RESUMO

This study aimed to determine if maternal fatty acids (FA) levels during pregnancy are associated with the occurrence of neural tube defects (NTDs) and to explore the correlation between FA and maternal vitamin D, homocysteine, vitamin B12, and folate in cases. Plasma FA composition was assessed using capillary gas chromatography. Comparisons between cases and controls were performed by independent samples t-test for continuous variables. Cases had significantly higher levels of heptadecanoic acid, linolelaidic acid, and arachidonic acid (ARA):(eicosapentaenoic acid+docosahexaenoic acid) ratio than controls (p < 0.05). Nervonic acid, ARA, adrenic acid, eicosapentaenoic acid, docosahexaenoic acid, and omega-3 polyunsaturated fatty acids (n-3 PUFA) levels were significantly lower in cases (p < 0.05). Maternal 25-hydroxyvitamin D (25(OH)D) levels were positively correlated with maternal polyunsaturated fatty acids and omega-6 polyunsaturated fatty acids. RBC folate levels were negatively correlated with n-3 PUFA.Further research is required to clarify the association of FA metabolism with NTDs.

Assuntos

Ácidos Graxos , Ácido Fólico , Defeitos do Tubo Neural , Vitamina D , Humanos , Feminino , Gravidez , Defeitos do Tubo Neural/sangue , Defeitos do Tubo Neural/diagnóstico , Adulto , Ácidos Graxos/sangue , Ácidos Graxos/metabolismo , Vitamina D/sangue , Vitamina D/análogos & derivados , Ácido Fólico/sangue , Estudos de Casos e Controles , Ácidos Docosa-Hexaenoicos/sangue , Vitamina B 12/sangue , Homocisteína/sangue , Ácido Araquidônico/sangue , Ácido Araquidônico/metabolismo , Ácido Eicosapentaenoico/sangue , Ácidos Graxos Ômega-3/sangue , Ácidos Graxos Ômega-3/metabolismo , Ácidos Graxos Monoinsaturados , Ácidos Graxos Insaturados

RESUMO

Folate and vitamin B12 (cobalamin) are essential for growth and development. This cross-sectional study aims to describe folate and vitamin B12 status according to infant age and breastfeeding practices in Norwegian infants. Infants aged 0-12 months (n = 125) were recruited through public health clinics. We registered breastfeeding status and measured serum concentrations of folate, cobalamin, total homocysteine (tHcy), and methylmalonic acid (MMA). The associations between infant age, breastfeeding, and biomarker concentrations were estimated in regression models. The mean (SD) age was 24 (16) weeks, and 42% were exclusively breastfed, 38% were partially breastfed, and 21% were weaned. Overall, median (IQR) folate, cobalamin, tHcy, and MMA concentrations were 47 (35-66) nmol/L, 250 (178-368) pmol/L, 6.99 (5.69-9.27) µmol/L, and 0.35 (0.24-0.83) µmol/L, respectively. None of the infants were folate deficient, 15% were vitamin B12 deficient (< 148 pmol/L), and 23% had low vitamin B12 status (148-221 pmol/L). Elevated tHcy (> 6.5 µmol/L) and MMA (> 0.26 µmol/L) were found in 62% and 69% of the infants, respectively. Compared to weaned, exclusively or partially breastfed infants were younger and had 46% higher tHcy concentrations (P < 0.001), in addition to 47% and 39% lower cobalamin concentrations (P < 0.001), respectively. However, the observed biomarker concentrations appeared to be independent of infant age. In conclusion, low vitamin B12 status was prevalent and appeared to be more common in the younger exclusively breastfed compared to older weaned infants. The implications of low vitamin B12 status in infancy are unknown and require further investigation.

Assuntos

Biomarcadores , Aleitamento Materno , Ácido Fólico , Homocisteína , Ácido Metilmalônico , Deficiência de Vitamina B 12 , Vitamina B 12 , Humanos , Vitamina B 12/sangue , Ácido Fólico/sangue , Estudos Transversais , Noruega , Lactente , Feminino , Biomarcadores/sangue , Homocisteína/sangue , Ácido Metilmalônico/sangue , Masculino , Deficiência de Vitamina B 12/sangue , Deficiência de Vitamina B 12/epidemiologia , Recém-Nascido , Estado Nutricional , Deficiência de Ácido Fólico/epidemiologia , Deficiência de Ácido Fólico/sangue

RESUMO

Aim: To investigate the association between serum homocysteine (HCY) levels, red blood cell folate (RCF) levels, methylenetetrahydrofolate reductase (MTHFR) gene polymorphism and infertility.Materials & methods: Serum HCY and RCF levels and C677T polymorphism of MTHFR gene were analyzed in 149 infertile patients and 223 women of normal reproductive age with healthy childbirth history.Results: The HCY level of MTHFR C677T TT genotype infertility patients was higher than that of women of normal reproductive age, while the RCF level was not significantly different between the two groups.Conclusion: Serum HCY levels increased in infertility patients, and the MTHFR C677T TT genotype in childbearing-aged women are associated with a higher risk of infertility. The results showed that HCY level and MTHFR C677T genotype were closely related to infertility.

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Assuntos

Eritrócitos , Ácido Fólico , Genótipo , Homocisteína , Infertilidade Feminina , Metilenotetra-Hidrofolato Redutase (NADPH2) , Humanos , Feminino , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Homocisteína/sangue , Ácido Fólico/sangue , Infertilidade Feminina/genética , Infertilidade Feminina/sangue , Adulto , Eritrócitos/metabolismo , Polimorfismo de Nucleotídeo Único , Estudos de Casos e Controles

RESUMO

BACKGROUND: Some studies have reported that homocysteine, vitamin B12, and folic acid levels are associated with polycystic ovary syndrome (PCOS), whereas other studies yielded controversial results. OBJECTIVES: This study aimed to systematize the available evidence of homocysteine, vitamin B12, and folate levels in women with and without PCOS. DESIGN: Systematic review and meta-analysis. DATA SOURCES AND METHODS: A systematic search without language restrictions was performed on PubMed, Ovid/Medline, Scopus, Embase, and Web of Science. In addition, the reference lists of the selected studies were reviewed. The Newcastle-Ottawa Scale was employed to evaluate the quality of studies. The means and standard deviations of the outcomes were pooled as standardized mean differences (SMDs) with 95% confidence intervals (CI). Furthermore, the DerSimonian and Laird method was employed for the quantitative synthesis. RESULTS: A total of 75 studies met the eligibility criteria for at least one outcome. Patients with PCOS had higher circulating homocysteine levels than those without (SMD: 0.82; 95% CI: 0.62-1.02, n = 70 studies, p < 0.001). This trend remained in the sensitivity and subgroup analyses by world regions of studies, assay methods, and insulin resistance. No significant differences were observed in circulating vitamin B12 (SMD: -0.11; 95% CI: -0.25 to 0.03; n = 17 studies, p = 0.13) and folate levels (SMD: -0.2; 95% CI: -0.68 to 0.27; n = 17 studies, p = 0.41) between patients with and without PCOS. CONCLUSIONS: (i) Patients with PCOS exhibited significantly higher homocysteine levels than those without, and (ii) no significant differences were observed in both vitamin B12 and folate levels in women with and without PCOS. REGISTRATION: PROSPERO ID (CRD42023432883).

Assuntos

Ácido Fólico , Homocisteína , Síndrome do Ovário Policístico , Vitamina B 12 , Humanos , Síndrome do Ovário Policístico/sangue , Ácido Fólico/sangue , Feminino , Vitamina B 12/sangue , Homocisteína/sangue

RESUMO

Background: DATATOP was a study of early Parkinson's disease (PD) conducted in the 1980 s, before mandatory folic acid fortification in the United States. Our analysis of its baseline serum samples revealed a geometric mean vitamin B12 of 369 pg/mL and homocysteine (tHcy) of 9.5µmol/l. We also found that low B12 predicted greater worsening of ambulatory capacity (AC) and elevated tHcy (>15µmol/L) predicted greater declines in cognitive function. Objective: We sought to measure B12 and tHcy in contemporary trial participants with early PD who had not started dopaminergic treatment and to determine whether these analytes were associated with clinical progression. Methods: We measured B12 and tHcy from baseline and end-of-study blood samples from three recent clinical trials. Results: Baseline geometric mean B12 levels for these studies ranged from 484- 618 pg/ml and for tHcy ranged from 7.4- 10µmol/L. Use of B12-containing supplements ranged from 41- 61%, and those taking supplements had higher B12 and lower tHcy. Those who began levodopa, but were not taking B12-supplements, had greater end-of-study tHcy. There was no association of baseline tHcy > 15µmol/L with annualized change in Montreal Cognitive Assessment and no association of baseline B12 tertiles with change in AC. Conclusions: In these longitudinal trials, B12 levels were higher than for DATATOP, due in large part to increased B12-supplement intake, while tHcy levels were similar. Initiation of levodopa was associated with increases of tHcy in those not taking a B12-containing supplement. These smaller studies did not replicate prior findings of low B12 and elevated tHcy with features of progression, possibly due to higher baseline B12.

Assuntos

Homocisteína , Doença de Parkinson , Vitamina B 12 , Humanos , Vitamina B 12/sangue , Homocisteína/sangue , Masculino , Feminino , Idoso , Doença de Parkinson/sangue , Doença de Parkinson/tratamento farmacológico , Pessoa de Meia-Idade , Progressão da Doença , Antiparkinsonianos/uso terapêutico , Levodopa/administração & dosagem , Levodopa/farmacologia , Suplementos Nutricionais , Disfunção Cognitiva/sangue , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/tratamento farmacológico

RESUMO

INTRODUCTION: Ischemic stroke (IS) is a global health concern, often tied to dyslipidemia and vascular endothelial dysfunction. MicroRNA-34a (miR-34a) was reported to be up-regulated in the blood samples of patients with IS, but the specific role of miR-34a and methylenetetrahydrofolate reductase (MTHFR) in IS remains to be elucidated. METHODS: We studied 143 subjects: 71 IS patients, and 72 healthy controls. Human umbilical vein endothelial cells (HUVECs) were cultured and transfected with a miR-34a mimic, inhibitor, or negative control. The miR-34a expression in serum and HUVECs was quantified via quantitative reverse transcription polymerase chain reaction (qRT-PCR). Viability and apoptosis of HUVECs were assessed using CCK-8 assay and flow cytometry. The expression levels of bcl-2, bax, cyt-c, cleaved caspase 3, MTHFR, and homocysteine were measured by Western blot or enzyme-linked immunosorbent assay (ELISA). The relationship between miR-34a and MTHFR was verified by luciferase reporter assay. The levels of MTHFR and homocysteine in serum were examined by ELISA. RESULTS: MiR-34a expression was increased in IS patients and inhibited viability of HUVECs while promoting their apoptosis. Overexpression of miR-34a up-regulated pro-apoptotic proteins (bax, cyt-c and cleaved caspase 3) and down-regulated anti-apoptotic protein bcl-2 in HUVECs. MTHFR was identified as the downstream target of miR-34a and its expression was reduced by miR-34a overexpression, while homocysteine levels increased. Consistently, MTHFR levels were lower and homocysteine levels were higher in IS patients compared with controls. DISCUSSION: Our results suggest that up-regulated miR-34a plays a role in the pathogenesis of IS, potentially through inhibiting MTHFR expression and increasing homocysteine in endothelial cells. Therefore, miR-34a might be a therapeutic target for IS.

Assuntos

Apoptose , Sobrevivência Celular , Homocisteína , AVC Isquêmico , Metilenotetra-Hidrofolato Redutase (NADPH2) , MicroRNAs , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Homocisteína/sangue , Células Endoteliais da Veia Umbilical Humana/metabolismo , AVC Isquêmico/metabolismo , AVC Isquêmico/sangue , AVC Isquêmico/patologia , Metilenotetra-Hidrofolato Redutase (NADPH2)/metabolismo , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , MicroRNAs/metabolismo , MicroRNAs/genética

RESUMO

OBJECTIVE: This study investigated the relationship of serum homocysteine (Hcy) and cystatin C (Cys C) levels with the prognosis of patients with heart failure with preserved ejection fraction (HFpEF). METHODS: A total of 178 patients with HFpEF who were admitted to our hospital between December 2019 and November 2020 were included. Patients were grouped based on their serum Hcy and Cys C levels: high Hcy level, normal Hcy level, high Cys C level, and normal Cys C level. Cardiac function, ventricular remodeling indices, and prognosis were compared among patients in these groups. Additionally, the predictive value of serum Hcy and Cys C levels for adverse cardiovascular events in HFpEF patients was analyzed. RESULTS: Patients' mean age in the high Hcy level, normal Hcy level, high Cys C level, and normal Cys C level groups was 69.21 ± 4.17,67.74 ± 4.28,69.95 ± 4.98, and 67.06 ± 4.13 years old, respectively. The high Hcy level group exhibited a lower proportion of class II cardiac function according to the New York Heart Association (NYHA) classification and a higher proportion of class IV cardiac function than the normal Hcy level group, with statistically significant differences. Similarly, the high Cys C level group had a lower proportion of class II cardiac function and a higher proportion of class IV cardiac function compared with the normal Cys C level group, with statistically significant differences. Left ventricular end-diastolic internal diameter (LVEDD), left ventricular end-systolic internal diameter (LVESD), and left ventricular mass index (LVMI) were significantly higher in both the high Hcy level and high Cys C level groups compared with the normal group, with statistically significant differences. The rates of all-cause mortality and class I endpoint events were significantly higher in the high Hcy level and high Cys C level groups than in the normal group. Multifactorial logistic regression analysis demonstrated that adverse cardiovascular events were significantly associated with cardiac function class, LVEDD, LVESD, LVMI, Hcy, and Cys C in patients with HFpEF. The area under the curve (AUC) values for Hcy and Cys C, determined using receiver operating characteristic (ROC) curve analysis, were 0.778 (optimal critical value, 25.38) and 0.681 (optimal critical value, 1.56), respectively, for predicting adverse cardiovascular events. Both Hcy and Cys C serum levels were positively correlated with LVEDD, LVESD, LVMI, and NYHA classification. CONCLUSION: Serum levels of Hcy and Cys C were closely associated with cardiac function, ventricular remodeling indices, and prognosis in patients with HFpEF. These levels may serve as valuable indices for assessing HFpEF patients' health status and prognosis, providing important insights into their potential role as biomarkers for HFpEF management and prognosis.

Assuntos

Biomarcadores , Cistatina C , Insuficiência Cardíaca , Homocisteína , Valor Preditivo dos Testes , Volume Sistólico , Função Ventricular Esquerda , Humanos , Homocisteína/sangue , Cistatina C/sangue , Masculino , Feminino , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/mortalidade , Biomarcadores/sangue , Idoso , Prognóstico , Pessoa de Meia-Idade , Medição de Risco , Estudos Retrospectivos , Remodelação Ventricular , Fatores de Risco

RESUMO

BACKGROUND: As a risk factor of cardiovascular diseases, homocysteine can be effectively lowered by folate. However, the associations of folate and homocysteine levels with the prognosis of ischemic stroke remained unclear. METHODS AND RESULTS: A total of 3530 patients with ischemic stroke were included. Serum folate and homocysteine levels were measured at admission. The primary outcome was composite of death and major disability (modified Rankin Scale score≥3) at 3 months after stroke onset. Univariate and multivariate logistic regression models were used. The mediation effect of homocysteine was examined. During follow-up, 1056 participants developed the primary outcome. In the univariate model, participants in the highest quartile of folate had a 29% (95% CI, 0.58-0.87) decreased risk of primary outcome compared with those in the lowest quartile. After multivariate adjustment, the odds ratio associated with the highest quartile of folate was 0.58 (95% CI, 0.46-0.73) for primary outcome. In contrast, participants in the highest quartile of homocysteine had a 52% (95% CI, 1.24-1.98) increased risk of primary outcome compared with those in the lowest quartile. After multivariate adjustment, the odds ratio associated with highest quartile of homocysteine was 1.57 (95% CI, 1.24-1.98) for primary outcome. In addition, 25.5% of the observed associations between folate and primary outcome was mediated through homocysteine (P=0.012). CONCLUSIONS: High folate levels were associated with low risks of death and major disability among Chinese patients with ischemic stroke, and homocysteine partially mediated the observed potential beneficial role of folate.

Assuntos

Ácido Fólico , Homocisteína , AVC Isquêmico , Humanos , Masculino , Homocisteína/sangue , Ácido Fólico/sangue , Feminino , AVC Isquêmico/sangue , AVC Isquêmico/mortalidade , AVC Isquêmico/epidemiologia , AVC Isquêmico/diagnóstico , Idoso , Pessoa de Meia-Idade , Fatores de Risco , Prognóstico , Biomarcadores/sangue , Medição de Risco , Avaliação da Deficiência , China/epidemiologia

RESUMO

The bioavailability of natural folates is 50% lower than that of synthetic folic acid (FA); however, it remains unclear whether this value is universally applicable to all foods. Therefore, the present study investigated the bioavailability of folate from spinach using multiple biomarkers in a folate depletion-repletion mouse model. Mice were fed a folate-deficient diet for 4 wk and subsequently divided into three groups: folate-deficient, FA, and spinach folate. The folate repletion group received either FA or spinach folate at 2 mg/kg diet for 9 d. On the 7th day of repletion, half of each group underwent low-dose total body X-ray irradiation to induce chromosomal damage in bone marrow. Folate bioavailability biomarkers included measurements of folate levels in plasma, liver, and bone marrow along with an analysis of plasma homocysteine levels and chromosome damage, both of which are functional biomarkers of body folate. The consumption of a folate-deficient diet led to decreased tissue folate levels, increased plasma homocysteine levels, and chromosomal damage. Repletion with spinach folate restored folate levels in plasma, liver, and bone marrow to 69, 13, and 68%, respectively, of FA levels. Additionally, spinach folate repletion reduced plasma homocysteine levels and chromosome damage to 83% and 93-117%, respectively, of FA levels. Collectively, the present results demonstrated that the bioavailability of spinach folate exceeded 83% of FA, particularly when assessed using functional biomarkers.

Assuntos

Disponibilidade Biológica , Biomarcadores , Deficiência de Ácido Fólico , Ácido Fólico , Homocisteína , Fígado , Spinacia oleracea , Animais , Spinacia oleracea/química , Ácido Fólico/sangue , Biomarcadores/sangue , Deficiência de Ácido Fólico/metabolismo , Fígado/metabolismo , Camundongos , Masculino , Homocisteína/sangue , Homocisteína/metabolismo , Medula Óssea/metabolismo , Dieta , Modelos Animais de Doenças

RESUMO

Incidence of esophageal and gastric cancer has been linked to low B-vitamin status. We conducted matched nested case-control studies of incident esophageal squamous cell carcinoma (ESCC; 340 case-control pairs) and gastric cancer (GC; 352 case-control pairs) within the Golestan Cohort Study. The primary exposure was plasma biomarkers: riboflavin and flavin mononucleotide (FMN) (vitamin B2), pyridoxal phosphate (PLP) (B6), cobalamin (B12), para-aminobenzoylglutamate (pABG) (folate), and total homocysteine (tHcy); and indicators for deficiency: 3-hydroxykyurenine-ratio (HK-r for vitamin B6) and methylmalonic acid (MMA for B12). We estimated odds ratios (ORs) and 95% confidence intervals (CIs) using conditional logistic regression adjusting for matching factors and potential confounders. High proportions of participants had low B-vitamin and high tHcy levels. None of the measured vitamin B levels was associated with the risk of ESCC and GC, but elevated level of MMA was marginally associated with ESCC (OR = 1.42, 95% CI = 0.99-2.04) and associated with GC (OR = 1.53, 95% CI = 1.05-2.22). Risk of GC was higher for the highest versus lowest quartile of HK-r (OR = 1.95, 95%CI = 1.19-3.21) and for elevated versus non-elevated HK-r level (OR = 1.59, 95% CI = 1.13-2.25). Risk of ESCC (OR = 2.81, 95% CI = 1.54-5.13) and gastric cancer (OR = 2.09, 95%CI = 1.17-3.73) was higher for the highest versus lowest quartile of tHcy. In conclusion, insufficient vitamin B12 was associated with higher risk of ESCC and GC, and insufficient vitamin B6 status was associated with higher risk of GC in this population with prevalent low plasma B-vitamin status. Higher level of tHcy, a global indicator of OCM function, was associated with higher risk of ESCC and GC.

Assuntos

Neoplasias Esofágicas , Neoplasias Gástricas , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Estudos de Casos e Controles , Neoplasias Gástricas/sangue , Neoplasias Gástricas/epidemiologia , Neoplasias Esofágicas/sangue , Neoplasias Esofágicas/epidemiologia , Estudos de Coortes , Idoso , Biomarcadores Tumorais/sangue , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/epidemiologia , Vitamina B 12/sangue , Carcinoma de Células Escamosas do Esôfago/sangue , Carcinoma de Células Escamosas do Esôfago/epidemiologia , Carcinoma de Células Escamosas do Esôfago/metabolismo , Carbono/metabolismo , Homocisteína/sangue , Adulto , Ácido Fólico/sangue , Ácido Metilmalônico/sangue , Riboflavina/sangue

RESUMO

BACKGROUND AND OBJECTIVE: Cerebral small vessel disease (CSVD) often coexists with cognitive dysfunction in patients, leading to significant challenges in treatment and management. This study aimed to examine the efficacy of combined application of donepezil and nimodipine on patients with comorbid CSVD and cognitive dysfunction and the effects on patients' albumin and prealbumin levels. METHODS: The records of 112 patients with comorbid CSVD and cognitive dysfunction treated at the People's Hospital of Suzhou New District from January 2019 to December 2022 were analysed retrospectively. A total of 50 patients receiving donepezil were allocated to the control group, and 62 patients receiving both nimodipine and donepezil to the study group. Outcomes compared between the two groups included serum homocysteine (Hcy), high sensitivity C-reactive protein (hs-CRP), albumin, and prealbumin before and after therapy, efficacy, and adverse reactions. Additionally, logistic regression was performed to analyze the risk factors impacting patient prognosis. RESULTS: Prior to therapy, the two groups did not differ significantly in Hcy and hs-CRP levels (p > 0.05), whereas after therapy, the levels in both groups dropped significantly (p < 0.01), with more obvious lower levels in the study group (p < 0.05). After treatment, the study group presented significantly higher albumin and prealbumin levels than the control group (p < 0.001). An obvious higher overall response rate was observed in the study group compared to the control group (p = 0.012). No significant inter-group discrepancy was found regarding the total incidence of adverse reactions (p = 0.752). Univariate analysis identified age, course of disease, heart rate (HR), Montreal Cognitive Assessment (MoCA) score, diastolic blood pressure (DBP), systolic blood pressure (SBP), drinking history, as well as medication regimen as risk factors impacting patient prognosis. Multivariate logistic regression analysis identified SBP, DBP, and medication regimen as the independent risk factors. CONCLUSION: Combined application of donepezil and nimodipine can effectively treat patients with comorbid CSVD and cognitive dysfunction. It can significantly lower the Hcy and hs-CRP levels and improve the nutritional status without increasing the frequency of adverse reactions. In addition, for CSVD patients with cognitive dysfunction, age, course of disease, MoCA score, HR, SBP, DBP, drinking history, and medication regimen are risk factors impacting patient prognosis, while SBP, DBP, and medication regimen are independent risk factors.

Assuntos

Doenças de Pequenos Vasos Cerebrais , Disfunção Cognitiva , Donepezila , Quimioterapia Combinada , Nimodipina , Estado Nutricional , Humanos , Feminino , Masculino , Donepezila/administração & dosagem , Donepezila/uso terapêutico , Doenças de Pequenos Vasos Cerebrais/tratamento farmacológico , Doenças de Pequenos Vasos Cerebrais/complicações , Disfunção Cognitiva/tratamento farmacológico , Estudos Retrospectivos , Idoso , Pessoa de Meia-Idade , Nimodipina/administração & dosagem , Nimodipina/uso terapêutico , Resultado do Tratamento , Nootrópicos/administração & dosagem , Nootrópicos/uso terapêutico , Nootrópicos/efeitos adversos , Homocisteína/sangue

RESUMO

Abnormal homocysteine (Hcy) levels in human serum have been associated with serious or vital diseases, making the reliable and easy detection of Hcy important to clinical analysis and biological study. In this work, five phosphorescent Ir(C^N)2(N^N) complexes (Irn) having aldehyde group were synthesized as probes (C^N and N^N denoted ligands). A discussion was conducted on their molecular structure, electronic structure, photophysical parameters, and Hcy sensing ability, revealing the correlations between their molecular structures and performances. Irn emission was enhanced (by âˆ¼ two folds) and blue-shifted (by 100 nm) after meeting Hcy (free state), via a cyclization reaction between the -CHO group (from Irn) and Hcy. In addition, using RE(BTC) as a supporting material (RE = Tb and Eu), the Ir(III) probe was loaded onto a supporting material of RE(BTC) (H3BTC = 1, 3, 5-benzenetricarboxylic acid). The emission color was changed by increasing Hcy concentration. Straight working curves were obtained with LOD (limit of detection) of 1.9 µM and a response time of ∼200 s. The novelty of this work was the combination of Irn with RE(BTC), which offered enhanced and blue-shifted emission upon Hcy via a cyclization reaction. This demonstrated a high level of sensitivity towards homocysteine detection.

Assuntos

Európio , Corantes Fluorescentes , Homocisteína , Espectrometria de Fluorescência , Térbio , Homocisteína/sangue , Homocisteína/análise , Humanos , Európio/química , Térbio/química , Espectrometria de Fluorescência/métodos , Corantes Fluorescentes/química , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/síntese química , Limite de Detecção

RESUMO

Atherosclerosis, the leading cause of cardiovascular disease, cannot be sufficiently explained by established risk factors, including cholesterol. Elevated plasma homocysteine (Hcy) is an independent risk factor for atherosclerosis and is closely linked to cardiovascular mortality. However, its role in atherosclerosis has not been fully clarified yet. We have previously shown that rabbits fed a diet deficient in B vitamins and choline (VCDD), which are required for Hcy degradation, exhibit an accumulation of macrophages and lipids in the aorta, aortic stiffening and disorganization of aortic collagen in the absence of hypercholesterolemia, and an aggravation of atherosclerosis in its presence. In the current study, plasma Hcy levels were increased by intravenous injections of Hcy into balloon-injured rabbits fed VCDD (VCDD+Hcy) in the absence of hypercholesterolemia. While this treatment did not lead to thickening of aortic wall, intravenous injections of Hcy into rabbits fed VCDD led to massive accumulation of VLDL-triglycerides as well as significant impairment of vascular reactivity of the aorta compared to VCDD alone. In the aorta intravenous Hcy injections into VCDD-fed rabbits led to fragmentation of aortic elastin, accumulation of elastin-specific electron-dense inclusions, collagen disorganization, lipid degradation, and autophagolysosome formation. Furthermore, rabbits from the VCDD+Hcy group exhibited a massive decrease of total protein methylated arginine in blood cells and decreased creatine in blood cells, serum and liver compared to rabbits from the VCDD group. Altogether, we conclude that Hcy contributes to atherogenic transformation of the aorta not only in the presence but also in the absence of hypercholesterolemia.

Assuntos

Aorta , Aterosclerose , Homocisteína , Hipercolesterolemia , Animais , Coelhos , Aterosclerose/patologia , Aterosclerose/metabolismo , Homocisteína/sangue , Aorta/patologia , Aorta/metabolismo , Hipercolesterolemia/sangue , Hipercolesterolemia/metabolismo , Hipercolesterolemia/patologia , Masculino , Colina/administração & dosagem , Modelos Animais de Doenças , Elastina/metabolismo , Complexo Vitamínico B/administração & dosagem , Complexo Vitamínico B/farmacologia

RESUMO

BACKGROUND: Cross-sectional and longitudinal studies have inconsistently linked cognitive performance and change over time to an elevated level of homocysteine (Hcy), with few conducted among urban adults. METHODS: Longitudinal data [Visit 1 (2004-2009) and Visit 2 (2009-2013)] were analyzed from up to 1430 selected Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) participants. Baseline and follow-up blood Hcy was measured, while 11 cognitive function test scores were assessed at either of these two visits. Overall, sex- and race-stratified associations were evaluated using mixed-effects linear regression models, adjusting for key potential confounders. Interaction effects between Hcy and serum levels of folate and vitamin B-12 were also tested. RESULTS: We found that greater LnHcyv1 was significantly associated with poorer baseline attention based on higher Loge (TRAILS A, in seconds) [ß (SE): 0.101 (0.031), P = 0.001]. Heterogeneity was also found by sex and by race. Most notably, among men only, LnHcyv1 was associated with faster decline on the BVRT (# of errors), a measure of visuo-spatial memory (ß (SE): 0.297(0.115), P = 0.010, reduced model); while among African American adults only, an elevated and increasing LnHcy over time was associated with faster rate of decline on Loge (TRAILS B, in seconds) [ß (SE): +0.012 (0.005), p = 0.008], a measure of executive function. Interactions between Hcy, folate and vitamin B-12 blood exposures were also detected. CONCLUSIONS: In summary, sex- and race-specific adverse association between elevated Hcy and cognitive performance over time were detected among middle-aged urban adults, in domains of attention, visuo-spatial memory and executive functioning.

Assuntos

Cognição , Ácido Fólico , Homocisteína , População Urbana , Vitamina B 12 , Humanos , Masculino , Feminino , Homocisteína/sangue , Estudos Longitudinais , Pessoa de Meia-Idade , Cognição/fisiologia , População Urbana/estatística & dados numéricos , Idoso , Vitamina B 12/sangue , Ácido Fólico/sangue , Testes Neuropsicológicos/estatística & dados numéricos , Atenção/fisiologia , Função Executiva/fisiologia , Fatores Sexuais , Estudos Transversais

RESUMO

BACKGROUND: Pre-eclampsia is a syndrome that chiefly includes the development of new-onset hypertension and proteinuria after 20 weeks of pregnancy. Pre-eclampsia is one of the major causes of mortality and morbidity in Nepal. Hyperhomocysteinemia may be a cause of the endothelial dysfunction provoked by oxidative stress in pre-eclampsia. This study was designed to evaluate the association of homocysteine with Vitamin B12 and folate in patients with pre-eclampsia. METHOD: An observational cross sectional study was performed in the Gynecology and Obstetrics Department of TUTH involving seventy two subjects with pre-eclampsia. Blood pressure, urinary protein levels, serum homocysteine, Vitamin B12 and folate levels were compared in both mild and severe forms of pre-eclampsia. Concentration of Vitamin B12 and folate were measured using Vitros ECI and homocysteine was measured using CLIA. SPSS 23.0 was used to analyze the data. Tests were performed with Mann Whitney Test and Spearman's rank correlation test. A p-value < 0.05 was considered statistically significant. RESULTS: This study showed no significant difference in age and weeks of gestation in both mild and severe forms of pre-eclampsia. Mean concentration of homocysteine was higher (13.1 ± 6.4 micromol/L) in severe Pre-eclampsia as compared to mild cases (7.6 ± 2.8 micromol/L). Mean concentration of folate was lower in severe cases (35.4 ± 24.1 micromol/L) when compared with mild cases of pre-eclampsia (57 ± 23.4 micromol/L). CONCLUSION: Homocysteine levels were increased in severe Pre-eclampsia when compared with mild pre-eclampsia and this finding can be used to predict and prevent complications in patients with pre-eclampsia.

Assuntos

Ácido Fólico , Homocisteína , Pré-Eclâmpsia , Centros de Atenção Terciária , Vitamina B 12 , Humanos , Feminino , Pré-Eclâmpsia/sangue , Pré-Eclâmpsia/epidemiologia , Gravidez , Homocisteína/sangue , Ácido Fólico/sangue , Vitamina B 12/sangue , Nepal/epidemiologia , Adulto , Estudos Transversais , Centros de Atenção Terciária/estatística & dados numéricos , Adulto Jovem , Hiper-Homocisteinemia/sangue , Hiper-Homocisteinemia/epidemiologia , Índice de Gravidade de Doença , Proteinúria/sangue

RESUMO

A disturbance in the metabolism of homocysteine in both the mother and the fetus has been implicated in several placental vasculopathy-related disorders, including pregnancy loss. This study aimed to provide insights into the potential role of homocysteine, Vitamin B12, and folic acid in early pregnancy losses, with a specific focus on the Turkish population. The results of 93 pregnant women who experienced miscarriage between 5 and 14 gestational weeks and 93 healthy pregnant women at the same gestational weeks were compared. The demographic and pregnancy characteristics of all pregnant women were recorded. Vitamin B12, folic acid, and homocysteine levels were measured in serum samples obtained from the groups at similar gestational weeks. In addition, any associations between these biomarkers and different types of pregnancy loss, such as spontaneous abortion and missed abortion, were evaluated. Vitamin B12 and folic acid serum levels were significantly lower in women with miscarriages (P = .019, P < .001, respectively). Homocysteine levels were higher in the patient group (P < .001). Logistic regression analysis showed that a higher homocysteine level was the only predictive factor of miscarriage (P = .001, odds ratio = 0.596); however, folic acid and Vitamin B12 were not predictive factors. There was no significant difference in homocysteine and micronutrient levels between women with missed abortions and women with spontaneous abortions (P > .05). Our results support the continuing evidence of a link between maternal homocysteine levels and fetal loss. However, in exploring the shared pathways in the underlying mechanisms causing the 2 forms of pregnancy loss, maternal blood analysis showed no relationship.

Assuntos

Aborto Espontâneo , Ácido Fólico , Homocisteína , Hiper-Homocisteinemia , Vitamina B 12 , Humanos , Feminino , Hiper-Homocisteinemia/sangue , Hiper-Homocisteinemia/epidemiologia , Gravidez , Adulto , Ácido Fólico/sangue , Vitamina B 12/sangue , Estudos Retrospectivos , Aborto Espontâneo/epidemiologia , Aborto Espontâneo/sangue , Homocisteína/sangue , Estudos de Casos e Controles , Turquia/epidemiologia , Biomarcadores/sangue , Centros de Atenção Terciária

RESUMO

BACKGROUND: Cerebral venous sinus thrombosis (CVST) is a rare cause of stroke. Acquired and inherited prothrombotic conditions are the most common risk factors for CVST. Sometimes, an etiology is not found. Wide utilization of next generation sequencing technologies in clinical practice may lead to identification of risk factors other than those classically associated with CVST. METHOD AND RESULTS: This retrospective clinical-laboratory observational study has a reference patient who presented with CVST as an adolescent. Work up for prothrombotic conditions showed high homocysteine level secondary to homozygosity for a common polymorphism, c.677 C > T in the methylenetetrahydrofolate reductase (MTHFR) gene. His older unaffected brother has a similar MTHFR genotype and high homocysteine. The whole exome sequencing revealed a likely pathogenic variant in the sodium voltage gated channel, alpha subunit 1(SCN1A) gene. CONCLUSION: CVST is a multifactorial disease. Prothrombotic conditions are the most common risk factors for CVST. High homocysteine due to the common MTHFR polymorphisms was previously attributed to various thrombotic conditions including CVST. Although high homocysteine due to MTHFR polymorphism may be a contributing factor, additional risk factors such as blood flow abnormalities during SCN1A related seizures may be needed for thrombosis.

Assuntos

Metilenotetra-Hidrofolato Redutase (NADPH2) , Canal de Sódio Disparado por Voltagem NAV1.1 , Trombose dos Seios Intracranianos , Humanos , Trombose dos Seios Intracranianos/genética , Masculino , Canal de Sódio Disparado por Voltagem NAV1.1/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Adolescente , Estudos Retrospectivos , Predisposição Genética para Doença , Fatores de Risco , Homocisteína/sangue , Sequenciamento do Exoma/métodos , Polimorfismo de Nucleotídeo Único/genética

RESUMO

Hyperhomocysteinaemia (elevated blood levels of the amino acid homocysteine) attracted the interest of researchers in the middle of the 20th century. At first. Butz and du Vigneaud in 1932 described a disorder of methionine metabolism in children, which was manifested by homocysteinuria (homocysteine is not normally detected in the urine). In 1962 Cavon and Neil found that homocysteinuria in children is associated with a defect in cystathione-B-synthase and manifests early development of atherosclerosis. It is quite possible that these facts would have remained unnoticed by the medical community had it not been for further research by Kilmer McQuilley, a professor in the Department of Pathology at Harvard Medical School. The scientist suggested that while high concentrations of homocysteine could damage blood vessels in young people, it was likely that lower concentrations of homocysteine, acting over a longer period of time, could cause cardiovascular disease in adults. Subsequent studies enabled him to formulate the "homocysteine" theory of atherosclerosis and to publish its main points in 1969. Hyperhomocysteinaemia in young men has been shown to cause damage to the endothelium of blood vessels, and consequently males face the consequent equally global problem of developing erectile dysfunction. Erection is a state regulated by a neurovascular process, characterized by blood filling of the cavernous bodies, provided by neural and humoral mechanisms occurring at different levels of the nervous system. Erectile dysfunction (ED) refers to the inability to achieve and maintain an erection at a level necessary to ensure satisfactory sexual intercourse, Although ED is not life-threatening. it is a serious psychological and physiological problem, and it has now been shown to correlate the quality of intimate life with general health and even with life expectancy, In the USA alone, ED is reported in 20-30 million men, and the prevalence of these disorders increases with age. A study of the homocysteine level of multidisciplinary hospital patients was used as the main marker. The work used laboratory and statistical research methods, as well as analysis and synthesis methods. Using patient analyses, laboratory and statistical data, it has been shown that hyperhomosysteinaemia is one of the molecular mechanisms in the development of erectile dysfunction.

Assuntos

Disfunção Erétil , Homocisteína , Hiper-Homocisteinemia , Humanos , Hiper-Homocisteinemia/complicações , Masculino , Disfunção Erétil/etiologia , Homocisteína/sangue

RESUMO

Homocysteine, methionine, methylmalonic acid and 2-methylcitric acid are clinically relevant markers in the methionine, propionate, and cobalamin metabolism. This study aimed to develop and validate an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for simultaneously determining total homocysteine, methionine, methylmalonic acid and 2-methylcitric acid in dried blood spots. Three 3.2 mm discs were punched from each calibrator, quality control, and sample dried blood spot into a 96-well U-plate. Each sample was spiked with internal standards and extracted. Then the supernatant was transferred to another 96-well U-plate. After nitrogen drying, the dried residues were reconstituted, centrifuged, and the resulting supernatant was transferred to another 96-well plate for analysis. The method was performed using UPLC-MS/MS within 3 min, validated according to guidance documents, and applied to 72 samples from confirmed patients with methionine, propionate, and cobalamin metabolism disorders. The UPLC-MS/MS method provided satisfactory separation of the four analytes. The R2 values were ≥ 0.9937 for all analytes. The recoveries ranged from 94.17 to 114.29 %, and the coefficients of variation for intraday and interday precision were 0.19 % to 5.23 % and 1.02 % to 6.89 %, respectively. No significant carry-over was detected for the four analytes, and most of confirmed samples exhibited biomarker patterns characteristic of the relevant disorders. A simple and fast UPLC-MS/MS method was successfully developed, validated, and applied to clinical samples for the simultaneous determination of total homocysteine, methionine, methylmalonic acid, and 2-methylcitric acid in dried blood spots.

Assuntos

Citratos , Teste em Amostras de Sangue Seco , Homocisteína , Limite de Detecção , Metionina , Ácido Metilmalônico , Espectrometria de Massas em Tandem , Humanos , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida de Alta Pressão/métodos , Homocisteína/sangue , Homocisteína/análogos & derivados , Ácido Metilmalônico/sangue , Ácido Metilmalônico/análogos & derivados , Teste em Amostras de Sangue Seco/métodos , Reprodutibilidade dos Testes , Metionina/sangue , Metionina/análogos & derivados , Metionina/química , Modelos Lineares , Citratos/sangue , Citratos/química , Masculino , Feminino , Pré-Escolar

RESUMO

Plasma homocysteine (Hcy) has been globally recognized as an independent risk factor for various neurovascular diseases. In this study, the authors investigated the relationship between critical Hcy concentration and the risk of rupture in intracranial aneurysms (IAs). This study collected data from 423 patients with both ruptured and unruptured IAs. We compared demographic data, vascular rupture risk factors, and laboratory test results between the two groups. Multivariable logistic regression analysis was employed to determine the correlation between critical plasma Hcy levels and the risk of rupture in small to medium-sized IAs. A total of 330 cases of ruptured intracranial aneurysms (RIA) and 93 cases of unruptured intracranial aneurysms (UIA) were included. Univariate analysis revealed statistically significant differences between the ruptured and unruptured groups in terms of hypertension, hyperlipidemia, plasma Hcy levels, and IA morphology (all P < 0.05). Multivariable logistic regression analysis indicated that hypertension (odds ratio [OR] 0.504; 95% confidence interval [CI] 0.279-0.911; P = 0.023), hyperlipidemia (OR 1.924; 95% CI 1.079-3.429; P = 0.027), and plasma Hcy levels (OR 1.420; 95% CI 1.277-1.578; P < 0.001) were independently associated with the rupture of small to medium-sized IAs, all with statistical significance (P < 0.05). Our study suggests that critical plasma Hcy levels are an independent risk factor for increased rupture risk in small to medium-sized intracranial aneurysms. Therefore, reducing plasma Hcy levels may be considered a valuable strategy to mitigate the risk of intracranial vascular abnormalities rupture and improve patient prognosis.

Assuntos

Aneurisma Roto , Homocisteína , Aneurisma Intracraniano , Humanos , Aneurisma Intracraniano/sangue , Homocisteína/sangue , Masculino , Feminino , Aneurisma Roto/sangue , Pessoa de Meia-Idade , Fatores de Risco , Idoso , Adulto , Hipertensão/sangue , Hipertensão/complicações , Modelos Logísticos , Relevância Clínica