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1.
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
2.
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
3.
Arterioscler Thromb Vasc Biol ; 40(3): 839-846, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31941381

RESUMO

OBJECTIVES: To investigate the relationship of homocysteine levels with the efficacy and safety of dual antiplatelet therapy in female and male patients. Approach and Results: The CHANCE trial (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events) randomized patients with acute minor ischemic stroke or high-risk transient ischemic attack to clopidogrel plus aspirin or aspirin alone from October 1, 2009, to July 30, 2012, in China. A subgroup of 3044 consecutive patients with baseline homocysteine levels from 73 (64%) prespecified clinical sites was analyzed. Participants were grouped by sex. Primary outcome was stroke recurrence within 90 days. Secondary outcomes consisted of composite vascular events and independent living or death. Safety outcome was any bleeding. Cox proportional-hazards models were used to assess the interaction of homocysteine levels with randomized antiplatelet therapy on efficacy and safety outcomes. A significant interaction between homocysteine levels and the randomized antiplatelet therapies was found on recurrent stroke after adjustment for confounding factors in women (P=0.010) but not in men (P=0.595). Compared with aspirin alone, clopidogrel plus aspirin significantly reduced the risk of recurrent stroke in women without elevated homocysteine levels (adjusted hazard ratio, 0.459 [95% CI, 0.271-0.776]; P=0.004). Such benefit disappeared in female patients with increased homocysteine level. No significant interaction on functional outcome or bleeding rate was observed. CONCLUSIONS: Homocysteine could be a potential biomarker to discriminate the effects of dual and single antiplatelet therapy in female patients with minor ischemic stroke or high-risk transient ischemic attack. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00979589.


Assuntos
Aspirina/uso terapêutico , Clopidogrel/uso terapêutico , Homocisteína/sangue , Hiper-Homocisteinemia/sangue , Ataque Isquêmico Transitório/tratamento farmacológico , Inibidores da Agregação de Plaquetas/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Idoso , Aspirina/efeitos adversos , Biomarcadores/sangue , China/epidemiologia , Clopidogrel/efeitos adversos , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Hemorragia/induzido quimicamente , Humanos , Hiper-Homocisteinemia/diagnóstico , Hiper-Homocisteinemia/epidemiologia , Ataque Isquêmico Transitório/sangue , Ataque Isquêmico Transitório/diagnóstico , Ataque Isquêmico Transitório/epidemiologia , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/efeitos adversos , Recidiva , Medição de Risco , Fatores de Risco , Fatores Sexuais , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Fatores de Tempo , Resultado do Tratamento
4.
Biomed Res Int ; 2020: 1710452, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31998781

RESUMO

Background: This study aims to investigate the coronary microcirculatory resistance and prognosis of patients with acute myocardial infarction (AMI) concomitant with hyperhomocysteinemia (HHcy) after an elective percutaneous coronary intervention (PCI). Methods: A total of 101 patients that underwent elective PCI between May 2015 and July 2018 due to AMI were consecutively enrolled in this study. Patients were divided into a HHcy group (53) and a normal Hcy group (control; 48) based on their plasma homocysteine concentration. The characteristics of coronary angiography, the index of microcirculatory resistance (IMR) of infarct-related vessels (IRV), changes in left ventricular end diastolic diameter (LVEDd) and left ventricular ejection fraction (LVEF) before and after PCI, and the incidence of major adverse cardiovascular events (MACE) three months after PCI were compared between these groups. Results: Compared to the results from the Hcy group, the HHcy group had a higher IMR. The HHcy group had significantly higher LVEDd and a lower LVEF than the Hcy group 3 months after PCI. Additionally, the incidence of MACE at three months after PCI was higher in the HHcy group than in the Hcy group. Pearson correlation analysis revealed a positive correlation with IMR in the HHcy group. Furthermore, there was a difference in the LVEDd measured at one day after PCI and at three months after PCI in the HHcy group. Conclusion: AMI patients concomitant with HHcy that undergo elective PCI are prone to coronary microcirculatory dysfunction and have a poor cardiac function and poor prognosis at three months after PCI.


Assuntos
Resistência Capilar , Circulação Coronária , Procedimentos Cirúrgicos Eletivos/efeitos adversos , Infarto do Miocárdio , Intervenção Coronária Percutânea/efeitos adversos , Complicações Pós-Operatórias , Idoso , Feminino , Humanos , Hiper-Homocisteinemia/sangue , Hiper-Homocisteinemia/diagnóstico , Hiper-Homocisteinemia/etiologia , Hiper-Homocisteinemia/fisiopatologia , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/cirurgia , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/fisiopatologia , Prognóstico , Fatores de Tempo
5.
J Formos Med Assoc ; 119(3): 720-727, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31630933

RESUMO

BACKGROUND/PURPOSE: Our previous study found that 56 of 1064 atrophic glossitis (AG) patients have vitamin B12 deficiency. This study assessed whether the AG patients with vitamin B12 deficiency (B12D/AG patients) had significantly higher frequencies of anemia, hematinic deficiencies, hyperhomocysteinemia, and serum gastric parietal cell antibody (GPCA) positivity than healthy control subjects. METHODS: The blood hemoglobin (Hb) and serum iron, vitamin B12, folic acid, homocysteine, and GPCA levels in 56 B12D/AG patients and 532 healthy control subjects were measured and compared. RESULTS: We found that 56 B12D/AG patients had significantly lower mean blood Hb and serum iron levels as well as significantly higher mean corpuscular volume (MCV) and mean serum homocysteine level than healthy control subjects (all P-values < 0.05). Moreover, 56 B12D/AG patients had significantly higher frequencies of macrocytosis (53.6%), blood Hb (64.3%), iron (26.8%), and folic acid (3.6%) deficiencies, hyperhomocysteinemia (89.3%), and serum GPCA positivity (55.4%) than 532 healthy control subjects (all P-values < 0.005). In addition, of 36 anemic B12D/AG patients, 22 (61.1%) had pernicious anemia (PA), 6 (16.7%) had macrocytic anemia other than PA, 4 (11.1%) had normocytic anemia, 3 (8.3%) had iron deficiency anemia (IDA), and one (2.8%) had microcytic anemia other than IDA and thalassemia trait-induced anemia. CONCLUSION: We conclude that B12D/AG patients have significantly higher frequencies of macrocytosis, blood Hb, iron, and folic acid deficiencies, hyperhomocysteinemia, and serum GPCA positivity than healthy control subjects. PA is the most common type of anemia in our B12D/AG patients.


Assuntos
Anemia/epidemiologia , Deficiência de Ácido Fólico/epidemiologia , Glossite/epidemiologia , Hiper-Homocisteinemia/epidemiologia , Deficiência de Vitamina B 12/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia/sangue , Autoanticorpos/sangue , Estudos de Casos e Controles , Comorbidade , Índices de Eritrócitos , Feminino , Ácido Fólico/sangue , Deficiência de Ácido Fólico/sangue , Hematínicos , Hemoglobinas/análise , Humanos , Hiper-Homocisteinemia/sangue , Ferro/sangue , Masculino , Pessoa de Meia-Idade , Células Parietais Gástricas/imunologia , Vitamina B 12/sangue , Deficiência de Vitamina B 12/sangue
6.
Clin Exp Hypertens ; 42(1): 61-66, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-30689431

RESUMO

An increased platelet distribution width (PDW) value has been found in various cardiovascular diseases. The objective of this study was to evaluate the association between the PDW and hypertension with hyperhomocysteinemia in an elderly cohort. We performed a cross-sectional analysis among 2,685 elderly individuals who underwent hematological testing and blood pressure assessment. Individuals were divided according to the PDW quartiles. An unconditional multiple logistic regression analysis was used to determine the association between PDW and hypertension with hyperhomocysteinemia, after adjustments for gender, age, drinking status, creatinine levels, glucose levels, uric acid levels, triglyceride levels, platelet counts and body mass index. Homocysteine was observed to steadily and remarkably increase in the PDW quartiles. The PDW values of the hypertension with hyperhomocysteinemia group were significantly greater than the PDW values in the hypertension without hyperhomocysteinemia group or the normotension group. The PDW levels were associated with hypertension and hyperhomocysteinemia independently of the previously mentioned risk factors, and the odds ratio of the hypertension with hyperhomocysteinemia group was steadily and remarkably increased, by as much as two-fold, in the fourth quartile vs. the first quartile. In this elderly population-based cohort, elevated PDW levels were independently associated with hypertension and hyperhomocysteinemia, which may indicate that hypertension and hyperhomocysteinemia can induce platelet activation.


Assuntos
Plaquetas , Hiper-Homocisteinemia/sangue , Hipertensão/sangue , Idoso , Idoso de 80 Anos ou mais , Pressão Sanguínea , Índice de Massa Corporal , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Hiper-Homocisteinemia/complicações , Hipertensão/complicações , Masculino , Volume Plaquetário Médio , Pessoa de Meia-Idade , Ativação Plaquetária
7.
Ann Vasc Surg ; 62: 335-341, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31472234

RESUMO

BACKGROUND: Elevated plasma total homocysteine level is a risk factor for various vascular diseases; however, an association with risk of thromboangiitis obliterans (TAO) has not been defined. This study aims to assess whether elevated plasma total homocysteine level is associated with risk of TAO. METHODS: We performed a matched case-control study including 64 patients with TAO and 256 controls. Multivariate logistic regression models were used to estimate the association between elevated plasma homocysteine level and the risk of TAO. Interaction and stratified analyses were conducted according to age, sex, smoking, alcohol consumption, and histories of chronic diseases. RESULTS: Patients with TAO versus controls had a higher mean plasma total homocysteine level (21.2 ± 12.8 µmol/L vs. 14.1 ± 4.9 µmol/L; P < 0.01). The risk of TAO was 3.68-fold increased in participants with plasma total homocysteine level >15 µmol/L (95% confidence interval [95% CI], 1.2-11.7). A 1 µmol/L increase in plasma total homocysteine level was associated with 20% higher risk of TAO (odds ratio, 1.2; 95% CI, 1.1-1.3). CONCLUSIONS: Our findings suggest that the risk of TAO was significantly associated with elevated plasma total homocysteine level independently of other factors analyzed, including smoking. Studies on the use of homocysteine-lowering therapy to prevent TAO would allow testing causality of the latter association.


Assuntos
Homocisteína/sangue , Hiper-Homocisteinemia/complicações , Tromboangiite Obliterante/etiologia , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , China , Feminino , Humanos , Hiper-Homocisteinemia/sangue , Hiper-Homocisteinemia/diagnóstico , Masculino , Pessoa de Meia-Idade , Medição de Risco , Fatores de Risco , Tromboangiite Obliterante/diagnóstico , Regulação para Cima
8.
Vet J ; 254: 105358, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31836166

RESUMO

Serum homocysteine (Hcy) increases in people and dogs with chronic kidney disease (CKD). Hyperhomocysteinemia (HHcy) has also been associated with CKD-related hypertension and proteinuria. The aims of this study were to: (1) validate an enzymatic method for quantification of Hcy in feline serum; (2) evaluate whether HHcy was associated with the presence and severity of CKD, proteinuria or hypertension; and (3) determine whether HHcy could predict disease progression. The intra- and inter-assay coefficients of variation (CVs) and the recovery rates of linearity under dilution and spiking recovery tests of the enzymatic method were 3.1-6.7%, 11.6-12.5%, 96.9±5.4% and 96.9±5.4%, respectively. Healthy cats at risk of CKD (n=17) and cats with CKD (n=19) were sampled over a 6-month period (63 samples in total). Cats with CKD had significantly higher Hcy concentrations (P=0.005) than cats at risk. The concentration of Hcy was higher (P=0.002) in moderate-severe CKD than in mild CKD and correlated moderately with serum creatinine (P<0.0001; r=0.51). The concentration of Hcy increased with the magnitude of proteinuria and correlated weakly with urinary protein to creatinine ratio (P=0.045; r=0.26). HHcy was not associated with hypertension. At the time of enrollment, Hcy concentration was significantly higher (P=0.046) in cats that developed CKD compared to cats that remained stable. The enzymatic method for Hcy measurement in feline serum was precise and accurate. HHcy was relatively common in cats with advanced CKD and seemed to predict disease progression, but further studies are warranted.


Assuntos
Doenças do Gato/sangue , Ensaios Enzimáticos/veterinária , Homocisteína/sangue , Hiper-Homocisteinemia/veterinária , Insuficiência Renal Crônica/veterinária , Animais , Azotemia/sangue , Azotemia/veterinária , Gatos , Ensaios Enzimáticos/métodos , Feminino , Hiper-Homocisteinemia/sangue , Hipertensão/sangue , Hipertensão/veterinária , Estudos Longitudinais , Masculino , Proteinúria/sangue , Proteinúria/veterinária , Insuficiência Renal Crônica/sangue
9.
Ann Afr Med ; 18(3): 143-152, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31417015

RESUMO

Background: This study aimed to determine the prevalence of hyperhomocysteinemia and folate status in a sample of normal healthy Nigerians living in Zaria as well as assess the relationship between homocysteine, folate, and blood pressure (BP) levels. Methods: It was a cross-sectional analytical study carried out among 65 normal healthy volunteers aged 18-65 years. Participants were randomly selected from willing patient escorts, hospital employees, and willing staff presenting at the Ahmadu Bello University Medical Centre, Zaria and Ahmadu Bello University Teaching Hospital, Zaria, Nigeria. The percentage of participants who had high homocysteine levels as well as their plasma folate status was determined. Results: There were 9.2% with hyperhomocysteinemia >15 µmol/L and 51% with hyperhomocysteinemia >10 µmol/L. The mean plasma homocysteine level was 10.8 ± 2.7 µmol/L with male and female values of 10.7 ± 2.6 and 10.8 ± 2.8, respectively (P = 0.87). The mean plasma folate level was high (116.7 ± 44.0 ng/mL) with male value of (111.5 ± 44.9 ng/mL) which did not differ significantly (P = 0.37) from that of females (121.4 ± 43.3 ng/mL). Homocysteine showed a positive significant (P = 0.01) relationship with folate but not with BP's (P > 0.05). Conclusion: There is a high prevalence of hyperhomocysteinemia in normal healthy Northern-Nigerians which cannot be accounted for by suboptimal folate levels. Hyperhomocysteinemia may not be a risk factor for cardiovascular disease in normal healthy Nigerians despite its high levels as it showed no significant relationship with BP.


Assuntos
Ácido Fólico/sangue , Homocisteína/sangue , Hiper-Homocisteinemia/epidemiologia , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Glicemia/metabolismo , Pressão Sanguínea/fisiologia , Criança , Pré-Escolar , Estudos Transversais , Feminino , Voluntários Saudáveis , Humanos , Hiper-Homocisteinemia/sangue , Hiper-Homocisteinemia/diagnóstico , Masculino , Pessoa de Meia-Idade , Nigéria/epidemiologia , Prevalência , Adulto Jovem
10.
Rom J Ophthalmol ; 63(2): 188-192, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31334400

RESUMO

Purpose: To report a case with monocular transient vision loss (TVL) associated with Hyperhomocysteinemia. Methods: We present a case with persistent TVL attacks and high level of homocysteine. Results: A 32-year-old male had a history of episodes of recurrent monocular TVL. Extensive ophthalmic, systemic and laboratory studies were unremarkable with the exception of high plasma homocysteine level. He never experienced TVL during the 36-month follow-up after starting folate, B12 and B6 except for one episode in which he had discontinued the treatment for three months. Conclusion: This case may suggest hyperhomocysteinemia as one of the underlying causes of recurrent attacks of TVL without any known source of emboli.


Assuntos
Amaurose Fugaz/etiologia , Encéfalo/patologia , Homocisteína/sangue , Hiper-Homocisteinemia/complicações , Acuidade Visual , Adulto , Amaurose Fugaz/diagnóstico , Amaurose Fugaz/fisiopatologia , Biomarcadores/sangue , Humanos , Hiper-Homocisteinemia/sangue , Hiper-Homocisteinemia/diagnóstico , Embolia Intracraniana , Imagem por Ressonância Magnética , Masculino , Artéria Oftálmica/diagnóstico por imagem , Recidiva , Ultrassonografia Doppler em Cores
11.
Zhonghua Er Ke Za Zhi ; 57(8): 620-624, 2019 Aug 02.
Artigo em Chinês | MEDLINE | ID: mdl-31352748

RESUMO

Objective: To improve the awareness of methylmalonic acidemia and hyperhomocysteinemia with diffuse lung disease as an initial or main presentation. Methods: A retrospective analysis of the clinical manifestations, radiological features, laboratory tests, genetic variations, treatments and prognoses was conducted in six children presented with diffuse lung disease and finally diagnosed with methylmalonic acidemia and hyperhomocysteinemia in Ward 2 of Department of Respiratory Diseases, Beijing Children's Hospital, from August 2017 to November 2018. Results: Six children were included in this study. Two children were male and four were female. The average age of onset was 28 months. The mean age at diagnosis was 34 months. The average interval from onset to diagnosis was 6 months. Four children who underwent genetic tests were found to have variants of gene MMACHC and diagnosed with CblC type. All children had respiratory symptoms and signs as initial or main presentation, which were tachypnea (5 cases), exercise intolerance (5 cases), cough (4 cases), cyanosis (4 cases), clubbing (4 cases), dyspnea (3 cases) and retractions (3 cases). Pulmonary arterial hypertension was found in all six children. Pericardial effusion (4 cases), kidney involvement (3 cases), nervous system involvement (3 cases), gastrointestinal system involvement (3 cases) and anemia (2 cases) also coexisted. The high resolution computed tomography (HRCT) features included dilated pulmonary artery (6 cases), ground-glass opacities (4 cases), diffuse poorly defined ground-glass centrilobular nodules (3 cases), pleural effusion (3 cases), thickening of interlobular septum (2 cases), etc. All children had an elevated concentration of methylmalonic acid in urine and homocysteine in plasma. Genetic tests were performed in four patients, and MMACHC genetic mutations were found in all of them. Clinical manifestations, HRCT features and pulmonary arterial hypertension turned better in five children after treatment. One patient who was not regularly followed-up died. Conclusions: Pulmonary involvement including diffuse lung disease and pulmonary arterial hypertension could coexist with methylmalonic acidemia and hyperhomocysteinemia, which may have respiratory symptoms and signs as the initial or main presentation. Characteristic HRCT features were found in some patients. Plasma homocysteine test is a quick method for screening the disease in children with diffuse lung disease and (or) pulmonary arterial hypertension. Both diffuse lung disease and pulmonary arterial hypertension may turn better after treatment.


Assuntos
Erros Inatos do Metabolismo dos Aminoácidos/diagnóstico , Hiper-Homocisteinemia/diagnóstico , Pneumopatias/etiologia , Pulmão/fisiopatologia , Artéria Pulmonar/diagnóstico por imagem , Idade de Início , Erros Inatos do Metabolismo dos Aminoácidos/urina , Proteínas de Transporte , Criança , Pré-Escolar , Feminino , Humanos , Hiper-Homocisteinemia/sangue , Lactente , Masculino , Oxirredutases , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
13.
Biochimie ; 165: 19-31, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31269461

RESUMO

Homocysteine (Hcy) is a key metabolite generated during methionine metabolism. The elevated levels of Hcy in the blood are reffered to as hyperhomocystenimeia (HHcy). The HHcy is caused by impaired metabolism/deficiency of either folate or B12 or defects in Hcy metabolism. Accumulating evidence suggests that HHcy is associated with cardiovascular and brain diseases including atherosclerosis, endothelial injury, and stroke etc. Vitamin B12 (cobalamin; B12) is a water-soluble vitamin essential for two metabolic reactions. It acts as a co-factor for methionine synthase and L-methylmalonyl-CoA mutase. Besides, it is also vital for DNA synthesis and maturation of RBC. Deficiency of B12 is associated with haematological and neurological disorders. Hyperhomocysteinemia (HHcy)-induced toxicity is thought to be mediated by the accumulation of Hcy and its metabolites, homocysteinylated proteins. Cellular protein quality control (PQC) is essential for the maintenance of proteome integrity, and cell viability and its failure contributes to the development of multiple diseases. Chaperones, unfolded protein response (UPR), ubiquitin-proteasome system (UPS), and autophagy are analogous strategies of PQC that maintain cellular proteome integrity. Recently, multiple studies reported that HHcy responsible for perturbation of PQC by reducing chaperone levels, activating UPR, and impairing autophagy. Besides, HHcy also induce cytotoxicity, inflammation, protein aggregation and apoptosis. It has been shown that some of the factors including altered SIRT1-HSF1 axis and irreversible homocysteinylation of proteins are responsible for folate and/or B12 deficiency or HHcy-induced impairment of PQC. Therefore, this review highlights the current understanding of HHcy in the context of cellular PQC and their pathophysiological and clinical consequences, epigenomic changes, therapeutic implications of B12, and chemical chaperones based on cell culture and experimental animal models.


Assuntos
Homocisteína/metabolismo , Hiper-Homocisteinemia/sangue , Vitamina B 12/metabolismo , Animais , Apoptose , Autofagia , Linhagem Celular , Humanos , Camundongos , Chaperonas Moleculares/metabolismo , Agregação Patológica de Proteínas , Processamento de Proteína Pós-Traducional , Ratos , Ubiquitinação , Resposta a Proteínas não Dobradas
14.
Biotechnol Appl Biochem ; 66(5): 715-719, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31314127

RESUMO

Homocysteine [HSCH2 CH2 CH(NH2 )COOH] (Hcy) is a sulfur-containing amino acid of 135.18 Da of molecular weight, generated during conversion of methionine to cysteine. If there is a higher accumulation of Hcy in the blood, that is usually above 15 µmol/L, it leads to a condition referred to as hyperhomocysteinemia. A meta-analysis of observational study suggested an elevated concentration of Hcy in blood, which is termed as the risk factors leading to ischemic heart disease and stroke. Further experimental studies stated that Hcy can lead to an increase in the proliferation of vascular smooth muscle cells and functional impairment of endothelial cells. The analyses confirmed some of the predictors for Hcy presence, such as serum uric acid (UA), systolic blood pressure, and hematocrit. However, angiotensin-converting enzyme inhibitors angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) alone are inadequate for controlling UA and creatinine level, although the addition of folic acid may be beneficial in hypertensive patients who are known to have a high prevalence of elevated Hcy. We hypothesized that combination therapy with an ARB (olmesartan) and folic acid is a promising treatment for lowering the UA and creatinine level in hyperhomocysteinemia-associated hypertension.


Assuntos
Antagonistas de Receptores de Angiotensina/farmacologia , Creatinina/sangue , Ácido Fólico/farmacologia , Hiper-Homocisteinemia/tratamento farmacológico , Hipertensão/tratamento farmacológico , Ácido Úrico/sangue , Humanos , Hiper-Homocisteinemia/sangue , Hipertensão/sangue , Estudos Observacionais como Assunto
15.
Ideggyogy Sz ; 72(5-6): 201-207, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31241265

RESUMO

Background and purpose: Migraine is a risk factor for ischemic stroke in women of childbearing ages. Previous researches revealed a higher prevalence of hyperhomocysteinemia in migraineurs. Possible differences on the frequencies of hyperhomocysteinemia between migraine with aura and migraine without aura could contribute the established variances in stroke risk between these migraine types. Therefore, we aimed to search if the frequency of hyperhomocysteinemia was different between these subtypes of migraine or not. Methods: We analyzed the findings of serum homocysteine levels in female migraineurs of 16-49 years old who admitted to our outpatient clinic. Results: Homocysteine level was elevated in 13.3% of study population. There were not any significant differences on median serum homocysteine levels between migraine with aura (8.0 mikromol/L) and without aura (8.5 mikromol/L). (p=0.426) The frequencies of hyperhomocysteinemia were also similar (9.1% versus 16.7%, respectively; p=0.373). Correlation analyses did not reveal any linear correlation between ages and homocysteine levels either in group of migraine with aura or in group of migraine without aura (p=0.417 and p=0.647, respectively). Similarly, any linear correlation between disease ages and homocysteine levels either in group of migraine with aura or in group of migraine without aura was not detected (p=0.359 and p=0.849, respectively). Conclusion: The median serum homocysteine levels and the frequencies of hyperhomocysteinemia are similar between migraine with aura and without aura in women of childbearing ages. Therefore, the variances on stroke risk ratios between these types of migraine are probably not originated from the differences of serum homocysteine status.


Assuntos
Homocisteína/sangue , Hiper-Homocisteinemia/epidemiologia , Transtornos de Enxaqueca/epidemiologia , Adolescente , Adulto , Feminino , Humanos , Hiper-Homocisteinemia/sangue , Transtornos de Enxaqueca/sangue , Transtornos de Enxaqueca/fisiopatologia , Enxaqueca com Aura/epidemiologia , Enxaqueca sem Aura/epidemiologia , Saúde Reprodutiva , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Adulto Jovem
16.
J Formos Med Assoc ; 118(10): 1401-1407, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31242967

RESUMO

BACKGROUND/PURPOSE: Microcytosis is defined as having mean corpuscular volume (MCV) < 80 fL. This study evaluated whether 79 atrophic glossitis (AG) patients with microcytosis and 985 AG patient without microcytosis had higher frequencies of anemia, hematinic deficiencies, hyperhomocysteinemia, and serum gastric parietal cell antibody (GPCA) positivity than 532 healthy control subjects. METHODS: Complete blood count, serum iron, vitamin B12, folic acid, homocysteine, and serum GPCA levels in 79 AG patients with microcytosis, 985 AG patient without microcytosis, and 532 healthy control subjects were measured and compared. RESULTS: We found that 69.6%, 43.0%, 5.1%, 3.8%, 11.4%, and 22.8% of 79 AG patients with microcytosis and 14.9%, 14.8%, 5.3%, 2.1%, 12.0%, and 27.0% of 985 AG patients without microcytosis were diagnosed as having blood hemoglobin, iron, vitamin B12, and folic acid deficiencies, hyperhomocysteinemia, and serum GPCA positivity, respectively. Both 79 AG patients with microcytosis and 985 AG patients without microcytosis had significantly higher frequencies of blood hemoglobin, iron, vitamin B12, and folic acid deficiencies, hyperhomocysteinemia, and serum GPCA positivity than 532 healthy control subjects (all P-values < 0.01). Moreover, 79 AG patients with microcytosis had significantly higher frequencies of blood hemoglobin and iron deficiencies than 985 AG patients without microcytosis. CONCLUSION: There are significantly higher frequencies of anemia, serum iron, vitamin B12, and folic acid deficiencies, hyperhomocysteinemia, and serum GPCA positivity in AG patients with or without microcytosis than in healthy control subjects. AG patients with microcytosis have significantly higher frequencies of blood hemoglobin and iron deficiencies than AG patients without microcytosis.


Assuntos
Anemia/etiologia , Autoanticorpos/sangue , Glossite/sangue , Glossite/complicações , Hiper-Homocisteinemia/etiologia , Células Parietais Gástricas/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia/sangue , Atrofia/sangue , Estudos de Casos e Controles , Índices de Eritrócitos , Eritropoese , Feminino , Ácido Fólico/sangue , Deficiência de Ácido Fólico/sangue , Deficiência de Ácido Fólico/etiologia , Glossite/patologia , Hemoglobinas/metabolismo , Homocisteína/sangue , Humanos , Hiper-Homocisteinemia/sangue , Ferro/sangue , Ferro/deficiência , Masculino , Pessoa de Meia-Idade , Língua/patologia , Vitamina B 12/sangue , Deficiência de Vitamina B 12/sangue , Deficiência de Vitamina B 12/etiologia , Adulto Jovem
17.
J Formos Med Assoc ; 118(9): 1299-1307, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31202497

RESUMO

BACKGROUND/PURPOSE: Our previous studies found relatively higher frequencies of anemia, hematinic deficiencies, and hyperhomocysteinemia in patients with different types of oral mucosal diseases. This study evaluated whether patients with oral precancerous lesions (oral precancer patients) had significantly higher frequencies of anemia, hematinic deficiencies, and hyperhomocysteinemia than healthy control subjects. METHODS: The complete blood count, serum iron, vitamin B12, folic acid, and homocysteine levels in 131 oral precancer patients including 96 oral leukoplakia, 26 oral erythroleukoplakia, and 9 oral verrucous hyperplasia patients and in 131 age- and sex-matched healthy control subjects were measured and compared. RESULTS: We found significantly lower mean serum iron (for women only), vitamin B12, and folic acid levels and a significantly higher mean serum homocysteine level in oral precancer patients than in healthy control subjects (all P-values < 0.05). Moreover, 131 oral precancer patients had significantly higher frequencies of blood hemoglobin (3.1%), vitamin B12 (43.5%), and folic acid (46.6%) deficiencies and hyperhomocysteinemia (22.1%) than 131 healthy control subjects (all P-values < 0.05). Of 131 oral precancer patients, lower mean serum folic acid levels were found in 87 cigarette smokers than in 44 non-smokers (P = 0.002), in 26 smokers consuming > 20 cigarettes per day than in 61 smokers consuming ≤ 20 cigarettes per day (P = 0.024), and in 52 betel quid chewers than in 79 non-chewers (P = 0.051). CONCLUSION: There are significantly higher frequencies of anemia, serum vitamin B12, and folic acid deficiencies, and hyperhomocysteinemia in oral precancer patients than in healthy control subjects.


Assuntos
Autoanticorpos/sangue , Hiper-Homocisteinemia/sangue , Leucoplasia Oral/sangue , Doenças da Boca/sangue , Adulto , Idoso , Anemia/etiologia , Estudos de Casos e Controles , Índices de Eritrócitos , Feminino , Ácido Fólico/sangue , Deficiência de Ácido Fólico/sangue , Hematínicos , Hemoglobinas/análise , Humanos , Ferro/sangue , Masculino , Pessoa de Meia-Idade , Doenças da Boca/patologia , Células Parietais Gástricas/imunologia , Fatores Sexuais , Taiwan , Vitamina B 12/sangue , Deficiência de Vitamina B 12/sangue
18.
Biol Pharm Bull ; 42(6): 1054-1057, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31155583

RESUMO

Mental retardation is the most common feature among inborn errors of amino acid metabolism. Patients with homocystinuria/homocysteinemia caused by cystathionine ß-synthase (CBS) deficiency suffer from thromboembolism and mental retardation from early ages; therefore, detection by newborn screening is performed. Furthermore, elevated levels of serum homocysteine during pregnancy are associated with the occurrence of neural tube defects (NTDs) in newborns. However, the causes of such central nervous system (CNS) defects are unknown. We found previously impaired learning abilities in Cbs-deficient (Cbs-/-) mice (but not NTD births). Here, we investigated the amino acid profiles of serum and cerebrospinal fluid (CSF) from Cbs-/- mice. Mice deficient in cystathionine γ-lyase (Cth), a downstream enzyme of CBS in transsulfuration, as well as wild-type mice, were analyzed as controls. Cbs-/- and Cth-/- mice were smaller than wild-type mice, and CSF yields in Cbs-/- mice were lower than the others. CSF amino acid levels were generally lower than those in serum, and compared with the dramatic amino acid level alterations in Cbs-/- mouse serum, alterations in CSF were less apparent. However, marked upregulation (versus wild-type) of aspartic acid/asparagine (Asp/Asn), glutamine (Gln), serine (Ser), threonine (Thr), phenylalanine (Phe), tyrosine (Tyr), methionine (Met), total homocysteine, and citrulline, and downregulation of lysine (Lys) were found in Cbs-/- mouse CSF. Because similar regulation of total homocysteine/citrulline/Lys was observed in the CSF of Cth-/- mice, which are free of CNS dysfunction, the reduced CSF volumes and the level changes of other amino acids could be relevant to Cbs-/--specific CNS defects.


Assuntos
Aminoácidos/sangue , Aminoácidos/líquido cefalorraquidiano , Cistationina beta-Sintase/genética , Hiper-Homocisteinemia/sangue , Hiper-Homocisteinemia/líquido cefalorraquidiano , Animais , Cistationina gama-Liase/genética , Modelos Animais de Doenças , Camundongos Knockout
19.
J Vasc Res ; 56(3): 152-159, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31132776

RESUMO

Growing evidence has reported that a history of preeclampsia (PE) increases the risk of developing cardiovascular disease (CVD). Arterial stiffness plays a predictive role in CVD. Previous studies have demonstrated the close association between homocysteine (Hcy) level and arterial stiffness in community-based populations. This study was to assess whether Hcy level was independently associated with arterial stiffness in 168 women with a PE history who were analyzed at a 5-year follow-up. Brachial-ankle pulse wave velocity (baPWV) was measured by an automatic pulse-wave analyzer and a value >1,400 cm/s was defined as high arterial stiffness. Biochemical parameters were recorded and an Hcy value >10 µmol/L was defined as having hyperhomocysteine (H-Hcy). Variables that were significantly associated with baPWV were tested for independence by multivariate logistic regression analysis. We found that body mass index (OR 1.017, 95% CI 1.008-1.029), systolic blood pressure (OR 1.048, 95% CI 1.019-1.072), total cholesterol (OR 1.059, 95% CI 1.007-1.086), and Hcy level (OR 1.021, 95% CI 1.010-1.037) were independent determinants of baPWV in women with previous PE. Our findings indicate that Hcy pathway might be involved in arterial stiffness in women with a PE history. Whether Hcy would be a promising biomarker for serial stratified CVD risk management in these women deserves further evaluation on a large scale.


Assuntos
Homocisteína/sangue , Hiper-Homocisteinemia/complicações , Doença Arterial Periférica/etiologia , Pré-Eclâmpsia , Rigidez Vascular , Adulto , Biomarcadores/sangue , Pressão Sanguínea , Estudos de Casos e Controles , China , Estudos Transversais , Feminino , Humanos , Hiper-Homocisteinemia/sangue , Hiper-Homocisteinemia/diagnóstico , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/fisiopatologia , Pré-Eclâmpsia/diagnóstico , Pré-Eclâmpsia/fisiopatologia , Gravidez , Prognóstico , Medição de Risco , Fatores de Risco , Fatores de Tempo
20.
J Stroke Cerebrovasc Dis ; 28(7): 1816-1823, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31080137

RESUMO

OBJECTIVE: To study the inflammatory mechanism of hyperhomocysteinemia on large-artery atherosclerosis based on hypersensitive C-reactive protein in patients. METHODS: In all, 153 inpatients and 1357 physical examinees were selected. The levels of homocysteine were compared between the carotid/intracranial artery stenosis group and the nonstenosis group, between the carotid artery unstable plaque group and the nonplaque group, and between the intima-media thickness (IMT) greater than or equal to 1 group and the normal IMT group. The hypersensitive C-reactive protein levels were compared between the lacunar infarction (LI) group and the nonstroke control group and between the unstable plaque group and the nonplaque group. RESULTS: Homocysteine level was significantly higher in the carotid/intracranial artery stenosis group than in the nonstenosis group, in the LI group than in the inpatient nonstroke group, and in the IMT greater than or equal to 1 group than in the normal IMT group. The hypersensitive C-reactive protein level was significantly higher in the LI group than in the nonstroke group and in the unstable plaque group than in the nonplaque group. CONCLUSIONS: Hyperhomocysteinemia may aggravate the development of IMT, carotid atherosclerotic plaque instability, and carotid/intracranial artery stenosis by increasing inflammation, ultimately leading to the occurrence of LI. Hyperhomocysteinemia-induced inflammation mechanism warrants further study.


Assuntos
Proteína C-Reativa/análise , Estenose das Carótidas/sangue , Homocisteína/sangue , Hiper-Homocisteinemia/sangue , Mediadores da Inflamação/sangue , Inflamação/sangue , Arteriosclerose Intracraniana/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Espessura Intima-Media Carotídea , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/etiologia , Estudos de Casos e Controles , China , Feminino , Humanos , Hiper-Homocisteinemia/complicações , Hiper-Homocisteinemia/diagnóstico , Inflamação/diagnóstico , Inflamação/etiologia , Arteriosclerose Intracraniana/diagnóstico por imagem , Arteriosclerose Intracraniana/etiologia , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica , Prognóstico , Fatores de Risco , Ruptura Espontânea , Índice de Gravidade de Doença
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