Copper sulfate and arginine supplements on performance, thyroid hormones and blood biochemistry of broilers fed with canola meal-based diets / Avaliação da suplementação com sulfato de cobre e arginina sobre o desempenho, hormônios tireoidianos e bioquímica sanguínea de frangos alimentados com dietas à base de canola

The present evaluated the effects of copper sulfate solution (CSS) and arginine powder (Arg) supplements on performance, thyroid hormones and blood biochemistry of broiler chickens fed with canola meal (CM)-based diets. The experimental design was completely randomized with a 3 × 3 factorial and 9 treatments, corresponding to 3 levels of CSS (0, 125 and 250 mg/kg) and 3 levels of Arg (0, 0.1 and 0.2%) (n = 45 per treatment). Feeds were offered ad libitum for 21 days, from 22 to 42 days of age. Feed efficiency was significantly affected by the dietary addition of 250 mg/kg CSS and 0.2% Arg, and by the CSS × Arg interaction. CM supplemented with CSS improved the thyroid gland status and increased the plasma levels of triiodothyronine and thyroxine. Birds fed diets supplemented with 0.2% Arg had lower blood glucose level than the other treatments. The addition of 250 mg/kg CSS and 0.2% Arg reduced the stress caused by the rapid growth of broilers, also increasing the overall bird welfare.

O objetivo do presente trabalho foi avaliar os efeitos da suplementação com solução de sulfato de cobre (SSC) e arginina em pó (Arg) sobre o desempenho, hormônios tireoidianos e bioquímica sanguínea de frangos de corte alimentados com dietas à base de canola DC. O desenho experimental foi completamente casualizado com fatorial 3 × 3 e nove tratamentos correspondentes a três níveis de inclusão de SSC (0, 125 e 250 mg/kg) e três níveis de Arg (0, 0,1 e 0,2%) (n = 45 para cada tratamento). As rações foram oferecidas ad libitum por 21 dias, de 22 até 42 dias de idade. A eficiência alimentar foi significativamente afetada pela adição de 250 mg/kg de SSC e 0,2% de Arg, assim como pela interação SSC × Arg. A suplementação da DC com SSC melhorou os parâmetros da glândula tireoide e aumentou os níveis plasmáticos de triiodotironina e tiroxina. As aves alimentadas com dietas suplementadas com 0,2% de Arg apresentaram menor nível de glicose sanguínea do que as dos demais tratamentos. A adição de 250 mg/kg de SSC e 0,2% de Arg reduz o estresse causado pelo rápido crescimento dos frangos, além de melhorar as condições gerais de bem estar das aves.

L-arginine-induced esophagitis, report of six cases / Reporte de seis casos de esofagitis inducida por L-arginina

Abstract Background: Drug-induced esophagitis is an uncommon diagnosis in the pediatric population. The following is a report of six adolescents with L-arginine-induced esophagitis. Case reports: All patients were under treatment with L-arginine for short stature. After using the prescribed medication for 1-3 months, all cases started with severe retrosternal pain, odynophagia, and dysphagia. The upper gastrointestinal endoscopies showed ulcers located in the mid esophageal mucosa. Conclusions: In the presence of acute severe odynophagia, dysphagia, and retrosternal pain, drug-induced esophagitis should be considered as a possible diagnosis. Treatment includes liquid diet, pain control, sucralfate, omeprazole, and interruption of L-arginine. In addition, the physician should explain preventive measures focused on patient and family education on the drug side effects and precise instructions on how to take medications, as well as a careful balance of risk and benefits of any medication. At present, there are no clinical trials that support the use of L-arginine in treatment of short stature.

Resumen Introducción: La esofagitis inducida por medicamentos es un diagnóstico poco frecuente en pacientes pediátricos. A continuación, se describe una serie de seis casos de pacientes menores de 15 años con esofagitis inducida por L-arginina. Casos clínicos: Los seis casos se encontraban en tratamiento con L-arginina por talla baja e iniciaron con dolor retroesternal, odinofagia y disfagia de rápida instalación. Cuatro de ellos acudieron al servicio de urgencias por la intensidad de los síntomas. Los hallazgos en la endoscopia del tubo digestivo alto fueron úlceras en la mucosa del esófago a la altura del tercio medio, zona de estrechez natural por la compresión del bronquio izquierdo. Conclusiones: En presencia de odinofagia, disfagia, dolor retroesternal y el antecedente de la ingesta de L-arginina, la esofagitis inducida por fármacos debe considerarse como una posibilidad diagnóstica. El tratamiento está basado en el manejo del dolor, sucralfato, omeprazol, así como la suspensión del medicamento y medidas preventivas centradas en la educación del paciente y los familiares sobre los riesgos y beneficios de un medicamento y la forma correcta de administrarlo.

Nitric oxide modulates ATP-evoked currents in mouse Leydig cells

Testosterone synthesis within Leydig cells is a calcium-dependent process. Intracellular calcium levels are regulated by different processes including ATP-activated P2X purinergic receptors, T-type Ca2+ channels modulated by the luteinizing hormone, and intracellular calcium storages recruited by a calcium-induced calcium release mechanism. On the other hand, nitric oxide (NO) is reported to have an inhibitory role in testosterone production. Based on these observations, we investigated the interaction between the purinergic and nitrergic systems in Leydig cells of adult mice. For this purpose, we recorded ATP-evoked currents in isolated Leydig cells using the whole cell patch clamp technique after treatment with L-NAME (300 μM and 1 mM), L-arginine (10, 100, 300, and 500 μM), ODQ (300 μM), and 8-Br-cGMP (100 μM). Our results show that NO produced by Leydig cells in basal conditions is insufficient to change the ATP-evoked currents and that extra NO provided by adding 300 μM L-arginine positively modulates the current through a mechanism involving the NO/cGMP signaling pathway. Thus, we report an interaction between the nitrergic and purinergic systems in Leydig cells and suggest that Ca2+ entry via the purinergic receptors can be regulated by NO.

Recomendação de arginina na terapia nutricional de pacientes queimados: aspectos atuais / Recommendation of arginine in the nutritional therapy of burned patients: current aspects / Recomendación de la arginina en la terapia nutricional de los pacientes quemados: aspectos actuales

Objetivo: Identificar se existe um padrão de recomendação de arginina para terapia nutricional de pacientes queimados, a partir de revisão integrativa da literatura. Método: Realizou-se uma revisão integrativa da literatura, com busca nos artigos on-line indexados na Biblioteca Virtual em Saúde (BVS) e no Google Acadêmico, no período entre janeiro de 2011 e julho de 2017, publicados em português, inglês e espanhol. Os resultados foram apresentados em quadros. Resultados: No total, foram encontrados 112 artigos, sendo que apenas seis foram adequados ao critério de inclusão do estudo. Em cinco, que foram lidos e analisados, a quantidade de suplementação recomendada de arginina foi a mesma, sendo de 17g/dia; e um foi acima de 12g/dia. Além disso, esses mesmos autores concordaram que a quantidade adequada de suplementação com arginina, tempo de uso, método de administração e nível de segurança ainda não estão bem estabelecidos como rotina de uso em pacientes com grandes queimaduras. Conclusões: Mesmo sendo a arginina considerada um aminoácido condicionalmente essencial e muito importante no processo de cicatrização em pacientes queimados, ainda são necessários mais estudos clínicos para especificar a dose propícia para a terapia nutricional segura e eficaz com arginina em paciente queimados.

Objective: To identify whether there is a standard of arginine recommendation for nutritional therapy of burned patients, from the integrative review of the literature. Methods: An integrative revision of the literature was conducted, searching for articles on line indexed in the Virtual Health Library (BVS) and Google scholar, in the period from January of 2011 to July 2017, published in portuguese, english and spanish. The results were presented in paintings. Results: In total, 112 articles were found, and only six were suitable for the inclusion criterion of the study. In five, of which were read and analyzed, the quantity of recommended supplementation of arginine was the same, being of 17g/day; and one was above 12g/day. Moreover, these same authors agreed that the appropriate amount of supplementation with arginine, time of use, method of administration and security level are not yet well established as routine of use in patients with large burns. Conclusions: Even though arginine is considered a conditionally essential amino acid and is very important in the healing process in burnt patients, more clinical studies are still necessary to specify the correct dose for safe and effective nutritional therapy with arginine in a burnt patient.

Objectivo: Identificar si hay un estándar de la recomendación de la arginina para la terapia alimenticia de pacientes quemados, a partir de una revisión integradora de la literatura. Método: Se realizó una revisión integradora de la literatura, buscando artículos on-line indexados en la biblioteca virtual de salud (BVS) y Google Scholar, en el período de enero de 2011 a julio de 2017, publicados en portugués, inglés y español. Los resultados fueron presentados en cuadros. Resultados: En total, se encontraron 112 artículos, y sólo seis fueron apropiados para el criterio de inclusión del estudio. En cinco de los que estudios analisados, la cantidad de suplementación recomendada de arginina era la misma, siendo de 17g/día; y uno recomendaba cantidad superior a 12g/dia. Además, estos mismos autores convinieron que la cantidad apropiada de la suplementación con arginina, tiempo de uso, método de administración y nivel de seguridad no estén pero bien establecidas como rutina para el uso en pacientes con grandes quemaduras. Conclusiones: A pesar de arginina considerada un aminoácido condicionalmente esencial y es muy importante en el proceso de la cicatrización de heridas en pacientes quemados, aún son necesarios más estudios clínicos que especifiquen la dosis segura y efectiva terapia nutricional con arginina en pacientes quemados.

Impacto do uso de dieta imunomoduladora e dieta enteral em adultos, durante a quimioterapia e radioterapia em pacientes com câncer de cabeça e pescoço: uma revisão da literatura / Diet use of immunomodulatory impact and enteral diet in adults during chemotherapy and radiotherapy in patients with head and neck cancer: a literature review

Objetivo: Analisar, a partir de evidências científicas, se o uso de imunonutrição é benéfico para pacientes com câncer de cabeça e pescoço. Método: Revisão de literatura, a partir da base de dados Academic Google, com a seguinte frase: Diet immunonutrition in head and neck cancer. A consulta à base de dados foi realizada durante o período janeiro a agosto de 2016. Os critérios de inclusão foram: últimos cinco anos, em seres humanos, artigos originais, inglês, português, espanhol; adultos e idosos entre 18 e 89 anos. Foram lidos na íntegra 17 artigos e selecionados para esta revisão 11 artigos. Dentre estes, 10 estudos tiveram consenso para o uso de imunonutrição de arginina e ácidos graxos ômega 3 em relação aos benefícios para pacientes com câncer de cabeça e pescoço, enquanto um não encontrou resultados significativos. Resultados: Observamos melhora no estado imunológico e inflamatório, a prevenção de mucosite, principalmente nos pacientes com tratamento de quimioterapia e radioterapia com uso de imunonutrição de arginina e ômega 3 no câncer de cabeça e pescoço. Conclusão: Evidencia-se a importância do acompanhamento nutricional, do início até o final do tratamento, em pacientes com câncer de cabeça e pescoço por desenvolver perda de peso importante com causas multifatoriais, aumentando o risco nutricional, morbidade e mortalidade.(AU)

Objective: To analyze, from scientific evidences, if the use of immunonutrition is beneficial for patients with head and neck cancer. Methods: A literature review from the Academic Google database, using the following phrase: Diet immunonutrition in head and neck cancer. The query the database was conducted during the period from January to August 2016. The criteria inclusion were the last five years, in humans, original articles, in English, Portuguese, Spanish and adults and the elderly of 18-89 years. They were read in full 17 articles and selected for this review, 11 articles. Among the findings, 10 of the 11 studies had consensus for the use of immunonutrition arginine and ômega 3 fatty acids in relation to the benefits for patients with head and neck cancer, while one did not find significant results. Results: We observed an improvement in the imune and inflammatory state, prevention of mucositis in patients primarily with chemotherapy and radiation therapy with the use of immunonutrition, arginine and ômega 3 in head and neck cancer. Conclusion: Therefore, highlights the importance of nutritional monitoring from the beginning to the end of treatment in patients with head and neck cancer by developing important weight loss; the causes are multifactorial increasing nutritional risk, morbidity and mortality.(AU)

Oral or topical administration of L-arginine changes the expression of TGF and iNOS and results in early wounds healing

ABSTRACT PURPOSE: To evaluate the contribution of L-arginine oral or topical rout of administration in the surgical wound healing process. METHODS: L-arginine was orally or topically administrated to mice after a laparotomy model procedure. The wounds were analyzed to evaluate the granulation tissue by HE analysis, collagen deposition, iNOS and cytokines production by immunochemisyry on wound progress. Mice used in this model were healthy, immunosupressed or diabetic and all of them were treated with different concentration of L-arginine and rout of administration. RESULTS: Suggested that groups treated with L-arginine orally or topically improved wound repair when compared with non-treatad mice. L- arginine treatment stimulated TGF-β and restricted NO production leading to a mild Th1 response and collagen deposition in injured area, when it was orally administrated. Topical administration decreased IL-8 and CCR1 expression by wound cells but did not interfere with TNF-α and IL-10 production, ratifying the decrease of inflammatory response, the oral administration however, presented a higher iNOS and TGF-β expression then. L-arginine treatment also improved the improved the wound healing in immunosupressed or diabetic mice. CONCLUSION: L-arginine administrated orally or topically can be considered an important factor in the recuperation of tissues.

L-arginina: suplemento nutricional sin beneficios demostrados en patologías del embarazo / L-arginine supplementation in patients with disorders of pregnancy

Objetivo: análisis crítico de estudios clínicos randomizados para determinar si el suplemento con L-arginina mejora el resultado perinatal en pacientes embarazadas en riesgo o que presenten patologías como parto prematuro, síndrome hipertensivo del embarazo o restricción de crecimiento fetal intrauterino. Métodos: se realizó una búsqueda bibliográfica en base de datos Pubmed, Tripdatabase y una multibúsqueda en el Sistema de Bibliotecas de la Pontificia Universidad Católica de Chile con posterior análisis crítico de los estudios seleccionados. Resultados: se seleccionaron 14 estudios clínicos randomizados; 4 de ellos corresponden a estudios de L-arginina en hipertensión gestacional, 5 estudios de L-arginina en preeclampsia, 1 estudio de L-arginina en parto prematuro, 1 estudio de L-arginina en hipertensión crónica y 4 estudios de L-arginina en restricción de crecimiento intrauterino. Solo dos de los estudios son de buena calidad metodológica, pero uno de ellos estudia un resultado intermedio y no clínicamente relevante. El resultado más promisorio muestra que el uso de L-arginina asociada a vitaminas antioxidantes reduce significativamente la incidencia de preeclampsia en mujeres de riesgo (antecedente personal o familiar de preeclampsia). Conclusiones: no se ha demostrado la efectividad de la suplementación antenatal con L-arginina para mejorar el resultado perinatal en embarazadas en riesgo o que presentan patologías como parto prematuro, síndrome hipertensivo del embarazo o restricción de crecimiento fetal. Se requieren estudios de buen diseño que permitan conclusiones definitivas.

Objective: critical analysis of randomized clinical trials to determine whether supplementation with L-arginine improves perinatal outcome in pregnant patients at risk or presenting conditions such as preterm labor, hypertensive disorders or intrauterine fetal growth restriction. Methods: we performed a literature search in Pubmed, Tripdatabase and multisearch in the Library System of the Pontifical Catholic University of Chile to further critical analysis of selected studies. Results: We selected 14 randomized trials, 4 of them are for studies of L-arginine in gestational hypertension, 5 studies of L-arginine in preeclampsia, one study of L-arginine in preterm labor, one study of L-arginine in chronic hypertension and 4 studies of L-arginine in intrauterine growth restriction. Only two of the studies were of good methodological quality, but one these studies analyzes an intermediate result that is not clinically relevant. The most promising result shows that the use of L-arginine associated with antioxidant vitamins significantly reduced the incidence of preeclampsia in women at risk (personal or family history of preeclampsia). Conclusions: is not shown the effectiveness of antenatal supplementation with L-arginine to improve perinatal outcome in pregnant women at risk or with pathological conditions such as premature labor, hypertensive disorders and fetal growth restriction. More studies of good design are needed to allow definitive conclusions.

Effects of starter diet supplementation with arginine on broiler production performance and on small intestine morphometry / Efeito da suplementação de arginina na dieta de frangos na performance produtiva e na morfologia do intestino delgado

The effects of starter diet (days 1 to 21) supplemented with arginine (Arg) on the production performance and duodenum and jejunum mucosa morphometry of broilers were studied. Male Cobb broiler chickens (990) were randomly assigned to one of five treatments in a complete random design. Measurements of 33 chicks per treatment were made in six repetitions. The treatments consisted of a basal diet with 1.390% digestible Arg (no supplementation) and four dietary levels (1.490%, 1.590%, 1.690%, and 1.790%), providing a relationship with lysine of 1.103; 1.183; 1.262; 1.341 and 1.421%, respectively. From the age of 22 days on, all birds received conventional grower diet. The data were submitted to regression analysis by polynomial decomposition of the degrees of freedom in relation to the levels of Arg. The Arg supplementation increased (P<0.05) the live weight and the feed conversion ratio without increasing the feed intake of the birds. However, no effect was observed (P>0.05) in the growth phase (days 22 to 42) in the absence of the Arg supplementation. The supplementation of Arg over of NRC recommendation during the starter phase may be necessary for the expression of the maximal weight gain potential in birds. No effect (P<0.05) of Arg dietary supplementation was observed either on small intestine weight and length at any age. However, the duodenum villus:crypt ratio increased and the crypt depth decreased in the first week in response to increasing dietary Arg. It is concluded that broiler Arg dietary supplementation in the starter diet improved production performance and small intestine morphometry, especially in the first week.

O efeito na dieta inicial (1-21 dias) da suplementação de arginina (Arg) foi estudada sobre o desempenho e a morfologia da mucosa do jejuno em frangos de corte. Pintos machos Cobb (990) foram utilizados em um delineamento inteiramente casualizado com 5 tratamentos e 6 repetições com 33 aves cada. Os tratamentos consistiram em uma dieta basal com 1,390% de Arg digestível (sem suplementação) e 4 dietas com adição (1,490%; 1,590%; 1,690% e 1,790%), fornecendo uma relação de lisina de 1,103; 1,183; 1,262; 1,341 e 1,421%, respectivamente. A partir de 22 dias todas as aves receberam ração convencional. Os dados foram submetidos à análise de regressão pela decomposição polinomial dos graus de liberdade, referentes aos níveis de Arg A suplementação de Arg melhorou (P<0,05) o peso vivo e a conversão alimentar sem aumentar o consumo de ração. No entanto, não houve efeito (P>0,05) na fase de crescimento (22 a 42 dias) na ausência de suplementação de Arg. A suplementação acima do recomendado pelo NRC na fase inicial pode ser necessária para a expressão máxima do potencial de ganho de peso em aves. Não houve efeito da suplementação de Arg na dieta no peso e comprimento do intestino delgado em nenhuma idade. No entanto, a relação vilo:cripta no duodeno aumentou e a profundidade da cripta diminuiu na primeira semana em resposta ao incremento de Arg na dieta. Concluiu-se que em frangos de corte a suplementação de Arg na dieta inicial melhorou o desempenho e a morfometria do intestino delgado, especialmente na primeira semana.

Ação do tacrolimus na pancreatite aguda experimental induzida pela arginina / Action of tacrolimus in arginine induced experimental acute pancreatitis

OBJETIVO: verificar se o tacrolimus administrado em ratos, em vigência de pancreatite induzida pela L-Arginina, interfere nos níveis séricos da amilase e glicose e no padrão histológico do parênquima pancreático. MÉTODOS: quarenta ratos Wistar foram distribuídos em quatro grupos com 10 ratos cada. Grupo controle (C), grupo tacrolimus (T), grupo pancreatite (P) e grupo pancreatite-tacrolimus (PT). Foram avaliados os níveis séricos de amilase, glicose e tacrolimus e feitas avaliações histológicas do pâncreas, A indução de pancreatite foi feita pela inoculação de L-Arginina na dose de 500mg/100g de peso corporal por via intraperitoneal e o tratamento com tacrolimus na dose de 1ìg/kg por via subcutânea durante quatro dias. RESULTADOS: a amilasemia estava mais elevada (p=0,0000) nos grupos PT, T e P do que no grupo controle. A média do grupo PT foi maior (p=0,0009) que a do grupo T, mas não diferiu (p=0,6802) da média do grupo P. Entre os grupos P e T não houve diferença (p=0,2568). Não houve diferença nas médias de glicemia entre os grupos (p=0,4920) e os níveis séricos de tacrolimus foram similares nos grupos PT e T (p=0,7112). Não ocorreram alterações histológicas nos grupos T e C e não ocorreu hemorragia no pâncreas dos ratos dos grupos P e PT. No grupo P, em 30 por cento não se observou edema, em 20 por cento observou-se a forma leve e em 50 por cento, a moderada; quanto à infiltração inflamatória, em 80 por cento moderada e em 20 por cento não ocorreu, e a atrofia do parênquima foi de 60 por cento moderada e 40 por cento acentuada. No grupo PT, houve ocorrência de edema, infiltração inflamatória e atrofia do pâncreas em todos os ratos. CONCLUSÃO: o tratamento pelo tacrolimus induziu aumento nos níveis séricos de amilase em ratos normais, não alterou a glicemia nem o padrão histológico do parênquima pancreático. Na vigência de pancreatite induzida pela L-Arginina o tacrolimus induziu edema, infiltração inflamatória e atrofia com maior gravidade no parênquima pancreático.

OBJECTIVE: To determine whether tacrolimus administered to rats, in the presence of pancreatitis induced by L-Arginine, interferes with the serum levels of amylase and glucose and the histological pattern of the pancreatic parenchyma. METHODS: Forty Wistar rats were divided into four groups with 10 rats each: control group (C), tacrolimus group (T), pancreatitis group (P) and pancreatitis-tacrolimus group (PT). We evaluated serum levels of amylase, glucose, and tacrolimus and made histological assessments of the pancreas. Induction of pancreatitis was made by inoculation of L-Arginine at a dose of 500mg/100g body weight intraperitoneally, and tacrolimus treatment at a dose of 1ìg/kg subcutaneously for four days. RESULTS: Serum amylase was higher (p = 0.0000) in groups PT, P and T than in the control group. The PT group mean was higher (p = 0.0009) than in the T group, but did not differ (p = 0.6802) from the average of the P group. There was no difference between groups P and T (p = 0.2568). Neither in mean blood glucose between the groups (p = 0.4920); serum levels of tacrolimus were similar in PT and T groups (p = 0.7112). There were no histological changes in groups T and C and no hemorrhage in the pancreas of rats in groups P and PT. In group P, there was no edema in 30 percent, mild edema in 20 percent and in 50 percent, moderate; as for inflammatory infiltration, it was moderate in 80 percent and absent in 20 percent, and atrophy of the parenchyma was moderate in 60 percent and severe in 40 percent. In the PT group, there was edema, inflammatory infiltration or atrophy in the pancreas in all rats. CONCLUSION: Treatment with Tacrolimus induced an increase in serum amylase in normal mice, but did not affect blood glucose or the histological pattern of the pancreatic parenchyma. In the presence of pancreatitis induced by L-Arginine tacrolimus induced edema, inflammatory infiltration and more severe atrophy in the pancreatic parenchyma.

Efeito da suplementação dietética com L-arginina em subpopulações linfocitárias de ratos submetidos a esplenectomia total isolada ou combinada com autoimplante esplênico / Effect of dietary supplmentation with L-arginine on lymphocyte subpopulations of rats submitted to total splenectomy isolated or combined with splenic autoimplantation

A L-aginina é reconhecida como um nutriente de fundamental importância na resposta imune, apesar de seus efeitos serem, por vezes, considerados inconstantes. O autoimplante esplênico tem sido proposto como alternativa à esplenectomia total isolada, mas existem preocupações quanto à eficácia do restabelecimento da resposta imune, haja vista que o paciente pode permanecer com risco aumentado de desenvolvimento de infecção fulminante pós esplenectomia, mesmo após a regeneração morfológica do órgão. O objetivo deste estudo foi avaliar a participação da suplementação dietética com L-arginina em subpopulações linfocitárias no sangue, no baço e nos autoimplantes esplênicos de ratos submetidos a esplenectomia isolada ou combinada com autoimplante esplênico. Foram utilizados 42 ratos Sprague-Dawlay machos, randomicamente distribuídos em seis grupos: 1 - Controle - operação simulada; 2 - esplenectomia total; 3 - esplenectomia total combinada com autoimplante esplênico; 4 - Controle - operação simulada, com suplementação de L-arginina; 5 - esplenectomia total, com suplementação de L-arginina; e 6 - esplenectomia total combinada com autoimplante esplênico, com suplementação de L-arginina. Os animais dos grupos 4, 5 e 6 receberam suplementação de L-arginina, uma vez ao dia, durante 15 dias anteriores a coleta sangüínea realizada imediatamente antes dos procedimentos operatórios (semanas 0 e 12). A dose utilizada foi de 1,0 g/kg/dia, administrada por via intragástrica em bolus. As avaliações foram realizadas por meio de hemograma e citometria de fluxo. A análise estatística utilizou testes paramétricos e não-paramétricos, sendo p<0,05 considerado para a rejeição da hipótese nula. A suplementação com L-arginina acarretou elevação da contagem relativa e absoluta de neutrófilos periféricos, 12 semanas após a realização de esplenectomia total combinada com autoimplante esplênico. A esplenectomia total ocasionou diminuição da contagem relativa de linfócitos T totais, T CD4+...

L-arginine is recognized as a nutrient of fundamental importance in immune implants has been proposed as an alternative to total splenectomy isolated, but there are concerns about the effectiveness of the restoration of the immune response, considering that the patient can remain at increased risk of developing overwhelming postsplenectomy infection, even after morphological regeneration of the organ. The aim of this study was to determine the role of dietary supplementation with L-arginine in lymphocyte subsets in blood, spleen, and splenic auto-transplantation in rats subjected to total splenectomy alone or in combination with splenic auto-transplantation. Forty two male Sprague-Dawley rats, were randomly divided into six groups: 1 - Control - sham operation, 2 - total splenectomy, 3 - total splenectomy combined with splenic auto-implants, 4 - Control - sham operation, with L-arginine supplementation, 5 - total splenectomy, supplemented with L-arginine, and 6 - total splenectomy combined with splenic auto-implants, supplemented with L-arginine. Animals in groups 4, 5 and 6 were supplemented with L-arginine, once daily for 15 days before blood sample was collected immediately before the operative procedures (weeks 0 and 12). The dose was 1.0 g/kg/day administered by intragastric bolus. The laboratory evaluations were made by blood count and flow cytometry. Statistical analysis used parametric tests and nonparametric, p<0.05 was considered to reject the null hypothesis. Supplementation with L-arginine led to increase in relative and absolute count of peripheral neutrophils, 12 weeks after completion of total splenectomy combined with splenic auto-implants. Total splenectomy caused a decrease in relative count of T lymphocytes, CD4+ and CD8B in blood, but dietary supplementation with L-arginine prevented the decrease in the percentage of total T cells and CD8B in the blood of animals subjected to splenic auto-transplantation...

Efeitos da suplementação oral com L-arginina e L-glutamina sobre a próstata ventral de ratos submetidos à irradiação / Effects of oral supplementation with L-arginine and L-glutamine on the ventral prostate of rats subjected to irradiation

O objetivo deste trabalho foi verificar o possível efeito protetor da L-glutamina e da L-arginina sobre a próstata ventral de ratos quando administradas por gavagem. Procurou-se simular as condições clinicas de pacientes submetidos à radioterapia pélvica tendo como órgão alvo outro órgão pélvico que não a próstata. Foram analisados os efeitos desta irradiação sobre a próstata considerando este órgão como normal. Foram utilizados ratos Wistar divididos em quatro grupos: Controle, animais não submetidos à irradiação (n=10); Irradiado, submetidos à irradiação abdominal e sem suplementação adicional de aminoácido por 21 dias (n=10); Irradiado + L-glutamina, submetidos à irradiação abdominal e com suplementação adicional de L-glutamina por 21 dias (n=10); e Irradiado + L-arginina, submetidos à irradiação abdominal e com suplementação adicional de L-arginina por 21 dias (n=9). Os grupos foram mantidos em condições padrão de laboratório durante todas as etapas do experimento. Os animais submetidos à irradiação abdominal receberam uma dose única de 1000 cGy no dia 8 da experimentação. A L-glutamina e a L-arginina foram dissolvidas em água destilada e administrada por gavagem através da agulha IC-810®. As próstatas foram removidas e processadas para inclusão em parafina. Foram estudados os seguintes parâmetros: estrutura acinar (área dos ácinos e altura do epitélio) e colágeno analisados por métodos morfométricos e peso corporal. O ganho de peso nos grupos suplementados foi significativamente maior se comparado ao grupo irradiado. Houve redução da altura do epitélio no grupo irradiado quando comparado ao controle. A altura do epitélio no grupo suplementado com L-arginina foi significativamente maior do que nos grupos irradiado e suplementado com L-glutamina. Houve diminuição, de aproximadamente 18%, da área dos ácinos no grupo suplementado com L-glutamina. Já no grupo suplementado com L-arginina o valor foi similar ao do controle. O efeito da L-glutamina...

The aim of this study was to investigate the possible protective effect of L-glutamine and L-arginine on the rat ventral prostate when administered by gavage. We tried to simulate the clinical conditions of patients undergoing pelvic radiotherapy as with other pelvic organ target organ than the prostate. We analyzed the effects of irradiation on prostate considering this organ as normal. Wistar rats were divided into four groups: Control, animals not exposed to irradiation (n=10); Irradiated, submitted to abdominal irradiation and without additional amino acid supplementation (n=10); Irradiated + L-glutamine, submitted abdominal irradiation and additional supplementation with L-glutamine for 21 days (n=10), and Irradiated + L-arginine, underwent abdominal irradiation and additional supplementation with L-arginine for 21 days (n=9). The groups were kept under standard laboratory conditions during all stages of the experiment. The animals underwent abdominal irradiation received a single dose of 1000 cGy in eight days of trial. L-glutamine and L-arginine were dissolved in distilled water and administered by gavage needle through the IC-810®. The prostates were removed and processed for paraffin embedding. We studied the following parameters: acinar structure (area of acini and epithelial height) and collagen analyzed by morphometric methods and body weight. Weight gain in the supplemented groups was significantly higher compared to the irradiated group. There was a reduction in epithelial height in the irradiated group compared to control. The height of the epithelium in the group supplemented with L-arginine was significantly higher than in irradiated and supplemented with L-glutamine. There was a decrease of approximately 18% of the area of the lobes in the group supplemented with L-glutamine. In the group supplemented with L-arginine was similar to the value of control. The effect of L-glutamine on the prostatic parenchyma was to keep the collagen...

The effect of chronic administration of L-arginine on the learning and memory of estradiol-treated ovariectomized rats tested in the morris water maze

OBJECTIVE: The present study was carried out to evaluate the effect of L-arginine on the learning and memory of estradiol-treated ovariectomized (OVX) rats. METHODS: Forty-eight rats were divided into six groups: (1) sham, (2) OVX, (3) sham-Est, (4) OVX-Est, (5) sham-Est-LA, and (6) OVX-Est-LA. The animals of the sham-Est and OVX-Est groups were treated by weekly injection of estradiol valerate (2mg/kg). The sham-Est-LA and OVX-Est-LA groups were treated in the same manner but with an additional daily injection of L-arginine (200mg/kg). After eight weeks, animals of all groups were tested in the Morris water maze. The escape latency and path traveled to reach the platform were compared between groups. RESULTS: Time latency and path length in the OVX group were significantly higher than in the sham group (P<0.05). The OVX-Est group had a significantly shorter traveled path length and time latency compared to the OVX group (P<0.001). Time latency and path length in the sham-Est group was significantly higher than in the sham group (P<0.001). Time latency and path length in the OVX-Est-LA group were significantly higher than in the OVX-Est group. CONCLUSIONS: These results allow us to propose that chronic treatment with estradiol enhances the spatial learning and memory of OVX rats, and that long term L-arginine treatment attenuates the effects of improvement produced by estradiol in OVX rats.

[Influence of intracerebral administration of l-arginine in dorsal hippocampus [CA1] on win55, 212-2 induced state-dependent memory]

Cannabinoids are a class of psychoactive compounds that produce a wide array of effects in a large number of species. In the present study, the effects of bilateral intra-CA1 injections of L-arginine on WIN55, 212-2 induced state-dependent memory of passive avoidance task was examined in mice. One-trial step-down paradigm was used for the assessment of memory retention in adult male NMRI mice. Post-training intraCA1 administration of cannabinoid receptor agonist, WIN55, 212-2 [0.5 and 1 micro g/mouse], decreased the memory retrieval. The memory impairment induced by post-training administration of WIN55, 212-2 [1micro g/mouse]was restored by pre-test administration of the same dose of the drug, showing the state-dependent memory of WIN55, 212-2. Single intra-CA1 administration of L-arginine [0.3, 1 and 3 micro g/mouse] 5min pre-test could not alter the memory retrieval. On the other hand, in the animals in which retrieval was impaired due to post-training administration of WIN55, 212-2 [1micro g/ mouse], pre-test intra-CA1 administration of L-arginine [1 and 3 micro g/ mouse], 24hr after training restored memory retrieval. Furthermore, in the animals under influence of post-training administration of WIN55, 212-2 [1 micro g/mouse], pre-test co-administration of non-effective doses of WIN55, 212-2 and L-arginine, increased the restoration of memory by the pre-test WIN55, 212-2. The findings of the present study suggest that NO system of dorsal hippocampus may play an important role in WIN55,212-2-induced amnesia and WIN55,212-2 state-dependent memory

Therapeutic role of L-arginine on free radical scavenging system in ischemic heart diseases.

Increased production of free radicals under oxidative stress conditions plays a vital role in the impairment of endothelial function and also in the pathogenesis of ischemic heart diseases. Ischemia, followed by reperfusion, leads to the exacerbated formation of oxy- free radicals. These reactive oxygen species through a chain of reactions damage the cardiomyocytes and cause more injury to the myocardium. L-Arginine is reported to act as free radical scavenger, inhibits the activity of pro-oxidant enzymes and thus acts as an antioxidant and these roles of L-arginine are mediated by nitric oxide (NO). In the present study, the effect of oral administration of L-arginine (3 g/day for 7 days) on some antioxidant enzymes, total thiols, lipid peroxidation measured as malondialdehyde (MDA), and plasma ascorbate levels in myocardial ischemic patients was investigated. We observed an increase in the activity of superoxide dismutase (SOD), total thiols (T-SH) and plasma ascorbate levels and a decrease in the activity of xanthine oxidase (XO), MDA levels, carbonyl content and serum cholesterol in the patients on oral administration of L-arginine. The present study demonstrates that L-arginine administration may be beneficial to patients with myocardial ischemic disorders, such as acute myocardial infarction and acute angina.

Local administration of L-Arginine accelerates wound closure

The process of wound healing involves tightly integrated events including inflammation, granulation tissue formation and remodeling. Systemic administration of L-arginine promotes wound healing but its global side effects are undesirable. To confine the action of L-arginine at the site of injury, we tested the effects of local administration of L-arginine on the healing of excisional wound in the rat. Full thickness excisional wounds were generated on the dorsum of adult male rats. The test wounds received 200 micro m or 400 micro m of L-arginine on day 3 and 5 post-wounding. Normal saline was injected into the sham wounds which were otherwise treated as the test wounds. Control wounds remained unmanipulated. The wound size was monitored daily by imaging. To determine the rate of wound closure, wound images were scanned and the rate of size reduction was analyzed and quantified by ScnImage software. The repaired tissues were harvested on day 12 post-wounding. The tissue sections were prepared and stained for microscopic examination. Wounds treated with L-arginine showed a significant increase in the rate of wound closure. The morphology of basal keratinocytes was altered, and the thickness of neoepidermis was markedly reduced in the wounds treated with L-arginine. Both tested dose of L-arginine were equally effective. Local administration of L-arginine accelerates wound closure and has profound effects on keratinocytes performance during the process of healing. Therefore, it can be potentially used for treatment of skin disorders, in particular, those characterized by hyperkeratosis

Efecto de la Arginina sobre el sistema inmunológico y parámetros nutricionales en pacientes con cirugías abdominales complicadas / Effect of Arginine on the inmune system and nutritional parameters in patients wth complicated abdominal surgery

La suplementación de la nutrición enteral con Arginina a dosis mínima (6 g. día) desde el primer día de alimentación posterior a una cirugía abdominal complicada tendría efectos sobre la respuesta inmunológica y los niveles de proteínas plasmáticas. Se encontró un aumento significativo del Recuento Total de Linfocitos y de los niveles de Transferrina en el grupo que recibió la Arginina. Las demás variables no tuvieron una variación significativa...

Efeito da suplementação de L-arginina sobre a secreção de hormônio do crescimento e fator de crescimento semelhante à insulina em adultos / Effect of L-arginine supplementation on secretion of human growth hormone and insuline-like growth factor in adults

Baseado nos pressupostos de que a infusão de aminoácidos pode aumentar a secreção de hormônio de crescimento (GH), e que o metabolismo deste hormônio está relacionado com a secreção do fator de crescimento semelhante à insulina (IGF-I), o objetivo deste estudo foi verificar o efeito da suplementação de L-arginina sobre o GH e IGF-I em adultos. Participaram do estudo 17 indivíduos do sexo masculino, que foram randomizados para receber L-arginina (n= 10) ou placebo (n= 7), sete gramas ao dia, durante um período de sete dias. Antes e após o período de suplementação, os voluntários realizaram coleta de sangue em jejum para verificação dos níveis séricos de GH e IGF-I, bem como coleta de urina para verificação da excreção de uréia. Ao final do período experimental, verificamos que o grupo que recebeu L-arginina aumentou a excreção de uréia na urina (de 2684,1 ± 475,2 mg/dl para 2967,2 ± 409,7 mg/dl, p= 0,002), entretanto não modificou significativamente a secreção dos hormônios avaliados. O grupo que recebeu placebo não alterou significativamente nenhum parâmetro avaliado. A suplementação de L-arginina durante sete dias mostrou-se ineficaz para aumentar a secreção de GH e IGF-I em indivíduos adultos do sexo masculino.

Based on presumptions that the infusion of amino acids can augment the release of human growth hormone (hGH) and that this metabolism is related with secretion of insulin-like growth factor I (IGF-I), the purpose of this study was to verify the effect of L-arginine supplementation on GH and IGF-I in adults. Seventeen male individuals participated on the study and were randomized to receive L-arginine (n= 10) or placebo (n= 7), seven grams per day for seven days. Before and after the supplementation period, the volunteers realized blood collection in fasting to verify both GH and IGF-I levels, as well as urine collection to verify urea excretion. At the end of the experimental period, it was verified that the group that received L-arginine augmented the urea in urine excretion (to 2684.1 ± 475.2 mg/dl from 2967.2 ± 409.7 mg/dl, p= 0.002), therefore it did not alter significantly the release of hormones evaluated. The group which received placebo did not alter significantly any evaluated parameters. The L-arginine supplementation during seven days was ineffective to augment both GH and IGF-I release in individual male adults.

Effect of long term oral administration of L-arginine on experimentally produced myocardial ischemia in rabbits.

L-arginine a semi essential amino acid and a precursor of nitric oxide (NO) was orally supplemented in diet (standard rabbit feed) of hypercholesterolemic (n=6) and normal rabbits (n=6) for 16 weeks. Myocardial ischemia was produced in both groups of rabbits by subcutaneous single bolus injection of isoproteronol. Severity of myocardial ischemia was assessed by estimating the serum CPK and AST levels after 6 hour of ischemia-reperfusion. The result suggests that severity of ischemia was lesser in the L-arginine primed hypercholesterolemic group.