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1.
Med Hypotheses ; 149: 110539, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33662863

RESUMO

Using folic acid (FA) as placebo complicates the interpretation of the findings of few RCTs evaluating safety and efficacy of hydroxychloroquine prophylaxis in COVID-19. FA is found to bind to furin-protease and spike: ACE2 interface of SARS-CoV-2. In clinical studies, FA level was lowest among severe patients compared to mild and moderate disease. A single controlled study reported the benefit of combination of folic acid with Pyridoxine & cyanocobalamin in terms of clinical and laboratory cure parameters. One hypothesis associates the differences in geographical variation of disease severity with prevalence of methyl tertahydrofolic acid reductase (MTHFR) C677T polymorphism. Other possible domains, where FA is hypothesized to be beneficial are COVID-19 associated pulmonary hypertension and hyper-homocystinemia. So, scientific justification of using folic acid as placebo in COVID-19 trials seems scientifically not credible and this may be one of the major factors for failure of many agents. We need to be more careful in choosing our placebo especially when conducting a placebo controlled trial.


Assuntos
/prevenção & controle , Ácido Fólico/uso terapêutico , Hidroxicloroquina/uso terapêutico , Placebos , /metabolismo , /tratamento farmacológico , Humanos , Hiper-Homocisteinemia/complicações , Hiper-Homocisteinemia/tratamento farmacológico , Hipertensão Pulmonar/complicações , Hipertensão Pulmonar/tratamento farmacológico , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Modelos Teóricos , Óxido Nítrico Sintase Tipo III/metabolismo , Ligação Proteica , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa
2.
Int J Mol Sci ; 22(4)2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33567540

RESUMO

The influence of hyperhomocysteinemia (HHCy) on cardiovascular disease (CVD) remains unclear. HHCy is associated with inflammation and atherosclerosis, and it is an independent risk factor for CVD, stroke and myocardial infarction. However, homocysteine (HCy)-lowering therapy does not affect the inflammatory state of CVD patients, and it has little influence on cardiovascular risk. The HCy degradation product hydrogen sulfide (H2S) is a cardioprotector. Previous research proposed a positive role of H2S in the cardiovascular system, and we discuss some recent data suggesting that HHCy worsens CVD by increasing the production of H2S, which decreases the expression of adenosine A2A receptors on the surface of immune and cardiovascular cells to cause inflammation and ischemia, respectively.


Assuntos
Doenças Cardiovasculares/etiologia , Homocisteína/metabolismo , Sulfeto de Hidrogênio/metabolismo , Hiper-Homocisteinemia/complicações , Receptor A2A de Adenosina/metabolismo , Animais , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/patologia , Humanos , Hiper-Homocisteinemia/metabolismo
3.
BMC Neurol ; 21(1): 6, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407217

RESUMO

BACKGROUND: This study aimed to investigate the relationship between H-type hypertension and retinal vessel abnormalities. METHODS: Hypertensive patients were retrospectively enrolled in this study. According to plasma homocysteine (HCY), patients were divided into isolated hypertension and H-type hypertension groups. The diameter of retinal vessels and retinopathy were evaluated by retinal fundus photography. The differences of retinal vessel abnormalities between H-type hypertension and isolated hypertension were investigated by univariate and multivariate regression. RESULTS: A total of 191 hypertensive patients were included, of which 86 were with isolated hypertension and 105 with H-type hypertension. The H-type hypertension group had a higher ratio of retinopathy(P = 0.004) and higher degree of retinal arteriosclerosis (P = 0.005) than the isolated hypertension group. CRAE (107.47 ± 13.99µ m vs. 113.49 ± 11.72µ m, P = 0.002) and AVR (0.55 ± 0.06 vs. 0.58 ± 0.06, P = 0.001) were smaller in H-type hypertension group than those in isolated hypertension group. Multivariate analysis showed that after adjusting for age, sex, course of hypertension and diabetes, H-type hypertension was an independent risk factor of retinopathy (OR, 2.259; 95%CI, 1.165-4.378; P = 0.016), CRAE (ß=-5.669; 95%CI, -9.452--1.886; P = 0.004), and AVR (ß=-0.023; 95%CI, -0.039--0.007; P = 0.005). CONCLUSIONS: H-type hypertension is closely related to more retinal vessel abnormalities than isolated hypertension. Controlling H-type hypertension may reduce the risk of small vascular damage.


Assuntos
Hiper-Homocisteinemia/complicações , Hipertensão/complicações , Doenças Retinianas/etiologia , Vasos Retinianos/patologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Retinianas/patologia , Estudos Retrospectivos , Fatores de Risco
4.
Clinics (Sao Paulo) ; 76: e2233, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33503187

RESUMO

OBJECTIVES: To explore the risk factors of essential hypertension with hyperhomocysteinemia (H-type hypertension) and design a nomogram to predict this risk. METHODS: A hospital-based study was conducted on 1,712 individuals, including 282 patients with H-type hypertension, 105 patients with simple hypertension, 645 individuals with hyperhomocysteinemia, and 680 healthy controls. Logistic regression and nomogram models were applied to evaluate the risk factors. RESULTS: Logistic regression showed that advanced age, male sex, high body mass index (BMI), high total cholesterol levels, high glucose levels, and high creatinine levels were risk factors of H-type hypertension in the healthy population and were integrated into the nomogram model. Advanced age, male sex, high BMI, high total cholesterol levels, and high glucose levels were shown to be risk factors of H-type hypertension in the hyperhomocysteinemia population. Male sex and high creatinine levels were shown to be risk factors of H-type hypertension in the hypertension population. Nomogram analysis showed that the total factor score ranged from 106 to 206, and the corresponding risk rate ranged from 0.05 to 0.95. CONCLUSIONS: Men are more likely to have H-type hypertension, and advanced age, high BMI, high total cholesterol levels, and high glucose levels are risk factors of H-type hypertension in healthy and hyperhomocysteinemia populations. Furthermore, high creatinine level is a risk factor of H-type hypertension in healthy and hypertension populations. Nomogram models may be used to intuitively evaluate H-type hypertension risk and provide a basis for personalized interventions.


Assuntos
Hiper-Homocisteinemia , Hipertensão , Hipertensão Essencial , Hospitais , Humanos , Hiper-Homocisteinemia/complicações , Hiper-Homocisteinemia/epidemiologia , Hipertensão/complicações , Hipertensão/epidemiologia , Masculino , Nomogramas , Fatores de Risco
6.
BMJ Case Rep ; 13(12)2020 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-33372010

RESUMO

A 50-year-old woman was incidentally diagnosed to have unilateral disc oedema during comprehensive ophthalmological evaluation. She had a prior history of ulcerative colitis. She had normal visual function and was initially diagnosed to have incipient non-arteritic anterior ischaemic optic neuropahty. Risk factor evaluation revealed hyperhomocysteinaemia. She was asked to come for a follow-up in 2 months. However, she was lost to follow-up and returned to the clinic for the evaluation for headaches, 23 months later. Her ocular examination was stable and she had persistent unilateral disc oedema unchanged from the prior visit. Repeat MRI brain and MR venogram brain with contrast-established diagnosis of cerebral sinus venous thrombosis (CSVT). She denied any neurological symptoms. Later on, she was diagnosed to have hyperhomocysteinaemia with methyl tetrahydrofolate reductase gene mutation. This case highlights the importance of recognising although rare, unilateral disc oedema secondary to elevated intracranial pressure from CSVT.


Assuntos
Papiledema/etiologia , Trombose dos Seios Intracranianos/complicações , Anticoagulantes/uso terapêutico , Diagnóstico Diferencial , Feminino , Angiofluoresceinografia , Cefaleia/etiologia , Humanos , Hiper-Homocisteinemia/complicações , Hiper-Homocisteinemia/tratamento farmacológico , Hiper-Homocisteinemia/genética , Angiografia por Ressonância Magnética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Pessoa de Meia-Idade , Mutação , Fatores de Risco , Trombose dos Seios Intracranianos/diagnóstico por imagem
7.
BMC Med Genet ; 21(1): 183, 2020 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-32957924

RESUMO

BACKGROUND: Disorders of the metabolism and absorption of vitamin B12 can lead to decrease in activity of methionine synthetase and methylmalonate coenzyme A mutase (MMUT), which results in increased levels of methylmalonic acid and homocysteine in blood and urine. Often, combined methylmalonic acidemia (MMA) and homocysteinemia is misdiagnosed due to a lack of specific symptoms. The clinical manifestations are diverse, but proteinuria as the initial presentation is rare. CASE PRESENTATION: Two cases of MMA with homocysteinemia in children are reported. Proteinuria were a primary presenting symptom, followed by anemia and neurologic symptoms (frequent convulsions and unstable walking, respectively). Screening of amino acids and acyl carnitine in serum showed that the propionyl carnitine:acetylcarnitine ratio increased. Profiling of urinary organic acids by gas chromatography-mass spectrometry revealed high levels of methylmalonic acid. Homocysteine content in blood was increased. Comprehensive genetic analyses of peripheral blood-derived DNA demonstrated heterozygous variants of methylmalonic aciduria type C and homocystinuria (MMACHC) and amnionless (AMN) genes in our two patients, respectively. After active treatment, the clinical manifestations in Case 1 were relieved and urinary protein ceased to be observed; Case 2 had persistent proteinuria and was lost to follow-up. CONCLUSIONS: Analyses of the organic acids in blood and urine suggested MMA combined with homocysteinemia. In such diseases, reports of renal damage are uncommon and proteinuria as the initial presentation is rare. Molecular analysis indicated two different genetic causes. Although the pathologic mechanisms were related to vitamin B12, the severity and prognosis of renal lesions were different. Therefore, gene detection provides new insights into inherited metabolic diseases.


Assuntos
Erros Inatos do Metabolismo dos Aminoácidos/complicações , Hiper-Homocisteinemia/complicações , Proteinúria/diagnóstico , Adolescente , Erros Inatos do Metabolismo dos Aminoácidos/genética , Aminoácidos/sangue , Sequência de Bases , Carnitina/análogos & derivados , Carnitina/sangue , Pré-Escolar , DNA/sangue , DNA/genética , Cromatografia Gasosa-Espectrometria de Massas , Homocisteína/sangue , Humanos , Hiper-Homocisteinemia/genética , Masculino , Ácido Metilmalônico/urina , Proteinúria/etiologia
8.
Medicine (Baltimore) ; 99(35): e21953, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32871943

RESUMO

H-type hypertension, defined as a combination of hypertension and hyperhomocysteinemia (Hhcy), is associated with atherosclerosis and, therefore, increased stroke risk. However, the role of hypertension and Hhcy in high-risk stroke populations has not been studied. The present study investigated the prevalence of H-type hypertension in a high-risk stroke population of Hainan Province, China and to assess possible joint effects between hypertension and Hhcy for increased carotid intima-media thickness (CIMT). In this community-based cross-sectional study, 959 high-risk stroke subjects (age, 65.8 ±â€Š10.8 years; 46.6% men) were recruited from Hainan Province, China. The demographic and clinical characteristics were collected, and blood samples were obtained. Analysis of variance or chi-square tests were performed to compare variates among groups based on both homocysteine levels and blood pressure status. The associations of hypertension and Hhcy with increased CIMT were evaluated through logistic regression. The prevalence of H-type hypertension was 34.8% in this population, with a higher ratio of H-type hypertension in men than in women. Compared with the normotension and normal homocysteine subgroup, the risk of increased CIMT was significantly higher in the subgroup with hypertension and Hhcy (odds ratio [OR] = 2.639; 95% confidence interval [CI], 1.690-4.091) after adjusting for age and sex. Increased CIMT was affected by an additive synergetic interaction between Hhcy and hypertension (synergy index = 1.105). It emphasized the clinical importance of anti-hypertension and lowering Hhcy in the high-risk stroke population.


Assuntos
Espessura Intima-Media Carotídea , Hiper-Homocisteinemia/complicações , Hipertensão/complicações , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Hiper-Homocisteinemia/fisiopatologia , Hipertensão/epidemiologia , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos
9.
Int J Nanomedicine ; 15: 4501-4521, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32606691

RESUMO

Purpose: Elevation of blood homocysteine (Hcy) level (hyperhomocysteinemia) is a risk factor for cardiovascular disorders and is closely associated with endothelial dysfunction. The present study aims to investigate the protective effect and underlying mechanism of nanoscale selenium (Nano-Se) in Hcy-mediated vascular endothelial cell dysfunction in vitro and in vivo. Materials and Methods: By incubating vascular endothelial cells with exogenous Hcy and generating hyperhomocysteinemic rat model, the effects of Nano-Se on hyperhomocysteinemia-mediated endothelial dysfunction and its essential mechanisms were investigated. Results: Nano-Se inhibited Hcy-induced mitochondrial oxidative damage and apoptosis by preventing the downregulation of glutathione peroxidase enzyme 1 and 4 (GPX1, GPX4) in the vascular endothelial cells, thus effectively prevented the vascular damage in vitro and in vivo in the hyperhomocysteinemic rats. Nano-Se possessed similar protective effects but lower toxicity against Hcy in vascular endothelial cells when compared with other forms of Se. Conclusion: The application of Nano-Se could serve as a novel promising strategy against Hcy-mediated vascular dysfunction with reduced risk of Se toxicity.


Assuntos
Antioxidantes/farmacologia , Células Endoteliais da Veia Umbilical Humana/patologia , Hiper-Homocisteinemia/tratamento farmacológico , Hiper-Homocisteinemia/fisiopatologia , Nanopartículas/uso terapêutico , Selênio/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Disponibilidade Biológica , Glutationa Peroxidase/metabolismo , Homocisteína , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Hiper-Homocisteinemia/complicações , Hipertensão/complicações , Masculino , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Nanopartículas/ultraestrutura , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Selênio/farmacologia
10.
Int Heart J ; 61(4): 705-712, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32727999

RESUMO

There is increasing evidence linking plasma homocysteine levels and atrial fibrillation (AF). The association between an elevated level of plasma homocysteine and AF was examined by meta-analysis in this study.The PubMed and ScienceDirect databases until August 2019 were utilized to collect previous literature on homocysteine and the potential relation to AF. The pooled effects were evaluated depending on standardized mean differences (SMDs) or odds ratios (ORs) with 95% confidence intervals (CIs), and the calculation was performed using Stata 12 software.A total of 11 validated articles were included in the meta-analysis. For pooled effect, the results confirmed that AF patients had higher homocysteine levels than control subjects (SMD: 0.58, 95%CI: 0.09-1.06). Compared with control subjects, homocysteine levels were higher in paroxysmal AF (SMD: 0.45, 95%CI: 0.18-0.72) and persistent AF patients (SMD: 1.21, 95%CI: 0.50-1.92). The pooled analysis suggested that patients with elevated homocysteine levels had markedly higher risk of AF compared with lower homocysteine levels in the categorical variable (OR: 2.21, 95%CI: 1.16-4.21) and continuous variable analyses (OR: 1.13, 95%CI: 1.00-1.27), respectively. In addition, the pooled analysis indicated that recurrent AF patients had significantly higher homocysteine levels than those without recurrence (SMD: 0.65, 95%CI: 0.42-0.88). The pooled analysis of the categorical variables indicated that elevated homocysteine levels were associated with increased risk of AF recurrence (OR: 3.81, 95%CI: 3.11-4.68). However, the association was weak in the pooled analysis of continuous variables (OR: 1.88, 95%CI: 0.74-4.81).Our meta-analysis identified that plasma homocysteine levels were significantly elevated in AF and recurrent AF patients. Elevated homocysteine is associated with increased risk of AF and AF recurrence.


Assuntos
Fibrilação Atrial/sangue , Homocisteína/metabolismo , Hiper-Homocisteinemia/complicações , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/mortalidade , Estudos de Casos e Controles , Humanos , Recidiva , Medição de Risco , Software
11.
J Stroke Cerebrovasc Dis ; 29(8): 104925, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32689606

RESUMO

BACKGROUND: Ischemic stroke is related to the level of total homocysteine and the stability of carotid atherosclerotic plaque. In this study, the characteristics of carotid plaque in hypertensive patients with hyperhomocysteinemia were preliminarily studied by conventional ultrasound, contrast-enhanced ultrasound and virtual touch image quantification. METHODS: Hypertensive patients (n=196) hospitalised in the Department of Neurology and Cardiology of our hospital from April 2016 to February 2019 were studied to compare and analyse differences in general clinical data, conventional ultrasound, contrast-enhanced ultrasound and virtual touch image quantification between hypertension with hyperhomocysteinemia and hypertension with normal tHcy. RESULTS: 1. There was no statistical difference in other clinical data, except fasting blood sugar (P=0.021) and the history of cerebral infarction (P=0.0001). 2. There were significant differences in plaque thickness, stenosis degree, contrast-enhanced ultrasound level, The maximum shear wave velocity (SWVmax) , the minimum shear wave velocity (SWVmin) and the mean shear wave velocity (SWVmean) (P<0.05), except intima-media thickness between the two groups (t=0.160, P=0.873). 3. Blood tHcy level in hypertensive patients with hyperhomocysteinemia was positively correlated with carotid plaque thickness, stenosis degree and contrast-enhanced ultrasound level (r=0.349, 0.647, 0.421), but negatively correlated with SWVmax, SWVmin and SWVmean (r=-0.348, -0.409, -0.393). CONCLUSIONS: Ultrasonography can reflect the vulnerability of hypertensive patients with hyperhomocysteinemia, providing reliable and comprehensive information for the prevention and treatment of stroke in hypertensive patients with hyperhomocysteinemia.


Assuntos
Espessura Intima-Media Carotídea , Estenose das Carótidas/diagnóstico por imagem , Hiper-Homocisteinemia/complicações , Hipertensão/complicações , Placa Aterosclerótica , Idoso , Biomarcadores/sangue , Pressão Sanguínea , Estenose das Carótidas/etiologia , Feminino , Homocisteína/sangue , Humanos , Hiper-Homocisteinemia/sangue , Hiper-Homocisteinemia/diagnóstico , Hipertensão/diagnóstico , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Fatores de Risco , Índice de Gravidade de Doença
12.
Adv Exp Med Biol ; 1195: 213-225, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32468480

RESUMO

Vascular dementia (VaD) is well recognized as the second most familiar form of dementia in the aged population. The present study is aimed to investigate the neuroprotective effects of ethanolic extract of leaves of Ocimum sanctum (EEOS) against hyperhomocysteinemia (HHcy)-induced vascular dementia (VaD) in Wistar rats. HHcy was induced by administering L-methionine (1.7 g/kg, p.o) for 4 weeks. Donepezil (0.1 mg/kg, p.o.) and EEOS (100 mg/kg, 200 mg/kg, 400 mg/kg, p.o.) were administered from the 14th day of L-methionine treatment. The behavioral impairment caused due to HHcy in rats was assessed by the Morris water maze (MWM) and Y-maze tests using a video tracking system. Biochemical estimations and aortic ring assay were also performed followed by a molecular docking analysis of active chemical constituents present in the leaves of Ocimum sanctum Linn. In this study, the EEOS treatment in hyperhomocysteinemic rats has showed significant improvement in spatial learning and working memory performance. The EEOS treatment further increased nitric oxide bioavailability and significantly altered all serum and brain biochemical parameters in a dose-dependent manner. The docking analysis revealed that among all the phytoconstituents of Ocimum sanctum compound (IX), molludistin has showed good inhibitory activity against S-adenosyl homocysteine, thus preventing homocysteine formation and may be responsible for potential effects of EEOS against HHcy-induced VaD. From our results, we conclude that EEOS can be used as a promising adjunct therapy for treatment of HHcy-induced VaD and oxidative stress.


Assuntos
Demência Vascular/tratamento farmacológico , Demência Vascular/etiologia , Hiper-Homocisteinemia/complicações , Ocimum sanctum/química , Extratos Vegetais/uso terapêutico , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Demência Vascular/sangue , Demência Vascular/metabolismo , Homocisteína/sangue , Homocisteína/metabolismo , Hiper-Homocisteinemia/sangue , Aprendizagem em Labirinto/efeitos dos fármacos , Simulação de Acoplamento Molecular , Óxido Nítrico/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Ratos , Ratos Wistar
13.
J Neurol Neurosurg Psychiatry ; 91(5): 540-546, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32234968

RESUMO

OBJECTIVE: To examine the association between serum total homocysteine levels (tHcy) and dementia risk. METHODS: A total of 1588 Japanese adults aged ≥60 years without dementia were prospectively followed from 2002 to 2012. Cox proportional hazards models and restricted cubic splines were used to estimate the HRs of tHcy levels on the risk of dementia. RESULTS: During the follow-up, 372 subjects developed all-cause dementia; 247 had Alzheimer's disease (AD) and 98 had vascular dementia (VaD). Compared with the lowest tHcy quintile (≤6.4 µmol/L), the multivariable-adjusted HRs (95% CI) of the highest quintile (≥11.5 µmol/L) were 2.28 (1.51-3.43) for all-cause dementia, 1.96 (1.19-3.24) for AD and 2.51 (1.14-5.51) for VaD. In restricted cubic splines, the risk of all-cause dementia steadily increased between approximately 8-15 µmol/L and plateaued thereafter, with a similar non-linear shape observed for AD and VaD (all p for non-linearity ≤0.02). In stratified analyses by the most recognised genetic polymorphism affecting tHcy concentrations (methylenetetrahydrofolate reductase C677T), the positive association of tHcy with all-cause dementia persisted in both non-carriers and carriers of the risk allele, and even tended to be stronger in the former (p for heterogeneity=0.07). CONCLUSION: High serum tHcy levels are associated with an elevated risk of dementia, AD and VaD in a non-linear manner, such that an exposure-response association is present only within a relatively high range of tHcy levels. Non-genetic factors affecting serum tHcy concentrations may play important roles in tHcy-dementia associations irrespective of the genetic susceptibility for raised tHcy.


Assuntos
Demência/etiologia , Homocisteína/sangue , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/sangue , Doença de Alzheimer/etiologia , Demência/sangue , Demência/genética , Demência Vascular/sangue , Demência Vascular/etiologia , Predisposição Genética para Doença/genética , Humanos , Hiper-Homocisteinemia/sangue , Hiper-Homocisteinemia/complicações , Japão/epidemiologia , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco
14.
PLoS One ; 15(4): e0231011, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32282799

RESUMO

PURPOSE: There is a strong association between severe hyperhomocysteinemia and myopia. Thus we studied the hypothesis that even moderately increased levels of homocysteine (Hcy) might be a potentially treatable risk factor for myopia. METHODS: The Gutenberg Health Study (GHS) is a population-based, prospective, observational cohort study in Germany, including 15,010 participants aged between 35 and 74 at recruitment. The baseline examination was conducted from 2007-2012. Refraction was measured using autorefraction (HARK 599, Carl Zeiss AG, Jena, Germany). Hcy was measured by an immunoassay. We included only phakic participants without a history of corneal surgery or corneal laser treatment. We used linear regression models to evaluate the potential association between Hcy and refraction at baseline, and between Hcy and change in refraction between baseline and 5-year-follow-up examination. We used generalized estimating equation models to account for the correlation between fellow eyes. RESULTS: We included 13,749 participants, categorized as having no myopia (spherical equivalent > -0.75 D, 65.2%), low myopia (-0.75 D--2.75 D, 21.5%), moderate myopia (-3.00 D- 5.75 D, 9.8%) and high myopia (≤ -6 D, 3.5%). Median Hcy levels were similar in all groups (µmol/l). We observed no association of Hcy with refraction or 5-year change in refraction in the models adjusted for age, sex and socioeconomic status. CONCLUSION: We found no evidence for an association of Hcy levels and refractive error.


Assuntos
Homocisteína/sangue , Erros de Refração/sangue , Adulto , Idoso , Feminino , Alemanha , Humanos , Hiper-Homocisteinemia/sangue , Hiper-Homocisteinemia/complicações , Masculino , Pessoa de Meia-Idade , Miopia/sangue , Miopia/etiologia , Estudos Prospectivos , Fatores de Risco
15.
J Stroke Cerebrovasc Dis ; 29(5): 104633, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32122776

RESUMO

CASE: Two years ago, annual magnetic resonance imaging for unruptured right internal carotid artery aneurysm of a 47-year-old woman detected a cerebral infarct in her right occipital lobe which was unknown etiology and antiplatelet therapy was initiated. She presented with sensory disorder of her left fingers 4 months ago. Infarction in right parieto-occipital cortex and severe stenosis of right middle cerebral artery was revealed. Her laboratory test was normal except remarkably high homocysteine value. Regardless of dual anti-platelet therapy, she suffered from repeated minor stroke and the stenosis was progressing. Therefore, right superficial temporal artery - middle cerebral artery bypass was undertaken. Aspirin and clopidogrel were withdrawn 1 week before the surgery. Two branches were anastomosed with 2 separate frontal M4 branches. Although patency was confirmed immediately after the anastomosis, thrombus formation was revealed after 10 minutes. We needed to perform removal of the thrombus and re-anastomosis twice. Intraoperative administration of aspirin and ozagrel alleviated thrombotic tendency. After surgery, antiplatelet therapy and supplementation with folate and vitamin B were performed. Her postoperative course was uneventful and patency of both anastomoses was confirmed. DISCUSSION: Controversy still exists regarding preoperative antiplatelet therapy before superficial temporal artery-middle cerebral artery bypass, and folates and B6-12 vitamins supplementation for hyperhomocysteinemia. Considering intraoperative thrombo tendency in our case, it is recommended to evaluate the homocysteine level before bypass surgery for intracranial stenosis especially for young patients or patients with unknown etiology. Before bypass surgery of the patient with hyperhomocysteinemia, continuation of perioperative antiplatelet drugs and supplementation with folates and B6-12 vitamins are mandatory.


Assuntos
Hiper-Homocisteinemia/complicações , Infarto da Artéria Cerebral Média/cirurgia , Artéria Cerebral Média/cirurgia , Artérias Temporais/cirurgia , Enxerto Vascular/efeitos adversos , Trombose Venosa/etiologia , Suplementos Nutricionais , Feminino , Fibrinolíticos/administração & dosagem , Humanos , Hiper-Homocisteinemia/diagnóstico , Hiper-Homocisteinemia/tratamento farmacológico , Infarto da Artéria Cerebral Média/diagnóstico por imagem , Infarto da Artéria Cerebral Média/etiologia , Pessoa de Meia-Idade , Artéria Cerebral Média/diagnóstico por imagem , Recidiva , Fatores de Risco , Índice de Gravidade de Doença , Artérias Temporais/diagnóstico por imagem , Trombectomia , Resultado do Tratamento , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/terapia , Complexo Vitamínico B/administração & dosagem
16.
Medicine (Baltimore) ; 99(12): e19467, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32195946

RESUMO

BACKGROUND: The findings on the association between elevated plasma homocysteine levels and the risk of the trial of org 10172 in acute stroke treatment (TOAST) of ischemic stroke have been inconsistent in Chinese. So far, there is no meta-analysis about the association between Hcy and the TOAST subtypes of ischemic stroke in Chinese. This study; therefore, aimed to evaluate whether elevated homocysteine levels are associated with the TOAST subtypes of ischemic stroke using a meta-analysis. MATERIALS AND METHODS: A systematic search of electronic databases were conducted for studies reporting homocysteine levels in ischemic stroke and the TOAST of ischemic stroke to April 18, 2018. The data were extracted after the application of inclusion and exclusion criteria. All the data were analyzed using Stata software version 9.0 (Stata Corp LP, College Station, TX). The standardized mean difference (SMD) and 95% confidence interval (CI) were used to compare continuous variables. RESULTS: Thirteen studies comprising 3114 participants (2243 patients and 871controls) met the eligibility criteria and were included in the meta-analysis. The meta-analysis revealed that the ischemic stroke group had significantly higher levels of homocysteine than controls (SMD = 1.15, 95% CI = 0.85-1.45, P < .05). The subgroup analyses suggested that the groups of patients with large-artery atherosclerosis, small-vessel occlusion, cardioembolism, stroke of other determined etiology and stroke of undetermined etiology had significantly higher levels of homocysteine compared to those in the control group (large-artery atherosclerosis: SMD = 2.12, 95% CI = 1.40-2.84, P < .05; small-vessel occlusion: SMD = 1.10, 95% CI = 0.72-1.48, P < .05; CE: SMD = 1.17, 95% CI = 0.64-1.71, P < .05; stroke of other determined etiology: SMD = 0.88, 95% CI = 0.53-1.24, P < .05; stroke of undetermined etiology: SMD = 1.50, 95% CI = 0.66-2.33, P < .05, respectively). CONCLUSION: This meta-analysis found that ischemic stroke patients and the TOAST of ischemic stroke patients in Chinese had significantly higher homocysteine levels than the controls, suggesting that serum homocysteine levels may be a risk factor for ischemic stroke and the TOAST subtypes of ischemic stroke in Chinese.


Assuntos
Isquemia Encefálica/metabolismo , Homocisteína/sangue , Acidente Vascular Cerebral/metabolismo , Aterosclerose/complicações , Aterosclerose/patologia , Isquemia Encefálica/epidemiologia , Isquemia Encefálica/patologia , China/epidemiologia , Humanos , Hiper-Homocisteinemia/complicações , Hiper-Homocisteinemia/epidemiologia , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/patologia
18.
Biomed Res Int ; 2020: 6960497, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32090108

RESUMO

Objective: This study aimed to evaluate the potential effect of hyperhomocysteinemia on multiple organ failure (MOF) in patients with acute pancreatitis (AP). Method: In this cohort study, a total of 1880 AP patients were enrolled and divided into the hyperhomocysteinemia group (study group) and the control group based on serum homocysteine (HCY) levels. Clinical data including demographics, clinical outcomes, and characteristics were collected for analysis. Risk factors of MOF in AP patients were determined by univariate and multivariate logistic regression analyses. Results: The hyperhomocysteinemia group showed higher multiple organ failure rates (31.83% vs 20.77%, P < 0.001), compared with the control group. A positive correlation between homocysteine level and APACHE II score was obtained by Pearson correlation analysis (r = 0.420, P < 0.001), compared with the control group. A positive correlation between homocysteine level and APACHE II score was obtained by Pearson correlation analysis (P < 0.001), compared with the control group. A positive correlation between homocysteine level and APACHE II score was obtained by Pearson correlation analysis (. Conclusion: A high serum homocysteine level may be an independent risk factor of multiple organ failure in patients with acute pancreatitis.


Assuntos
Hiper-Homocisteinemia/complicações , Insuficiência de Múltiplos Órgãos/complicações , Pancreatite/complicações , Proteína C-Reativa/metabolismo , Estudos de Casos e Controles , Feminino , Homocisteína/sangue , Humanos , Hiper-Homocisteinemia/sangue , Contagem de Leucócitos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/sangue , Análise Multivariada , Pancreatite/sangue , Curva ROC , Índice de Gravidade de Doença , Resultado do Tratamento
19.
West Afr J Med ; 37(1): 246-252, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32030711

RESUMO

BACKGROUND: Clinical evidence had suggested that hyperhomocysteinaemia features in hypertensive disorders of pregnancy. However, there is still conflicting evidence on the extent to which elevated maternal homocysteine contributes to this deadly complication of pregnancy. OBJECTIVES: This study investigated the impact of elevated maternal homocysteine levels in early pregnancy on preeclampsia and its severity among Nigerian women in Lagos. METHODS: This was a prospective cohort study conducted at the Lagos University Teaching Hospital. Participants were enrolled in the first trimester of pregnancy following which their sociodemographic data were obtained by interview. Venous blood samples were collected for measurement of homocysteine concentration using the ELISA method. Data on the occurrence of preeclampsia was obtained from the delivery records. Binary logistic regression model was used to study the effects of the major baseline characteristics on the development of preeclampsia. RESULTS: The final analysis included 167 patients; hyperhomocysteinaemia was recorded in 24 (24.6%) patients. Women with hyperhomocysteinaemia had no statistically significant risk of developing preeclampsia or severe preeclampsia, compared with women with a normal homocysteine concentration. CONCLUSION: The prevalence of hyperhomocysteinaemia in the study was relatively low. The absence of a significant association between maternal hyperhomocysteinaemia and preeclampsia reported in this study could create room for the conduct of a more robust, adequately powered longitudinal research needed to answer some of the major reservations that remain from the present study.


Assuntos
Homocisteína/sangue , Hiper-Homocisteinemia/complicações , Pré-Eclâmpsia/diagnóstico , Adulto , Biomarcadores/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Hiper-Homocisteinemia/epidemiologia , Nigéria/epidemiologia , Pré-Eclâmpsia/sangue , Pré-Eclâmpsia/epidemiologia , Gravidez , Prevalência , Estudos Prospectivos , Índice de Gravidade de Doença
20.
Mol Med Rep ; 21(1): 371-378, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31746381

RESUMO

As a novel anti­inflammatory cytokine of the interleukin (IL)­1 family, IL­37 protects the human body from diseases characterized by excessive inflammation. The pathologic process of hyperhomocysteinemia (hHcy) is accompanied by persistent inflammation. However, little is known regarding the role of IL­37 in hHcy. In the present study, the levels of cytokines including IL­37, IL­1ß, IL­6 and tumor necrosis factor­α in the supernatant were detected by ELISA. mRNA and protein expression were detected by Reverse transcription­quantitative PCR and western blotting, respectively. LDH level was determined by ELISA and the cell viability was detected through CCK­8 kit. In the present study, mean serum IL­37 levels of patients with hHcy were 32.3% lower than those of controls (P<0.01). In peripheral blood mononuclear cells (PBMCs) from patients with hHcy, mean IL­37 mRNA expression was 73.5% lower (P<0.01) and IL­37 protein expression was 77.7% lower compared with that of healthy controls (P<0.01). Furthermore, the results demonstrated that exogenous homocysteine (Hcy) stimulation markedly downregulated the mRNA and protein expression levels of IL­37 in PBMCs in vitro. In 293T cells, overexpression of IL­37 restored the cell viability impaired by Hcy, and reduced the release of lactate dehydrogenase and the proinflammatory cytokines IL­1ß, IL­6 and tumor necrosis factor­α. In conclusion, IL­37 was downregulated by Hcy in vivo and in vitro, and IL­37 exhibited a protective role against cell injury induced by Hcy.


Assuntos
Homocisteína/metabolismo , Hiper-Homocisteinemia/sangue , Inflamação/sangue , Interleucina-1/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Homocisteína/farmacologia , Homocisteína/toxicidade , Humanos , Hidroliases/sangue , Hiper-Homocisteinemia/induzido quimicamente , Hiper-Homocisteinemia/complicações , Hiper-Homocisteinemia/genética , Inflamação/induzido quimicamente , Inflamação/complicações , Inflamação/genética , Interleucina-1/sangue , Interleucina-1beta/sangue , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/sangue , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/genética
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