Exercise attenuates the perioperative neurocognitive disorder induced by hyperhomocysteinemia in mice.

The perioperative neurocognitive disorder (PND) is a severe complication that affects millions of surgical patients each year. Homocysteine (Hcy) is known to increase the risk of developing PND in both young and elderly mice. However, whether Hcy alone can induce cognitive deficits in middle-aged mice (12-month-old), whether exercise can attenuate Hcy-induced hippocampus-related cognitive deficits after surgery through suppressing neuroinflammation, synaptic elimination, and the level of Hcy remains unknown. The present study aimed to answer these questions through testing the possibility of establishing a PND model using 12-month-old mice which received homocysteine injections before exploratory laparotomy and the therapeutic mechanism of exercise. In the present study, it was found that levels of serum homocysteine were age-dependently increased in mice with a significant difference between that of 18-month-old mice and 6-week, 6-month, and 12-month-old mice. PND occurred in 18-month but not in 12-month-old mice after exploratory laparotomy under isoflurane anesthesia. Intraperitoneal injection of Hcy for 3 consecutive days before surgery rendered 12-month-old mice to develop PND after abdominal laparotomy under isoflurane anesthesia at a minimal dosage of 20 mg/kg. Neuroinflammation and synaptic elimination was present in 12-month-old preoperative Hcy-injected mice. Preoperative voluntary wheel exercise could prevent PND in 12-month-old mice that have received Hcy injection before surgery, which might be related to the decreased level of serum Hcy. Activation of glial cells, proinflammatory phenotype markers and synaptic elimination were attenuated in the hippocampus of 12-month-old preoperative Hcy-injected mice by this exercise. These results provide direct evidence that hyperhomocysteinemia can induce postoperative cognitive deficits in middle-aged mice. Pre-surgery exercise can effectively prevent Hcy-precipitated postoperative cognitive dysfunction.

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.

The specific impact of uremic toxins upon cognitive domains: a review / O impacto específico de toxinas urêmicas em domínios cognitivos: uma revisão

ABSTRACT One of the mechanisms proposed for chronic kidney disease (CKD)-related cognitive impairment is the accumulation of uremic toxins due to the deterioration of the renal clearance function. Cognition can be categorized into five major domains according to its information processing functions: memory, attention, language, visual-spatial, and executive. We performed a review using the terms 'uric acid', 'indoxyl sulfate', 'p-cresyl sulfate', 'homocysteine', 'interleukins' and 'parathyroid hormone'. These are the compounds that were found to be strongly associated with cognitive impairment in CKD in the literature. The 26 selected articles point towards an association between higher levels of uric acid, homocysteine, and interleukin 6 with lower cognitive performance in executive, attentional, and memory domains. We also reviewed the hemodialysis effects on cognition. Hemodialysis seems to contribute to an amelioration of CKD-related encephalopathic dysfunction, although this improvement occurs more in some cognitive domains than in others.

RESUMO Um dos mecanismos propostos para explicar o comprometimento cognitivo relacionado à doença renal crônica (DRC) é o acúmulo de toxinas urêmicas devido à deterioração da função de depuração renal. A cognição pode ser categorizada em cinco domínios principais de acordo com suas funções de processamento de informações: memória, atenção, linguagem, visual-espacial e executiva. Realizamos uma revisão usando os termos "ácido úrico", "indoxil sulfato", "p-cresil sulfato", "homocisteína", "interleucinas" e "paratormônio". Estes são os compostos que se mostraram fortemente associados ao comprometimento cognitivo na DRC na literatura. Os 26 artigos selecionados apontam para uma associação entre níveis mais elevados de ácido úrico, homocisteína e interleucina-6 com menor desempenho cognitivo nos domínios executivo, atenção e de memória. Também revisamos os efeitos da hemodiálise na cognição. A hemodiálise parece contribuir para uma melhoria da disfunção encefalopática relacionada à DRC, embora essa melhora ocorra mais em alguns domínios cognitivos do que em outros.

Metabolismo da homocisteína em doenças neurológicas / Homocysteine metabolism in neurologic disorders

OBJETIVO: Realizar uma revisão sobre o metabolismo do aminoácido sulfurado homocisteína, analisando como elevações de seus níveis séricos se correlacionam com a fisiopatologia das mais diversas doenças neurológicas, assim como sobre o tratamento da hiper-homocisteinemia. MÉTODO: Revisão não sistemática de artigos que abordassem o papel da homocisteína associado a doenças neurológicas.Foi priorizada a utilização de artigos que apresentassem no título as palavras-chave "homocisteína" ou "hiper-homocisteinemia",associadas a palavras-chave contendo as enfermidades neurológicas de maior prevalência como acidente vascular cerebral, doença de Alzheimer, doença de Parkinson e outras. Foram utilizadas as bases de dados do PubMed, Lilacs e Google Scholar. RESULTADOS: Foram utilizados 35 artigos em inglês e 2 artigos em português para a confecção desta revisão. CONCLUSÃO: A homocisteína se encontra elevada em associação com as mais diversas doenças neurológicas. Contudo, em muitas delas não está estabelecido se esse aumento é um achado secundário ou se representa um papel da homocisteína na patogênese dessas enfermidades. Mais estudos são necessários para estabelecer o papel da homocisteína em situações neurológicas.O tratamento da hiper-homocisteinemia é fácil, sendo feito com reposição de vitamina B12 e, principalmente, de folatos.

OBJECTIVE: Review the metabolism of sulfur amino acid homocysteineand how elevation of its serum levels is correlated with the pathophysiologyof several neurological diseases, as well as the treatment of hyperhomocysteinemia. METHOD: A non-systematic review of articles discussing the role of homocysteine associated with neurological diseases was performed. The use of articles that presented in the title the keywords "homocysteine" or "hyperhomocysteinemia" associated with keywords containing the most prevalent neurological disorders such as stroke, Alzheimer's disease, Parkinson's disease and others were preferred. The search was underdone through PubMed, Google Scholar and Lilacs databases. RESULTS: There were selected 35 articles in English and 2 articles in Portuguese in this this review. CONCLUSION: High levels of homocysteine are associated with various neurological disorders. However, in many of these are not established whether this increase is a consequence of these disorders or if homocysteine plays a role in the pathogenesis of these diseases. More studies are needed to establish the participation ofhomocysteine in neurological disorders. The treatment of hyperhomocysteinemia is easy, being done with replacement of vitamin B12and especially folate.

Betaína e Colina dietéticas relacionadas à homocisteína plasmática: estudo de base populacional, São Paulo, Brasil / Betaine and Choline Intakes are related to total plasma homocysteine: health survey of São Paulo, Brazil

Fundamentos: Elevadas concentrações de homocisteína plasmática (Hcyp) têm sido associadas ao risco aumentado de doenças cardiovasculares. A Hcyp pode ser diminuída por meio da remetilação à metionina, que usa folato ou betaína como doador do grupo metil.Objetivos: Avaliar a ingestão de betaína e colina e sua relação com a homocisteína em residentes do município de São Paulo. Métodos: Obtidos dados de 584 indivíduos, de ambos os sexos, a partir do estudo de base populacional ISA-SP 2008. Médias geométricas de Hcyp foram analisadas de acordo com tercis de ingestão de colina e betaína e foi aplicado teste de tendência.Resultados: Foram analisados 584 indivíduos: 222 (38,0%) homens e 362 (62,0%) mulheres, com média de idade 55,0±19,0 anos. A prevalência de hiper-homocisteinemia foi maior entre os homens (28,0%), idosos (21,0%) e indivíduos com menor renda familiar (21,0%). Cerca de 31,0% dos indivíduos com hiper-homocisteinemia apresentou deficiência de folato (<7,5 nmol/L) e 26,0%, deficiência de vitamina B12 (<200 pmol/L). Observou-se diminuição nas médias geométricas de homocisteína conforme aumento nos tercis de betaína em ambos os sexos,adultos, eutróficos e em todas as categorias de escolaridade. A colina esteve relacionada à Hcyp em ambos os sexos, indivíduos de maior renda familiar, não fumantes e consumidores de bebidas alcoólicas. Conclusões: Este estudo sugere a importância da ingestão de betaína por sua associação inversa com a concentração de Hcyp em adultos e idosos do município de São Paulo. A colina desempenhou papel protetor em subgrupos específicos da população.

Background: High concentrations of plasma homocysteine (Hcyp) have been associated with increased risk of cardiovascular diseases. Hcyp can be decreased by remethylation to methionine, which uses folate or betaine as a donor of the methyl group. Objectives: To evaluate the intake of betaine and choline and its relation to homocysteine in residents of the city of São Paulo. Methods: Data from 584 individual, of both sexes, from the population-based study ISA-SP 2008. Geometric averages of Hcyp were analyzed according to choline and betaine intake tertiles and trend test was applied. Results: The study analyzed 584 individuals: 222 (38.0%) men and 362 (62.0%) women, mean age 55.0 ± 19.0 years. The prevalence of hyperhomocysteinemia was higher among men (28.0%), the elderly (21.0%) and those with lower household income (21.0%). Approximately 31.0% of individual with hyperhomocysteinemia presented folate deficiency (<7.5 nmol/L) and 26.0% presented vitamin B12 deficiency (<200 pmol/L). There was a decrease in the geometric means of homocysteine according to an increase in betaine tertiles in both sexes, adults, normal and in all categories of education. Choline was related to Hcyp in both sexes, higherhousehold income individuals, non-smokers and alcohol consumers. Conclusions: This study suggests the importance of betaine intake due to its inverse relationship with the concentration of Hcyp in adults and elderly in the city of São Paulo. Choline played a protective role in specific subgroups of the population.

Estudio prospectivo de cinco años de los niveles de homocisteinemia y riesgo cardiovascular en pacientes de una unidad de hemodiálisis / A prospective study of five years about homocysteinemia levels and cardiovascular risk in patients in a hemodialysis unit

La enfermedad cardiovascular es compleja y multifactorial. Uno de los marcadores conocido como factor de riesgo vascular independiente es la homocisteína; el aumento en 5 µmol/l por encima del rango normal equivale, en riesgo vascular, a un aumento de 20 mg/ dl por encima del colesterol normal. En la población general niveles ligeramente elevados de homocisteína (>15µmol/l), se asocian al incremento de la mortalidad y de los eventos cardiovasculares. Este factor también está presente en pacientes renales, siendo sus niveles 3-4 veces superiores a la población en general. Los mecanismos por los que la homocisteína está elevada en la insuficiencia renal no están claros, ya que su excreción renal sólo representa el 1% de su eliminación; si embargo, si está comprobado que la utilización de membranas de diálisis de alto flujo, diálisis lenta nocturna, o hemodiafiltración on-line diarias reducen significativamente los niveles de este aminoácido. Tal vez estos tratamientos, al conseguir una mayor reducción de los niveles de homocisteína, puedan reducir la morbimortalidad cardiovascular renal y, por ello, es aconsejable medir los niveles de homocisteína anualmente en los pacientes renales. Nos planteamos conocer el riesgo vascular de nuestros pacientes renales a lo largo de cinco años, según valores de homocisteína y determinar su relación con modalidad y tiempo en tratamiento, edad, sexo y grupo étnico. Realizamos un estudio observacional prospectivo en pacientes de una unidad renal durante cinco años. Recogimos datos sobre: edad, sexo, grupo étnico, modalidad de tratamiento (hemodiafiltración versus hemodiálisis), tiempo en tratamiento y valores de homocisteína. Estudiamos 115 pacientes, de edad media 59 años, 68 hombres y 47 mujeres; 107 pacientes caucásicos mediterráneo, 4 caucásicos norteafricano y 4 negroide. El 54,8% llevaba menos de 4 años en tratamiento renal. Un 63% estaba en hemodiálisis, 27% en hemodiafiltración alterna y 10% en diaria. El valor medio de homocisteína en varones fue de 23.47 µmol/l y en mujeres 24.29 µmol/l. Los valores de homocisteína en el tercer y cuarto año de estudio según el grupo cultural fueron en pacientes negroides 51,50 y 69,35 µmol/l respectivamente, con significación estadística. En la población general el riesgo cardiovascular se asocia a la edad y el sexo sin embargo, los niveles de homocisteína versus estas variables en nuestra población renal a estudio no se ven modificados. Otras diferencias vienen marcadas por el grupo étnico: menores en raza negra y asiáticos que en personas de raza blanca, mientras que los latinoamericanos tenían concentraciones intermedias. Estas afirmaciones no coinciden con los resultados de nuestro estudio, ya que el grupo caucásico mediterráneo (la mayoría de nuestros pacientes) que presenta valores intermedios con riesgo moderado y el grupo de etnia negroide valores más elevados incluso de riesgo elevado. Concluimos que nuestros pacientes presentaban un nivel moderado de riesgo vascular. Al enfrentar homocisteína con sexo, edad, modalidad y tiempo de tratamiento sustitutivo no encontramos relación estadística significativa. Sin embargo, el grupo étnico si presentaba variaciones significativas siendo el grupo negroide el de mayor riesgo vascular con niveles más elevados en los tres últimos años del estudio (AU)

Cardiovascular disease is complex and multifactorial. One of the markers known as independent vascular risk factor is homocysteine. In relation to vascular risk, the increase of 5 mmol/l above the normal range, corresponds to an increase of 20 mg/dl above normal cholesterol. In the general population, slightly elevated homocysteine levels (> 15µmol/l), are associated with increased mortality and cardiovascular events. Also, this factor is present in renal patients, at 3-times higher levels than the general population. Mechanisms by which homocysteine is elevated in renal failure are unclear, since renal excretion represents only 1% of its elimination. However, it has been shown that the use daily of membranes of high flux dialysis, slow nocturnal home dialysis, or on-line hemodiafiltration, significantly reduce these amino acid levels. These treatments could achieve a greater reduction in homocysteine levels and reduce the cardiovascular renal morbid-mortality, therefore, it is advisable to measure homocysteine levels in renal patients annually. The aim was to study the vascular risk in our renal patients in a study of five years, according to the homocysteine levels and determine their relationship with modality and time of treatment, age, sex and ethnicity. A prospective observational study of five year was carried out in our dialysis unit. Data about age, sex, ethnicity, type of treatment (hemodiafiltration versus hemodialysis), duration of treatment and homocysteine levels were collected. 115 patients (68 men and 47 women) with a mean age of 59 years were studied. 107 patients were Mediterranean Caucasians, 4 North African Caucasian and 4 African blacks. 54.8% had less than four years in renal treatment. 63% were on hemodialysis, 27% patients were in alternating hemodiafiltration, and 10% in daily hemodialysis. The mean level of homocysteine in males was 23.47 mmol/l, and in women of 24.29 mmol/l. According to the cultural group, homocysteine levels in the third and fourth year of study, were significant in African black patients, with levels of 51.50 and 69.35 mol/l respectively. In the general population, cardiovascular risk is associated with age and sex. However, homocysteine levels versus these variables in our renal study population are not modified. Other differences are marked by ethnic group: lower in blacks and Asians than in Caucasians, while Latin American had intermediate concentrations. This information do not coincide with our findings, because the Caucasian Mediterranean group (most of our patients) had intermediate values at moderate risk and the African black group had higher values, even of the high risk. We conclude that our patients had a moderate level of vascular risk. When relating homocysteine with sex, age, mode and time of replacement therapy no statistical significant relationship was found. However, ethnicity if present significant variations being the African black the group with higher vascular risk with higher levels in the last three years of the study (AU)

Hiperhomocisteinemia/homocisteinuria como factor de riesgo cardiovascular en niños y adolescentes / Hyperhomocysteinemia/homocystinuria as cardiovascular risk factor children and adolescents

Actualmente, las enfermedades cardiovasculares son la primera causa de muerte a nivel mundial. Aunque, este tipo depatologías afectan en mayor proporción a adultos mayores, su proceso inicia desde la infancia. Hoy por hoy la hiperhomocisteinemia/homocisteinuria se ha considerado un factor de riesgo cardiovascular independiente y tan importante o másque otros clásicos. Existen cada vez más evidencias que resulta necesario identificar a tiempo esta alteración y procedera su tratamiento preventivo. Algunas de las causas para padecer esta patología en edad temprana son; la insuficienteingestión de ácido fólico, vitamina B6 o vitamina B12, las cuales son un conjunto de vitaminas importantes que funcionancomo cofactores de la 5-10-metilentetrahidrofolato reductasa (MTHFR), cistationina β sintetasa (CBS) y metionina adenosiltransferasa(MAT); tres enzimas principales del metabolismo de la homocisteína. Sin embargo, aún no se conoce en sutotalidad las consecuencias del incremento de homocisteína en niños y jóvenes.

Currently, cardiovascular disease is the leading cause of death worldwide. Although, this type of disease affects a greaterproportion to older adults, the process starts since childhood. Today, hyperhomocysteinemia has been considered anindependent cardiovascular risk factor, as important or more than other classic factors. There is increasing evidence thattime is necessary to identify the disorder and provide treatment for prevention. Some of the reasons for developingthis disease at an early age: the insufficient intake of folic acid, vitamin B6 and vitamin B12, which are a set of importantvitamins that act as cofactors 5-10-methylenetetrahydrofolate reductase (MTHFR), cystathionine β synthase (CBS) andmethionine adenosyltransferase (MAT), three major enzymes of homocysteine metabolism. However, still not fully knownconsequences of homocysteine increase in children and youth.

Homocisteína y deterioro cognitivo en la enfermedad de Parkinson / Homocysteine and cognitive impairment in Parkinson’s disease

Introducción. La relación entre homocisteína (Hc) y enfermedades vasculares se conoce desde hace más de 30 años. En los últimos años se ha relacionado también con deterioro cognitivo y motor. En la enfermedad de Parkinson (EP), el tratamiento crónico con levodopa puede inducir un incremento en los niveles de Hc, implicando un riesgo añadido para el deterioro cognitivo. Objetivos. Confirmar la elevación de los niveles de Hc en pacientes con EP tratados con levodopa, su relación con los niveles de vitamina B12 y folato, y si podía existir una relación entre dichas variables y la función cognitiva. Pacientes y métodos. Se incluyeron 58 pacientes diagnosticados de EP (45 en tratamiento con levodopa), se determinaron los niveles basales de Hc, vitamina B12 y folato, y se realizó una evaluación neuropsicológica en 45 de los pacientes. Resultados. El nivel de Hc estaba significativamente más elevado en los pacientes en tratamiento con levodopa, sin relación con la dosis ni el tiempo en tratamiento. Existía una correlación negativa entre los valores de Hc y vitamina B12 y folato en los hombres, que no se observó en las mujeres. Tomar entacapona no redujo los niveles de Hc. El nivel de Hc estaba significativamente más elevado en los pacientes con deterioro cognitivo (9 de los 45 evaluados).Conclusiones. Nuestro estudio confirma la elevación de los niveles de Hc en pacientes con EP en tratamiento con levodopa, y de forma más evidente en los pacientes con deterioro cognitivo (AU)

Introduction. The relationship between homocysteine (Hc) and vascular diseases has been known for more than 30 years. Lately, Hc has also been related to cognitive and motor impairment. In Parkinson’s disease (PD), chronic treatment with levodopa could induce higher levels of Hc, and thus may increase risk of cognitive impairment. Aims. To confirm that PD patients treated with levodopa have higher levels of Hc and to establish a relationship between Hc, folic acid and vitamin B12 levels. Also, we studied a possible link between those variables and cognitive function. Patients and methods. 58 patients with diagnosis of PD were included (45 under treatment with levodopa). Basal levels of Hc, vitamin B12 and folic acid were determined. Forty five patients underwent neuropsychological evaluation. Results. Hc levels were significantly higher in patients taking levodopa and were not related to levodopa dosage or treatment duration. There was a negative correlation between Hc levels and those of vitamin B12 and folic acid in men but we found no such correlation in women. Entacapone was not found to reduce Hc levels. Hc levels were significantly higher in patients with cognitive impairment (9 out of 45 patients). Conclusions. Our study confirms presence of high levels of Hc in PD patients under treatment with levodopa, more evidentin patients with cognitive impairment (AU)

Level of homocysteine in patients with peripheral arterial disease treated at a public health care facility

Contexto: Estudos recentes indicam que a concentração elevada de homocisteína é um fator de risco importante e prevalente para doença vascular aterosclerótica coronariana, cerebral e periférica. Objetivo: Tendo em vista a escassez de informações relacionadas à hiper-homocisteinemia em doença arterial periférica (DAP) no Brasil e as peculiaridades de nossa população, o objetivo deste estudo foi avaliar a frequência de hiper-homocisteinemia em amostra dessa população em um ensaio clínico com indivíduos portadores e não portadores de DAP atendidos em um serviço público brasileiro. Métodos: Foi realizado um estudo ensaio clínico caso-controle com 40 indivíduos portadores de DAP confirmada por Doppler ultrassom (grupo DAP) em comparação com 20 indivíduos voluntários sem DAP (grupo-controle). Resultados: A DAP predominante foi a isquemia crônica de membros (75 por cento). As concentrações plasmáticas medianas de homocisteína de jejum foram significantemente maiores no grupo DAP do que no grupo-controle (16,7 versus 12,9 µmol/L, p = 0,001), tanto nos homens (18,9 versus 14,0 µmol/L, p = 0,005) quanto nas mulheres (13,9 versus 11,2 µmol/L, p = 0,025). Quanto à proporção de indivíduos com hiper-homocisteinemia, observou-se tendência a uma maior frequência no grupo DAP (60 por cento) em relação ao grupo-controle (30 por cento) (p = 0,054). Nos indivíduos com idade inferior a 60 anos foram encontrados valores medianos de homocisteína significantemente mais elevados no grupo DAP (p = 0,041). Conclusões: A hiper-homocisteinemia é um fator de risco importante e foi encontrada em 60 por cento dos indivíduos portadores de DAP atendidos em um serviço público no Brasil.

Background: Recent studies have suggested that high level of homocysteine is an important and prevalent risk factor for coronary, cerebral and peripheral arterial disease. Objective: In light of the lack of information on hyperhomocysteinemia in peripheral arterial disease (PAD) in Brazil and the peculiarities of its population, the objective of the present study was to evaluate the frequency of hyperhomocysteinemia in a sample of the Brazilian population by means of a clinical trial involving individuals with and without PAD being treated at a public health care facility. Methods: A case-controlled clinical trial was conducted with 40 individuals with a PAD diagnosis confirmed by Doppler ultrasound (PAD group) compared with 20 volunteer individuals without PAD (control group). Results: The predominant PAD was chronic limb ischemia (75 percent). Median fasting plasma levels of homocysteine were significantly higher in the PAD group than in the control group (16.7 vs. 12.9 ìmol/L, p = 0.001), both in men (18.9 vs. 14.0 ìmol/L, p = 0.005) and women (13.9 vs. 11.2 ìmol/L, p = 0.025). As to the proportion of individuals with hyperhomocysteinemia, a tendency toward a higher frequency was observed in the PAD group (60 percent) in relation to the control group (30 percent) (p = 0.054). Individuals aged less than 60 years had significantly high median values of homocysteine in the PAD group (p = 0.041). Conclusions: Hyperhomocysteinemia was a prevalent and important risk factor in individuals with PAD treated at a public health care facility in Brazil.

Homocisteína en la clínica humana / Present role of homocysteine in clinical medicine

En las últimas décadas ha existido un especial interés por conocer el significado clínico de los valores elevados de la homocisteína plasmática total (HPT) y, en especial, su posible relación con el riesgo cardiovascular. La determinación de los valores de HPT está claramente indicada cuando existe la sospecha clínica de homocistinuria en adolescentes o adultos (presencia de miopía atípica por su gravedad, rápida evolución o ausencia de fondo de ojo miópico, y/o tromboembolia venosa y/o arteriopatía precoz o atípica) y en el estudio de las deficiencias de vitamina B12 y/o ácido fólico. Por el contrario, dada la evidencia actual, no pueden recomendarse de forma generalizada la determinación de la HPT ni el tratamiento con ácido fólico y/o vitamina B12 en pacientes con enfermedad cardiovascular. Es muy importante recordar que está por demostrar la inocuidad de la administración del ácido fólico durante períodos prolongados y en dosis farmacológicas (AU)

There has been a great interest in the last decades about the clinical significance of elevated total plasma homocysteine (tHcy), and especially its possible association with an increased cardiovascular risk. Measurement of tHcy is clearly indicated when homocystinuria is suspected in young or adult patients (in the presence of a severe, atypical or progressive miopia with ectopia lentis and/or venous thromboembolism and/or severe, premature or atypical atherosclerotic vascular disease) and in the evaluation of vitamin B12 and/or folic acid deficiencies. The current evidence does not support either the screening measurement of tHcy or the treatment with vitamin B12 and/or folic acid supplementation in patients with cardiovascular disease. It is important to remember that it remains to be proved whether the long-term administration of folic acid at pharmacological doses is safe (AU)

Homocisteina: nuevo factor de riesgo cardiovascular / Homocysteine: new factor cardiovascular risk

La gran cantidad de evidencia acumulada sobre el papel de la homocisteína como factor de riesgo cardiovascular es cada día más fuerte. Una concentración de homocisteína plasmática elevada induce cambios patológicos en la pared arterial asociándose a un incremento en el riesgo de desarrollar aterosclerosis, la cual se manifiesta comúnmente como accidentes cerebrovasculares, cardiovasculares y vasculares periféricos. Diferentes estudios realizados han sido dirigidos a determinar si la disminución de los niveles de homocisteína plasmáticos pueden ser de utilidad para prevenir eventos oclusivos. En la actualidad la realización de exámenes de laboratorio para cuantificar los niveles de homocisteína pueden ser considerados en pacientes con ateroesclerosis prematuras con una historia familiar de arteroesclerosis, donde la hiperhomocisteinemia es un factor de riesgo común en estos pacientes. El tratamiento de la hiperhomocisteinemia es simple y con riesgo terapéutico mínimo. Este desorden es usualmente corregido con suplementos vitamínicos que contienen ácido fólico.

O consumo de café e sua relação com a hiperhomocisteinemia: revisão / Coffee intake and the relation with hyperhomocisteinemia: a review

Coffee is one of the most worldwide consumed beverages, and Brazil is its major source. Coffee plants belong to the Rubiacea e family, and there are many species, although only C. arabica and C. canephora (Robusta) have commercial value. The chemical composition of green coffee depends on the species, climatic conditions, processing and storage. Recently, coffee intake has been related to increased plasma homocysteine levels ­ this non-proteica minoacid is one of the risk factors for occlusive cardiovascular diseases,one of the main causes of death in industrialized countries. This finding points out to the relevance of analysis of coffee constituents involved inincreased homocysteine plasma levels. Caffeine, chlorogenic acid and diterpenes (caffestol and caveol) are important substances present in coffee,which exert physiological effects

El café es una de las bebidas mas consumidas en el mundo, siendo Brasil el mayor produto rmundial. El café pertenece a la família Rubiáceas, y existen numerosas especies, pero solamente la C. arabica y la C. canéfora (Robusta) tienen valor comercial. La composición química del café verde depende dela especie, condiciones climáticas, de procesamiento y de almacenamiento. Recientemente, el consumo de café ha sido relacionado al aumento de los niveles de homocisteína plasmática ­ este aminoácido no proteico es uno de los factores de riesgo para las enfermedades cardiovasculares oclusivas, las cuales responden por las principales causas de muerte en países industrializados ­ esto es relevante para la investigación que busca los componentes del café, responsables por el aumento de los niveles de homocisteínaplasmática. La cafeína, el acido clorogénico, diterpenos (cafestol y cahweol) son importantes substancias presentes en el café que ejercen efectos fisiológicos en el organismo

A bebida de café é uma das bebidas mais consumidas no mundo, sendo o Brasil o seu maior produtor. As plantas de café pertencem à família Rubiaceae, e possuem inúmeras espécies, mas somente a C. arábica e C. canéfora (Robusta) têm valor comercial. A composição química do café verde depende da espécie, condições climáticas, processamento e estocagem. Recentemente, o consumo de café tem sido relacionado ao aumento dos níveis de homocisteína plasmática - esse aminoácido não protéico é um dos fatores de risco para a ocorrência de doenças cardiovasculares oclusivas, uma das principais causas de morte em países industrializados - tal fato torna relevante a investigação sobre os componentes do café, envolvidos no incremento dos níveis de homocisteína plasmática. A cafeína, o ácido clorogênico e os diterpenos (cafestol e caveol) são importantes substâncias presentes no café, exercendo efeitos fisiológicos no organismo

Hiper-homocisteinemia causando aterogênese na aorta de coelhos: modelo experimental / Hyperhomocysteinemia causing atherogenesis in rabbits´aorta: an experimental model

Objetivo: Este estudo tem por objetivo avaliar os efeitos da homocisteinemia plasmática elevada na formação da placa aterosclerótica na aorta de coelhos. Material e método: Realizou-se estudo experimental comparativo em dois grupos homogêneos de coelhos durante 60 dias. Foram utilizados 20 coelhos da linhagem New Zealand divididos em dois grupos de 10 animais: grupo controle (C) e grupo metionina (M). Todos os animais receberam a mesma dieta sólida e 500 ml de água. Os animais do grupo M receberam 2 ml de uma solução de metionina na concentração de 200 mg/ml a cada 24 horas. Foram colhidas amostras de sangue para a dosagem de colesterol, triglicerídeos, HDL, LDL e homocisteína após 0, 30 e 60 dias. Os animais foram submetidos a eutanásia por dose letal de anestésico no 60° dia. A aorta torácica e a aorta abdominal foram retiradas para estudo anatomopatológico...

La homocisteína: más allá del colesterol / Homocystein: beyond cholesterol

La homocisteína constituye un factor de riesgo emergente que puede permitir mejorar la prevención de las enfermedades cardiovasculares, debido a que en los últimos tiempos se ha visto que la capacidad de predecir el riesgo cardiovascular de los factores de riesgo tradicionales (obesidad, colesterol, hipertensión, tabaquismo) es limitada. Las concentraciones de homocisteína pueden ser elevadas debido a, entre otras causas, si las concentraciones de ácido fálico, vitaminas B6 y B12 se encuentran en los límites bajos de la normalidad (AU)

Factores de riesgo y factores pronósticos en la arteriosclerosis precoz de extremidades inferiores / Risk factors and factors in the prognosis of early arteriosclerosis of the lower limbs

Objetivo. Presentar una revisión actualizada de los factores de riesgo clásicos y emergentes asociados a enfermedad arterial precoz en el territorio vascular periférico, y describir las técnicas de imagen que permiten valorar el estadio evolutivo de la placa arteriosclerótica. Desarrollo. El manejo de un paciente con enfermedad arterial periférica ha de plantearse en el contexto de la historia natural de la enfermedad y, en particular, en el conocimiento y control de los factores de riesgo y marcadores que puedan predecir el deterioro clínico de la misma. La arteriosclerosis se inicia en épocas muy tempranas de la vida y debe considerarse como una enfermedad inflamatoria crónica. A los clásicos factores que influyen en esta patología, como la hipercolesterolemia, el tabaco, la diabetes o el más reciente síndrome de resistencia a la insulina, hay que añadir otros más modernos, como la hiperhomocisteinemia, la carga infecciosa global, los factores procoagulantes y los todavía poco conocidos marcadores genéticos. La enfermedad presenta unas características evolutivas que empiezan a descubrirse gracias a técnicas de imagen, como los ultrasonidos, la tomografía computadorizada por haz de electrones y la resonancia magnética, que permiten conocer qué placas pueden considerarse vulnerables. Conclusiones. El concepto de arteriosclerosis ha variado sustancialmente en los últimos años. El desarrollo precoz de esta entidad inflamatoria crónica se liga a una multiplicidad de factores que deben conocerse y controlarse. Las determinaciones analíticas y las técnicas de diagnóstico al alcance permitirán un mejor control de esta entidad. (AU)

Homocyst(e)ine and atherosclerosis: recent advances

Los resultados de numerosos estudios que incluyen más de 10.000 pacientes, sugieren que los niveles elevados de homocisteína en plasma (>10 µM) constituyen un factor de riesgo para la arteriosclerosis. Asimismo, diferentes análisis han demostrado la asociación de niveles elevados de homocisteína en plasma con enfermedad [vascular periférica], infarto de miocardio, enfermedad coronaria y enfermedad cerebrovascular, siendo además un factor predictivo de accidente cerebrovascular o de mortalidad. Estudios más recientes sugieren que el ácido fólico sería la piedra angular en el tratamiento de los niveles elevados de homocisteína. Aunque en 1990 se sugirió que la hiperhomocisteinemia era un factor de riesgo fácilmente reversible para aterosclerosis oclusiva, fueron necesarios numerosos ensayos clínicos para determinar si la disminución de la homocisteína afectaría la evolución de la enfermedad aterosclerótica; sin embargo los resultados de los ensayos clínicos en curso no estarán disponibles por muchos años.

Homocyst(e)ine and atherosclerosis: recent advances

Los resultados de numerosos estudios que incluyen más de 10.000 pacientes, sugieren que los niveles elevados de homocisteína en plasma (>10 AM) constituyen un factor de riesgo para la arteriosclerosis. Asimismo, diferentes análisis han demostrado la asociación de niveles elevados de homocisteína en plasma con enfermedad [vascular periférica], infarto de miocardio, enfermedad coronaria y enfermedad cerebrovascular, siendo además un factor predictivo de accidente cerebrovascular o de mortalidad. Estudios más recientes sugieren que el ácido fólico sería la piedra angular en el tratamiento de los niveles elevados de homocisteína. Aunque en 1990 se sugirió que la hiperhomocisteinemia era un factor de riesgo fácilmente reversible para aterosclerosis oclusiva, fueron necesarios numerosos ensayos clínicos para determinar si la disminución de la homocisteína afectaría la evolución de la enfermedad aterosclerótica; sin embargo los resultados de los ensayos clínicos en curso no estarán disponibles por muchos años. (AU)

Homocisteína y patología del embarazo / Homocysteine and abnormal pregnancy

La homocisteína es un aminoácido no esencial que ha resultado ser un nuevo factor de riesgo cardiovascular independiente y un posible marcador biológico de las complicaciones ocurridas durante la gestación. Su tratamiento es fácil e inocuo, la prevalencia parece ser alta y su determinación mediante nuevas técnicas automatizadas hará posible que se realice en cualquier laboratorio. Esto nos hace pensar en la homocisteína como un posible factor de cribado poblacional, especialmente en aquellos pacientes con un mayor riesgo cardiovascular y en mujeres gestantes con antecedentes de embarazo complicado. Pero, por ahora, es una prueba que sólo se realiza en la investigación clínica. (AU)