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1.
Nutrients ; 13(7)2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34371949

RESUMO

Homocysteine (Hcy) is well known to be increased in the metabolic syndrome (MetS) incidence. However, it remains unclear whether the relationship is causal or not. Recently, Mendelian Randomization (MR) has been popularly used to assess the causal influence. In this study, we adopted MR to investigate the causal influence of Hcy on MetS in adults using three independent cohorts. We considered one-sample MR and two-sample MR. We analyzed one-sample MR in 5902 individuals (2090 MetS cases and 3812 controls) from the KARE and two-sample MR from the HEXA (676 cases and 3017 controls) and CAVAS (1052 cases and 764 controls) datasets to evaluate whether genetically increased Hcy level influences the risk of MetS. In observation studies, the odds of MetS increased with higher Hcy concentrations (odds ratio (OR) 1.17, 95%CI 1.12-1.22, p < 0.01). One-sample MR was performed using two-stage least-squares regression, with an MTHFR C677T and weighted Hcy generic risk score as an instrument. Two-sample MR was performed with five genetic variants (rs12567136, rs1801133, rs2336377, rs1624230, and rs1836883) by GWAS data as the instrumental variables. For sensitivity analysis, weighted median and MR-Egger regression were used. Using one-sample MR, we found an increased risk of MetS (OR 2.07 per 1-SD Hcy increase). Two-sample MR supported that increased Hcy was significantly associated with increased MetS risk by using the inverse variance weighted (IVW) method (beta 0.723, SE 0.119, and p < 0.001), the weighted median regression method (beta 0.734, SE 0.097, and p < 0.001), and the MR-Egger method (beta 2.073, SE 0.843, and p = 0.014) in meta-analysis. The MR-Egger slope showed no evidence of pleiotropic effects (intercept -0.097, p = 0.107). In conclusion, this study represented the MR approach and elucidates the significant relationship between Hcy and the risk of MetS in the Korean population.


Assuntos
Predisposição Genética para Doença , Homocisteína/sangue , Síndrome Metabólica/genética , Idoso , Feminino , Humanos , Masculino , Análise da Randomização Mendeliana , Síndrome Metabólica/sangue , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Pessoa de Meia-Idade , Razão de Chances , Polimorfismo de Nucleotídeo Único
2.
Medicine (Baltimore) ; 100(33): e26875, 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34414939

RESUMO

BACKGROUND: Elevated homocysteine (Hcy) levels showed increasing significance as the predisposing factor for the pathogenesis of atherosclerotic sequelae, including cardiovascular mortality, coronary artery disease, and stroke. There is increasing evidence linking plasma Hcy levels and heart failure (HF). The association between the elevated level of plasma Hcy and HF was examined by meta-analysis and systematic review in this study. METHODS: The PubMed and ScienceDirect databases until April 2020 were utilized to collect previous literature on plasma Hcy levels and the potential relation to HF. The pooled effects were evaluated depending on standardized mean differences (SMDs) with 95% confidence intervals (CIs), and the calculation was performed using Stata 12 software. Potential sources of heterogeneity were assessed with subgroup analysis and sensitivity analysis. RESULTS: A total of 12 research projects including 5506 subjects were selected. For pooled effect, the results confirmed that patients with HF had higher Hcy levels than the control subjects (SMD,1.148 and 95%CI, [0.715, 1.581]). Based on the classification of New York Heart Association (NYHA), the Hcy levels for the group of NYHA I or II (SMD, 1.484 and 95% CI, [0.442, 2.527]) and the group of NYHA III or IV (SMD, 3.361 and 95% CI, [1.902, 4.820]) were significantly increased compared to controls, while the increase was more intensive for the group of NYHA III or IV. Subgroup analyses revealed similar results. CONCLUSION: Our meta-analysis identified that plasma Hcy levels were significantly elevated in HF patients compared to control subjects, which is positively related to the advancement of NYHA class.


Assuntos
Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/complicações , Homocisteína/sangue , Humanos
3.
Medicine (Baltimore) ; 100(33): e26893, 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34414944

RESUMO

ABSTRACT: A high homocysteine level is known to be an independent risk factor for cardiovascular diseases; however, whether or not low homocysteine level contributes to any damage to the body has not been extensively studied. Furthermore, acquiring healthy subject databases from domestic studies on homocysteine is not trivial. Therefore, we aimed to investigate the causality between serum homocysteine levels and health status and lifestyle factors, particularly with a focus on low serum homocysteine levels. Additionally, we discussed a systematic methodical platform for data collection and statistical analysis, using the descriptive analysis of the chi-square test, t test, multivariate analysis of variance, and logistic regression.This study was a cross-sectional analysis of 5864 subjects (i.e., clients of a health examination clinic) in Taipei, Taiwan during a general health check-up in 2017. The patients' personal information and associated links were excluded. A sample group was selected as per the health criteria defined for this research whose data were processed using SPSS for descriptive statistical analysis using chi-square test, t test, multivariate analysis of variance, and logistic regression analysis.Those working for >12 hours/day had a higher homocysteine level than those working for <12 hours/day (P < .001). The average serum homocysteine level was 7.9 and 8.6 mol/L for people with poor sleep quality and good sleep quality, respectively (P = .003). The homocysteine value of people known to have cancer was analyzed using the logistic regression analysis, revealing a Δodds value of 0.898. The percentage of subjects with a homocysteine value of ≤6.3 µmol/L, who perceived their health status as "not very good" or "very bad," was higher than those with a higher homocysteine level. The number of subjects who perceived their health as poor was higher than expected.The results suggest that the homocysteine level could be an effective health management indicator. We conclude that normal homocysteine level should not be ≤6.3 µmol/L. Moreover, homocysteine should not be considered as harmful and its fluctuations from the normal range could be utilized to infer a person's physical status for health management.


Assuntos
Mineração de Dados , Nível de Saúde , Homocisteína/sangue , Estilo de Vida , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
4.
J Clin Neurosci ; 90: 273-278, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34275563

RESUMO

OBJECTIVES: This study aimed to explore the association of homocysteine (Hcy) with third ventricle (V3) dilatation and mesencephalic area (MA) atrophy as determined by transcranial sonography (TCS) in Parkinson's disease (PD) with cognitive impairment. METHODS: The final statistical analysis included 101 PD patients and 20 age- and sex-matched controls. Using the Movement Disorder Society (MDS) level II criteria for PD with cognitive impairment, we categorized the PD patients into PD with normal cognition group (PD) and PD with cognitive impairment group (PDC). All subjects underwent TCS and laboratory analysis. RESULTS: The V3 width (r = 0.349, P = 0.005) and the MA (r = -0.484, P < 0.001) were significantly correlated with the Hcy concentration in the PDC patients. Binary logistic regression analysis revealed that age (OR [95% CI] = 1.114 [0.991-1.251], P = 0.002), and Hcy level (OR [95% CI] = 0.931 [0.752-1.153], P = 0.411) were independent risk factors for V3 dilatation. Hcy level (OR [95% CI] = 0.557 [0.323-0.967], P = 0.035) were independent risk factors for MA atrophy. After adjustment for confounding factors, the odds ratio of V3 dilatation was 3.50 (95% CI 1.054-11.399, P = 0.031) and the odds ratio of MA atrophy was 4.67 (95% CI 1.395-15.602, P = 0.012) in the patients with higher Hcy level compared with the lower level. CONCLUSIONS: The results revealed a close association between the V3 width, MA and Hcy concentration in PD patients with cognitive impairment. We hypothesized that increased Hcy concentration played a significant role in the development of brain atrophy in PD with cognitive impairment.


Assuntos
Transtornos Cognitivos/etiologia , Homocisteína/sangue , Mesencéfalo/patologia , Doença de Parkinson/sangue , Doença de Parkinson/patologia , Terceiro Ventrículo/patologia , Idoso , Idoso de 80 Anos ou mais , Atrofia , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Mesencéfalo/diagnóstico por imagem , Pessoa de Meia-Idade , Razão de Chances , Doença de Parkinson/psicologia , Fatores de Risco , Terceiro Ventrículo/diagnóstico por imagem , Ultrassonografia Doppler Transcraniana
5.
J Alzheimers Dis ; 82(3): 975-984, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34120900

RESUMO

BACKGROUND: Homocysteine is a common risk factor for cognitive impairment and sarcopenia. However, very few studies have shown an association between sarcopenia and serum homocysteine levels after adjustment for cognitive function. OBJECTIVE: The purpose of this study was to investigate the relationship between homocysteine and sarcopenia in memory clinic patients. METHODS: This cross-sectional study investigated outpatients in a memory clinic. We enrolled 1,774 participants (≥65 years old) with measured skeletal muscle mass index (SMI), hand grip strength (HGS), and homocysteine. All participants had undergone cognitive assessments and were diagnosed with dementia, mild cognitive impairment, or normal cognition. Patient characteristics were compared according to sarcopenia presence, SMI level, or HGS. Multivariate logistic regression analysis was performed to determine the association of homocysteine with sarcopenia, low SMI, or low HGS. Next, linear regression analysis was performed using HGS as a continuous variable. RESULTS: Logistic regression analysis showed that low HGS was significantly associated with homocysteine levels (p = 0.002), but sarcopenia and low SMI were not. In linear regression analysis, HGS was negatively associated with homocysteine levels after adjustment for Mini-Mental State Examination score (ß= -2.790, p < 0.001) or clinical diagnosis of dementia (ß= -3.145, p < 0.001). These results were similar for men and women. CONCLUSION: Our results showed a negative association between homocysteine and HGS after adjustment for cognitive function. Our findings strengthen the assumed association between homocysteine and HGS. Further research is needed to determine whether lower homocysteine levels lead to prevent muscle weakness.


Assuntos
Força da Mão/fisiologia , Homocisteína/sangue , Ambulatório Hospitalar/tendências , Pacientes Ambulatoriais/psicologia , Sarcopenia/sangue , Sarcopenia/psicologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Disfunção Cognitiva/sangue , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/psicologia , Estudos Transversais , Feminino , Humanos , Masculino
6.
Molecules ; 26(11)2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34064073

RESUMO

BACKGROUND: Among non-communicable diseases, cardiovascular diseases (CVDs) are the leading cause of mortality and morbidity in global communities. By 2030, CVD-related deaths are projected to reach a global rise of 25 million. Obesity, smoking, alcohol, hyperlipidemia, hypertension, and hyperhomocysteinemia are several known risk factors for CVDs. Elevated homocysteine is tightly related to CVDs through multiple mechanisms, including inflammation of the vascular endothelium. The strategies for appropriate management of CVDs are constantly evolving; medicinal plants have received remarkable attention in recent researches, since these natural products have promising effects on the prevention and treatment of various chronic diseases. The effects of nutraceuticals and herbal products on CVD/dyslipidemia have been previously studied. However, to our knowledge, the association between herbal bioactive compounds and homocysteine has not been reviewed in details. Thus, the main objective of this study is to review the efficacy of bioactive natural compounds on homocysteine levels according to clinical trials and animal studies. RESULTS: Based on animal studies, black and green tea, cinnamon, resveratrol, curcumin, garlic extract, ginger, and soy significantly reduced the homocysteine levels. According to the clinical trials, curcumin and resveratrol showed favorable effects on serum homocysteine. In conclusion, this review highlighted the beneficial effects of medicinal plants as natural, inexpensive, and accessible agents on homocysteine levels based on animal studies. Nevertheless, the results of the clinical trials were not uniform, suggesting that more well-designed trials are warranted.


Assuntos
Produtos Biológicos/sangue , Homocisteína/sangue , Plantas Medicinais , Animais , Humanos
7.
Int J Mol Sci ; 22(9)2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-34066973

RESUMO

L-methionine, an essential amino acid, plays a critical role in cell physiology. High intake and/or dysregulation in methionine (Met) metabolism results in accumulation of its intermediate(s) or breakdown products in plasma, including homocysteine (Hcy). High level of Hcy in plasma, hyperhomocysteinemia (hHcy), is considered to be an independent risk factor for cerebrovascular diseases, stroke and dementias. To evoke a mild hHcy in adult male Wistar rats we used an enriched Met diet at a dose of 2 g/kg of animal weight/day in duration of 4 weeks. The study contributes to the exploration of the impact of Met enriched diet inducing mild hHcy on nervous tissue by detecting the histo-morphological, metabolomic and behavioural alterations. We found an altered plasma metabolomic profile, modified spatial and learning memory acquisition as well as remarkable histo-morphological changes such as a decrease in neurons' vitality, alterations in the morphology of neurons in the selective vulnerable hippocampal CA 1 area of animals treated with Met enriched diet. Results of these approaches suggest that the mild hHcy alters plasma metabolome and behavioural and histo-morphological patterns in rats, likely due to the potential Met induced changes in "methylation index" of hippocampal brain area, which eventually aggravates the noxious effect of high methionine intake.


Assuntos
Comportamento Animal , Hipocampo/patologia , Hiper-Homocisteinemia/sangue , Hiper-Homocisteinemia/metabolismo , Metabolômica , Animais , Homocisteína/sangue , Hiper-Homocisteinemia/patologia , Marcação In Situ das Extremidades Cortadas , Espectroscopia de Ressonância Magnética , Masculino , Metionina , Ratos Wistar , Coloração e Rotulagem
8.
J Clin Neurosci ; 88: 226-231, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33992189

RESUMO

INTRODUCTION: Previous studies have suggested a significant increase in plasma homocysteine (Hcy) levels in levodopa-treated Parkinson's disease (PD) patients, and vitamin B12 and folate supplementation may decrease Hcy levels. However, the effects of catechol-O-methyltransferase inhibitors on levodopa-induced increase in Hcy levels were conflicting. The aim of this study was to evaluate whether Hcy levels are increased in levodopa-treated PD patients and to evaluate the effects of vitamin B12 and folate or entacapone on Hcy levels in levodopa-treated PD patients. METHODS: We analyzed and compared plasma Hcy levels in 20 levodopa-naïve PD patients and 42 levodopa-treated PD patients, followed by randomized assignment of 42 levodopa-treated patients to treatment groups with either vitamin B12 and folate, entacapone, or no medication. RESULTS: Plasma Hcy levels in levodopa-treated PD patients were higher than those in the control group, but the difference was not statistical significant (15.25 ± 6.70 and 13.13 ± 4.68, P = 0.216). Patients treated with vitamin B12 and folate had a significant decrease in plasma Hcy levels (P < 0.001). In the entacapone group, Hcy levels were mildly decreased, but the change did not reach statistical significance. CONCLUSION: Levodopa-treated PD patients had higher plasma Hcy than levodopa-naive PD patients. Unlike entacapone, combination supplementation with vitamin B12 and folate was associated with significantly decreased plasma Hcy. We suggest that plasma Hcy levels should be monitored during levodopa treatment, and supplementation with inexpensive vitamin B12 and folate is beneficial for levodopa-treated patients.


Assuntos
Antiparkinsonianos/uso terapêutico , Catecóis/uso terapêutico , Homocisteína/sangue , Nitrilas/uso terapêutico , Doença de Parkinson/sangue , Doença de Parkinson/tratamento farmacológico , Idoso , Feminino , Ácido Fólico/uso terapêutico , Homocisteína/efeitos dos fármacos , Humanos , Hiper-Homocisteinemia/induzido quimicamente , Hiper-Homocisteinemia/prevenção & controle , Levodopa/uso terapêutico , Masculino , Pessoa de Meia-Idade , Projetos de Pesquisa , Vitamina B 12/uso terapêutico
10.
J Alzheimers Dis ; 81(4): 1781-1792, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33998538

RESUMO

BACKGROUND: Although it is known that the nutritional status among elderly persons and, in particular, patients with dementia, is compromised, malnutrition that results in insufficient uptake of several vitamins is often not diagnosed. OBJECTIVE: An elevated homocysteine level is a known strong risk factor for vascular dementia (VaD) and Alzheimer's disease (AD). Several B vitamins are involved in the metabolism of homocysteine. Therefore, we investigated the serum levels of vitamin B1, vitamin B6, folate, and vitamin B12 in 97 patients with mild cognitive impairment (MCI) or different forms of dementia and 54 elderly control persons without dementia. RESULTS: Compared to aged non-demented people, vitamins B1, B6, B12, and folate were decreased in serum of patients with AD, and patients with Lewy body dementia had reduced vitamin B12 level. Vitamin B6 was diminished in VaD. Patients with frontotemporal dementia showed no alterations in vitamin levels. Age was identified as an important factor contributing to the concentrations of vitamin B1 and B6 in serum, but not vitamin B12 and folate. Increased levels of total homocysteine were detected especially in MCI and AD. Homocysteine correlated negatively with levels of vitamins B6, B12, and folate and positively with Q Albumin. CONCLUSION: Our data suggest that despite increased homocysteine already present in MCI, vitamin levels are decreased only in dementia. We propose to determine the vitamin levels in patients with cognitive decline, but also elderly people in general, and recommend supplementing these nutrients if needed.


Assuntos
Demência/sangue , Ácido Fólico/sangue , Homocisteína/sangue , Tiamina/sangue , Vitamina B 12/sangue , Vitamina B 6/sangue , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
11.
J Alzheimers Dis ; 82(2): 527-540, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34024827

RESUMO

BACKGROUND: Serum homocysteine (Hcy) level is considered to be an important biomarker for Alzheimer's disease (AD); however, the status of Hcy in brain tissue, and the association between brain and serum levels of Hcy in AD patients remain unclear. OBJECTIVE: We aimed to examine whether the changes of three thiols are consistent in serum of AD patients and the brain of APP/PS1 mice, and to verify the effectiveness of Hcy as a biomarker for early AD detection. METHODS: The levels of Hcy, cysteine (Cys), and glutathione (GSH) in Aß1-42-treated PC12 cells, the brain and hippocampus of APP/PS1 mouse, and the serum of AD patients were evaluated using ethyl (E)-3-(9-chloro-11-oxo-2,3,6,7-tetrahydro-1H,5H,11H-pyrano[2,3-f] pyrido [3,2,1 -ij] quinolin-10-yl)-2-cyanoacrylate (Probe 1) and ELISA assay or LC-MS. RESULTS: Measurement by Probe 1 revealed a significant increase in Hcy level, and a decrease in Cys and GSH levels in Aß1-42-treated PC12 cells and the serum of AD patients. The hippocampus and whole brain of APP/PS1 mice also showed a significant increase in Hcy level alongside the accumulation of age-related AD symptoms. The upregulation of Hcy and the downregulation of Cys and GSH were reversed in the Aß1-42-treated PC12 cells and the brain of APP/PS1 mice when supplemented with VB6. CONCLUSION: Changes in Hcy, Cys, and GSH levels in the brain of APP/PS1 mice and Aß1-42-treated PC12 cells were observed in situ with a new fluorescent probe, which were consistent with the abnormal changes in Hcy, Cys, and GSH levels in the serum of AD patients. VB6 supplementation was successful in ameliorating abnormal increases in Hcy levels.


Assuntos
Doença de Alzheimer , Encéfalo/metabolismo , Homocisteína , Compostos de Sulfidrila , Vitamina B 6/farmacologia , Doença de Alzheimer/sangue , Doença de Alzheimer/diagnóstico , Animais , Biomarcadores/sangue , Biomarcadores/metabolismo , Cisteína/metabolismo , Regulação para Baixo , Diagnóstico Precoce , Feminino , Corantes Fluorescentes , Glutationa/metabolismo , Homocisteína/sangue , Homocisteína/metabolismo , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Células PC12 , Ratos , Espectrometria de Fluorescência/métodos , Compostos de Sulfidrila/classificação , Compostos de Sulfidrila/metabolismo , Regulação para Cima , Complexo Vitamínico B/farmacologia
12.
Biomed Res Int ; 2021: 6652231, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34036101

RESUMO

Homocysteine (Hct) is a substance produced in the metabolism of methionine. It is an essential type of amino acid gained from the daily diet. Methylenetetrahydrofolate reductase (MTHFR) gene mutation is related to elevated total homocysteine (tHct) expressions, in particular, among women with low folate intake. Hyperhomocysteinemia (HHct) is caused by numerous factors, such as genetic defects, lack of folic acid, vitamin B6 and B12 deficiency, hypothyroidism, drugs, aging, and renal dysfunction. Increased Hct in peripheral blood may lead to vascular illnesses, coronary artery dysfunction, atherosclerotic changes, and embolic diseases. Compared to nonpregnant women, the Hct level is lower in normal pregnancies. Recent studies have reported that HHct was associated with numerous pregnancy complications, including recurrent pregnancy loss (RPL), preeclampsia (PE), preterm delivery, placental abruption, fetal growth restriction (FGR), and gestational diabetes mellitus (GDM). Besides, it was discovered that neonatal birth weight and maternal Hct levels were negatively correlated. However, a number of these findings lack consistency. In this review, we summarized the metabolic process of Hct in the human body, the levels of Hct in different stages of normal pregnancy reported in previous studies, and the relationship between Hct and pregnancy complications. The work done is helpful for obstetricians to improve the likelihood of a positive outcome during pregnancy complications. Reducing the Hct level with a high dosage of folic acid supplements during the next pregnancy could be helpful for females who have suffered pregnancy complications due to HHct.


Assuntos
Homocisteína/sangue , Complicações na Gravidez , Aborto Habitual , Envelhecimento , Peso ao Nascer , Diabetes Gestacional , Suplementos Nutricionais , Feminino , Retardo do Crescimento Fetal , Ácido Fólico/sangue , Homocisteína/metabolismo , Humanos , Hiper-Homocisteinemia/sangue , Hiper-Homocisteinemia/metabolismo , Placenta , Pré-Eclâmpsia , Gravidez , Vitamina B 12/sangue , Deficiência de Vitamina B 12 , Vitamina B 6/sangue , Deficiência de Vitamina B 6
13.
J Alzheimers Dis ; 82(1): 235-248, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34057086

RESUMO

BACKGROUND: Alzheimer's disease (AD) may be a vascular disorder with neurodegenerative consequences opening possibility of preventing AD by targeting vascular risk factors including homocysteine. OBJECTIVE: The study aims were to assess homocysteine distribution in different forms and severity of cognitive impairment (CogI) [mild cognitive impairment (MCI), probable AD (Prob-AD), possible AD (Poss-AD), and vascular dementia (VaD)] and in NoCogI, and to estimate possible association between hyperhomocysteinemia levels with functional deficit severity and psychobehavioral complications. METHODS: In total, 929 (M = 366, F = 563; mean age of 72.55±6.24 years) patients were evaluated with cognitive, neuropsychiatric, affective, and functional assessment scales. Homocysteine serum was set on two levels: between 0 and 10µmol/L and > 10µmol/L. For each patient, blood concentration of folate, vitamin B12, hemoglobin, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), cholesterol, triglycerides, and glycemia were measured. RESULTS: CogI patients demonstrated significantly a higher frequency of homocysteine > 10 (p = 0.003), than NoCogI patients. Patients with moderate and severe dementia had a higher frequency of homocysteine > 10 (p < 0.0001), than MCI and mild dementia. Poss-AD and VaD had a higher frequency of homocysteine > 10 (p = 0.003), than Prob-AD patients. Homocysteine > 10 frequency is directly proportional to increased neuropsychiatric symptom severity (p < 0.0001), and functional impairment severity respectively for ADL (p < 0.0001) and IADL (p < 0.0001). CONCLUSION: Higher homocysteine level seems to be significantly related to cognitive impairment frequency and severity, possible AD and VaD, neuropsychiatric symptom severity, and functional impairment severity.


Assuntos
Atividades Cotidianas , Doença de Alzheimer/sangue , Escalas de Graduação Psiquiátrica Breve/estatística & dados numéricos , Disfunção Cognitiva/sangue , Demência Vascular/sangue , Homocisteína/sangue , Idoso , Feminino , Humanos , Entrevistas como Assunto , Masculino
14.
Neurology ; 97(2): e203-e214, 2021 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-33986139

RESUMO

OBJECTIVE: To determine the influence of patent foramen ovale (PFO) closure on circulatory biomarkers. METHODS: Consecutive patients with PFO-related stroke were prospectively enrolled and followed with serial sampling of cardiac atrial and venous blood pre- and post-PFO closure over time. Candidate biomarkers were identified by mass spectrometry in a discovery cohort first, and lead candidates were validated in an independent cohort. RESULTS: Patients with PFO-related stroke (n = 254) were recruited and followed up to 4 years (median 2.01; interquartile range 0.77-2.54). Metabolite profiling in the discovery cohort (n = 12) identified homocysteine as the most significantly decreased factor in intracardiac plasma after PFO closure (false discovery rate 0.001). This was confirmed in a validation cohort (n = 181), where intracardiac total homocysteine (tHcy) was immediately reduced in patients with complete closure, but not in those with residual shunting, suggesting association of PFO shunting with tHcy elevation (ß 0.115; 95% confidence interval [CI] 0.047-0.183; p = 0.001). tHcy reduction was more dramatic in left atrium than right (p < 0.001), suggesting clearance through pulmonary circulation. Long-term effect of PFO closure was also monitored and compared to medical treatment alone (n = 61). Complete PFO closure resulted in long-term tHcy reduction in peripheral blood, whereas medical therapy alone showed no effect (ß -0.208; 95% CI -0.375∼-0.058; p = 0.007). Residual shunting was again independently associated with persistently elevated tHcy (ß 0.184; 95% CI 0.051-0.316; p = 0.007). CONCLUSIONS: PFO shunting may contribute to circulatory tHcy elevation, which is renormalized by PFO closure. PFO is not just a door for clots, but may itself enhance clot formation and injure neurovasculature by clot-independent mechanisms. Biomarkers such as tHcy can potentially serve as cost-effective measures of residual shunting and neurovascular risk for PFO stroke.


Assuntos
Forame Oval Patente/sangue , Forame Oval Patente/complicações , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/complicações , Adulto , Biomarcadores/sangue , Feminino , Homocisteína/sangue , Humanos , Masculino , Espectrometria de Massas , Pessoa de Meia-Idade , Estudos Prospectivos
15.
Medicine (Baltimore) ; 100(18): e25677, 2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-33950947

RESUMO

ABSTRACT: Homocysteine (Hcy) is a risk factor for the presence of atherosclerotic vascular disease and hypercoagulability states, which is associated with increased risk of cardiovascular events in cardiovascular disease patients. Whereas the role of Hcy in premature acute coronary syndrome (ACS) female patients is still obscure. Hence, we aimed to explore the relationship of Hcy with clinical features, and more importantly, to probe its predictive value for major adverse cardiovascular events (MACE) risk in premature ACS female patients.By retrospectively reviewing the medical charts of 1441 premature ACS female patients, we collected patients' Hcy level (at diagnosis) and other clinical data. According to the follow-up records, the accumulating MACE occurrence was calculated.Hcy presented with a skewed distribution with median value 11.3 µmol/L (range: 4.4-64.0 µmol/L, inter quartile: 9.2-14.1 µmol/L). Hcy was associated with older age, heavy body mass index, dysregulated liver/renal/cardiac indexes, hypertension history, and old myocardial infarction history. The 1-year, 3-year, 5-year MACE incidence was 2.9%, 10.7%, and 12.6%, respectively. Interestingly, Hcy was increased in 1-year MACE patients compared with 1-year non-MACE patients, in 3-year MACE patients compared with 3-year non-MACE patients, in 5-year MACE patients compared with 5-year non-MACE patients, and it had a good value for predicting 1-year/3-year/5-year MACE risk. Furthermore, Hcy was also correlated with increased accumulating MACE occurrence.Hcy associates with increased age and body mass index, dysregulated liver, renal, and cardiac indexes; more interestingly, it predicts increased MACE risk in premature ACS female patients.


Assuntos
Síndrome Coronariana Aguda/complicações , Fatores de Risco de Doenças Cardíacas , Homocisteína/sangue , Hipertensão/epidemiologia , Infarto do Miocárdio/epidemiologia , Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/epidemiologia , Fatores Etários , Idade de Início , Biomarcadores/sangue , Índice de Massa Corporal , Feminino , Seguimentos , Humanos , Hipertensão/etiologia , Pessoa de Meia-Idade , Infarto do Miocárdio/etiologia , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de Risco/métodos
16.
J Alzheimers Dis ; 81(1): 413-426, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33814443

RESUMO

BACKGROUND: Identifying modifiable risk factors for cognitive decline can reduce burden of dementia. OBJECTIVE: We examined whether homocysteine was associated with memory performance, mediated by entorhinal volume, hippocampal volume, total gray matter volume, or white matter lesions, and moderated by APOE ɛ4 allele, B vitamins, creatinine, total cholesterol, or triglycerides. METHODS: All 204 members of the Czech Brain Aging Study with subjective cognitive decline (SCD; n = 60) or amnestic mild cognitive impairment (aMCI; n = 144) who had valid data were included. Linear regression was used, followed by conditional process modeling to examine mediation and moderation. RESULTS: Controlling for age, sex, and education, higher homocysteine was related to poorer memory performance overall (b = -0.03, SE = 0.01, p = 0.017) and in participants with SCD (b = -0.06, SE = 0.03, p = 0.029), but less so in aMCI (b = -0.03, SE = 0.02, p = 0.074); though sensitivity analyses revealed a significant association when sample was reduced to aMCI patients with more complete cognitive data (who were also better functioning; b = -0.04, SE = 0.02, p = 0.022). Results were unchanged in fully adjusted models. Neither mediation by markers of brain integrity nor moderation by APOE ɛ4, B vitamins, creatinine, and cardiovascular factors were significant. Memory sub-analyses revealed that results for SCD were likely driven by non-verbal memory. The homocysteine-memory relationship was significant when hippocampal volume was below the median (b = -0.04, SE = 0.02, p = 0.046), but not at/above the median (p = 0.247). CONCLUSION: Higher homocysteine levels may adversely influence memory performance, which appears particularly apparent in those without cognitive impairment. Results appear to be independent of brain health, suggesting that homocysteine may represent a good target for intervention.


Assuntos
Substância Cinzenta/diagnóstico por imagem , Homocisteína/sangue , Memória/fisiologia , Substância Branca/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Feminino , Hipocampo/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Tamanho do Órgão/fisiologia
17.
Aging (Albany NY) ; 13(8): 11352-11362, 2021 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-33833133

RESUMO

BACKGROUND: Three polymorphisms in the Methylenetetrahydrofolate reductase (MTHFR) gene (C677T, A1298C, and A1793G) were reported associated with AD. However, their genotype distributions and associations with age at onset (AAO), homocysteine, and white matter lesions (WML) were unclear in the Chinese AD population. METHOD: We determined the presence of C677T, A1298C, and A1793G polymorphisms in the MTHFR gene using Sanger sequencing in a Chinese cohort comprising 721 AD patients (318 early-onset AD patients (EOAD) and 403 late-onset AD patients (LOAD)) and 365 elderly controls. Additionally, the homocysteine level and WML were evaluated in 121 AD patients. RESULTS: The frequency of allele T of C677T polymorphism was significantly higher in AD patients than in controls (P = 0.040), while no statistical difference was observed in A1298C and A1793G (P > 0.05). Besides, genotype distributions of C677T and A1298C polymorphisms statistically varied between AD patients and controls (P = 0.021, P = 0.012). Moreover, the AAO was significantly lower in CT/TT (C677T) genotypes carriers (P = 0.042) and higher in AC/CC (A1298C) and AG/GG (A1793G) genotypes carriers (P = 0.034, P = 0.009) in patients with LOAD. We also found that patients with CT/TT (C677T) genotypes were prone to present an increased homocysteine level (P = 0.036) and higher Fazekas score (P = 0.024). In comparison, patients with AG/GG genotypes (A1793G) had a significantly lower Fazekas score (P = 0.013). CONCLUSIONS: The genotype distributions of C677T and A1298C polymorphisms are associated with AD in the Chinese population. Moreover, AD patients with C677T polymorphism are prone to present an earlier onset, higher homocysteine level, and more severe WML.


Assuntos
Doença de Alzheimer/genética , Predisposição Genética para Doença , Homocisteína/sangue , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Substância Branca/patologia , Idade de Início , Idoso , Alelos , Doença de Alzheimer/sangue , Doença de Alzheimer/epidemiologia , Doença de Alzheimer/patologia , Apolipoproteínas E/genética , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , China/epidemiologia , Feminino , Homocisteína/metabolismo , Humanos , Masculino , Metilenotetra-Hidrofolato Redutase (NADPH2)/metabolismo , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único
18.
Gynecol Obstet Invest ; 86(1-2): 193-199, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33906193

RESUMO

BACKGROUND: Inflammatory response state is related to the pathogenesis of gestational diabetes mellitus (GDM). OBJECTIVE: To investigate the changes of serum sex hormone-binding globulin (SHBG), homocysteine (Hcy), and hypersensitive CRP (hs-CRP) levels during pregnancy and their relationship with GDM. METHODS: The nested case-control study method was used. Sixty nonobese single pregnant women diagnosed with GDM were divided into the GDM group (GDM, n = 60), together with another 60 pregnant women with normal glucose tolerance who were matched in the same period and divided into the control group (control, n = 60). The serum Hcy, hs-CRP, and SHBG levels were measured. RESULTS: The serum levels of Hcy and hs-CRP were significantly higher in the GDM group compared with the control group, and serum levels of SHBG was significantly lower in the GDM group compared with the control group at different stages of pregnancy. The serum levels of Hcy and hs-CRP in pregnant women increased with the increase of gestational age, and serum levels of SHBG decreased with the increase of gestational age. Increased Hcy and hs-CRP levels in the second trimester and decreased SHBG levels in the first trimester were related to GDM. The odds ratio (OR) and 95% confidence interval (CI) were as follows: OR: 4.5, 95% CI: 1.5-13.0; OR: 4.2, 95% CI: 1.5-10.1; and OR: 0.4, 95% CI: 0.3-0.7, respectively. CONCLUSION: Increased Hcy and hs-CRP in the second trimester and decreased SHBG in the first trimester were independent predictors of GDM, which provides a new idea for early prevention and treatment of GDM.


Assuntos
Proteína C-Reativa/análise , Diabetes Gestacional/sangue , Homocisteína/sangue , Globulina de Ligação a Hormônio Sexual/análise , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Idade Gestacional , Humanos , Gravidez , Primeiro Trimestre da Gravidez/sangue , Segundo Trimestre da Gravidez/sangue
19.
Nutrients ; 13(4)2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-33923969

RESUMO

Methylenetetrahydrofolate reductase (MTHFR) has various polymorphisms, and the effects of periconceptional folic acid supplementation for decreasing neural tube defects (NTDs) risk differ depending on the genotypes. This study analyzed the effectiveness of multivitamin supplementation on folate insufficiency and hyperhomocysteinemia, depending on MTHFR polymorphisms. Of 205 women, 72 (35.1%), 100 (48.8%) and 33 (16.1%) had MTHFR CC, CT and TT, respectively. Serum folate and homocysteine levels in women with homozygous mutant TT were significantly lower and higher, respectively, than those in women with CC and CT. In 54 women (26.3% of all women) with a risk of NTDs, multivitamin supplementation containing folic acid and vitamin D for one month increased folate level (5.8 ± 0.9 to 19.2 ± 4.0 ng/mL, p < 0.0001) and decreased the homocysteine level (8.2 ± 3.1 to 5.8 ± 0.8 nmol/mL, p < 0.0001) to minimize the risk of NTDs in all women, regardless of MTHFR genotype. Regardless of MTHFR genotype, multivitamin supplements could control folate and homocysteine levels. Tests for folate and homocysteine levels and optimal multivitamin supplementation in women with risk of NTDs one month or more before pregnancy should be recommended to women who are planning a pregnancy.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Suplementos Nutricionais , Ácido Fólico/sangue , Variação Genética , Homocisteína/sangue , Infertilidade Feminina/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Vitaminas/farmacologia , Adulto , Feminino , Humanos , Infertilidade Feminina/sangue , Infertilidade Feminina/enzimologia , Gravidez , Resultado da Gravidez , Vitamina D/sangue
20.
Int J Mol Sci ; 22(6)2021 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-33799869

RESUMO

The possible cardioprotective effects of translocator protein (TSPO) modulation with its ligand 4'-Chlorodiazepam (4'-ClDzp) in isoprenaline (ISO)-induced rat myocardial infarction (MI) were evaluated, alone or in the presence of L-NAME. Wistar albino male rats (b.w. 200-250 g, age 6-8 weeks) were divided into 4 groups (10 per group, total number N = 40), and certain substances were applied: 1. ISO 85 mg/kg b.w. (twice), 2. ISO 85 mg/kg b.w. (twice) + L-NAME 50 mg/kg b.w., 3. ISO 85 mg/kg b.w. (twice) + 4'-ClDzp 0.5 mg/kg b.w., 4. ISO 85 mg/kg b.w. (twice) + 4'-ClDzp 0.5 mg/kg b.w. + L-NAME 50 mg/kg b.w. Blood and cardiac tissue were sampled for myocardial injury and other biochemical markers, cardiac oxidative stress, and for histopathological evaluation. The reduction of serum levels of high-sensitive cardiac troponin T hs cTnT and tumor necrosis factor alpha (TNF-α), then significantly decreased levels of serum homocysteine Hcy, urea, and creatinine, and decreased levels of myocardial injury enzymes activities superoxide dismutase (SOD) and glutathione peroxidase (GPx) as well as lower grades of cardiac ischemic changes were demonstrated in ISO-induced MI treated with 4'-ClDzp. It has been detected that co-treatment with 4'-ClDzp + L-NAME changed the number of registered parameters in comparison to 4'-ClDzp group, indicating that NO (nitric oxide) should be important in the effects of 4'-ClDzp.


Assuntos
Benzodiazepinonas/farmacologia , Proteínas de Transporte/metabolismo , Infarto do Miocárdio/prevenção & controle , NG-Nitroarginina Metil Éster/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Receptores de GABA-A/metabolismo , Animais , Biomarcadores/sangue , Biomarcadores/metabolismo , Inibidores Enzimáticos/farmacologia , Glutationa Peroxidase/metabolismo , Homocisteína/sangue , Isoproterenol , Masculino , Infarto do Miocárdio/induzido quimicamente , Infarto do Miocárdio/metabolismo , Miocárdio/enzimologia , Óxido Nítrico Sintase/antagonistas & inibidores , Óxido Nítrico Sintase/metabolismo , Ratos Wistar , Superóxido Dismutase/metabolismo , Troponina T/sangue , Fator de Necrose Tumoral alfa/sangue
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