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Homocysteine
Kinds of Homocysteine Terms modified by Homocysteine Selected AbstractsHomocysteine enhances cardiac neural crest cell attachment in vitro by increasing intracellular calcium levelsDEVELOPMENTAL DYNAMICS, Issue 8 2008David J. Heidenreich Abstract Elevated homocysteine (Hcys) increases the risk of neurocristopathies. Previous studies show Hcys inhibits neural crest (NC) cell migration in vivo. However, the mechanisms responsible for this effect are unknown. Here, we evaluated the effect of Hcys on NC cell attachment in vitro and determined if any of the effects were due to altered Ca2+ signaling. We found Hcys enhanced NC cell attachment in a dose and substrate-dependent manner. Ionomycin mimicked the effect of Hcys while BAPTA-AM and 2-APB blocked the effect of Hcys on NC attachment. In contrast, inhibitors of plasma membrane Ca2+ channels had no effect on NC attachment. Hcys also increased the emission of the intracellular Ca2+ -sensitive probe, Fluo-4. These results show Hcys alters NC attachment by triggering an increase in intracellular Ca2+ possibly by generating inositol triphosphate. Hence, the teratogenic effect ascribed to Hcys may be due to perturbation of intracellular Ca2+ signaling. Developmental Dynamics 237:2117,2128, 2008. © 2008 Wiley-Liss, Inc. [source] Homocysteine inhibits cardiac neural crest cell formation and morphogenesis in vivoDEVELOPMENTAL DYNAMICS, Issue 1 2004Brent J. Tierney Abstract Elevated homocysteine increases the risk of neurocristopathies. Here, we determined whether elevating homocysteine altered the proliferation or number of chick neural crest cells that form between the midotic and third somite in vivo. Homocysteine increased the number of neural tube cells but decreased neural crest cell number. However, the sum total of cells was not different from controls. In controls, the 5-bromo-2,-deoxyuridine-labeling index was higher in newly formed neural crest cells than in their progenitors, paralleling reports showing these progenitors must pass the restriction point before undergoing epithelial,mesenchymal transition. Homocysteine decreased the labeling index of newly formed neural crest cells, suggesting that it inhibited cell cycle progression of neural crest progenitors or the S-phase entry of newly formed neural crest cells. Homocysteine also inhibited neural crest dispersal and decreased the distance they migrated from the neural tube. These results show neural crest morphogenesis is directly altered by elevated homocysteine in vivo. Developmental Dynamics 229:63,73, 2004. © 2003 Wiley-Liss, Inc. [source] An Assessment of the Potential Value of Elevated Homocysteine in Predicting Alcohol-withdrawal SeizuresEPILEPSIA, Issue 5 2006Stefan Bleich Summary:,Purpose: Higher homocysteine levels were found in actively drinking patients with alcohol dependence. Recent studies have shown that high homocysteine levels are associated with alcohol-withdrawal seizures. The aim of the present study was to calculate the best predictive cutoff value of plasma homocysteine levels in actively drinking alcoholics (n = 88) with first-onset alcohol-withdrawal seizures. Methods: The present study included 88 alcohol-dependent patients of whom 18 patients had a first-onset withdrawal seizure. All patients were active drinkers and had an established diagnosis of alcohol dependence, according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). Sensitivity and specificity were calculated by using every homocysteine plasma level found in the study population as cut-off value. A Bayes theorem was used to calculate positive (PPV) and negative (NPV) predictive values for all cutoff values used. Results: The highest combined sensitivity and specificity was reached at a homocysteine plasma cutoff value of 23.9 ,M. Positive predictive values ranged from 0.23 to 0.745; the maximum was reached at a homocysteine plasma level of 41.7 ,M. Negative predictive values ranged from 0.50 to 0.935, with a maximum at a homocysteine plasma level of 15.8,M. Conclusions: Homocysteine levels above this cutoff value on admission are a useful screening tool to identify actively drinking patients at higher risk of alcohol-withdrawal seizures. This pilot study gives further hints that biologic markers may be helpful to predict patients at risk for first-onset alcohol-withdrawal seizures. [source] The effects of tobacco smoke on the homocysteine level,a risk factor of atherosclerosisADDICTION BIOLOGY, Issue 2 2003ANDRZEJ SOBCZAK Homocysteine may promote atherogenesis and thrombogenesis. There is evidence from case,control and cross-sectional cohort studies that there is a positive association between plasma homocysteine levels and coronary artery disease, cerebrovascular disease and peripheral vascular disease. There is also some evidence that certain life-style factors such as cigarette smoking may affect homocysteine levels. In this work is presented a review of recent opinion about the influence of tobacco smoking on homocysteine levels. [source] Uremic hyperhomocysteinemia: A randomized trial of folate treatment for the prevention of cardiovascular eventsHEMODIALYSIS INTERNATIONAL, Issue 2 2007Areuza C. A. VIANNA Abstract Homocysteine is a risk factor for atherosclerosis in the general population, and serum homocysteine levels are almost universally elevated in chronic renal failure patients. When such patients are treated with dialysis, cardiovascular disease accounts for more than 50% of their mortality, which, in some proportion, may be pathophysiologically related to the elevated serum homocysteine levels. From April 2003 to March 2005, we conducted a 2-year, double-blind, randomized, placebo-controlled trial of 186 patients with end-stage kidney disease due to any cause, who were older than 18 years and stable on hemodialysis. Patients were assigned to receive either oral folic acid 10 mg 3 times a week immediately after every dialysis session under nurse supervision or an identical-appearing placebo for the entire study. On admission, plasma total homocysteine (tHcy) levels were above 13.9 ,mol/L in 96.7% of patients (median 25.0 ,mol/L, range 9.3,104.0 ,mol/L). In the placebo group, tHcy levels remained elevated at 6, 12, and 24 months, while oral folate significantly decreased tHcy to a median value of 10.5 (2.8,20.3) ,mol/L, (p<0.01). During the study, 38 patients (folic acid group 17 vs. placebo group 21; p=0.47) died from cardiovascular disease. Kaplan,Meier life table analysis dealing with the incidence of cardiovascular events, both fatal and nonfatal (myocardial infarction, arrhythmias, angina, heart failure, cerebrovascular accident), showed that 2 years of folic acid treatment and the lowering of the homocysteine blood levels had no effect on cardiovascular events (p=0.41; hazard ratio 1.24, 95% CI 0.74,2.10). However, the carotid artery intima-media wall thickness measured in a blinded fashion decreased from 1.94 ± 0.59 mm to 1.67 ± 0.38 mm (p<0.01) after 2 years of folate therapy. In this short-term study of uremic patients, 2 years of folic acid supplementation normalized the tHcy blood levels in 92.3% of patients but did not change the incidence of cardiovascular events compared with the control group. However, ultrasonography of the common carotid arteries performed at entry and 24 months later showed a significant decrease in intima-media thickness with folate supplementation. This suggests that early folate supplementation may benefit patients with chronic renal failure by preventing cardiovascular deterioration. [source] Mechanisms of protection by the betaine-homocysteine methyltransferase/betaine system in HepG2 cells and primary mouse hepatocytes,HEPATOLOGY, Issue 5 2007Cheng Ji Betaine-homocysteine methyltransferase (BHMT) regulates homocysteine levels in the liver. We previously reported that the alteration of BHMT is associated with alcoholic liver steatosis and injury. In this study, we tested whether BHMT protects hepatocytes from homocysteine-induced injury and lipid accumulation. Both BHMT transfectants of HepG2 cells and primary mouse hepatocytes with suppressed BHMT were generated. Comparisons were made between the cell models with respect to their response to homocysteine treatments. Homocysteine metabolism was impaired in HepG2 cells, and the expression of BHMT in HepG2 cells ameliorated the impairment and stabilized the levels of intracellular homocysteine after the addition of exogenous homocysteine. BHMT expression inhibited homocysteine-induced glucose-regulated protein 78 (GRP78) and C/EBP-homologous protein (CHOP) and homocysteine-induced cell death. A betaine treatment protected primary mouse hepatocytes from a homocysteine-induced increase in GRP78 and cell death but not a tunicamycin-induced increase. Homocysteine induced greater CHOP expression (2.7-fold) in BHMT small interfering RNA (siRNA),transfected cells than in a control (1.9-fold). Homocysteine-induced cell death was increased by 40% in the siRNA-treated cells in comparison with the control. Apolipoprotein B (apoB) expression was higher and triglycerides and cholesterol were lower in HepG2 expressing BHMT. In primary mouse hepatocytes, homocysteine induced the accumulation of triglycerides and cholesterol, which was reduced in the presence of betaine. Betaine partially reduced homocysteine-induced sterol regulatory element binding protein 1 expression in HepG2 cells and increased S-adenosylmethionine in primary mouse hepatocytes. Conclusion: The BHMT/betaine system directly protects hepatocytes from homocysteine-induced injury but not tunicamycin-induced injury, including an endoplasmic reticulum stress response, lipid accumulation, and cell death. This system also exhibits a more generalized effect on liver lipids by inducing ApoB expression and increasing S-adenosylmethionine/S-adenosylhomocysteine. (HEPATOLOGY 2007.) [source] High dietary methionine plus cholesterol stimulates early atherosclerosis and late fibrous cap development which is associated with a decrease in GRP78 positive plaque cellsINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 3 2009Anthony Zulli Summary The role of homocysteine, or its precursor methionine, in the formation of fibrous caps and its association with endoplasmic reticulum (ER) stress is unclear. Homocysteine can stimulate collagen accumulation and upregulate the ER stress chaperone glucose regulated protein 78 (GRP78). The aim of this study was to determine if high dietary methionine would increase fibrous caps, and that removal of an atherogenic diet would decrease the amount of ER stressed cells. New Zealand white rabbits were fed for 2, 4, or 12 weeks an atherogenic diet [1% methionine + 0.5% cholesterol (2MC, 4MC or 12MC)]; for 4 or 12 weeks a 0.5% cholesterol diet (4Ch, 12Ch); and to study plaque regression, an MC diet for 2 or 4 weeks accompanied by 10 weeks of a normal diet (2MCr, 4MCr). Endothelial function, atherosclerosis and GRP78 positive cells were studied. Endothelial function was abolished in 4MC and atherosclerosis increased 17-fold (P < 0.05) compared with 4Ch. Fibrous caps composed 48% of total plaque area in 12MC vs. 10% in 12Ch (P < 0.01), and 12MC expressed less GRP78 plaque cells vs. 12Ch (P < 0.01). Four MCr had less plaque GRP78 cells than 12MC (P < 0.05) and less endothelial GRP78 cells (P < 0.01). In addition, GRP78 positive cells were the highest in 4MC, but decreased in all other groups (P < 0.01). GRP78 positive cells within the fibrous cap inversely correlated with cap size (r2 = 0.9). These studies suggest that high dietary methionine could be beneficial for plaque stabilisation, and a normal diet also stabilises plaque and decreases the number of stressed plaque cells. [source] Relationship Between Homocysteine and Cardiovascular Diseases in Older AdultsJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 11 2004Hsu-Ko Kuo MD No abstract is available for this article. [source] Homocysteine induces metalloproteinase and shedding of ,-1 integrin in microvessel endothelial cells,JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 1 2004Suresh Shastry Abstract Although studies have suggested microvessel endothelial cells (MVEC) activation and induction of matrix metalloproteinases (MMPs) by homocysteine (Hcy), the transduction mechanism leading to endothelial activation was unclear. We hypothesized that Hcy induced metalloproteinase and altered the levels of integrin in MVEC. MVEC from mouse brain were isolated and characterized by CD-31 (PECAM-1) FITC labeling. The MVEC were activated with different doses (6,40 ,M) of Hcy. The cultured-conditioned-medium was analyzed for MMP activity by gelatin gel-zymography. TIMP-1, -4, ,-1 integrin, and a disintegrin and metalloproteinase-12 (ADAM-12) were quantified by Western blot analysis. We used MVEC in cell culture to study the effect of increasing concentrations of Hcy upon the secretion of various proteins into the culture medium. MMP-9, ,-1 integrin, ADAM-12, and TIMP-1 were found in increased concentrations in the culture medium of Hcy-treated cells whereas TIMP-4 was decreased. We have shown that purified TIMP-4 blocked the increase of ,-1 integrin shedding in Hcy-treated cells. Interestingly, our results suggest that TIMP-1 and TIMP-4 function antagonistically in Hcy-induced signaling pathways. © 2004 Wiley-Liss, Inc. [source] Homocysteine, the MTHFR 677 C,T polymorphism and family history of premature cardiovascular diseaseJOURNAL OF HUMAN NUTRITION & DIETETICS, Issue 3 2009A. Carey Background:, Cardiovascular disease (CVD) is the main cause of premature death in the UK and accounts for 36% of all premature male deaths and 27% of female deaths every year (British Heart Foundation, 2006). Although many risk factors for CVD are known, family history has been identified as being of particular importance in premature CVD (Lloyd-Jones et al., 2004). Recently, it was suggested that an elevated homocysteine (tHcy) may be associated with premature CVD (Homocystiene Studies Collaboration, 2002). The main genetic determinant of tHcy is the common 677 C,T polymorphism, in the enzyme methylenetetrahydrofolate reductase (MTHFR), which is prevalent in approximately 10% of the UK population. Relatively few studies have examined the association between tHcy and premature CVD and hardly any have considered the role of this polymorphism. The aim of this study therefore was to examine the relationships between the MTHFR 677 C,T polymorphism, tHcy and a family history of CVD in patients with established premature CVD. Methods:, An analysis was conducted on medical, lifestyle and family history data collected from patients and age-sex matched controls, recruited through the GENOVIT study in 2003. This case,control study involved n = 404 premature CVD patients and a similar number of age-sex matched controls, all of whom were screened for the TT genotype. A subset of patients (n = 196) and controls (n = 167) provided a blood sample, from which the tHcy concentration was established. Independent sample t -tests were used to determine differences between patients and controls and differences among genotype groups were examined using a one-way analysis of variance, followed by a Tukey's post hoc test. Results:, Plasma tHcy was significantly elevated in patients with a family history of CVD (compared to those without) (P = 0.013). A nonsignificant trend towards higher tHcy (compared to those without) was observed in patients with the TT genotype (P = 0.419). Furthermore, specifically in those with the TT genotype, those with a family history of CVD (compared to those without) showed significantly higher tHcy concentrations (P < 0.005). Those with the TT genotype who smoked had significantly higher tHcy (P < 0.05) than the CC and CT genotypes. Discussion:, The findings presented provide evidence to support an association between the MTHFR 677C,T polymorphism, elevated homocysteine and family history of premature CVD. Given that dietary levels of riboflavin have been shown to lower homocysteine specifically in individuals with the TT genotype (McNulty et al., 2006), these results have implications for the dietary management of premature CVD in those individuals with a genetic predisposition for elevated tHcy. In conclusion, further research in larger cohort numbers, regarding the correlation between family history, tHcy and the MTHFR polymorphism, would be beneficial for establishing their cause and effect relationship. References British Heart Foundation (2006) All Deaths and Deaths Under 75 by Cause and Sex, 2005, England, Wales, Scotland, N Ireland and United Kingdom. Available at http://www.bhf.org.uk/research_health_professionals/resources/heart_statistics.aspx. Homocystine Studies Collaboration (2002) Homocysteine and the risk of ishaemic heart disease and stroke. JAMA288, 2015,2022. Llyod-Jones, D.M., Nam, B.H., D'Agostino, R.B., Levy, D., Murabito, J.M., Wang, T.J., Wilson, P.W. & O'Donnell, C.J. (2004) Parental cardiovascular disease as a risk factor for cardiovascular disease in middle-aged adults, a prospective study of parents and offspring. JAMA291, 2204,2211. McNulty, H., Dowey le, R.C., Strain, J.J., Dunne, A., Ward, M., Molloy, A.M., McAnena. L.B., Hughes, J.P., Hannon-Fletcher, M. & Scott, J.M. Riboflavin lowers homocysteine in individuals homozygous for the MTHFR 677C->T polymorphism. Circulation113, 74,80. [source] Homocysteine, malondialdehyde and endothelial markers in dialysis patients during low-dose folinic acid therapyJOURNAL OF INTERNAL MEDICINE, Issue 5 2002T. Apeland Abstract. Apeland T, Mansoor MA, Seljeflot I, Brønstad I, Gøransson L, Strandjord RE (Rogaland Central Hospital, Stavanger; and Ullevål University Hospital, Oslo; Norway). Homocysteine, malondialdehyde and endothelial markers in dialysis patients during low-dose folinic acid therapy. J Intern Med 2002; 252: 456,464. Objectives. Haemodialysis patients have elevated levels of the atherogenic amino acid homocysteine. We wanted to assess the effects of small doses of intravenous folinic acid (the active form of folic acid) on some biochemical risk factors of cardiovascular disease. Design. Longitudinal and open intervention study. Setting. Two dialysis units in the County of Rogaland. Subjects. All patients on maintenance haemodialysis were invited, and 32 of 35 patients gave their informed consent. Interventions. After each dialysis session, the patients were given 1.0 mg of folinic acid intravenously thrice a week for a period of 3 months. Prior to and during the study, all patients were on maintenance supplementation with small doses of vitamins B1, B2, B3, B5, B6 and B12. Main outcome measures. Changes in the levels of (i) plasma total homocysteine (p-tHcy) and folate, (ii) circulating endothelium related proteins , markers of endothelial activation and (iii) serum malondialdehyde (S-MDA) , a marker of oxidative stress and lipid peroxidation. Results. The p-tHcy levels were reduced by 37% (P < 0.0001), whilst the serum and erythrocyte folate levels increased by 95 and 104%, respectively (P < 0.0001 for both). The circulating levels of endothelium related cellular adhesion molecules and haemostatic factors remained high and unchanged, except the thrombomodulin (TM) levels increased (P = 0.0004). The high levels of S-MDA were reduced by 26% (P = 0.003). Conclusions. Low doses of folinic acid given intravenously to dialysis patients reduced their levels of p-tHcy and S-MDA and thus improved their cardiovascular risk profile. The concurrent increment in TM levels was unexpected and of unknown clinical significance. [source] Homocysteine in Health and DiseaseJOURNAL OF INTERVENTIONAL CARDIOLOGY, Issue 2 2003Article first published online: 28 APR 200 No abstract is available for this article. [source] Dietary folate deficiency and elevated homocysteine levels endanger dopaminergic neurons in models of Parkinson's diseaseJOURNAL OF NEUROCHEMISTRY, Issue 1 2002Wenzhen Duan Abstract Although the cause of Parkinson's disease (PD) is unknown, data suggest roles for environmental factors that may sensitize dopaminergic neurons to age-related dysfunction and death. Based upon epidemiological data suggesting roles for dietary factors in PD and other age-related neurodegenerative disorders, we tested the hypothesis that dietary folate can modify vulnerability of dopaminergic neurons to dysfunction and death in a mouse model of PD. We report that dietary folate deficiency sensitizes mice to MPTP-induced PD-like pathology and motor dysfunction. Mice on a folate-deficient diet exhibit elevated levels of plasma homocysteine. When infused directly into either the substantia nigra or striatum, homocysteine exacerbates MPTP-induced dopamine depletion, neuronal degeneration and motor dysfunction. Homocysteine exacerbates oxidative stress, mitochondrial dysfunction and apoptosis in human dopaminergic cells exposed to the pesticide rotenone or the pro-oxidant Fe2+. The adverse effects of homocysteine on dopaminergic cells is ameliorated by administration of the antioxidant uric acid and by an inhibitor of poly (ADP-ribose) polymerase. The ability of folate deficiency and elevated homocysteine levels to sensitize dopaminergic neurons to environmental toxins suggests a mechanism whereby dietary folate may influence risk for PD. [source] Dual effect of DL -homocysteine and S -adenosylhomocysteine on brain synthesis of the glutamate receptor antagonist, kynurenic acidJOURNAL OF NEUROSCIENCE RESEARCH, Issue 3 2005E. Luchowska Abstract Increased serum level of homocysteine, a sulfur-containing amino acid, is considered a risk factor in vascular disorders and in dementias. The effect of homocysteine and metabolically related compounds on brain production of kynurenic acid (KYNA), an endogenous antagonist of glutamate ionotropic receptors, was studied. In rat cortical slices, DL -homocysteine enhanced (0.1,0.5 mM) or inhibited (concentration inducing 50% inhibition [IC50] = 6.4 [5.5,7.5] mM) KYNA production. In vivo peripheral application of DL -homocysteine (1.3 mmol/kg intraperitoneally) increased KYNA content (pmol/g tissue) from 8.47 ± 1.57 to 13.04 ± 2.86 (P < 0.01; 15 min) and 11.4 ± 1.72 (P < 0.01; 60 min) in cortex, and from 4.11 ± 1.54 to 10.02 ± 3.08 (P < 0.01; 15 min) in rat hippocampus. High concentrations of DL -homocysteine (20 mM) applied via microdialysis probe decreased KYNA levels in rabbit hippocampus; this effect was antagonized partially by an antagonist of group I metabotropic glutamate receptors, LY367385. In vitro, S -adenosylhomocysteine acted similar to but more potently than DL -homocysteine, augmenting KYNA production at 0.03,0.08 mM and reducing it at ,0.5 mM. The stimulatory effect of S -adenosylhomocysteine was abolished in the presence of the L -kynurenine uptake inhibitors L -leucine and L -phenyloalanine. Neither the N -methyl- D -aspartate (NMDA) antagonist CGS 19755 nor L -glycine influenced DL -homocysteine- and S -adenosylhomocysteine-induced changes of KYNA synthesis in vitro. DL -Homocysteine inhibited the activity of both KYNA biosynthetic enzymes, kynurenine aminotransferases (KATs) I and II, whereas S -adenosylhomocysteine reduced only the activity of KAT II. L -Methionine and L -cysteine, thiol-containing compounds metabolically related to homocysteine, acted only as weak inhibitors, reducing KYNA production in vitro and inhibiting the activity of KAT II (L -cysteine) or KAT I (L -methionine). The present data suggest that DL -homocysteine biphasically modulates KYNA synthesis. This seems to result from conversion of compound to S -adenosylhomocysteine, also acting dually on KYNA formation, and in part from the direct interaction of homocysteine with metabotropic glutamate receptors and KYNA biosynthetic enzymes. It seems probable that hyperhomocystemia-associated brain dysfunction is mediated partially by changes in brain KYNA level. © 2004 Wiley-Liss, Inc. [source] Plasma Homocysteine, Fasting Insulin, and Androgen Patterns among Women with Polycystic Ovaries and InfertilityJOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 3 2001Dr. E. Scott Sills Abstract Objective: To measure plasma homocysteine, androgen, and insulin concentrations in women with normal and polycystic-appearing ovaries in an infertility setting. Methods: Among women referred for infertility evaluation (n = 54), homocysteine, androstenedione, DHEAS, total testosterone, fasting insulin/glucose and methyltetrahydrofolate reductase (MTHFR) polymorphism status (C677T mutation) were studied. Ovaries were examined via transvaginal sonogram by one observer and scored as either normal (n = 18) or polycystic (n = 36). Results: When polycystic ovaries were identified, mean total testosterone was significantly higher than when non-polycystic ovaries were present (p = 0.01), although no measured androgen was outside the normal reference range in either group. Average BMI was higher in the polycystic group, but the difference was not significant (p = 0.10). We observed a trend toward higher mean fasting insulin levels in women with polycystic ovaries, but this increase did not reach statistical significance (p = 0.07). Median plasma homocysteine was identical (7.0 mmol/l) in both populations, and no study subject exceeded the current recommended maximum reference value. Conclusions: In this population, the presence of polycystic ovaries was associated with higher serum androgens (especially total testosterone) although none of the measured androgens were above the normal range. While fasting insulin levels were also higher in this group, median plasma homocysteine levels were similar irrespective of ovarian morphology. Concomitant plasma homocysteine derangements in this population of young, lean patients with polycystic-appearing ovaries seem unlikely. Further studies are needed to clarify the role(s) of homocysteine in human reproductive physiology. [source] Homocysteine and cardiovascular disease: A review of current recommendations for screening and treatmentJOURNAL OF THE AMERICAN ACADEMY OF NURSE PRACTITIONERS, Issue 3 2005KarenL. Purpose To review the literature for, and provide advanced practice nurses (APNs) with, current recommendations for screening and treatment of hyperhomocysteinemia. Data sources Medscape literature search of selected research studies and related journal articles. Conclusions While data from most epidemiologic studies support the argument that hyperhomocysteinemia is an independent risk factor for cardiovascular disease, the debate continues as to when screening and treating patients is appropriate. The consensus is that more randomized controlled trials are needed to further study the benefits of routine screening and the efficacy of treating hyperhomocysteinemia. Implications for practice Until the results of ongoing clinical trials are available, APNs should follow the American Heart Association guidelines for screening for elevated levels of homocysteine and continue to promote a well-balanced diet that includes foods rich in folic acid as part of health promotion through primary prevention. [source] Plasma Homocysteine, B Vitamins, and Amino Acid Concentrations in Cats with Cardiomyopathy and Arterial ThromboembolismJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 5 2000M.A. McMichael Arterial thromboembolism (ATE) is a common complication of cats with cardiomyopathy (CM), but little is known about the pathophysiology of ATE. In people, high plasma concentrations of homocysteine and low B vitamin concentrations are risk factors for peripheral vascular disease. In addition, low plasma arginine concentrations have been linked to endothelial dysfunction. The purpose of this study was to compare concentrations of homocysteine, B vitamins, and amino acids in plasma of normal cats to those of cats with CM and ATE. Plasma concentrations of homocysteine, vitamin B6, vitamin B12, folate, and amino acids were measured in 29 healthy cats, 27 cats with CM alone, and 28 cats with both CM and ATE. No differences were found between groups in homocysteine or folate. Mean vitamin B12 concentration (mean ± standard deviation) was lower in cats with ATE (866 ± 367 pg/mL) and cats with CM (939 ± 389 pg/mL) compared with healthy controls (1,650 ± 700 pg/mL; P < .001). Mean vitamin B6 concentration was lower in cats with ATE (3,247 ± 1,215 pmol/mL) and cats with CM (3,200 ± 906 pmol/mL) compared with healthy control animals (4,380 ± 1,302 pmol/mL; P= .005). Plasma arginine concentrations were lower in cats with ATE (75 ± 33 nmol/mL) compared with cats with CM (106 ± 25 nmol/mL) and healthy control animals (96 ± 25 nmol/ mL; P < .001). Vitamin B12 concentration was significantly correlated with left atrial size. We interpret the results of this study to suggest that vitamin B12 and arginine may play a role in CM and ATE of cats. [source] Homocysteine levels and sustained virological response to pegylated-interferon ,2b plus ribavirin therapy for chronic hepatitis C: a prospective studyLIVER INTERNATIONAL, Issue 2 2009Guglielmo Borgia Abstract Background: Chronic hepatitis C affects about 3% of the world's population. Pegylated interferon (IFN) , plus ribavirin is the gold standard treatment. Methylenetetrahydrofolate reductase(MTHFR) is a key enzyme in the metabolism of homocysteine. MTHFR gene polymorphisms and high levels of homocysteine are associated with a high degree of steatosis and fibrosis, conditions associated with a low sustained virological response (SVR) rate. Aims: To evaluate whether MTHFR polymorphisms and homocysteine levels are predictors of the outcome of treatment in 102 prospectively enrolled patients with chronic hepatitis C naive to treatment. Methods: Patients were treated with pegylated interferon ,-2b plus ribavirin. All patients underwent blood tests, assessment of homocysteine, vitamin B12, folate, hepatitis C virus (HCV)-RNA levels, screening for MTHFR gene polymorphisms and liver ultrasound examination. Results: Homocysteine levels were deranged (>16 ,mol/L) in 10.5% of MTHFR wild-type patients vs 40.3% of non-wild-type patients (P=0.015). Homocysteine levels were 14.4 ,mol/L in SVR patients and 15.5 ,mol/L in non-SVR patients (P=0.049). The SVR rate was 40.0% in MTHFR wild-type patients, 52.0% in heterozygote mutants and 39.3% in homozygote mutants (P=0.467). At logistic regression analysis, genotypes 2 and 3 (odds ratio: 12.328, 95% confidence interval: 3.390,44.837, P=0.0001), homocysteine <16 ,mol/L (odds ratio: 3.397, 95% confidence interval: 1.033,11.177, P=0.044) and aspartate aminotransferase (AST) levels <48 U/L (odds ratio: 3.262, 95% confidence interval: 1.125,9.458, P=0.029) were independent predictors of SVR. Conclusions: In patients with chronic hepatitis C, homocysteine levels are associated with the outcome of pegylated-IFN, plus ribavirin treatment, while polymorphisms of MTHFR are not. [source] Homocysteine, Folate Deficiency, and Parkinson's DiseaseNUTRITION REVIEWS, Issue 12 2002Article first published online: 16 SEP 200 Folate deficiency sensitizes mice to dopaminergic neurodegeneration and motor dysfunction caused by the neurotoxin 1-methyl-4-pheny-1,2,3,6-tetrahydropyridine (MPTP). Additional experiments indicate that this effect of folate deficiency may be mediated by homocysteine. These findings suggest that folate deficiency and hyperhomocysteinemia are risk factors for Parkinson's disease. [source] Homocysteine: A History in ProgressNUTRITION REVIEWS, Issue 7 2000James D. Finkelstein M.D. This paper shows that the linkage between basic science and clinical research has characterized the field of sulfur amino acid metabolism since 1810, when Wollaston isolated cystine from a human bladder stone. The nature and consequences of this relationship are discussed. [source] Homocysteine, white matter hyperintensities, and cognition in healthy elderly peopleANNALS OF NEUROLOGY, Issue 2 2003Carole Dufouil PhD Hyperhomocysteinemia is associated with an increased risk of vascular disease, and recent results suggest that it also could increase the risk of dementia. We examined the relationship between homocysteine and cognitive decline in 1,241 subjects aged 61 to 73 years, followed up over 4 years. Plasma homocysteine levels were determined in all participants as well as cardiovascular risk factors, apolipoprotein E genotype, plasma levels of folate, and vitamin B12. Cognitive performances were assessed repeatedly by using Mini-Mental State Examination, Trail Making Test, Digit Symbol Substitution Test, and Finger Tapping Test. At 2-year follow-up, 841 subjects underwent cerebral magnetic resonance imaging, and white matter hyperintensities were rated visually. Analyses were adjusted for all cardiovascular risk factors. Cross-sectional analyses showed that higher concentrations of homocysteine were significantly related to poorer performances at all neuropsychological tests. Longitudinal analyses confirmed this finding. The odds of cognitive decline was 2.8-fold (p < 0.05) higher in subjects with homocysteine levels above 15,mol/L compared with those with homocysteine levels below 10,mol/L. In participants who underwent magnetic resonance imaging, the relationship between homocysteine and cognition was unchanged after taking into account white matter hyperintensities suggesting that white matter hyperintensities do not mediate the association between homocysteine and cognition. Ann Neurol 2003;53:000,000 [source] The Effect of Glutathione Modulation on the Concentration of Homocysteine in Plasma of RatsBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 3 2000Kjell K. Øvrebø Elevated plasma homocysteine concentration in humans is associated with increased risk of arteriosclerosis and ischaemic heart disease. We studied whether the plasma homocysteine concentration could be changed by administration of drugs that modulate the concentration of glutathione in both plasma and tissue. Male wistar rats received reduced glutathione (0.5 mmol/kg), N -acetylcysteine (0.5 mmol/kg), L-buthionine-[S,R]-sulfoximine (2 mmol/kg) or Ringer acetate intravenously. Twenty min. later an arterial blood sample was drawn for the measurement of homocysteine and other thiols in the plasma. The thiols were quantified by reversed-phase ion-pair liquid chromatography and fluorescence detection. The total homocysteine concentration in plasma of fasted rats was 6.1±0.5 ,M. Intravenous administration of reduced glutathione or N -acetylcysteine reduced the homocysteine concentration in plasma significantly by 51% to 3.0±0.3 ,M and 63% to 2.2±0.2 ,M, respectively (P<0.05). In contrast, L-buthionine-[S,R]-sulfoximine increased the concentration of homocysteine by 41% to 8.6±0.6 ,M (P<0.05). The glutathione concentration in plasma was 19.5±1.9 ,M in controls and was unchanged by N -acetylcysteine administration. Reduced glutathione increased plasma glutathione to 379.7±22.9 ,M (P<0.05), whereas L-buthionine-[S R]-sulfoximine lowered the plasma glutathione concentration to 5.3±0.4 ,M. Homocysteine was negatively correlated to the glutathione (r=,0.399, P<0.01) and the cysteine (r=,0.52, P<0.01) concentrations in plasma. Our conclusion is that modulation of the glutathione levels influences the concentration of homocysteine in plasma of rats. [source] Homocysteine metabolism and its relation to health and diseaseBIOFACTORS, Issue 1 2010Kelly T. Williams Abstract Homocysteine is a metabolic intermediate in methyl group metabolism that is dependent on a number of nutritional B-vitamin cofactors. An emerging aspect of homocysteine metabolism is its relation to health and disease. Perturbations of homocysteine metabolism, particularly intracellular and subsequently circulating accumulation of homocysteine (i.e., hyperhomocysteinemia), are associated with vascular disease risk, as well as other pathologies. However, intervention with B-vitamin supplementation has been shown to successfully restore normal homocysteine concentrations, but without concomitant reductions in disease risk. Thus, the mechanistic relation between homocysteine balance and disease states, as well as the value of homocysteine management, remains an area of intense investigation. [source] Homocysteine is positively associated with cytokine IL-18 plasma levels in coronary artery bypass surgery patientsBIOFACTORS, Issue 2 2005Craig Steven Mclachlan Abstract Homocysteine, cytokines (IL-18, IL-6, IL-8) are involved in vascular inflammation and coronary artery disease. Homocysteine influences endothelial IL-6 and IL-8 cytokine expression and release, however, an association between homocysteine and IL-18 has not been previously investigated in endothelial/smooth muscle cells and or in coronary artery disease. We report in 9 coronary artery bypass surgery (CABG) patients a positive correlation r=0.86 between homocysteine and IL-18 plasma levels (p<0.05). Plasma IL-18 levels are significantly higher in those patients with elevated homocysteine compared to those with normal levels (p<0.02; 153 ± 19 pg/ml versus 116 ± 14 pg/ml respectively). Our in vitro cell culture studies suggest that the source of IL-18 in CABG patients with elevated homocysteine is not from vascular smooth muscle or endothelial cells. [source] Association between hyperhomocysteinaemia and abdominal aortic aneurysmBRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 4 2001S. Caldwell Background: Hyperhomocysteinaemia is associated with occlusive vascular disease. In vitro evidence has demonstrated the induction of a serine elastase by homocysteine in vascular smooth muscle. Anecdotal evidence from case reports and post-mortem studies has suggested an association with abdominal aortic aneurysm (AAA). The aim was to determine the prevalence of hyperhomocysteinaemia in patients with AAA. Methods: Some 120 subjects (60 controls and 60 patients with AAA) were studied prospectively. Epidemiological, clinical and haematological data were collected. Patients were defined as having AAA if ultrasonographic measurement of the aorta was greater than 4·5 cm. Those with evidence of occlusive peripheral vascular disease or an ankle: brachial pressure index lower than 0·8 were excluded. Homocysteine was measured with a commercial high-pressure liquid chromatography analyser. The reference range from age-matched controls was 8·9,14·3 µmol l,1. Results: The median(s.d.) value of homocysteine for patients was significantly higher than that for the control group: 13·1(7·88) versus 10·9(5·07) µmol l,1 (P = 0·03, Mann,Whitney U test). Hyperhomocysteinaemia (homocysteine concentration greater than 14·3 µu;mol l,1) was present in 48 per cent of patients with AAA, compared with 24 per cent of the control population (P < 0·01, ,2 test). There were no significant differences between groups with regard to age, folate levels, vitamin B12 concentration or renal function. Conclusion: These results strongly suggest an association between hyperhomocysteinaemia and AAA. If studies currently ongoing demonstrate a causal relationship between hyperhomocysteinaemia and vascular disease progression, it raises the possibility of treating small aneurysms with vitamin supplementation to slow their growth. © 2001 British Journal of Surgery Society Ltd [source] A Highly Selective FRET-Based Fluorescent Probe for Detection of Cysteine and HomocysteineCHEMISTRY - A EUROPEAN JOURNAL, Issue 11 2010Hoi-Yan Shiu Fluorescent probe: A "turn-on" FRET-based fluorescent probe for selective detection of cysteine (Cys) and homocysteine (Hcy) under physiological conditions was synthesised (see figure). The probe features excellent selectivity, fast response times and good linearity towards Cys and Hcy detection. [source] Experimental hyperhomocysteinaemia: differences in tissue metabolites between homocystine and methionine feeding in a rat modelACTA PHYSIOLOGICA, Issue 1 2009A. Pexa Abstract Aim:, Hyperhomocysteinaemia, diagnosed by serum levels, is regarded as an independent risk indicator for cardiovascular events and is associated with various diseases. The pathomechanisms seem to be partly due to concentrations of homocysteine metabolites and their effect on the cellular transmethylation processes. Methods:, We compared two common models for experimental hyperhomocysteinaemia , high methionine diet and homocystine-enriched diet , regarding their effects on tissue concentrations of homocysteine metabolites. Results:, Both diets induced hyperhomocysteinaemia without affecting renal function or vitamine status. However, the tissue contents of homocysteine and its precursors S -adenosyl-homocysteine (SAH) and S -adenosyl-methionine exhibited major differences between both models. Transmethylation potential was elevated 1.7-fold in liver of rats fed the methionine diet, whereas it was unaltered after homocystine-enriched diet. Kidneys of rats fed the methionine diet did not show any alterations in tissue content of homocysteine and its precursors, whereas in the homocystine group homocysteine and the transmethylation inhibitor SAH were elevated from 23.1 ± 10.4 to 78.0 ± 26.0 nmol g,1 and from 106 ± 4 to 170 ± 22 nmol g,1 respectively. Homocysteine tissue content was elevated in the homocystine, but not in the methionine group. Conclusions:, Alterations to homocysteine metabolism are distinct in both models. These findings may explain divergent results, which have been published for these models of hyperhomocysteinaemia and which have resulted in controversial discussions in the past. [source] Homocysteine enhances cardiac neural crest cell attachment in vitro by increasing intracellular calcium levelsDEVELOPMENTAL DYNAMICS, Issue 8 2008David J. Heidenreich Abstract Elevated homocysteine (Hcys) increases the risk of neurocristopathies. Previous studies show Hcys inhibits neural crest (NC) cell migration in vivo. However, the mechanisms responsible for this effect are unknown. Here, we evaluated the effect of Hcys on NC cell attachment in vitro and determined if any of the effects were due to altered Ca2+ signaling. We found Hcys enhanced NC cell attachment in a dose and substrate-dependent manner. Ionomycin mimicked the effect of Hcys while BAPTA-AM and 2-APB blocked the effect of Hcys on NC attachment. In contrast, inhibitors of plasma membrane Ca2+ channels had no effect on NC attachment. Hcys also increased the emission of the intracellular Ca2+ -sensitive probe, Fluo-4. These results show Hcys alters NC attachment by triggering an increase in intracellular Ca2+ possibly by generating inositol triphosphate. Hence, the teratogenic effect ascribed to Hcys may be due to perturbation of intracellular Ca2+ signaling. Developmental Dynamics 237:2117,2128, 2008. © 2008 Wiley-Liss, Inc. [source] Homocysteine inhibits cardiac neural crest cell formation and morphogenesis in vivoDEVELOPMENTAL DYNAMICS, Issue 1 2004Brent J. Tierney Abstract Elevated homocysteine increases the risk of neurocristopathies. Here, we determined whether elevating homocysteine altered the proliferation or number of chick neural crest cells that form between the midotic and third somite in vivo. Homocysteine increased the number of neural tube cells but decreased neural crest cell number. However, the sum total of cells was not different from controls. In controls, the 5-bromo-2,-deoxyuridine-labeling index was higher in newly formed neural crest cells than in their progenitors, paralleling reports showing these progenitors must pass the restriction point before undergoing epithelial,mesenchymal transition. Homocysteine decreased the labeling index of newly formed neural crest cells, suggesting that it inhibited cell cycle progression of neural crest progenitors or the S-phase entry of newly formed neural crest cells. Homocysteine also inhibited neural crest dispersal and decreased the distance they migrated from the neural tube. These results show neural crest morphogenesis is directly altered by elevated homocysteine in vivo. Developmental Dynamics 229:63,73, 2004. © 2003 Wiley-Liss, Inc. [source] Effect of elevated homocysteine on cardiac neural crest migration in vitroDEVELOPMENTAL DYNAMICS, Issue 2 2002Philip R. Brauer Abstract A positive correlation between elevated maternal homocysteine (Hcys) and an increased risk of neural tube, craniofacial, and cardiac defects is well known. Studies suggest Hcys perturbs neural crest (NC) development and may involve N-methyl-D-aspartate (NMDA) receptors (Rosenquist et al., 1999). However, there is no direct evidence that Hcys alters NC cell behavior. Here, we evaluated the effect of Hcys on cardiac NC cell migratory behavior in vitro. Neural tube segments from chick embryos treated in ovo with or without Hcys were placed in culture and the migratory behavior of emigrating NC cells was monitored. Hcys significantly increased in vitro NC cell motility at all embryonic stages examined. NC cell surface area and perimeter were also increased. However, the relative distance NC cells migrated from their original starting point only increased in NC cells treated in ovo at stage 6 or at the time neural tube segments were cultured. Cysteine had no effect. NMDA mimicked Hcys' effect on NC motility and migration distance but had no effect on cell area or perimeter. The noncompetitive inhibitor of NMDA receptors, MK801+, significantly inhibited NC cell motility, reduced migration distance, and also blocked the effects of NMDA and Hcys on NC motility and migratory distance in vitro. A monoclonal antibody directed against the NMDA receptor immunostained NC cells in vitro and, in western blots, bound a single protein with the appropriate molecular weight for the NMDA receptor in NC cell lysates. These data are consistent with the hypothesis that a Hcys-sensitive NMDA-like receptor is expressed by early emigrating NC cells or their precursors, which is important in mediating their migratory behavior. Perturbation of this receptor may be related to some of the teratogenic effects observed with elevated Hcys. © 2002 Wiley-Liss, Inc. [source] | |||||||||||||||||||||||||||||||||||||