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Objective • This study aimed to investigate the prognostic impact of serum homocysteine-lowering therapy on patients with hemorrhagic stroke (HS) and its influence on their National Institutes of Health Stroke Scale (NIHSS) and China Stroke Scale (CSS) scores. Methods • A double-blind study involving 120 patients with HS and hyperhomocysteinemia (Hhcy) who were admitted to our hospital was conducted in 2021. They were evenly divided into two groups: the control group (n=60) received low-dose folic acid, methylcobalamin, and vitamin B6 as part of serum homocysteine-lowering therapy, while the study group (n=60) received high-dose folic acid, methylcobalamin, and vitamin B6. The prognosis of each group was compared using the NIHSS and CSS to assess the neurological function of the patients. Results • Before treatment, the levels of oxidative stress markers and vascular endothelial function markers were comparable between the two groups (t = 0.051, 0.015, 0.010, 0.011, 0.013, 0.022, P = .960, .988, .992, 0.991, .989, 0.982). However, after treatment, the study group exhibited higher levels of MDA and ET-1 compared to the control group (t = 3.418, 1.978, P < .001). Additionally, SOD, GSH-Px, and PON1 levels were lower in the study group (t = 3.435, 3.783, 2.735, 3.893, P < .001). The NIHSS scores before treatment were comparable among patients (t = 0.058, P = 0.954), but after treatment, the study group showed significantly lower NIHSS scores (t = 20.105, P < .001). Similarly, the CSS scores before treatment were comparable (t = 0.046, P = .963), but the CSS scores in the study group after treatment were significantly lower (t = 5.027, P < .001). Conclusions • High-dose folic acid, methylcobalamin, and vitamin B6 as part of serum homocysteine-lowering therapy can improve oxidative stress and vascular endothelial function in HS patients. This treatment also enhances prognosis and ameliorates neurological deficits. Therefore, it holds significant clinical potential and should be considered for broader adoption. [ABSTRACT FROM AUTHOR]

Background/purpose: Atrophic glossitis (AG) patients are prone to have anemia, hematinic deficiencies, hyperhomocysteinemia, and serum gastric parietal cell antibody (GPCA) positivity. This study evaluated whether 1064 AG patients had significantly higher frequencies of anemia, hematinic deficiencies, hyperhomocysteinemia, and serum GPCA positivity than 532 healthy control subjects.Methods: The complete blood count, serum iron, vitamin B12, folic acid, homocysteine, and serum GPCA levels in 1064 AG patients and 532 age- and sex-matched healthy control subjects were measured and compared.Results: We found that 7.4%, 3.9%, 19.0%, 16.9%, 5.3%, 2.3%, 11.9%, and 26.7% of 1064 AG patients were diagnosed as having microcytosis, macrocytosis, hemoglobin, iron, vitamin B12, and folic acid deficiencies, hyperhomocysteinemia, and serum GPCA positivity, respectively. Moreover, 1064 AG patients had significantly higher frequencies of microcytosis, macrocytosis, hemoglobin, iron, vitamin B12, and folic acid deficiencies, hyperhomocysteinemia, and serum GPCA positivity than 532 healthy control subjects (all P-values < 0.005). Of the 202 anemic AG patients, 22 had pernicious anemia, eight had macrocytic anemia rather than pernicious anemia, 117 had normocytic anemia, 30 had iron deficiency anemia, and 21 had thalassemia trait-induced anemia, and four had microcytic anemia rather than iron deficiency anemia and thalassemia trait-induced anemia.Conclusion: There are significantly higher frequencies of anemia, serum iron, vitamin B12, and folic acid deficiencies, hyperhomocysteinemia, and serum GPCA positivity in AG patients than in healthy control subjects. The normocytic anemia and iron deficiency anemia are the two most common types of anemia in our 1064 AG patients. [ABSTRACT FROM AUTHOR]

Background: 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 hyper-homocysteinemia. Yet, given the limited penetrance of this genetic variant, it is necessary to individually predict the risk of hyperhomocysteinemia for an rs1801133 carrier. Objective: 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. Design: 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. Results: 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. Conclusions: 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 receive genetic data from commercial services without interpretation of its clinical relevance. [ABSTRACT FROM AUTHOR]

Aldosterone plays a key role in maintaining the homeostasis of the whole organism. Under some circumstances, aldosterone can contribute to the progression of cardiovascular diseases, including coronary artery disease. This study demonstrates that aldosterone associates negatively with some lipidogram parameters and positively with the concentration of homocysteine. These associations are characteristic for coronary artery disease and are not present in control subjects. The findings also indicate that in vitro aldosterone stimulates homocysteine production by rat adrenal glands, which may explain the associations observed with coronary artery disease. Moreover, we have found that aldosterone significantly modulates in vitro platelet reactivity to arachidonate and collagen - aldosterone increases the pro-aggregatory action of collagen, but decreases the pro-aggregatory potential of arachidonate. Therefore, the findings of these in vitro and ex vivo experiments indicate the existence of new pathways by which aldosterone modulates lipid- homocysteine- and platelet-dependent atherogenesis. [ABSTRACT FROM AUTHOR]

Background Both homocysteine (Hcy) and blood pressure variability (BPV) are independent predictors of stroke, however, their relationship is rarely evaluated before. This study aimed to investigate the association Hcy and ambulatory BPV in subjects with untreated primary hypertension. Methods A total of 252 eligible patients were recruited. Plasma Hcy was measured and 24-h ambulatory blood pressure monitoring was performed for each subject. The systolic and diastolic BPV values were calculated as the SD of individual blood pressure values during 24 h, daytime and nighttime, and then stratified by the tertiles of Hcy concentration (T1 to T3). Univariate and multivariate linear regression models were used to assess the relationships between Hcy tertiles and BPV variables. Results The mean values of Hcy from T1 to T3 were 7.51 ± 1.21 μmol/l, 11.09 ± 1.07 μmol/l and 19.14 ± 6.26 μmol/l, respectively. Systolic and diastolic mean blood pressures were similar among subjects with different Hcy tertiles. However, both systolic and diastolic BPV variables, no matter in 24-h, daytime or nighttime, were increasing significantly along with the rises in Hcy tertiles (all p < 0.05 for linear trends analysis). Multivariate linear regression analysis indicated that Hcy tertiles were significantly associated with BPV variables, independently of mean blood pressures other confounding factors. In subgroup analysis, the associations between Hcy tertiles and BPV variables were enhanced by the increased risk stratification of hypertension. Conclusions Plasma Hcy was positively and independently associated with ambulatory BPV in patients with untreated hypertension. [ABSTRACT FROM AUTHOR]

Background: Blood homocysteine concentration (BHC) is higher in patients with alcohol use disorder (AUD). Previous studies have found a relationship between depressive symptoms severity and BHC in AUD patients and recently some authors have found high BHC among patients with bipolar disorder, both during manic and depressive episodes and in euthymic state. However, BHC in patients with mixed mood episode has not yet been investigated. The aim of this study was to evaluate the BHC of patients with AUD and mixed mood episode. Methods: A sample of AUD outpatients was assessed by Mini-International Neuropsychiatric Interview (MINI Plus): those with a DSM-IV-TR mood disorder with mixed features were included in the MIXED group (n = 45), whereas those without mood episode were gathered in the NO MOOD group (n = 23). Two subgroups, MIXMANIA and MIXDEPRESSION, were formed according to the prevalence of manic or depressive symptoms, assessed by Young Mania Rating Scale (YMRS), and Hamilton Rating Scale for Depression (HDRS). The Alcohol Use Disorder Identification Test (AUDIT) was used to appraise the AUD. BHC was determined by High-Performance Liquid Chromatography. Results: The MIXED group showed greater severity of both depressive (26.35 ± 9.96 vs. 4.77 ± 0.92; p < 0.001) and manic (22.35 ± 3.30 vs. 6.14 ± 1.12; p < 0.001) symptoms, and higher BHC (28.80 ± 11.47 vs. 10.83 ± 2.81; p < 0.001), than the NO MOOD group. BHC was strongly correlated to the HDRS, YMRS and AUDIT scores, just as HDRS was to YMRS, and AUDIT was to both HDRS and YMRS, in the MIXED group only (p < 0.001). The MIXDEPRESSION subgroup showed higher BHC than the MIXMANIA subgroup (Mdn = 42.96, IQR = 10.44 vs. Mdn = 19.77, IQR = 5.93; p < 0.001). A linear regression model conducted on the MIXED group found a significant predictive value for BHC of both HDRS (β = 0.560, t = 2.43, p = 0.026) and AUDIT (β = 0.348, t = 2.17, p = 0.044). Conclusions: Depressive symptoms seem to be mainly implicated in the BHC elevation among patients with both mixed features mood disorder and AUD. [ABSTRACT FROM AUTHOR]

Aims/Introduction An elevated level of plasma homocysteine has long been suspected as a metabolic risk factor for the development of atherosclerotic vascular diseases in diabetes. Berberine ( BBR) has several preventive effects on cardiovascular diseases. The effects of BBR on atherosclerotic plaque stability increased by homocysteine thiolactone ( HTL) remain unknown. Materials and Methods The model of atherosclerotic vulnerable plaque was induced by placing a collar around the carotid artery in Apoe −/− mice. Endothelium-dependent relaxation was assayed by organ chamber. Results Homocysteine thiolactone (50 mg/kg/day, 8 weeks) reduced the atherosclerotic plaque stability in the carotid artery of Apoe −/− mice, which was reversed by BBR administration (1.0 g/kg/day). In vivo and ex vivo experiments showed that HTL dramatically reduced acetylcholine-induced endothelium-dependent relaxation and superoxide dismutase activity, and increased malondialdehyde content, which were inhibited by BBR. Importantly, all effects induced by BBR were abolished by GW9662, an antagonist of peroxisome proliferator-activated receptor-γ. Incubation of cultured endothelial cells with HTL significantly reduced cell viabilities and enhanced production of reactive oxygen species. Pretreatment of cells with BBR dose-dependently reversed HTL-induced detrimental effects, which were GW9662-reversible. Conclusions Berberine increases atherosclerotic plaque stability in hyperhomocysteinemia mice, which is related to the activation of peroxisome proliferator-activated receptor-γ and subsequent suppression of oxidative stress in endothelial cells. [ABSTRACT FROM AUTHOR]

Introduction: Hyperhomocysteinemia is common in end stage renal diseases. We aimed to determine the prevalence of hyperhomocysteinemia in dialysis cases and define independent risk factors of the development of hyperhomocysteinemia. Materials and Methods: The total plasma homocysteine values were measured in 46 dialysis patients including 20[43.4%] girls and 26[56.6%] boys aged 1.6-25 [19.9±6.5] years based on two different reference values for children [age dependent] and adults [cut off point of 15 µmol/L]. Results: Using the reference values for children, 26 cases [56.2%] had hyperhomocysteinemia including 41.6% of CAPD and 2/3 of hemodialysis patients with no significant difference based on age, gender, duration and modality of dialysis, and dosage of folate supplement [p>0.05 for all]. Using a cut-off point of 15 µmol/L, hyperhomocysteinemia was reported in 30.4% of the patients including 11 hemodialysis and one CAPD [P=0.022], 10 out of 19 girls [52.6%%] and 4 out of 26 boys [15.4%] [p=0.063], but logistic regression analysis did not show any significant differences in the incidence rate of hyperhomocysteinemia according to the modality of dialysis and gender [P=0.998 and 0.137 respectively]. Conclusions: We found mild hyperhomocysteinemia as a common finding in dialysis patients; also, the prevalence of hyperhomocysteinemia was comparable in children and young adults. However, we noted that hemodialysis patients and females were more prone to more intense elevations of plasma homocysteine levels. We found that neither gender nor modality of dialysis played a role as risk factors for development of hyperhomocysteinemia in children and young adults. [ABSTRACT FROM AUTHOR]

Hyperhomocysteinemia induces vascular endothelial dysfunction, an early hallmark of atherogenesis. While higher levels of circulating asymmetric dimethylarginine (ADMA) and symmetric dimethyl arginine (SDMA), endogenous inhibitors of nitric oxide synthesis, have been associated with increased cardiovascular risk, the role that ADMA and SDMA play in the initiation of hyperhomocysteinemia-induced endothelial dysfunction remains still controversial. In the present study, we studied the changes of circulating ADMA and SDMA in a rat model of acutely hyperhomocysteinemia-induced endothelial dysfunction. In healthy rats, endothelium-related vascular reactivity (measured as acetylcholine-induced transient decrease in mean arterial blood pressure), plasma ADMA and SDMA, total plasma homocysteine (tHcy), cysteine and glutathione were measured before and 2, 4 and 6 h after methionine loading or vehicle. mRNA expression of hepatic dimethylarginine dimethylaminohydrolase-1 (DDAH1), a key protein responsible for ADMA metabolism, was measured 6 h after the methionine loading or the vehicle. Expectedly, methionine load induced a sustained increase in tHcy (up to 54.9 ± 1.9 µM) and a 30 % decrease in vascular reactivity compared to the baseline values. Plasma ADMA and SDMA decreased transiently after the methionine load. Hepatic mRNA expression of DDAH1, cathepsin D, and ubiquitin were significantly lower 6 h after the methionine load than after the vehicle. The absence of an elevation of circulating ADMA and SDMA in this model suggests that endothelial dysfunction induced by acute hyperhomocysteinemia cannot be explained by an up-regulation of protein arginine methyltransferases or a down-regulation of DDAH1. In experimental endothelial dysfunction induced by acute hyperhomocysteinemia, down-regulation of the proteasome is likely to dampen the release of ADMA and SDMA in the circulation. [ABSTRACT FROM AUTHOR]

Objective Increasing white matter hyperintensity (WMH) burden is linked to risk of stroke and poor post-stroke outcomes. While the biology of WMH remains ill-defined, several lines of evidence implicate endothelial dysfunction. In this study, we sought to assess the association between metabolic markers of endothelial dysfunction and WMH severity in patients with acute ischemic stroke (AIS). Methods In this retrospective study, consecutive subjects, ≥18 years of age, admitted to our ED with AIS, brain MRI, and blood homocysteine (Hcy) and hemoglobin A1c (HgbA1c) measurements were eligible for this analysis. WMH volume (WMHV) was quantified using a validated semi-automated algorithm and log-transformed for linear regression analyses. Results There were 809 AIS subjects included (mean age 65.57 ± 14.7, median WMHV 6.25 cm 3 (IQR 2.8–13.1)). In univariate analysis, age, female gender, race, ethnicity, systolic blood pressure, history of hypertension, atrial fibrillation, coronary artery disease, prior stroke, and current alcohol and tobacco use (all p < 0.05), as well as Hcy (p < 0.0001) and HgbA1c levels (p = 0.0005) were associated with WMHV. However, only Hcy (β = 0.11, p = 0.003) and HgbA1c levels (β = 0.1, p = 0.008) independently predicted WMHV in the multivariate model, along with age (β = 0.03, p < 0.0001), race (β = 0.39, p = 0.01), ethnicity (β = −0.11, p = 0.03), and current alcohol use (β = 0.26, p = 0.002). Conclusions Elevated levels of Hcy and HgbA1c have been previously linked to endothelial dysfunction related to oxidative stress. The association between Hcy and HgbA1c and WMH burden in AIS suggests that the degree of endothelial dysfunction may be greater in patients with increased WMHV, and may in part explain the relationship between WMHV and poor post-stroke outcomes. [ABSTRACT FROM AUTHOR]

Objective: To investigate the clinical significance of blood Homocysteine levels measured in process of Levodopa Treatment of Parkinson’s disease(PD). Methods: 50 cases of PD patients from inpatient and outpatient in our hospital department of Internal Medicine from March 2012 to March 2014(the case group) were studied, and 50 cases of healthy were selected as control;Homocysteine, folic acid and vitamin B12 levels between the two groups were compared and correlation between homocysteine, folic acid,vitamin B12, levodopa dose and PD patients score(UPDRS score) were analyzed. Results: The plasma homocysteine of the case group was significantly higher than that of the control group(P<0.05), folic acid and vitamin B12 levels were lower than those of the control group, the difference between the two groups were statistically significant(P<0.05); The case group were divided into two subgroups according to plasma homocysteine levels, the high-level group(≥14 μmol/L) and low-level groups(<14 μmol/L), there was on difference in levodopa dose, folic acid and vitamin B12 and UPDRS score between the two subgroups,(P>0.05). Correlation analysis showed a negative correlation between homocysteine and folic acid, vitamin B12 and UPDRS score(r=-0.545,-0.337, =-0.233, P=0.001,0.009, 0.013), and a positive correlation with levodopa dose(r=0.518, P=0.001). Conclusion: Levodopa could elevate blood levels of homocysteine, and reduce the amount of folic acid, vitamin B12 in treatment of PD, so it is necessary to enhance the folic acid, vitamin B12 and other nutritional support clinically. [ABSTRACT FROM AUTHOR]

Abdominal aortic aneurysm (AAA) is a serious vascular disease with high mortality. Our previous study suggested that hyperhomocysteinemia (HHcy) exaggerates the occurrence of AAA. Here, we investigated whether macrophage inflammasome is involved in HHcy-aggravated AAA formation. Two independent HHcy-aggravated AAA models, perivascular calcium phosphate–treated C57BL/6 mice and angiotensin II (Ang II)–infused apolipoprotein E-deficient (ApoE −/− ) mice were used. NLPR3, caspase 1, and interleukin-1β (IL-1β) levels were higher in aneurysmal lesions of both HHcy models compared to controls, preferentially in macrophages. Similarly, macrophage inflammasome activation was observed in vitro . Folic acid administration reversed the HHcy-accelerated AAA, with ameliorated activation of inflammasome in the tunica adventitia. Lentiviral silencing of NLRP3 significantly ameliorated HHcy-aggravated AAA formation. We observed increased mitochondrial production of reactive oxygen species (ROS) and energy switch from oxidative phosphorylation to glycolysis with excess Hcy in macrophages. Blocking mitochondrial ROS production in macrophages abolished inflammasome activation. Our study highlights the potential importance of macrophage inflammasome in the pathogenesis and development of HHcy-aggravated AAA. [ABSTRACT FROM AUTHOR]

Background: Elevations in Homocyteine (Hcys) levels in the blood have been correlated with increased risk for coronary heart disease and stroke, loss of cognition and memory, and other chronic medical conditions. Objective: A retrospective study was initiated to determine if Hcys levels and other blood markers were altered in subjects taking an oral functional food supplement containing a mixture of phosphoglycolipids (NT Factor®) and vitamins. Methods: Thirty-five patients (28 females, 7 males, Av. Age=60.7±9.6 years) who had used the functional food Advanced Physician's FormulaTM with NTFactor® in tablet form each day were enrolled in a retrospective study on blood chemistry. This retrospective study followed a prospective study on the use of the same supplement to reduce fatigue in patients with chronic fatigue. Participants were patients with chronic fatigue syndrome (myalgic encephalomyelitis) or other fatiguing illnesses. Subjects had blood drawn over a 6-month period, and routine blood testing was performed. In this laboratory study the results were analyzed for differences, and statistical analyses were performed. Results: All participants responded in the study and showed an average reduction of 31.8% in Hcys levels (from 10.85±0.42 to 7.40±0.42 μmol/L; t-test, p<0.001; Wilcoxon, p<0.001). Women responded better than men: women (from 11.06±0.50 to 8.67±0.82 μmol/L, 34.4% reduction, t-test, p< 0.001; Wilcoxon, p<0.001) versus men (from 10.80±0.51 to 7.01±0.47 μmol/L, 21.6% reduction, t-test, p< 0.0862). Differences were also found in fasting insulin levels (from 12.80±3.11 to 5.30±1.77 μIU/mL, 58.6% reduction, t-test, p<0.005) and erythrocyte sedimentation rate (ESR). ESR increased from 10.5±2.21 to 20.19±3.20 mm/hr (92.2% increase, t-test, p<0.0314; Wilcoxon, p<0.0154). Other tests were not significantly different after 6 months of supplement, there were no side effects from the test supplement, and none of the participants had any cardiovascular events during the study. Conclusions: The test formulation was an effective method to reduce Hcys and fasting insulin blood levels and increase ESR rates in older subjects without adverse effects. [ABSTRACT FROM AUTHOR]

Purpose: The methylenetetrahydrofolate reductase ( MTHFR) 677C>T and 1298A>C polymorphisms, which are associated with hyperhomocysteinemia and nitric oxide (NO) deficiency (which is related to atherothrombosis and cerebral ischemia), have not been studied in moyamoya disease. A case-control study was performed to investigate whether the MTHFR 677C>T and 1298A>C polymorphisms contribute to moyamoya disease (MMD). Methods: One hundred and seven Korean patients with MMD (mean age, 20.85 ± 15.89 years; 66.4 % female) and 232 healthy control subjects (mean age, 23.99 ± 16.16 years; 56.8 % female) were included. Genotyping for the MTHFR 677C>T and 1298A>C polymorphisms and measurements of homocysteine, folate, vitamin B, and NO in the cerebrospinal fluid (CSF) were performed. The statistical analysis was performed by multivariate linear regression and logistic regression. Result: The MTHFR 677CT+TT genotype frequency was significantly increased with early-onset MMD (<10 years) compared with late-onset MMD (≥10 years) (adjusted odds ratio, 3.392; 95 % confidence interval, 1.294-8.893, P = 0.013). The MTHFR 677C-1298C/677T-1298A diplotype (1.71 ± 1.23 arbitrary units) presented significantly lower NO levels in the CSF compared with the 677C-1298A/677C-1298A diplotype (11.40 ± 12.24 arbitrary units). Conclusion: The MTHFR 677C>T and 1298A>C polymorphisms have restricted roles in the Korean MMD population. Therefore, further studies involving larger and more heterogeneous cohorts are needed to extend our understanding of the influence of polymorphisms in MTHFR and other thrombophilic genes on MMD. [ABSTRACT FROM AUTHOR]

Background and Purpose: This study aimed to explore the possible association of plasma total homocysteine with carotid plaque stability. Methods: A cross-sectional study was conducted from 2010 to 2011. A stratified random sample of 2,919 Chinese participants aged 40 years or older was enrolled. Plasma total homocysteine levels were measured and carotid plaques were evaluated by ultrasonography. Logistic regression model was used to analyze the association of homocysteine levels to the progression of carotid plaque development, while adjusting for demographics and vascular risk factors. Results: The mean level of plasma homocysteine in the subjects was 14.9 µmol/l. Along with increase in homocysteine level, the risk of advanced carotid plaque elevated (odds ratio = 1.28; 95% confidence interval = 1.09–1.51) after adjusting for age, sex, and other potential confounders. Stratified by sex, higher homocysteine level was strongly associated with advanced carotid plaque in men (OR = 1.41; 95% confidence interval = 1.17–1.70), but not in women. Conclusion: The findings suggest that plasma level of homocysteine may be associated with advanced carotid plaque, which constitutes high risks of stroke, in male Chinese adults. [ABSTRACT FROM AUTHOR]

Objective: To compare the mean homocysteine level of ESRD patients undergoing regular hemodialysis with normal age and gender matched controls. Methodology: This observational study was conducted at Dialysis Unit of Fauji Foundation Hospital, from January 2011 to October 2012. Cases included patients from 12-65 years age of either gender who were on regular hemodialysis for more than three months at a frequency of three times a week. Controls were chosen from the healthy relatives and hospital employees who had normal renal functions and were matched for age and gender. Total homocysteine in plasma was measured by HPLC and fluorescence detection. Results: We included 55 hemodialysis patients and 55 controls. The mean age of cases and controls was 45.67±10.68 and 45.94±10.50 years respectively. There were a total of 24 (21.8%) males. The two groups were similar in respect to age and gender distribution. The mean homocysteine level of cases and controls was 17.69±5.17 and 12.85±3.27 µmol/L respectively (p =0.00). Conclusion: Plasma homocysteine levels are significantly higher among homodialysis subjects as compared to normal controls. [ABSTRACT FROM AUTHOR]

Homocysteine is metabolized to methionine by the action of 5,10 methylenetetrahydrofolate reductase (MTHFR). Alternatively, by the transulfuration pathway, homocysteine is transformed to hydrogen sulphide (H2S), through multiple steps involving cystathionine β-synthase and cystathionine γ-lyase. Here we have evaluated the involvement of H2S in the thrombotic events associated with hyperhomocysteinemia. To this purpose we have used platelets harvested from healthy volunteers or patients newly diagnosed with hyperhomocysteinemia with a C677T polymorphism of the MTHFR gene (MTHFR++). NaHS (0.1-100 μM) or L-cysteine (0.1-100 μM) significantly increased platelet aggregation harvested from healthy volunteers induced by thrombin receptor activator peptide-6 amide (2 μ.M) in a concentration-dependent manner. This increase was significantly potentiated in platelets harvested from MTHFR++ carriers, and it was reversed by the inhibition of either cystathionine β-synthase or cystathionine γ-lyase. Similarly, in MTHFR++ carriers, the content of H2S was significantly higher in either platelets or plasma compared with healthy volunteers. Interestingly, thromboxane A2 production was markedly increased in response to both NaHS or L-cysteine in platelets of healthy volunteers. The inhibition of phospholipase A2, cyclooxygenase, or blockade of the thromboxane receptor markedly reduced the effects of H2S. Finally, phosphorylated-phospholipase A2 expression was significantly higher in MTHFR++ carriers compared with healthy volunteers. In conclusion, the H2S pathway is involved in the prothrombotic events occurring in hyperhomocysteinemic patients. [ABSTRACT FROM AUTHOR]

Background: Elevated total plasma homocysteine is an independent risk factor for arterial and venous thrombosis in patients with normal renal function. Patients on hemodialysis have a high prevalence of mild to moderate hyperhomocysteinemia. Conflicting retrospective analyses and prospective studies have been reported regarding the association between total homocysteine levels and hemodialysis vascular thrombosis. The purpose of this retrospective study was to investigate the relationship between hyperhomocysteinemia and vascular access thrombosis (VAT) in patients on hemodialysis. Methods: One hundred and twenty-five patients undergoing dialysis were selected as subjects. The experimental group participants were identified as those having one or more VAT during the previous 13 months and the control group participants had no access thrombosis during the same period. Additional subgroup analysis included the presence of hypertension, diabetes, low-density lipoprotein levels, sex, and use of aspirin. Results: No statistically significant difference was found in total homocysteine levels between the two groups (P = 0.27). No association was found between VAT and sex (P = 0.09), VAT and hypertension (P = 0.96), VAT and diabetes (P = 0.49), nor VAT and low-density lipoprotein level (P = 0.04). A lower rate of VAT was associated with aspirin intake (P = 0.04). Conclusion: This study did not demonstrate a relationship between total homocysteine concentrations and risk of VAT in patients with end-stage renal disease on hemodialysis. There were no significant differences in the number of VAT across additional variables of sex and previous morbidity. Aspirin intake was associated with a lower incidence of VAT. [ABSTRACT FROM AUTHOR]

Background/Purpose: Burning mouth syndrome (BMS) is characterized by a burning sensation of the oral mucosa in the absence of clinically apparent mucosal alterations. In this study, we evaluated whether there was an intimate association of the deficiency of hemoglobin (Hb), iron, vitamin B12, or folic acid; high blood homocysteine level; and serum gastric parietal cell antibody (GPCA) positivity with BMS. Methods: Blood Hb, iron, vitamin B12, folic acid, and homocysteine concentrations and the serum GPCA level were measured in 399 BMS patients and compared with the corresponding levels in 399 age- and sex-matched healthy control individuals. Results: We found that 89 (22.3%), 81 (20.3%), 10 (2.5%), and six (1.5%) BMS patients had deficiencies of Hb (men: <13 g/dL, women: <12 g/dL), iron (<60 μg/dL), vitamin B12 (<200 pg/mL), and folic acid (<4 ng/mL), respectively. Moreover, 89 (22.3%) BMS patients had abnormally high blood homocysteine level and 53 (13.3%) had serum GPCA positivity. BMS patients had a significantly higher frequency of Hb, iron, or vitamin B12 deficiency; of abnormally elevated blood homocysteine level; or of serum GPCA positivity than the healthy control group (all p < 0.001 except for vitamin B12 deficiency, for which p = 0.004). However, no significant difference in frequency of folic acid deficiency (p = 0.129) was found between BMS patients and healthy control individuals. Conclusion: We conclude that there is a significant association of deficiency of Hb, iron, and vitamin B12; abnormally high blood homocysteine level; and serum GPCA positivity with BMS. [Copyright &y& Elsevier]

Abstract: We aimed to examine the protective effects of resveratrol against homocysteine induced oxidative stress, apoptosis and cognitive impairment. Rats were randomly divided into three groups. Control group received standard rat food; homocysteine group (Hcy group) received daily methionine at a dose of 1g/kg-body weight dissolved in drinking water for thirty days; third group (Hcy+Res group) received same amount of methionine plus 20mg/kg/day resveratrol intraperitoneally for thirty days. Cognitive performances of the animals were tested by Morris water maze test. Then all animals were sacrificed to study lipid peroxidation (LPO), DNA fragmentation and p53 mRNA expression in the rat brain. The aortas of the sacrificed rats were processed for histopathological examination. Apoptosis in the aortas was assessed by TUNEL staining. Resveratrol significantly decreased serum levels of homocysteine, reversed Hcy induced LPO increase, decreased DNA fragmentation and p53 mRNA expression in the rat brains, and improved homocysteine induced impairment of long term spatial memory. Resveratrol could inhibit homocysteine induced apoptosis and histopathological deterioration in the rat aortic sections. In conclusion, resveratrol is effective in preventing homocysteine induced vascular and neural defects. In hyperhomocysteinemic rat model, our findings consequently warrant in future studies to reveal the true improvement mechanism of resveratrol. [Copyright &y& Elsevier]

J Oral Pathol Med (2012) 41: 500-504 Background: Atrophic glossitis (AG) is considered to be a marker of nutritional deficiency. In this study, we evaluated whether there was an intimate association of the deficiency of hemoglobin, iron, vitamin B12 or folic acid, high blood homocysteine level, and serum gastric parietal cell antibody (GPCA) positivity with AG. Methods: The blood hemoglobin, iron, vitamin B12, folic acid, and homocysteine concentrations and the serum GPCA level in 176 AG patients were measured and compared with the corresponding levels in 176 age- and sex-matched healthy control subjects. Results: We found that 39 (22.2%), 47 (26.7%), 13 (7.4%), and 3 (1.7%) AG patients had deficiencies of Hb (men < 13 g/dl, women < 12 g/dl), iron (<60 μg/dl), vitamin B12 (<200 pg/ml), and folic acid (<4 ng/ml), respectively. Moreover, 38 (21.6%) AG patients had abnormally high blood homocysteine level, and 47 (26.7%) AG patients had serum GPCA positivity. AG patients had a significantly higher frequency of Hb, iron, or vitamin B12 deficiency, of abnormally elevated blood homocysteine level, or of serum GPCA positivity than healthy control subjects (all P-values = 0.000). However, no significant difference in frequency of folic acid deficiency was found between AG patients and healthy control subjects. Conclusion: We conclude that there is a significant association of deficiency of hemoglobin, iron and vitamin B12, abnormally high blood homocysteine level, and serum GPCA positivity with AG. [ABSTRACT FROM AUTHOR]

Purpose: The objective of this study was to determine the changes in total plasma thiols (homocysteine, cysteine and cysteinylglycine), lipid peroxidation and nitric oxide concentrations during normal pregnancy. Methods: These variables were measured in 28 uncomplicated pregnant women at first, second and third trimesters and in 19 nonpregnant women. Results: The mean concentrations of homocysteine, cysteine and cysteinylglycine were significantly lower in all trimesters of pregnancy compared with nonpregnant controls. There was significant elevation in serum lipid peroxidation levels of pregnant women within first and third trimesters compared with nonpregnant women. In spite of increase in mean nitric oxide levels in pregnant women, this increase did not reach statistically significant levels. Conclusion: This study provides information about the changes in plasma levels of many variables having important role in pregnancy complication during all trimesters in uncomplicated pregnancy compared with nonpregnant women. [ABSTRACT FROM AUTHOR]

The article presents a study which investigates the beneficial health effects of vitamins and reduced homocysteine, and its role in preventing vascular disease. It states that elevated blood homocysteine was found to be among the independent risk factors of vascular disease. It adds that blood homocysteine reduction and dietary improvement by increasing folic acid, vitamin B-6, and cobalamin intake may prevent vascular disease.

Background: Vegetarians have a lower intake of vitamin B-12 than do omnivores. Early and reliable diagnosis of vitamin B-12 deficiency is very important. Objective: The objective was to investigate vitamin B-12 status in vegetarians and nonvegetarians. Design: The study cohort included 66 lactovegetarians or lactoovovegetarians (LV-LOV group), 29 vegans, and 79 omnivores. Total vitamin B-12, methylmalonic acid, holotranscobalamin II, and total homocysteine concentrations were assayed in serum. Results: Of the 3 groups, the vegans had the lowest vitamin B-12 status. In subjects who did not consume vitamins, low holotranscobalamin II (< 35 pmol/L) was found in 11% of the omnivores, 77% of the LV-LOV group, and 92% of the vegans. Elevated methylmalonic acid (> 271 nmol/L) was found in 5% of the omnivores, 68% of the LV-LOV group, and 83% of the vegans. Hyperhomocysteinemia (> 12 (xmol/L) was present in 16% of the omnivores, 38% of the LV-LOV group, and 67% of the vegans. The correlation between holotranscobalamin II and vitamin B-12 was weak in the low serum vitamin B-12 range (r = 0.403) and strong in the high serum vitamin B-12 range (r = 0.769). Holotranscobalamin II concentration was the main determinant of total homocysteine concentration in the vegetarians (β = -0.237, P < 0.001). Vitamin B-12 deficiency led to hyperhomocysteinemia that was not probable in the upper folate range (> 42.0 nmol/L). Conclusions: Vegan subjects and, to a lesser degree, subjects in the LV-LOV group had metabolic features indicating vitamin B-12 deficiency that led to a substantial increase in total homocysteine concentrations. Vitamin B-12 status should be monitored in vege tarians. Health aspects of vegetarianism should be considered in the light of possible damaging effects arising from vitamin B-12 deficiency and hyperhomocysteinemia. [ABSTRACT FROM AUTHOR]

The author discusses research on the role of vegetarianism in vitamin B-12 deficiency. The author references the study "Vitamin B-12 Status, Particularly Holotranscobalamin II and Methylmalonic Acid Concentrations, and Hyperhomocysteinemia in Vegetarians" by W. Hermann and colleagues published in the current issue of the journal. The author advises the international nutrition community to enact practical steps to ensure parity in the vitamin B-12 status of vegetarians and omnivores.

Background: High circulating total homocysteine (tHcy) concentrations are associated with stroke, which is a major cause of cognitive dysfunction. Blood homocysteine concentrations are inversely correlated with performance on some cognitive-function tests and a relation was recently shown between hyperhomocysteinemia and Alzheimer disease. Objective: The objective was to evaluate the relation between serum tHcy concentrations and performance on short delayed-recall tests of elderly men and women participating in the third National Health and Nutrition Examination Survey, phase 2 (1991-1994). Design: Subjects were aged ≥60 y. Subjects reported no previous stroke, completed ≥8 y of education, and took a test of delayed recall of story ideas (n = 1200) or words (n = 1270). Results: After adjustment for sex, age, race-ethnicity, income, years of education, and serum creatinine concentration, subjects in the upper half of the folate distribution recalled, on average, >4 of 6 story ideas; subjects with lower folate status recalled significantly fewer ideas (P < 0.001). Of the subjects with low folate status, story recall was significantly poorer in those with serum tHcy concentrations above the 80th percentile of the distribution (13.7 (µmol/L) than in those with lower tHcy concentrations (P < 0.03). The odds ratio relating hyperhomocysteinemia to recall of ≥ 1 of 3 previously learned words was 0.3 (95% CI: 0.2, 0.7) after adjustment for the 5 demographic factors alone and was 0.4 (0.2, 0.9) after further adjustment for serum folate concentration. Conclusion: Hyperhomocysteinemia is related to poor recall and this association was partially independent of folate status. [ABSTRACT FROM AUTHOR]

We determined reduced, oxidized, and protein-bound homocysteine, cysteine, and cysteinylglycine in plasma from 13 patients with hyperhomocysteinemia (total homocysteine in the range 30.6- 159.8 µmol/L) due to cobalamin deficiency. Reduced homocysteine (¯ ± SD: 1.87 ± 2.06 µmol/L was markedly above normal (0.24 ± 0.12 µmol/L in most patients, and the reduced fraction increased as an exponential function of the total homocysteine concentration. The ratio of reduced homocysteine to total homocysteine was positively correlated with the reduced-total ratio for cysteine and cysteinylglycine, suggesting redox equilibrium between different aminothiol species. The free oxidized and the protein-bound forms of homocysteine account for most of the homocysteine in plasma of these patients. The amount of protein-bound homocysteine was negatively correlated with the concentrations of both protein-bound cysteine and cysteinylglycine, indicating displacement of these aminothiols by homocysteine. [ABSTRACT FROM AUTHOR]

Measurements of the serum concentrations of the metabolites homocysteine, cystathionine, methylmalonic acid, and 2-methylcitnc acid, which accumulates when vitamin B-12-, folate-, and vitamin B-6-dependent enzymatic reactions are impaired, should provide a better indication of intracellular deficiency of these vitamins. We measured the serum concentration of these vitamins and the four metabolites in 99 healthy young people, 64 healthy elderly subjects, and 286 elderly hospitalized patients. A low serum vitamin B-12 concentration was found in 6% and 5%, low folate in 5% and 19%, and low vitamin B-6 in 9% and 51%, and one or more metabolites were elevated in 63% and 83% of healthy elderly subjects and elderly hospitalized patients, respectively. These results strongly suggest that the prevalence of tissue deficiencies of vitamin B-12, folate, and vitamin B-6 as demonstrated by the elevated metabolite concentrations is substantially higher than that estimated by measuring concentrations of the vitamins. [ABSTRACT FROM AUTHOR]

Hyperhomocysteinemia is a genetic disorder of metabolism and transport of amino acid, commonly present as a pro-coagulant state. Evan's syndrome is an autoimmune disorder with pancytopenia, a diagnosis of exclusion. The present report highlights the anesthetic management of a rare case, where both these clinical entities coexist. A 26-year-old male, a known case of hyperhomocyteinemia on medication for 4 years, came with a history of severe headache, blurring of vision and bleeding gums. Computerized tomography brain report showed subdural hematoma (SDH) of 16 mm with 9 mm right midline shift and on investigation had thrombocytopenia (5000 cells/cumm). Patient was diagnosed to have Evan's syndrome. Because he was refractory to the medical management, taken up for emergency splenectomy, followed by burr hole evacuation of SDH. Successful anesthetic management of the case is presented in this report. [ABSTRACT FROM AUTHOR]

Objective:The population-based “Asymptomatic Polyvascular Abnormalities in Community (APAC) Study was designed to examine prevalence and associations of asymptomatic polyvascular abnormalities (APA) in a general population. In this report, the objectives, design and baseline data of the APAC study are described. Methods:The study included 5,440 participants (40.1% women) with an age of 40+ years who were randomly selected from the population of the Kailuan Study which included 101,510 employees and retirees of the Kailuan Co. Ltd, a large coal mine industry located in Tangshan, Hebei, China. Exclusion criteria were previous cerebral stroke, transient ischemic attacks and coronary heart disease. In 2010 and 2011, information on potential cardiovascular risk factors was collected and all participants underwent transcranial Doppler sonography, measurement of the ankle brachial index, and bilateral carotid duplex sonography. In a first follow-up examination in 2012/2013, retinal photography and spectral-domain optical coherence tomography were additionally performed. In a planned long-term follow-up, data from clinical examinations and laboratory tests and the occurrence of cardiovascular or cerebrovascular events will be collected to build up a predicting model for the risk of ischemic events. Results:At baseline, mean age of the participants was 55.2±11.8 years, and men showed a significantly (P<0.001) higher prevalence of arterial hypertension (55.5% vs. 36.5%) and hyperlipidemia (50.7% vs. 46.0%) and a higher blood homocysteine concentration (18.68±10.28µmol/L versus 11.69±6.40µmol/L). Conclusions:The APAC is the first study to prospectively evaluate the relationship between intracranial arterial stenosis, retinal nerve fiber layer changes, retinal microvascular signs, and the eventual development of cerebrovascular or cardiovascular events. [ABSTRACT FROM AUTHOR]