MiR -18a -5p aggravates homocysteine -induced myocardial injury via autophagy / 中南大学学报(医学版)

OBJECTIVES@#Hyperhomocysteinaemia (Hcy) is an independent risk factor for cardiovascular and cerebrovascular diseases. MicroRNA (miR)-18a-5p is closely related to cardiovascular diseases. This study aims to investigate the effects of miR-18a-5p on homocysteine (Hcy)-induced myocardial cells injury.@*METHODS@#H9c2 cells were transfected with miR-18a-5p mimic/miR-18a-5p mimic negative control (NC) or combined with Hcy for intervention, and untreated cells were set as a control group. The transfection efficiency was verified by real-time RT-PCR, and cell counting kit-8 (CCK-8) assay was used to determine cell viability. Flow cytometry was used to detect apoptosis and reactive oxygen species (ROS) levels. Western blotting was performed to measure the protein levels of microtubule-associated protein 1 light chain 3 (LC3)-I, LC3-II, Beclin1, p62, Bax, Bcl-2, and Notch2. Dual luciferase reporter assay was used to detect the interaction of miR-18a-5p with Notch2.@*RESULTS@#Compared with the control, treatment with Hcy or transfection with miR-18a-5p mimic alone, or combined treatment with Hcy and miR-18a-5p mimic/miR-18a-5p mimic NC significantly reduced the H9c2 cell viability, promoted apoptosis and ROS production, up-regulated the expressions of Bax and Beclin, down-regulated the expressions of Bcl-2, p62, and Notch2, and increased the ratio of LC3-II/LC3-I (all P<0.05). Compared with the combined intervention of miR-18a-5p mimic NC and Hcy group, the above indexes were more significantly changed in the combined intervention of miR-18a-5p mimic and Hcy group, and the difference between the 2 groups was statistically significant (all P<0.05). There is a targeted binding between Notch2 and miR-18a-5p.@*CONCLUSIONS@#MiR-18a-5p could induce autophagy and apoptosis via increasing ROS production in cardiomyocytes, and aggravate Hcy-induced myocardial injury. Notch2 is a target of miR-18a-5p.

Hyperhomocysteinemia as an Independent Risk Factor for Coronary Heart Disease. Comparison with Conventional Risk Factors / Hiper-homocisteinemia como fator de risco independente para doença coronariana: comparação com fatores de risco convencionais

Abstract The present study was designed to evaluate the strength of association of raised plasma homocysteine concentration as a risk factor for coronary heart disease independent of conventional risk factor. It was a case control study conducted at Punjab Institute of Cardiology Lahore. A total of 210 subjects aged 25 to 60 years comprising of 105 newly admitted patients of CHD as cases and 105 age and sex matched healthy individuals with no history of CHD as control were recruited for the study. Fasting blood samples were obtained from cases and controls. Plasma homocysteine was analyzed by fluorescence polarization immunoassay (FPIA) method on automated immunoassay analyzer (Abbott IMX). Total cholesterol, triglyceride and HDL cholesterol were analyzed using calorimetric kit methods. The concentration of LDL cholesterol was calculated using Friedewald formula. The patients were also assessed for traditional risk factors such as age, sex, family history of CVD, hypertension, smoking and physical activity, and were compared with control subjects. The collected data was entered in SPSS version 24 for analysis and interpretation.The mean age in controls and experimental groups were 43.00± 8.42 years and 44.72± 8.59 years with statistically same distribution (p- value= 0.144). The mean plasma homocysteine for cases was 22.33± 9.22 µmol/L where as it was 12.59±3.73 µmol/L in control group. Highly significant difference was seen between the mean plasma level of homocysteine in cases and controls (p˂0.001).Simple logistic regression indicates a strong association of coronary heart disease with hyperhomocysteinemia (OR 7.45), which remained significantly associated with coronary heart disease by multivariate logistic regression (OR 7.10, 95%C1 3.12-12.83, p=0.000). The present study concludes that elevated levels of Plasma homocysteine is an independent risk factor for coronary heart disease independent of conventional risk factors and can be used as an indicator for predicting the future possibility for the onset of CVD.

Resumo O presente estudo foi desenhado para avaliar a força da associação da concentração elevada de homocisteína no plasma como um fator de risco para doença cardíaca coronária independente do fator de risco convencional. Foi um estudo de caso-controle realizado no Punjab Institute of Cardiology Lahore. Um total de 210 indivíduos com idade entre 25 e 60 anos, compreendendo 105 pacientes recém-admitidos de CHD como casos e 105 indivíduos saudáveis ​​pareados por idade e sexo sem histórico de CHD como controle, foi recrutado para o estudo. Amostras de sangue em jejum foram obtidas de casos e controles. A homocisteína plasmática foi analisada pelo método de imunoensaio de polarização de fluorescência (FPIA) em analisador de imunoensaio automatizado (Abbott IMX). Colesterol total, triglicerídeos e colesterol HDL foram analisados ​​usando métodos de kit calorimétrico. A concentração de colesterol LDL foi calculada pela fórmula de Friedewald. Os pacientes também foram avaliados para fatores de risco tradicionais, como idade, sexo, história familiar de DCV, hipertensão, tabagismo e atividade física, e foram comparados com indivíduos de controle. Os dados coletados foram inseridos no SPSS versão 24 para análise e interpretação. A média de idade nos grupos controles e experimentais foi de 43,00 ± 8,42 anos e 44,72 ± 8,59 anos com distribuição estatisticamente igual (p-valor = 0,144). A homocisteína plasmática média para os casos foi de 22,33 ± 9,22 µmol / L, enquanto no grupo controle foi de 12,59 ± 3,73 µmol / L. Diferença altamente significativa foi observada entre o nível plasmático médio de homocisteína em casos e controles (p ˂ 0,001). A regressão logística simples indica uma forte associação de doença cardíaca coronária com hiper-homocisteinemia (OR 7,45), que permaneceu significativamente associada com doença cardíaca coronária por multivariada regressão logística (OR 7,10, 95% C1 3,12-12,83, p = 0,000). O presente estudo conclui que níveis elevados de homocisteína plasmática são fator de risco independente para doença cardíaca coronária, independentemente dos fatores de risco convencionais, e pode ser usado como um indicador para prever a possibilidade futura de aparecimento de DCV.

Prevalence of thrombophilia-associated genetic risk factors in blood donors of a regional hospital in southern Brazil

ABSTRACT Introduction: Thromboembolic events occur due to an imbalance in the hemostasis and some factors associated with this condition can be inherited. In order to evaluate the frequency of genotypes considered to be common hereditary risk factors for thrombophilia associated with venous thrombosis (g.1691G>A and g.20210G>A) and hyperhomocysteinemia (g.677C>T and g.1298A>C), samples from voluntary healthy blood donors at the Hospital de Clínicas de Porto Alegre were tested. Methods: We examined 325 blood samples from blood donors collected from October 2017 to July 2018. Blood was collected on filter paper and the DNA was extracted for single nucleotide polymorphisms (SNPs) analysis using the qualitative real time polymerase chain reaction. Results: The calculated frequencies of each genetic variant in heterozygosity were 4% for the FV gene (g.1691G> A), 4% for the F2 gene (g.20210G> A) and 42% and 39% for methylenetetrahydrofolate reductase (MTHFR), g.677C>T and g.1298A>C, respectively. Only the genetic variants of MTHFR were found in homozygosity, with frequencies of 14% and 6% (g.677C>T and g.1298A>C), respectively. Discussion: Altogether, these results describe the frequencies of genetic variants associated with venous thrombosis and hyperhomocysteinemia in the analyzed group and are important to enhance our current knowledge about the genetic profiles of Brazilian blood donors.

The Role of High Concentrations of Homocysteine for the Development of Fetal Growth Restriction / O papel de altas concentrações de homocisteína para o desenvolvimento da restrição de crescimento fetal

Abstract Objective To assess homocysteine (Hcy) levels in the three trimesters of pregnancy in women with fetal growth restriction (FGR) and to evaluate the role of Hcy as a possible predictor of FGR. Methods A total of 315 singleton pregnant women were included in the present prospective cohort study and were monitored since the 1st trimester of pregnancy before delivery. Newborns were monitored for the first 7 days of life. Patients who had risk factors for FGR were excluded. Fetal growth restriction was defined according to uterine fundal height (< 10 percentile), ultrasound fetometry (< 5 percentile), and anthropometry of newborns (<5 percentile). The concentrations of Hcy were detected at between 10 and 14, between 20 and 24, and between 30 and 34 weeks of pregnancy by enzyme-linked immunosorbent assay (ELISA). Receiver operating characteristics (ROC) curve test and diagnostic odds ratio (DOR) were performed to evaluate the results of ELISA. Results The concentration of Hcy in patients with FGR was 19.65 umol/L at between 10 and 14 weeks, compared with 9.28 umol/L in patients with normal fetal growth (p<0.0001). The optimal cut-off level for Hcy in the 1st trimester of pregnancy was>13.9 umol/L with AUC 0.788, sensitivity of 75%, specificity of 83.6%, and DOR of 15.2. Conclusion Assessment of serum Hcy concentration may be used as a predictor of FGR, with the highest diagnostic utility in the 1st trimester of pregnancy.

Resumo Objetivo Avaliar os níveis de homocisteína (Hcy) em três trimestres da gravidez em mulheres com restrição de crescimento fetal (FGR, na sigla em inglês) e avaliar o papel da Hcy como possível preditor de FGR. Métodos Um total de 315 gestantes solteiras foram incluídas no presente estudo de coorte prospectivo e monitoradas desde o 1° trimestre de gravidez antes do parto. Os recém-nascidos foram acompanhados durante os primeiros 7 dias de vida. Pacientes que apresentam fatores de risco para FGR foram excluídos. A FGR foi definida de acordo com a altura do fundo do útero (< percentil 10), ultrassonografia fetometria (< percentil 5) e antropometria dos recém-nascidos (< percentil 5). As concentrações de Hcy foram detectadas entre 10 e 14, entre 20 e 24 e entre 30 e 34 semanas de gravidez por ensaio de imunoabsorção enzimática (ELISA, na sigla em inglês). O teste da curva das características de operação do receptor (ROC, na sigla em inglês) e a razão de chances de diagnóstico (DOR, na sigla em inglês) foram realizados para avaliar os resultados do ELISA. Resultados A concentração de Hcy em pacientes com FGR foi de 19,65 umol/L entre 10 e 14 semanas, em comparação com 9,28 umol/L em pacientes com crescimento fetal normal (p<0,0001). O nível de corte ideal para Hcy no 1° trimestre da gravidez foi>13,9 umol/L com AUC 0,788, sensibilidade de 75%, especificidade de 83,6%, e DOR 15,2. Conclusão A avaliação da concentração sérica de Hcy pode ser usada como um preditor de FGR, com maior utilidade diagnóstica no 1° trimestre de gravidez.

Biomarcadores cardiacos de aterotrombosis y su implicación en la estimación del riesgo de enfermedad cardiovascular / Cardiac biomarkers of atherothrombosis and their implication in estimating the risk of cardiovascular disease

Introducción: Las innovadoras estrategias para la estimación del riesgo cardiovascular que apelan al empleo de biomarcadores cardiacos de aterotrombosis, han evidenciado ser superiores en la estratificación del riesgo cardiovascular por encima de aquellas predicciones basadas exclusivamente en la evaluación de factores de riesgo tradicionales de manera aislada. Se realizó una revisión bibliográfica, análisis y categorización de diferentes artículos en las bases de datos Cumed, Lilacs, SciELO, Medline, los términos clave para la búsqueda fueron: homocisteína, lipoproteína (a) y riesgo cardiovascular, en español, inglés y portugués. Se consideraron artículos originales, de revisión, incluyendo revisiones sistemáticas y metaanálisis posteriores al año 2000. Objetivo: Analizar los biomarcadores cardiacos de aterotrombosis, involucrados en el desarrollo de la enfermedad cardiovascular aterosclerótica y sus complicaciones trombóticas. Desarrollo: La evidencia acumulada sustenta que biomarcadores cardiacos como la hiperhomocisteinemia, la hiperlipoproteinemia (a), el incremento de los niveles plasmáticos del fibrinógeno, el factor VII coagulante, el inhibidor del activador tisular del plasminógeno tipo 1 y la proteína C reactiva, son herramientas de gran utilidad para estratificar el riesgo cardiovascular en individuos de riesgo intermedio, o con riesgo inusual o de riesgo indefinido, esencialmente en el ámbito de la prevención primaria y secundaria de la enfermedad cardiovascular . Conclusiones: La identificación de biomarcadores emergentes de aterotrombosis predictivos adicionales, es trascendental para una prevención y terapéutica más eficaz de la enfermedad cardiovascular aterosclerótica(AU)

Introduction: Innovative cardiovascular risk estimation strategies that use cardiac biomarkers of atherothrombosis have been shown to be superior in cardiovascular risk stratification that those predictions based exclusively on the evaluation of traditional risk factors in isolation. A bibliographic review, analysis and categorization of different articles was performed in the databases Cumed, Lilacs, Scielo, Medline, the key terms for the search were: "homocysteine", "lipoprotein (a)" and "cardiovascular risk", in Spanish, English and Portuguese languages. Original review articles were considered, including systematic reviews and published meta-analyzes after 2000. Objective: To analyze some of the cardiac biomarkers of atherothrombosis that may be involved in the development of atherosclerotic cardiovascular disease and its thrombotic complications. Development: Accumulated evidence supports that cardiac biomarkers such as: hyperhomocysteinemia, hyperlipoproteinemia (a), increased plasma fibrinogen levels, coagulant factor VII, Plasminogen Tissue Activator Inhibitor type 1 and C-reactive protein are tools of Very useful for stratifying cardiovascular risk in those individuals with intermediate risk, or with unusual or undefined risk, essentially in the field of primary and secondary prevention of cardiovascular disease. Conclusions: The identification of additional predictive emergent atherothrombosis biomarkers is crucial for a more effective prevention and therapy of atherosclerotic cardiovascular disease(AU)

Exploration of the risk factors of essential hypertension with hyperhomocysteinemia: A hospital-based study and nomogram analysis

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.

n-3 Polyunsaturated fatty acid attenuates hyperhomocysteinemia-induced hepatic steatosis by increasing hepatic LXA / 生理学报

Nonalcoholic fatty liver disease (NAFLD) and hyperhomocysteinemia (HHcy) both are major health problems worldwide, whose incidence are closely related with each other. We previously reported the mechanism of HHcy-caused hepatic steatosis, but the role of n-3 polyunsaturated fatty acid (n-3 PUFA) in HHcy-induced hepatic steatosis remains unclear. In this study, 6-week-old C57BL/6 male mice were given a high methionine diet (HMD, 2% methionine diet), and plasma homocysteine levels were measured by ELISA to confirm the establishment of an HHcy model. Meantime, mice were fed HMD with or without n-3 PUFA supplement for 8 weeks to determine the role and mechanism of n-3 PUFA in hepatic steatosis induced by HHcy. Results showed that n-3 PUFA significantly improved hepatic lipid deposition induced by HHcy. qRT-PCR analysis demonstrated that n-3 PUFA inhibited the upregulation of Cd36, a key enzyme of fatty acid uptake, caused by HHcy. Further, the inhibition of hepatic Cd36 expression was associated with the inactivation of aryl hydrocarbon receptor (Ahr) induced by n-3 PUFA. Of note, mass spectrometry revealed that hepatic content of lipoxin A

Status of hyperhomocysteinemia in China: results from the China Stroke High-risk Population Screening Program, 2018 / 医学前沿

A nationwide survey was conducted from October 2018 to September 2019 to assess the prevalence of hyperhomocysteinemia (Hhcy) and its influencing factors in China. A standardized questionnaire was used to collect information. Hhcy was defined as the level of serum homocysteine (HCY) ⩾ 15.0µmol/L. The H-type hypertension (HHYP) was defined as hypertension with an elevated serum HCY 15.0µmol/L). Finally, 110 551 residents ⩾ 40 years of age from 31 provinces in the mainland of China were included. Overall, the median serum HCY level was 10.9µmol/L (interquartile range 7.9-15.1). A total of 28 633 participants (25.9%) were defined as Hhcy. The Hhcy prevalence ranged from 7.9% in Shanghai to 56.8% in Tianjin. The data showed that serum HCY levels were associated with age, male gender, cigarette smoking, hypertension, diabetes, ethnicity, endurance in exercise (inverse), and fruit and vegetable intake (inverse). In addition, 15 486 participants were defined as HHYP, and the rate was 14.0%. HHYP was an independent predictor of stroke with an adjusted odds ratio of 1.752 (95% CI 1.338-2.105). The geographical distribution pattern of the Hhcy epidemic reflects dynamic differences, and national strategies should be carried out to further improve the care of patients with Hhcy across China.

Association between maternal serum homocysteine concentrations in early pregnancy and adverse pregnancy outcomes

There is still conflicting evidence on the extent to which maternal hyperhomocysteinemia is a risk factor for pregnancy complications. Aims: The study aimed to investigate the impact of elevated maternal homocysteine concentrations on adverse pregnancy outcomes among Nigerian women in Lagos. Materials and Methods: This was a prospective cohort study conducted at the Lagos University Teaching Hospital, Idi-Araba, Lagos, Nigeria. Participants were enrolled during the first trimester of pregnancy following which relevant data were obtained by the interview. Fasting blood samples were collected for the measurement of maternal homocysteine concentration using the enzyme-linked immunosorbent assay method. Pregnancy outcomes and complications were obtained by abstracting the antenatal, delivery, and newborn medical records. Preterm births, low-birth weight (LBW), and antepartum fetal death were used as confirmatory outcome variables in the final analysis. Descriptive statistics for all data were computed using SPSS version 22.0. The associations between the variables were tested and multivariate analyses were used to study the effects of the major baseline characteristics on the pregnancy outcome. P < 0.05 was considered statistically significant. Results: Hyperhomocysteinemia was recorded in 41 (24.6%) patients. Women with a high homocysteine concentration and those with a normal homocysteine level did not differ significantly in terms of age (P = 0.684), level of education (P = 0.866), and parity (P = 0.647). Women with hyperhomocysteinemia had an approximately twelve-fold higher risk of preterm birth (P = 0.001) and a ten-fold higher risk of delivering a term neonate with LBW (P = 0.004), but had no risk of antepartum fetal death (P = 0.118) compared to women with a normal homocysteine concentration. Conclusions: The prevalence of hyperhomocysteinemia among mothers in Lagos was relatively low. The associations between hyperhomocysteinemia and adverse pregnancy outcomes could have implications in future for the prevention of these adverse outcomes

Analyse biochimique multi-paramétrique révélant une augmentation de l'homocystéinémie et de la NT-ProBNP chez les patients hypertendus à Bamako (Mali)

Introduction: l'hypertension artérielle est un problème majeur de santé publique en Afrique subsaharienne par sa fréquence élevée et le risque cardiovasculaire qu'elle entraine. L'objectif de cette étude était d'évaluer la prévalence des facteurs de risques cliniques et biologiques de l'hypertension artérielle à Bamako (Mali).Méthodes: il s'agit d'une étude cas-témoin, stratifiée en fonction du sexe, portant sur 72 participants dont 36 hypertendus et 36 contrôles. Vingt-deux paramètres biochimiques plasmatiques ont été mesurés et analysés par des tests univariés et multivariés.Résultats: une hyperhomocystéinémie a été retrouvée chez 55,6% des femmes (p = 0,03) et 100% des hommes (p = 0,007) hypertendus. Le N-terminal pro B-type natriuretic peptide (NT-ProBNP) était également augmenté chez 16,7% des femmes (VIP > 1 dans le modèle multivarié) et des hommes hypertendus (p = 0,00006). Un bon modèle multivarié prédictif (OPLS-DA) a uniquement été obtenu chez les femmes hypertendues, avec un Q2cum = 0,73, attestant ainsi d'un important dimorphisme sexuel associé à l'hypertension artérielle. Ce modèle impliquait huit paramètres dont la concentration plasmatique était modifiée (homocystéine, NT-ProBNP, potassium, urée, glycémie, sodium, chlore et protéines totales).Conclusion: nous avons noté une association significative entre l'hyperhomocystéinémie et l'hypertension artérielle. Par conséquent, le dosage de l'homocystéine associé à une bonne prise en charge diminuerait le risque cardiovasculaire tout en améliorant la qualité de vie des patients hypertendus

Deficiencia de cobalamina C de inicio temprano: presentación de caso clínico / Early onset cobalamin C deficiency: clinical case presentation

Cobalamin C (CblC) deficiency is an autosomal recessive disorder caused by mutations of the MMACHC gene that results in impaired synthesis of the methylcobalamin and adenosylcobalamin co-factors. This brings an impaired conversion of dietary cobalamin and therefore dysfunction of two key enzymes generating hyperhomocysteinemia, hypometionimemia and methylmalonic aciduria. It is the most common intracellular metabolism disorder of cobalamin. The early clinical form is the most frequent disorder and appears as a multisystemic disease with developmental delay, failure to thrive, and ocular, renal and hematological involvement during the first year of life. The thromboembolic events are associated with small vessel involvement, generating thrombotic microangiopathy responsible for renal involvement and pulmonary thromboembolism. The late-onset form is characterized by leukoencephalopathy, psychiatric disorders, subacute degeneration of the spinal cord, and thromboembolic events of medium to large vessels. The treatment currently available increases the survival of the patient and improves growth, neurological manifestations, biochemical, hematological profile and hydrocephalus. We present the neonatal debut of a case of CblC deficiency that appeared as a multisystem disease with initial neurological, ocular and hematological manifestations. The onset of symptoms was acute, a characteristic that is not frequent in CblC. The patient started treatment early, but in an unsatisfactory fashion, which led to increased neurological deterioration. Due to MRI images performed during the evolution of his condition, a superior and transverse sagittal sinus thrombosis, a rare manifestation of the disease, was observed.

La deficiencia de cobalamina C (CblC) es un defecto autosómico recesivo causado por la mutación del gen MMACHC, que resulta en la síntesis alterada de los cofactores metilcobalamina y adenosilcobalamina. Esto trae aparejado una disfunción de dos enzimas claves, lo cual genera hiperhomocisteinemia, hipometionimemia y aciduria metilmalónica. La presentación clínica de la deficiencia de CblC es heterogénea, y varía desde las formas de inicio temprano graves y potencialmente mortales, hasta los fenotipos más leves de inicio tardío. La forma clínica temprana es la más frecuente y se manifiesta como una enfermedad multisistémica, con restricción del desarrollo, restricción del crecimiento y alteraciones oculares, renales y hematológicas durante el primer año de vida. Las manifestaciones tromboembólicas están asociadas con el compromiso de pequeños vasos, lo que causa microangiopatía trombótica, responsable de compromiso renal y de tromboembolismo pulmonar. La forma tardía se caracteriza por leucoencefalopatía, trastornos psiquiátricos, degeneración subaguda de la médula espinal y eventos tromboembólicos de medianos o grandes vasos. El tratamiento disponible actualmente aumenta la supervivencia de la enfermedad y mejora el crecimiento, las manifestaciones neurológicas, el perfil bioquímico y hematológico y la hidrocefalia. Presentamos el debut neonatal de un caso de deficiencia de CblC que se manifestó con compromiso inicial neurológico, ocular y hematológico. El comienzo de los síntomas fue agudo, característica que no es frecuente en la deficiencia de CblC. El tratamiento se inició tempranamente, pero en forma insatisfactoria, con evolución de deterioro neurológico. En la evolución de su enfermedad en las imágenes de resonancia magnética, se puso de manifiesto trombosis de los senos sagital superior y transversos, una rara manifestación de la deficiencia de CblC.

Hyperhomocysteinemia and folate levels in normal healthy Nigerians living in Zaria: Subanalysis of ABU homocysteine cross-sectional survey

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 18­65 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

Prevalence of hyperhomocysteinemia and hypovitaminosis B12 among acute ischemic stroke patients

Background: Deficiency of Vitamin B12 can lead to hyperhomocysteinemia. Hyperhomocysteinemia constitutes an abnormally high level of homocysteine in the serum, above the upper limit of normal for an environment. The two conditions are significant risk factors for the development of stroke. There is a paucity of data on the prevalence of these biochemical risk factors in stroke patients in our environment which brought about this study. Objective: The objective of the study was to determine how prevalent hyperhomocysteinemia and hypovitaminosis B12 are in acute ischemic stroke patients in Zaria. Materials and Mthods: This is a cross­sectional prospective study conducted from February 2014 to March 2015 in ABUTH Zaria. One hundred patients with clinical diagnosis of first­ever ischemic stroke confirmed by brain computed tomography scan, and another apparently healthy age­ and sex­matched one hundred controls were recruited. Their fasting serum homocysteine and Vitamin B12 were determined using the enzyme­linked immunosorbent assay technique. Prevalence of high homocysteine and low Vitamin B12 was determined.Results: Thirty­four percent (34%) of patients had high and 66% patients had normal serum homocysteine, whereas 81% of patients had low and 19% of patients had normal serum Vitamin B12, and the difference was found to be statistically significant (P < 0.05).There was significant negative correlation between serum homocysteine and Vitamin B12 among cases with P = 0.04 and r = −0.198.Conclusion: The Prevalence rates of hyperhomocysteinemia and hypovitaminosis B12 among ischemic stroke pateints were 34% and 81%, respectively

Folate/Vitamin B Alleviates Hyperhomocysteinemia-Induced Alzheimer-Like Pathologies in Rat Retina / 神经科学通报·英文版

Hyperhomocysteinemia (Hhcy) is an independent risk factor for Alzheimer's disease (AD). Visual dysfunction is commonly found and is positively correlated with the severity of cognitive defects in AD patients. Our previous study demonstrated that Hhcy induces memory deficits with AD-like tau and amyloid-β (Aβ) pathologies in the hippocampus, and supplementation with folate and vitamin B12 (FB) prevents the Hhcy-induced AD-like pathologies in the hippocampus. Here, we investigated whether Hhcy also induces AD-like pathologies in the retina and the effects of FB. An Hhcy rat model was produced by vena caudalis injection of homocysteine for 14 days, and the effects of FB were assessed by simultaneous supplementation with FB in drinking water. We found that Hhcy induced vessel damage with Aβ and tau pathologies in the retina, while simultaneous supplementation with FB remarkably attenuated the Hhcy-induced tau hyperphosphorylation at multiple AD-related sites and Aβ accumulation in the retina. The mechanisms involved downregulation of amyloid precursor protein (APP), presenilin-1, beta-site APP-cleaving enzyme 1, and protein phosphatase-2A. Our data suggest that the retina may serve as a window for evaluating the effects of FB on hyperhomocysteinemia-induced Alzheimer-like pathologies.

Increased Carotid Intima-Media Thickness (IMT) in Hyperuricemic Individuals May Be Explained by Hyperhomocysteinemia Associated with Renal Dysfunction: a Cross-Sectional Study

BACKGROUND: Both hyperuricemia and hyperhomocysteinemia are known as main risk factors of cardiovascular diseases. There has been, however, no report on the relationship between carotid intima-media thickness (IMT) and homocysteine (Hcy) in hyperuricemic patients. This study aimed to investigate how hyperuricemia is associated with increased carotid IMT with a focus on hyperhomocysteinemia. METHODS: This cross-sectional study included 1,222 patients who visited the Chung-Ang University Hospital Health Promotion Center from January 2013 to December 2015. The serum Hcy levels were estimated with a competitive immunoassay using the direct chemiluminescence method. The carotid IMT was measured by B-mode carotid ultrasonography. The definition of hyperuricemia was a serum uric acid level > 7.0 mg/dL for men or > 5.6 mg/dL for women, and hyperhomocysteinemia was defined as serum levels > 15 μmol/L. RESULTS: The hyperuricemic patients showed significantly higher serum Hcy levels and lower estimated glomerular filtration rate (eGFR) than did normouricemic patients (13.39 ± 4.42 vs. 11.69 ± 3.65 μmol/L, P < 0.001; 85.16 ± 19.18 vs. 96.14 ± 16.63, P < 0.001, respectively). Serum Hcy level (odds ratio [OR], 1.050; 95% confidence interval [CI], 1.009–1.092) and fasting glucose level (OR, 1.018; 95% CI, 1.011–1.026) were independent risk factors for carotid plaque. In patients with hyperuricemia, the serum Hcy levels correlated with the eGFR (γ = −0.478, P < 0.001). The carotid IMT correlated with serum Hcy levels and eGFR (γ = 0.196, P = 0.008; γ = − 0.297, P < 0.001, respectively) but not with the serum lipid profile. CONCLUSION: These results suggest that renal function impairment in hyperuricemic patients may worsen carotid IMT by increasing serum Hcy levels.

Association between shift work and hyperhomocysteinemia in male workers

BACKGROUND: Shift work is associated with a higher risk of cardiovascular diseases. Here, we sought to assess the relationship between shift work and plasma homocysteine levels. Determining the correlations between shift work and homocysteine levels may provide a better understanding of the mechanisms underlying cardiovascular diseases. METHODS: This study was performed using data from routine health examinations of steel workers in 2017. In total, 431 male workers (70 daytime workers and 361 shift workers) employed on a rolling departure schedule were recruited. Plasma homocysteine levels > 15 μmol/L were considered elevated. The χ2, analysis of variance, and multiple logistic regression analyses were used to examine the association between shift work and plasma homocysteine levels. RESULTS: In comparison to daytime workers, the odds ratio (OR) of hyperhomocysteinemia in individuals with < 10 years of shift work was 1.14 (95% confidence interval [CI]: 0.64–2.03), compared to 2.01 (95% CI: 1.14–3.54) for workers with ≥ 10 years of experience. After adjusting for confounding variables, the adjusted OR for shift workers with < 10 years of experience was 0.95 (95% CI: 0.50–1.80), compared to 2.00 (95% CI: 1.07–3.74) for workers with ≥ 10 years of experience. CONCLUSIONS: The risk of hyperhomocysteinemia was significantly higher in shift workers compared to those working normal daytime hours, particularly among long-term shift workers.

Korean Alcohol Guidelines for Moderate Drinking Based on Facial Flushing / 가정의학회지

This study investigated advantages and potential risks associated with drinking alcohol in Koreans based on the alcohol flush reaction. Our investigation reviewed published studies and examined moderate-drinking levels for Koreans based on modified National Institute on Alcohol Abuse and Alcoholism guidelines. Fourteen articles out of a total 198 publications were searched using PubMed, EMBASE, KoreaMed, and RISS (Research Information Sharing Service) databases and selected for review. Individuals without alcohol flush reaction (non-flushers) exhibited lower risks associated with insulin resistance, metabolic syndrome, and hyperhomocysteinemia and their 10-year cardiovascular disease risk when alcohol consumption was ≤8 drinks/wk. Conversely, risks associated with insulin resistance, metabolic syndrome, high blood pressure, prediabetes or type-2 diabetes, and high intraocular pressure and increases in carbohydrate-deficient transferrin, gamma glutamyl transferase, and blood glucose levels were present when >8 drinks were consumed. For individuals with flushing reaction (flushers), advantages were reported in relation to risks of hyperhomocysteinemia when alcohol consumption was ≤4 drinks/wk, whereas consumption of >4 drinks/wk increased the risk of insulin resistance, metabolic syndrome, high blood pressure, pre-diabetes or type-2 diabetes, high-risk colorectal adenoma, and high intraocular pressure and increased carbohydrate-deficient transferrin, gamma glutamyl transferase, and blood glucose levels. The moderate drinking level for Koreans is ≤8 drinks/wk for men aged ≤65 years and ≤4 drinks/wk for men aged over 65. For women, these limits should be half of those for men. Furthermore, individuals with flushing reaction should maintain an alcohol consumption level half of that for non-flushers.