Níveis Séricos do BDNF na Proteção Cardiovascular e em Resposta ao Exercício / Serum Levels of BDNF in Cardiovascular Protection and in Response to Exercise

Resumo As doenças cardiovasculares (DCV) são atualmente a maior causa de morte no Brasil e no mundo. Em 2016 as DCV foram responsáveis por mais de 17 milhões de mortes, representando 31% de todas as mortes em nível global. Mecanismos moleculares e genéticos podem estar envolvidos na proteção cardiovascular e devem ser considerados nas novas abordagens terapêuticas. Nesse sentido, recentes estudos têm relatado que o Fator Neurotrófico Derivado do Encéfalo (Brain-Derived Neurotrophic Factor, BDNF) está reduzido em indivíduos predispostos a desenvolverem DCV, e que o treinamento físico aeróbio aumenta as quantidades de BDNF circulante. O BDNF é uma neurotrofina encontrada em altas concentrações no hipocampo e córtex cerebral, sendo considerada molécula-chave na manutenção da plasticidade sináptica e na sobrevivência das células neuronais. Além da plasticidade neuronal, BDNF também é importante na função vascular, promovendo angiogênese por meio da regulação por espécies reativas de oxigênio (ROS). Entretanto, uma variante do gene do BDNF em humanos, o polimorfismo Val66Met (substituição do aminoácido valina por uma metionina na posição 66 do códon), que ocorre em 20-30% da população caucasiana, pode afetar as concentrações de BDNF no plasma e sua atividade em todos os tecidos periféricos contendo receptores tirosina quinase B (TrkB), como o endotélio. De fato, recentemente observamos que o polimorfismo Val66Met prejudica a reatividade vascular e o BDNF circulante em resposta ao treinamento físico. Dessa forma, apresentaremos a seguir uma discussão sobre os níveis séricos de BDNF na proteção cardiovascular, a variante genética Val66Met na reatividade vascular e o efeito do exercício físico.

Abstract Cardiovascular disease (CVD) is currently the leading cause of death in Brazil and worldwide. In 2016, CVD accounted for more than 17 million deaths, representing 31% of all deaths globally. Molecular and genetic mechanisms may be involved in vascular protection and should be considered in new therapeutic approaches. In this sense, recent studies have reported that brain-derived neurotrophic factor (BDNF) is reduced in individuals predisposed to develop CVD, and that aerobic physical training increases the amounts of circulating BDNF. BDNF is a neurotrophin found at high concentrations in the hippocampus and cerebral cortex and is considered a key molecule for the maintenance of synaptic plasticity and survival of neuronal cells. In addition to neuronal plasticity, BDNF is also important in vascular function, promoting angiogenesis through the regulation of reactive oxygen species (ROS). However, a variant of the BDNF gene in humans, the Val66Met polymorphism (substitution of the amino acid valine for a methionine at position 66 of the codon), occurring in 20-30% of the Caucasian population, may affect plasma BDNF concentrations and its activity in all peripheral tissues containing tyrosine kinase B receptors (TrkB), such as the endothelium. Thus, we will present a discussion about the role of serum BDNF levels in cardiovascular protection, Val66Met genetic variant in vascular reactivity and the effect of physical exercise.

Branched-Chain amino acids intake is negatively related to body adiposity in individuals at cardiometabolic risk / Consumo de aminoácidos de cadeia ramificada está negativamente relacionado com adiposidade corporal em indivíduos com risco cardiometabólico

ABSTRACT Objective To assess the relationship between branched-chain amino acids intake in the current diet and the metabolic and body adiposity markers in a population at cardiovascular risk. Methods This is a cross-sectional study with 282 adults and elderly people from the Cardiovascular Health Care Program of the Universidade Federal de Viçosa. Sociodemographic, anthropometric and body composition data, as well as metabolic biomarkers were collected using standardized protocols. Dietary intake of branched amino acids was assessed using a 24-hour recall. Results Individuals with a higher branched-chain amino acids intake (≥2.6g/day, median value) had lower body fat (29.6 vs 32.2%; p=0.019), and higher serum ferritin (113.2 vs. 60.1mg/dL; p=0.006) and uric acid concentrations (4.4 vs. 4.0; p=0.023). In addition, a lower prevalence of overweight and excessive abdominal fat (p<0.05) was found in the individuals with higher branched-chain amino acids intake. They also had a higher daily intake of fiber, copper, zinc, magnesium, and iron, as well as a lower intake of total lipids. Conclusion In the present study, the intake of branched amino acids is negatively related to total and central adiposity, but more studies are needed to fully elucidate this possible relationship. (Brazilian Registry of Clinical Trials, code RBR-5n4y2g).

RESUMO Objetivo Avaliar a relação entre o consumo de aminoácidos de cadeia ramificada na dieta atual e os marcadores de adiposidade metabólica e corporal em uma população com perfil de elevado risco cardiovascular. Métodos Trata-se de um estudo transversal com 282 adultos e idosos do Programa de Atenção Cardiovascular da Universidade Federal de Viçosa. Dados sociodemográficos, antropométricos e de composição corporal, além de biomarcadores metabólicos, foram coletados utilizando protocolos padronizados. O consumo alimentar de aminoácidos ramificados foi avaliado através de um recordatório de 24 horas. Resultados Indivíduos com maior consumo de aminoácidos de cadeia ramificada (≥2,6g/dia, valor da mediana) apresentaram menores valores de gordura corporal (29,6 vs 32,2%; p=0,019) e maiores valores de séricos de ferritina (113,2 vs. 60,1mg/dL; p=0,006) e ácido úrico (4,4 vs. 4,0; p=0,023). Além disso, foi encontrada uma menor prevalência de sobrepeso e excesso de gordura abdominal (p<0,05) nos indivíduos com maior consumo de aminoácidos de cadeia ramificada. Eles também apresentaram um maior consumo diário de fibra, cobre, zinco, magnésio e ferro, além de um menor consumo de lipídios totais. Conclusão No presente estudo, o consumo de aminoácidos ramificados está negativamente relacionado à adiposidade total e central, porém mais estudos são necessários para elucidar completamente essa possível relação. (Registro Brasileiro de Ensaios Clínicos, código RBR-5n4y2g)

The brain-derived neurotrophic factor (BDNF) gene Val66Met polymorphism affects memory performance in older adults

Objective: Memory impairment is an important contributor to the reduction in quality of life experienced by older adults, and genetic risk factors seem to contribute to variance in age-related cognitive decline. Brain-derived neurotrophic factor (BDNF) is an important nerve growth factor linked with development and neural plasticity. The Val66Met polymorphism in the BDNF gene has been associated with impaired episodic memory in adults, but whether this functional variant plays a role in cognitive aging remains unclear. The purpose of this study was to investigate the effects of the BDNF Val66Met polymorphism on memory performance in a sample of elderly adults. Methods: Eighty-seven subjects aged > 55 years were recruited using a community-based convenience sampling strategy in Porto Alegre, Brazil. The logical memory subset of the Wechsler Memory Scale-Revised was used to assess immediate verbal recall (IVR), delayed verbal recall (DVR), and memory retention rate. Results: BDNF Met allele carriers had lower DVR scores (p = 0.004) and a decline in memory retention (p = 0.017) when compared to Val/Val homozygotes. However, we found no significant differences in IVR between the two groups (p = 0.088). Conclusion: These results support the hypothesis of the BDNF Val66Met polymorphism as a risk factor associated with cognitive impairment, corroborating previous findings in young and older adults.

Exigência de valina e isoleucina para codornas de corte no período de um a 14 dias e de 15 a 35 dias de idade / Valine and isoleucine requirement for meat quails in the period of 1 to 14 days and of 15 to 35 days old

Foram conduzidos dois experimentos, com o objetivo de estimar a exigência de valina e isoleucina digestível para codornas de corte em crescimento. No experimento 1, foram utilizadas 2.160 codornas de corte de um dia de idade, não sexadas, distribuídas em um delineamento inteiramente ao acaso, com arranjo fatorial 4x4, sendo quatro níveis de valina digestível (0,90, 1,10, 1,30 e 1,50%) e quatro níveis de isoleucina digestível (0,80, 1,00, 1,20 e 1,40%), totalizando 16 tratamentos, com três repetições e 45 codornas por unidade experimental. O peso corporal, o ganho de peso e a biomassa corporal acumulada aumentaram linearmente em função dos níveis de valina digestível e foram influenciados de forma quadrática, estimando 1,38% de isoleucina digestível. No experimento 2, foram utilizadas 1.440 codornas de corte não sexadas, distribuídas em um delineamento inteiramente ao acaso, com arranjo fatorial 4x4, sendo quatro níveis de valina digestível (0,82, 1,02, 1,22 e 1,42%) e quatro níveis de isoleucina digestível (0,73, 0,93, 1,13 e 1,33%), totalizando 16 tratamentos, com três repetições e 30 codornas por unidade experimental. O desempenho de codornas de corte, no período de 15 a 35 dias de idade, não foi influenciado pelo aumento dos níveis de valina e isoleucina digestível nas rações experimentais. Conclui-se que as exigências de valina e isoleucina digestível para o máximo desempenho de codornas de corte, no período de um a 14 dias de idade, foram de 1,50% e 1,38%, respectivamente, correspondendo às relações valina:lisina de 95% e isoleucina:lisina de 88%. Os menores níveis avaliados, no período de 15 a 35 dias de idade, de 0,82% de valina digestível e de 0,73% de isoleucina digestível, correspondendo às relações valina:lisina de 52% e isoleucina: lisina de 46%, foram suficientes para satisfazer as exigências nutricionais das codornas de corte sem comprometer o desempenho.(AU)

Two experiments were carried out in order to estimate the requirements of digestible valine and isoleucine for growing meat quails. In experiment 1, 2160 meat quails with 1 day of age, not sexed, were used, distributed in a completely randomized design with a 4x4 factorial arrangement, with four levels of digestible valine (0.90, 1.10, 1.30, and 1.50%) and four levels of digestible isoleucine (0.80, 1.00, 1.20, and 1.40 %), totaling 16 treatments with three replications and 45 quails per experimental unit. The body weight, the weight gain, and the accumulated body biomass linearly increased in function of digestible valine levels and were influenced in a quadratic way estimating 1.38% of digestible isoleucine. In experiment 2, 1440 meat quails, not sexed, were used, distributed in a completely randomized design with a 4x4 factorial arrangement, with four levels of digestible valine (0.82, 1.02, 1.22, and 1.42%) and four levels of digestible isoleucine (0.73, 0.93, 1.13, and 1.33%), totaling 16 treatments with three replications and 30 quails per experimental unit. The performance of meat quails from 15 to 35 days of age was not affected by increased levels of digestible valine and digestible isoleucine in the experimental diets. It was concluded that the requirements of digestible valine and digestible isoleucine for maximum performance of meat quail from one to 14 days of age were 1.50% and 1.38%, respectively, corresponding to relations: valine: lysine of 95% and isoleucine: lysine of 88%. The lower levels evaluated, in the period of 15 to 35 days old, 0.82% digestible valine and 0.73% of digestible isoleucine, corresponding to relations valine: lysine of 52% and isoleucine: lysine of 46% were sufficient to meet the nutritional requirements of meat quails without compromising performance.(AU)

Desempenho e rendimento de carcaça em frangos de corte de um a 46 dias alimentados com dietas contendo diferentes níveis de valina e reduzido teor proteico / Performance and carcass yield of broilers from 1 to 46 days fed diets containing different levels of valine and reduced protein content

Este estudo teve como objetivo avaliar as relações de valina:lisina digestíveis em dietas com teor reduzido de proteína bruta (PB) e os efeitos dessa redução sobre desempenho e rendimento de carcaça em frangos de corte. Foram utilizados 1200 pintos machos seguindo modelo inteiramente ao acaso, com seis tratamentos de seis repetições (exceto controle, com 10 repetições), compostos por 30 aves cada. O tratamento controle (T1) foi formulado conforme os níveis de proteína bruta e aminoácidos (AAs) recomendados por Rostagno et al . (2011), e os demais tratamentos (T2 a T6) tiveram seus níveis de PB reduzidos (4% em relação ao controle) e variaram em função da relação valina:lisina digestíveis, com cinco níveis equidistantes em intervalos de 0,07:1, variando de 0,63:1 e 0,91:1 (dietas até 21 dias) e de 0,64:1 e 0,92:1 (dietas após 21 dias). As seguintes características de desempenho foram avaliadas: ganho de peso, consumo de ração, conversão alimentar, viabilidade criatória e índice de eficiência produtiva. Aos 46 dias de idade, seis animais por repetição foram abatidos para determinação de rendimento de carcaça e de cortes comerciais. As diferentes relações valina:lisina digestíveis não influenciaram o desempenho dos animais (P>0,05) para nenhuma característica avaliada. A redução proteica piorou a conversão alimentar dos animais (P≤0,05) até os 21 dias. Os resultados sugerem que os níveis de valina utilizados não afetam o desempenho dos animais, apenas o rendimento de peito e que, portanto, a redução proteica não é recomendada durante as três primeiras semanas de criação.

This study aimed to evaluate valine:lysine ratios in diets with reduced content of crude protein and the effects of this reduction on the performance of broiler chickens. 1200 male chicks were used following a complete randomized design with six replicates of six treatments (except control, with 10 replicates), each one with 30 chicks. The control treatment (T1) was formulated following levels of crude protein (CP) and the amino acids (AAs) recommended by Rostagno et al. (2011), and the other treatments (T2 to T6) had reduced levels of CP (4 % compared to control) and varied in proportion valine:lysine, with 5 levels at equidistant intervals 0.07:1 ranging from 0.63:1 to 0.91:1 (up to 21 days) and from 0.64:1 to 0.92:1 (after 21 days). The performance characteristics measured were: weight gain, feed intake, feed conversion, viability and productive efficiency index. At 46 days six animals per replicate were slaughtered for evaluation of carcass and commercial cuts. The different valine:lysine ratios did not affect animal performance (P>0.05). Reducing protein impaired feed conversion (P≤.05) up to 21 days. The results suggest that levels of valine used did not affect the broilers' performance, however, breast meat yield and reduced protein are not recommended during the first three weeks.

Herpes zoster-associated acute urinary retention in immunocompetent patient

Herpes zoster-associated urinary retention is an uncommon event related to virus infection of the S2-S4 dermatome. The possible major reasons are ipsilateral hemicystitis, neuritis-induced or myelitis-associated virus infection. We report a case of a 65-year-old immunocompetent female patient who presented an acute urinary retention after four days under treatment with valacyclovir for gluteal herpes zoster. The patient had to use a vesical catheter, was treated with antibiotics and corticosteroids and fully recovered after eight weeks.

Efectos del polimorfismo Val108/158Met del gen dopaminérgico Catecol-O-metiltransferasa COMT en las funciones ejecutivas de preescolares / Effects of dopamine gene polymorphism Val108/158Met Catechol-O-methyltransferase COMT in executive functions in preschool

El nivel de Dopamina en la Corteza Prefrontal se ha relacionado al desempeño de las Funciones Ejecutivas (FE). El objetivo de este estudio es explorar el efecto del polimorfismo funcional del gen COMT (Val/Val,Val/Met y Met/Met) en las FE de preescolares. Se utilizó la Batería Neuropsicológica de Funciones Ejecutivas para niños, y se extrajo el ADN genómico según metodología estándar (N=248) de 3 a 6 años de edad (M=4.6). Se estudiaron las frecuencias genotípicas del gen COMT y se realizó un análisis de varianza (ANOVA one-way) estableciendo diferencias significativas con una p<0.05. Los niños con el polimorfismo de baja actividad Met/Met puntúan significativamente mejor en relación a los niños con polimorfismo Val/Val en pruebas que requieren de Inhibición y los niños con el polimorfismo de alta actividad Val/Val resultan con un mejor rendimiento en pruebas relacionadas a MT, Planeación y Abstracción que los niños con polimorfismo Met/Met y Val/Met. Estos resultados parecen reflejar el papel de la enzima COMT como regulador de DA y que tanto el hipermetabolismo como el hipometabolismo tiene implicaciones importantes en las FE.

The level of DA in the prefrontal cortex has been related to the performance on executive functions (EF). The objective of this study was to explore the effect of the COMT polymorphism (Val/Val, Val/Met, Met/Met) in the performance of EF in a population of preschool children. All subjects were evaluated with a Neuropsychological Battery and genomic DNA was extracted according to standard methodology (N=248) from 3 to 6 years of age (M=4.6). We studied genotypic frequencies of the COMT gene and an analysis of variance (one-way ANOVA) with post hoc analysis, establishing significant differences at p<0.05. In Children with a low activity polymorphism Met/Met scored significantly better in relation to the children with polymorphism Val/Val in tests requiring inhibition and children with high activity polymorphism Val/Val had better performance on tests related to working memory, planning and abstraction that children with polymorphism Met/Met and Val/Met. These results seem to reflect the role of COMT enzyme as a regulator of DA and that both hypermetabolism and hypometabolism has important implications for the EF.

Influencia de la radiación gamma como método de esterilización sobre el polímero poli VPAVG (Valina-Prolina-Alanina-Valina- Glicina) / Influence of gamma radiation as a sterilization method on polymer poli VPAVG (Valine- Proline- Alanine-Valine-Glicine)

El polímero poli (VPAVG) pertenece a la familia de materiales bioelásticos derivados de la elastina y ha demostrado poseer cualidades óptimas para la formación de sistemas de cesión controlada, así como una biocompatibilidad aceptable en determinados tejidos. Las formulaciones preparadas a partir del biomaterial deben ser estériles, si se pretende administrar por una vía que implique ruptura de barreras biológicas. Por lo anterior, resulta esencial conocer el comportamiento del polímero y sus formulaciones frente al proceso de esterilización empleado. El objetivo de este trabajo fue, por tanto, evaluar la influencia de la radiación gamma como método de esterilización sobre las ca - racterísticas físicas del poli (VPAVG) y de las partículas for - madas con éste. En cuanto al polímero, no se apreciaron diferencias en su apariencia física antes y después de la esterilización. Sin embargo, las partículas obtenidas a partir del poli (VPAVG) y posteriormente esterilizadas experimentaban cambios en su morfología. En cuanto al tamaño de las partículas, se determinó que las obtenidas con polímero esterilizado presentaban cierta tendencia a formar agregados de menor tamaño que los encontrados con el polímero sin esterilizar. Se concluyó que el biomaterial ensayado y las formulaciones eran susceptibles a las radiaciones gamma como método de esterilización final, proponiéndose recurrir a otro tratamiento que garantice su esterilidad final.

The poli polymer (VPAVG) belongs to the family of bioelastic materials derived from elastin, and it has showed the best qualities for the creation of systems of controlled cession, as well as an acceptable biocompatibility in certain tissues. If any preparation made from this biomaterial has to be administered in any way that implies the rupture of biological barriers, the preparation must be sterile. By this means, it is essential to know the behaviour of this polymer and its formulations, facing the sterilization process being used. The objective of this research was learn the influence of gamma radiation as a sterilization method over the physical characteristics of poli (VPAVG) and the particles formed by it. As the polymer, we did not observe any differences in physical appearance before and after sterilization. Particles formed by the polymer (VPAVG) and sterilized after, experimented changes in their morphology. As the size of the particles, we observed that those obtained with the sterilized polymer showed a tendency to form smaller aggregates than those found with the non-sterilized polymer. We concluded that the essayed biomaterial and its formulations were susceptible to gamma radiations as final sterilization method, proposing to use another treatment to guarantee the final sterile condition.

Varicela: consultas frecuentes acerca de su tratamiento y el manejo de los contactos / Varicella: frequent questions on treatment and recommendations for management of contacts

Dealing with varicella often causes doubts to general practitioners and pediatricians. In this article the author summaries guidelines based on solid evidence to treat varicella and prevent the disease in susceptible contacts in different clinical scenarios and presents his personal point of view in those controversial aspects commonly resolved by the authorized opinión of experts.

El manejo de la varicela despierta, con alta frecuencia, dudas en los médicos generales y pediatras. En este artículo, el autor resume aquellas recomendaciones basadas en sólida evidencia, para tratar la varicela y prevenir la enfermedad en los contactos susceptibles de un caso índice, en diferentes situaciones clínicas. Además emite su personal punto de vista en aquellos aspectos que despiertan controversia y comúnmente son resueltos en base a la opinión de reconocidos expertos.

Infección congénita por citomegalovirus: nuevos aspectos terapéuticos / Congenital cytomegalovirus infection: new therapeutic aspects

La infección por citomegalovirus es la infección congénita más frecuente, presentando morbimortalidad perinatal y secuela neurológica tanto en primoinfección como en reactivación durante el embarazo. Se presenta el caso de una embarazada con lupus eritematoso sistémico, en tratamiento inmunosupresor, que presentó reactivación de infección por citomegalovirus. Se discuten los mecanismos de transmisión y de diagnóstico prenatal, así como nuevas alternativas terapéuticas in útero.

Cytomegalovirus infection is the most common congenital infection, causing perinatal morbidity and neurological sequel in both primary infection and reactivation during pregnancy. A case of a pregnant woman with lupus, in immunosuppressive therapy that suffered reactivation of the cytomegalovirus infection is presented. We discuss the mechanisms of transmission and prenatal diagnosis, as well as new therapeutic alternatives wail in uterus.

Enfermedad de orina a jarabe de arce / Maple syrup urine disease

Las enfermedades metabólicas pueden presentarse con síntomas, signos y laboratorios inespecíficos, que si no se consideran entre los diagnósticos diferenciales pueden retrasar el diagnóstico de estos pacientes, lo que lleva a un alto grado de secuelas neurológicas o muerte en etapas tempranas. La enfermedad de Orina a Jarabe de Arce es una enfermedad metabólica de baja incidencia caracterizada por la acumulación de niveles tóxicos de valina, isoleucina y principalmente leucina. Se presenta un paciente sin antecedentes que a los 11 días de vida comienza con mala actitud alimentaria, letargia y fontanela tensa. Descartadas las causas infectológicas se realizó un screening para enfermedades metabólicas. Se diagnosticó Leucinosis (Enfermedad de orina con olor a Jarabe de Arce) y se inició el tratamiento con restricción de leucina, valina e isoleucina en la dieta. A los pocos días del tratamiento el paciente mostró evidencias de mejoría clínica y en los parámetros de laboratorio.

Clinical signs, symptoms and lab tests of neonatal metabolic diseases may be unspecific and a high grade of suspicion is necessary to include them among the differential diagnosis avoiding a significant delay in recognizing this condition and consequent risk of neurologic handicap or early dead. Maple syrup urine disease is a congenital metabolic disorder with a low rate of prevalence and characterized by a toxic accumulation of the amino acids valine, isoleucine and mainly leucine. In this report we describe the history of a patient apparently healthy that on the 11th day after birth initiates symptoms like poor feeding, lethargy and tense fontanel. Excluded sepsis a work up for metabolic disease was performed, being diagnosed a leucinosis (Maple syrup urine disease). A dietary treatment with leucine, valine and isoleucine restriction was immediately initiated and a few days after the patient showed significant clinical and lab improvement. A short description and discussion of this disease is presented.

Efecto de la n-acetilcisteína, valsartan y lisinopril en la prevención de la disfunción renal precoz secundaria a neumoperitoneo: modelo en ratas / Effect of n-acetylcysteine, valsartan and lisinopril in preventing renal insufficiency secondary to pneumoperitoneum in a rat model

Introducción: El trasplante renal es el tratamiento de elección para los pacientes en insuficiencia renal terminal. A pesar que la nefrectomía clásica del donante vivo ha resultado ser un procedimiento seguro y bien tolerado, existen factores que desincentivan este acto de donación. La nefrectomía laparoscópica del donante vivo ha dado una respuesta a este último punto. Sin embargo, varios investigadores han comunicado mayor disfunción renal precoz en riñones procurados laparoscópicamente en comparación con los procurados en forma clásica abierta. Existe información que la Nacetilcisteina y Valsartán tendrían un efecto protector frente al neumoperitoneo. Con respecto al Lisinopril (inhibidor ECA) existen datos disímiles. El objetivo de este trabajo es evaluar la utilidad dela N-acetilcisteína, Valsartán y Lisinopril en la prevención de la disfunción renal precoz de riñones sometidos a neumoperitoneo en un modelo en ratas. Material y métodos: Se utilizaron 40 ratas Sprague Dawley, macho, de 250 a 300 g, separadas en 4 grupos: Grupo 1: 10 ratas sometidas a hidratación subcutánea con solución salina (control), Grupo 2: 10 ratas sometidas a hidratación subcutánea con solución salina más N-acetilcisteina, Grupo 3: 10ratas sometidas a hidratación subcutánea con solución salina más Valsartán, y Grupo 4: 10 ratas sometidas a hidratación subcutánea con solución salina más Lisinopril. Las ratas fueron anestesiadas y colocadas en neumoperitoneo a 12 mmHg por 90 minutos. Luego las ratas se colocaron en jaula metabólica donde se midió diuresis, presión arterial, función renal, microalbuminuria y enzimas tubulares. Las ratas fueron sacrificadas al séptimo día realizándose estudio histológico. En el análisis estadístico se utilizaron modelos lineales generalizados, análisis de la varianza (Anova) y test exacto de Fisher y Chi-cuadrado...

Introduction: Renal transplant it the treatment of choice for patients with terminal renal insufficiency. Classic open live donor nephrectomy is a safe and well tolerated procedure, however there some factors that may inhibit patients from donating. Laparoscopic live donor nephrectomy has gained wide acceptance, nevertheless several authors have reported early renal insufficiency in these patients compared to those harvested through the classic approach. Apparently n-acetylcysteine and valsartan would have a protective effect against pneumoperitoneum, however there is contradicting data for Lisinopril. We evaluate n-acetylcysteine, valsartan and lisinopril for prevention of early renal insufficiencyin kidneys undergoing pneumoperitoneum in a rat model. Material and methods: A total of 40 male rats (Sprague Dawley) of 250 and 300 grams were divided in4 groups. Group 1 (control): 10 rats with subcutaneous hydration with saline. Group 2: 10 rats with subcutaneous hydration with saline and n-acetylcysteine. Group 3: 10 rats with subcutaneous hydration with saline and Valsartan and Group 4: 10 rats with subcutaneous hydration with saline and Valsartan. All rats underwent general anesthesia with pneumoperitoneum at 12 mmHg for 90 minutes. Rats were placed in a metabolic cage where urine output, blood pressure, renal function, microalbuminuria and tubular enzymes were measured. At postoperative day seven, all animals were put to sleep and histological analysis was performed. Statistics was done using lineal generalized models, Anova, Fisher and Chi-square models were also used. Results: Pneumoperitoneum did not produce early renal insufficiency. Rats with lisinopril presented a decrease in creatinine clearance (0,92 ml/min) p=0,056; higher microalbuminuria (27073,9 mg/dl/creatininuria) p < 0,001 and more histological lesions p=0,017. Urine output, blood pressure, tubular...

Dual renin-angiotensin system blockade plus oral methylprednisone for the treatment of proteinuria in IgA nephropathy / Doble bloqueo del sistema renina-angiotensina más metilprednisona oral para el tratamiento de la proteinuria en la nefropatía por IgA

Renin-angiotensin system inhibition is a widely accepted approach to initially deal with proteinuria in IgA nephropathy, while the role of immunosuppressants remains controversial in many instances. A prospective, uncontrolled, open-label trial was undertaken in patients with biopsy-proven IgA nephropathy with proteinuria more than 0.5 g/day and normal renal function to assess the efficacy of a combination treatment of angiotensin converting enzyme inhibitors plus angiotensin receptor blockers enalapril valsartan coupled with methylprednisone to decrease proteinuria to levels below 0.5 g/day. Twenty patients were included: Age 37.45 more or less 13.26 years (50% male); 7 patients (35%) were hypertensive; proteinuria 2.2 more or less 1.86 g/day; serum creatinine 1.07 more or less 0.29 mg/dl; mean follow-up 60.10 more or less 31.47 months. IgA nephropathy was subclassified according to Haas criteria. Twelve patients (60%) were class II; seven (35%) were class III and one (5%) class V. All patients received dual reninangiotensin system blockade as tolerated. Oral methylprednisone was started at 0.5 mg/kg/day for the initial 8 weeks and subsequently tapered bi-weekly until the maintenance dose of 4 mg was reached. Oral steroids were discontinued after 24 weeks (6 months) of therapy but renin-angiotensin inhibition remained unchanged. At 10 weeks of therapy proteinuria decreased to 0.15 more or less 0.07 g/day (P less than 0.001) while serum creatinine did not vary: 1.07 ± 0.28 mg/dl (P=ns). After a mean follow-up of 42.36 more or less 21.56 months urinary protein excretion (0.12 more or less 0.06 g/day) and renal function (serum creatinine 1.06 more or less 0.27 mg/dl) remained stable. No major side effects were reported during the study. Renin-angiotensin blockade plus oral steroids proved useful to significantly decrease proteinuria to less than 0.5 g/day in patients with IgA nephropathy without changes in renal function.

El doble bloqueo del sistema renina-angiotensina con inhibidores de la enzima convertidora de angiotensina junto a bloqueadores del receptor tipo I de angiotensina II es aceptado como tratamiento en la proteinuria de la nefropatía por IgA, ya que el rol de los inmunosupresores continúa siendo controvertido. Estudio prospectivo, no controlado, abierto para pacientes con nefropatía por IgA con proteinurias major que 0.5 g/día y creatininas séricas menor que 1.4 mg/dl, para evaluar la eficacia de tratamiento de enalapril más valsartán asociado a metilprednisona vía oral para disminuir las proteinurias a menor que 0.5 g/día. Fueron incluidos 20 pacientes: Edad: 37.45 más o menos 13.3 años (50% hombres); 7 pacientes (35%) eran hipertensos; proteinuria inicial 2.2 más o menos 1.86 g/día; creatinina inicial 1.07 más o menos 0.29 mg/dl; seguimiento promedio: 60.10 más o menos 31.47 meses (5 más o menos 2.62 años). La nefropatía por IgA fue subclasificada según Haas: 12 pacientes (60%) clase II; 7 (35%) clase III y 1 (5%) clase V. Todos recibieron enalapril más valsartán según tolerancia más metilprednisona vía oral en dosis de 0.5 mg/kg/día durante las primeras 8 semanas y subsecuentemente se redujo cada dos semanas hasta llegar a 4 mg. Se discontinuaron los esteroides luego de 24 semanas (6 meses). La inhibición del sistema renina angiotensina prosiguió indefinidamente. A las 10 semanas la proteinuria disminuyó de 2.2 más o menos 1.86 g/día a 0.15 más o menos 0.7 g/día (p menor que 0.001); la creatinina no varió significativamente (1.07 más o menos 0.29 mg/dl vs. 1.07 más o menos 0.28 mg/dl) (P=ns). Luego de 10 semanas y con un seguimiento de 42.36 más o menos 21.56 meses la proteinuria (0.12 más o menos 0.006 g/día) y la función renal (creatinina 1.06 más o menos 0.27mg/dl) permanecieron estables. No se informaron efectos adversos durante el estudio. El doble bloqueo del sistema renina angiotensina más bajas dosis de metilprednisona resultó útil para reducir...

Errores en la oportunidad y dosificación de aciclovir o valaciclovir en el tratamiento del herpes zoster / Erroneous prescriptions of aciclovir and valaciclovir in herpes zoster treatment

Medical prescription errors are frequent in community settings and information exploring its magnitude during antiviral treatment of herpes zoster is scarce. A questionnaire was applied to 31 physicians working in hospital- or community-based settings in Santiago, Chile in order to characterize their dosing and timing preferences for aciclovir or valaciclovir prescriptions. Aciclovir was more often prescribed than valaciclovir (71.9 and 28.1 percent, respectively), but less than a third of prescription (27.3 percent) fulfilled the minimal aciclovir dosing and timing criteria for clinical efficacy (4 gr per day and < 72 hours since rash initiaton). The limited size of the simple prevented exploring factors linked to a misleading prescription. Appropriate knowledge on dosing and timing of aciclovir/valaciclovir therapy for herpes zoster was infrequent in a sample of physicians working in various clinical settings in Chile.

Los errores en la prescripción de medicamentos son frecuentes en escenarios ambulatorios y no hay información disponible sobre el uso de antivirales en el tratamiento del herpes zoster. Para conocer la dosis y oportunidad en la prescripción de aciclovir o valaciclovir se aplicó un cuestionario a 31 médicos que trabajan en hospitales o sitios de atención primaria en Santiago y que declararon haber atendido este tipo de pacientes. El compuesto aciclovir fue más indicado que valaciclovir (71,9 vs 28,1 por ciento) pero menos de un tercio de las prescripciones (27,3 por ciento) cumplieron simultáneamente con una dosis mínima (4 g/día) y ventanas de tiempo apropiadas de aciclovir (hasta 72 horas del rash). El reducido tamaño de la muestra impidió efectuar un análisis de los factores ligados a este fenómeno. El conocimiento apropiado sobre dosis y oportunidad de aciclovir o valaciclovir fue infrecuente en un grupo de médicos que declararon atender pacientes con herpes zoster en Santiago.

Antagonistas de los receptores AT1 de la angiotensina II como drogas antiinflamatorias y citoprotectores gástricos / Angiotensin II AT1 receptor antagonists as anti-inflammatory and gastric citoprotections drugs

Objetivo: estudiar en grupos aleatorios de ratas Wistar el efecto antiinflamatorio y citoprotector gástrico de los antagonistas de los receptores AT 1 de la angiotensina II como candesartan, losartan y valsartan. Material y métodos: los animales fueron asignados en forma aleatoria a recibir: 1) etanol al 96% intragástrico 2) indometacina oral, 3) una comida sólida (pellets) durante dos horas e indometacina subcutánea (producción de úlceras del antro gástrico), 4) el edema plantar por carragenina. Resultados: los tres antagonistas de los receptores AT 1 de la angiotensina II dieron citoprotección gástrica ante el etanol 96º, con protección casi total de la mucosa gastrointestinal ante la indometacina oral, impidieron la producción de úlceras del antro gástrico inducidas por indometacina subcutánea, dando marcada respuesta antiinflamatoria ante el infiltrado de neutrófilos en la mucosa gastrointestinal (MPO), y tuvieron efecto antiinflamatorio en el modelo del edema plantar por carragenina. Conclusiones: los antagonistas de los receptores AT 1 de la angiotensinaII tienen un efecto citoprotector gástrico y antiinflamatorio.

Background: The antiinflammatory and gastric cytoprotector effect of angiotensin II AT1 receptor antagonist, such as candesartan, losartan and valsartan was studied. Material and methods: Wistar rats were ramdomly assigned to receive: 1) 96º ethanol; 2) oral indometacin, 3) solid food (pellets) during two hours and subcutaneous indometacin (production of ulcers in the gastric antrum), 4) Carrageen footpad edema. Results: The three AT1 receptor angiotensin antagonists yielded gastric cytoprotection against 96° ethanol, almost total gastrointestinal protection against oral indometacin, prevented gastric ulcers formation in the antrum induced by subcutaneous indometacin, remarkable antiinflammatory response against neutrophil infiltration on the gastrointestinal mucosa, and anti-inflammatory effect in carrageen footpad edema. Conclusions: The AT1 receptor antagonists of angiotensin II are gastric cytiprotectors with a remarkable antiinflammatory effect.

Actualización en el tratamiento agudo y crónico de la enfermedad orina olor a jarabe de arce de presentación neonatal / Update acute treatment and follow up of neonatal maple syrup urine disease

La enfermedad de la orina olor a jarabe de arce se produce por un defecto del complejo enzimático deshidrogenasa de los a-cetoácidos, acumulándose valina, isoleucina y leucina (VIL) y de sus metabolitos asociados a neurotoxicidad. Su herencia es autosómica recesiva y la incidencia varía de 1:290.000 a 1:200 recién nacidos. La forma más frecuente es la forma neonatal o clásica, que se manifiesta desde el 5º día de vida con rechazo de la alimentación, somnolencia y coma. Si no se diagnostica y trata a tiempo, los pacientes fallecen. El tratamiento durante la descompensación consiste en terapia intensiva nutricional para evitar catabolismo y disminuir la concentración plasmática de leucina bajo 200 µM/L. En el período crónico se entrega una dieta restringida en VIL, se suplementa con leche especial sin VIL, y aminoácidos libres (L-valina, L-isoleucina) y tiamina. Diversos estudios han demostrado que existe una estrecha correlación entre la edad de diagnóstico, control metabólico a largo plazo y el coeficiente intelectual.

Maple Syrup Urine Disease (MSUD) is caused by a deficiency of the enzyme complex of a-cetoacids dehydrogenases with the consequent accumulation of valine, isoleucine and leucine (VIL) and their metabolites associated with neurotoxicity. It is an autosomal recessive inherited disease and the incidence varies between 1:290.000 and 1:200 newborns. The most frequent presentation is during the neonatal period beginning at the 5th day of life with food refusal, somnolence and coma. If not diagnosed and treated, the patient dies. The treatment when the patient decompensate consists in intensive nutritional therapy to prevent catabolism and reduce leucine levels below 200 µM/L. During the chronic period a VIL- restricted diet is prescribed, supplementing with formula free of VIL, L-valine, L-isoleucine and thiamine. Different studies have demonstrated a strict correlation between age at diagnosis, long-term metabolic control and intellectual quotient.

Hb Köln [alfa2ß298(FG5) val-met] identified by DNA analysis in a Brazilian family

Hb Köln resulta da substituiçäo do aminoácido valina por metionina na posiçäo 98 da cadeia da hemoglobina. Embora seja a mais freqüente das hemoglobinas instáveis, possui poucas características que permitem distinguí-las sem a realizaçäo de análise estrutural da molécula. Com o objetivo de desenvolver um procedimento alernativo a análise proteíca, este trabalho descreve a identificaçäo da Hb Köln através de análise de DNA. Uma paciente branca, sexo feminino, 4 anos de idade, com icterícia desde o nascimento, foi analisada, apresentando uma banda anômala entre A2 e S em eletroforese em acetato de celulose, e migraçäo eletroforética semelhante a Hb C em gel de agar. Os testes de instabilidade térmica e de precipitaçäo pelo isopropanol foram positivos e foram observados corpúsculos de Heinz no sangue periférico. Os três exons do gene da globina foram seqüenciados e uma transiçäo de G A foi identificada na primeira posiçäo do codon 98. Essa alteraçäo näo cria ou abole nenhum sítio conhecido de enzima de restriçäo. Desta forma, a confirmaçäo da mutaçäo foi levada a efeito através de hibridizaçäo com oligonucleotídeos alelo-específicos, o que permitiu o estabelecimento de um método simples e rápido de identificaçäo de novos casos quando os dados clínicos e o padräo hematológico e eletroforético sugerem Hb Köln.

Enfermedad de la orina olor a jarabe de arce / Maple syrup urine disease

La enfermedad de la orina olor a jarabe de arce, es una afección metabólica producida por deficiencia en la descarboxilación oxidativa de los quetoácidos provenientes de los aminoácidos ramificados valina, isoleucina y leucina. Los pacientes parecen normales hasta los 5 a 7 días de vida, cuando muestran rechazo a la alimentación, vómitos, olor a jarabe de arce en la orina y la piel y deterioro neurológico progresivo, que lleva rápidamente al coma. Se presentan tres niños con enfermedad de la orina olor a jarabe de arce clásica, leucina >2 000 µmol/1, que fueron diagnosticados a los 10, 20 y 21 días de vida, iniciándose inmediatamente el tratamiento en base a la dieta especial. el seguimiento está basado en evaluaciones clínicas, nutricionales y bioquímicas periódicas, para adecuar los requerimientos nutricionales a la evolución de la enfermedad. La evaluación psicométrica, escala de Bayley, mostró que el coeficiente de desarrollo mental estaba entre 50 y 82, relacionándose éste con la edad de diagnóstico. Actualmente los niños tienen entre 2 y 3 años de edad, se encuentran con dieta restringida en los 3 aminoácidos ramificados. Su control debe ser frecuente para evitar desbalances metabólicos y prevenir daños neurológicos ocasionados por éstos