Treatment with N-methyl-D-aspartate receptor antagonist (MK-801) protects against oxidative stress in lipopolysaccharide-induced acute lung injury in the rat.

Acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) are common syndromes that affect both clinical and surgical patients. This study describes the effects of a potent and specific N-methyl-d-aspartate receptor antagonist (MK-801) against oxidative stress in acute lung injury induced by intratracheal lipopolysaccharide (LPS) injection. This study was performed using male Wistar rats weighing 200-250g. Rats were randomly divided into four groups: control with isotonic saline instillation (n=6); LPS (100µg/100g of body weight) treated with saline (n=6); LPS treated with MK-801 (0.3mg/kg, intraperitoneally; n=6); LPS treated with MK-801 (0.3mg/kg, intratracheally; n=6). Twelve hours after the LPS instillation, rats were anesthetized and a bronchoalveolar lavage (BAL) was performed in order to determine the alveolar-capillary membrane alterations and the inflammatory infiltrate level. Blood and lung samples were isolated and assayed for oxidative stress variables and histopathologic analysis. The use of MK-801 decreased bronchoalveolar lavage fluid protein, LDH activity and inflammatory cells. Indeed, the treatment with MK-801 significantly attenuated lung oxidative damage and histopathologic alterations after LPS instillation. Our data provide the first experimental demonstration that MK-801 decreases oxidative stress and limits inflammatory response and alveolar disarray in lipopolysaccharide-induced acute lung injury.

Efeito imunomodulador de hipoglicemiantes orais em cultura de linfócitos de pacientes com diabetes tipo 2 / Immunomodulatory effects of oral antidiabetic drugs in lymphocyte cultures from patients with type 2 diabetes

INTRODUCTION AND OBJECTIVE: It has been suggested that type 2 diabetes is an inflammatory response manifestation. The main drugs used to treat type 2 diabetes are sulphonylureas and biguanides. The aim of this study was to demonstrate the modulatory effects of oral hypoglycemic drugs (chlorpropamide and metformin) on lymphocyte proliferation in vitro and ex vivo. METHODS: Peripheral blood mononuclear cells were isolated from human blood by gradient centrifugation. T-lymphocytes were stimulated by phytohemagglutinin (PHA) and oral hypoglycemic drugs. RESULTS: In both in vitro and ex vivo experiments, there was a reduction in cell proliferation after treatment with oral hypoglycemic drugs. When both drugs were used in combination, a high level of cytotoxicity was observed, which made analysis of immunomodulatory effects unfeasible. DISCUSSION AND CONCLUSION: We demonstrated that diabetes itself may reduce cell proliferation significantly when stimulated by PHA, which may indicate that diabetic patients have difficulties in promoting an efficient inflammatory response. Moreover, the use of oral hypoglycemic drugs may aggravate this situation.

INTRODUÇÃO E OBJETIVOS: Tem sido sugerido que o diabetes mellitus tipo 2 (DM2) é uma manifestação da resposta inflamatória. As principais drogas utilizadas no tratamento do DM2 são as sulfonilureias e as biguanidas. O objetivo deste trabalho é demonstrar os efeitos moduladores na proliferação de linfócitos causada pelos hipoglicemiantes orais (clorpropamida e metformina), in vitro e ex vivo. MÉTODOS: Células mononucleares de sangue periférico foram isoladas de seres humanos por gradiente de centrifugação. Os linfócitos T foram estimulados com fito-hemaglutinina (PHA) e hipoglicemiantes. RESULTADOS: Nos experimentos in vitro e ex vivo, mostramos a redução da proliferação celular quando do tratamento com drogas hipoglicemiantes orais. Quando as drogas foram utilizadas em combinação, foi observado alto grau de citotoxicidade, tornando inviável a análise do efeito imunomodulador. DISCUSSÃO E CONCLUSÃO: Mostramos que o diabetes, por si, pode reduzir significativamente a proliferação celular quando estimulada por PHA, o que pode indicar que o paciente diabético tem dificuldade em promover a eficiente resposta inflamatória e que o uso de hipoglicemiantes pode piorar esta situação.

Anti-inflammatory and immunomodulatory effects of Ulomoides dermestoides on induced pleurisy in rats and lymphoproliferation in vitro.

The following study aimed to evaluate, in vitro and in vivo, the anti-inflammatory effect of Ulomoides dermestoides, a beetle commonly used as a remedy for a variety of diseases including respiratory disorders and asthma. We used an acute inflammation model of injury, injection of carrageenan into the pleural cavity of rats. The rats were treated intraperitoneally with the aqueous extract of U. dermestoides 8 and 16 mg/kg. The exudate volume, protein concentration, polymorphonuclear leukocytes (PMNs) and total leukocyte were measured. The peripheral blood mononuclear cells (PBMCs) were isolated from the blood of healthy subjects and we investigated the immunomodulatory and cytotoxic effect of aqueous extract of U. dermestoides. In conclusion, in vitro we observed a non-cytotoxic effect and antiproliferative activity on the dose of 12.5 mg/dL. In vivo, this paper clarifies the great clinical relevance of the aqueous extract of U. dermestoides in elucidating its role as an anti-inflammatory agent.

Intravenous toxicity of fructose-1,6-bisphosphate in rats.

Fructose-1,6-bisphosphate (FBP) is a bisphosphorilated sugar with a protective action against events that lead to cellular damage. The toxicity of the drug was assessed when administered intravenously in Wistar rats in doses of between 250 and 4000 mg/kg. Ionic calcium, total calcium, inorganic serum phosphate and the electrocardiographic profile of these animals were assessed. The lethal dose (LD(50)) was established by means of PROBIT processing. There was no reduction in the levels of total calcium, with the administration of increased doses of FBP, although there was a significant reduction in the levels of ionic calcium in those groups that received 250 mg/kg and over. The serum phosphate showed a significant statistical increase in those groups that received 750 mg/kg and over. The LD(50) obtained in 24 h was 1068 mg/kg. Though it was not possible to elucidate the toxic mechanism of FBP, the electrocardiogram (ECG) showed that all the rats died of cardiac arrest.

O antígeno prostático específico e sua importância na decisão clínica no câncer de próstata / The prostatic specific antigen and its importance in the clinical decision in the prostate cancer

O câncer de próstata (CaP) representa um problema de saúde pública de proporções cada vez mais importantes. É uma das neoplasias mais frequentes nos homens e representa uma das principais causas de morte na população. A busca de métodos diagnósticos para as neoplasias é um constante objetivo clínico laboratorial. Exame físico, métodos de imagem e dosagens laboratoriais compreendem o conjunto de auxílio diagnóstico no CaP. O antígeno prostático específico (PSA) é produzido pelo tecido prostático normal, bem como, em casos de Hiperplasia Prostática Benigna (HPB) e no CaP. Sua dosagem constitui importante método laboratorial na prática médica, uma vez que se apresenta com grande valor no rastreamento, diagnóstico e acompanhamento dos casos de CaP. O entendimento do seu papel pelo farmacêutico-bioquímico, bem como, a interação com a equipe clínica mostra-se promissor para influenciar as decisões diagnóstico-terapêuticas.

Prostate cancer represents a public health concern whose proportions are becoming increasingly important. It is one of the most common neoplasia among men and it represents one of the main causes of death in the population. The search for diagnostic methods for this neoplasia has been a constant laboratory clinic target. Physical checking, imaging methods and laboratory dosages compose the range of diagnostic support when dealing with prostate cancer...