid strength constants, pKA, including water. By differentiating this function with respect to pH, we obtain the general equation for the buffer value. In addition, by integrating the titration curve, TA, proposed by Kildeberg, and calculating its Legendre transform, we obtain the Gibbs free energy of pH (or pOH)-dependent titratable acid. Starting from the law of electroneutrality and applying suitable simplifications, it is possible to calculate the pH of the buffer solutions by numerical methods, available in software packages such as Excel. The concept of buffer capacity has also been clarified by Urbansky, but, at variance with our approach, not in an organic manner. In fact, for each set of monobasic, dibasic, tribasic acids, etc., various equations are presented which independently fit each individual acid-base category. Consequently, with the increase in acid groups (pKA), the equations become more and more difficult, both in practice and in theory. Some examples are proposed to highlight the boundary that exists between acid-base physiology and the thermodynamic concepts of energy, chemical potential, amount of substance and acid resistance.

  18. High School Students' Concepts of Acids and Bases.

    ERIC Educational Resources Information Center

    Ross, Bertram H. B.

    An investigation of Ontario high school students' understanding of acids and bases with quantitative and qualitative methods revealed misconceptions. A concept map, based on the objectives of the Chemistry Curriculum Guideline, generated multiple-choice items and interview questions. The multiple-choice test was administered to 34 grade 12…

  19. Natural honey lowers plasma glucose, C-reactive protein, homocysteine, and blood lipids in healthy, diabetic, and hyperlipidemic subjects: comparison with dextrose and sucrose.

    PubMed

    Al-Waili, Noori S

    2004-01-01

    This study included the following experiments: (1) effects of dextrose solution (250 mL of water containing 75 g of dextrose) or honey solution (250 mL of water containing 75 g of natural honey) on plasma glucose level (PGL), plasma insulin, and plasma C-peptide (eight subjects); (2) effects of dextrose, honey, or artificial honey (250 mL of water containing 35 g of dextrose and 40 g of fructose) on cholesterol and triglycerides (TG) (nine subjects); (3) effects of honey solution, administered for 15 days, on PGL, blood lipids, C-reactive protein (CRP), and homocysteine (eight subjects); (4) effects of honey or artificial honey on cholesterol and TG in six patients with hypercholesterolemia and five patients with hypertriglyceridemia; (5) effects of honey for 15 days on blood lipid and CRP in five patients with elevated cholesterol and CRP; (6) effects of 70 g of dextrose or 90 g of honey on PGL in seven patients with type 2 diabetes mellitus; and (7) effects of 30 g of sucrose or 30 g of honey on PGL, plasma insulin, and plasma C-peptide in five diabetic patients. In healthy subjects, dextrose elevated PGL at 1 (53%) and 2 (3%) hours, and decreased PGL after 3 hours (20%). Honey elevated PGL after 1 hour (14%) and decreased it after 3 hours (10%). Elevation of insulin and C-peptide was significantly higher after dextrose than after honey. Dextrose slightly reduced cholesterol and low-density lipoprotein-cholesterol (LDL-C) after 1 hour and significantly after 2 hours, and increased TG after 1, 2, and 3 hours. Artificial honey slightly decreased cholesterol and LDL-C and elevated TG. Honey reduced cholesterol, LDL-C, and TG and slightly elevated high-density lipoprotein-cholesterol (HDL-C). Honey consumed for 15 days decreased cholesterol (7%), LDL-C (1%), TG (2%), CRP (7%), homocysteine (6%), and PGL (6%), and increased HDL-C (2%). In patients with hypertriglyceridemia, artificial honey increased TG, while honey decreased TG. In patients with hyperlipidemia

  20. Collaborative Strategies for Teaching Common Acid-Base Disorders to Medical Students

    ERIC Educational Resources Information Center

    Petersen, Marie Warrer; Toksvang, Linea Natalie; Plovsing, Ronni R.; Berg, Ronan M. G.

    2014-01-01

    The ability to recognize and diagnose acid-base disorders is of the utmost importance in the clinical setting. However, it has been the experience of the authors that medical students often have difficulties learning the basic principles of acid-base physiology in the respiratory physiology curriculum, particularly when applying this knowledge to…