Atorvastatin attenuates intestinal mucositis induced by 5-fluorouracil in mice by modulating the epithelial barrier and inflammatory response.

Chemotherapy-induced intestinal mucositis is a major side effect of cancer treatment. Statins are 3-hydroxy-3-methyl glutaryl coenzyme reductase inhibitors used to treat hypercholesterolemia and atherosclerotic diseases. Recent studies have demonstrated that atorvastatin (ATV) has antioxidant, anti-inflammatory, and resulting from the regulation of different molecular pathways. In the present study, we investigated the effects of ATV on intestinal homeostasis in 5-fluorouracil (5-FU)-induced mucositis. Our results showed that ATV protected the intestinal mucosa from epithelial damage caused by 5-FU mainly due to inflammatory infiltrate and intestinal permeability reduction, downregulation of inflammatory markers, such as Tlr4, MyD88, NF-κB, Tnf-a, Il1ß, and Il6 dose-dependent. ATV also improved epithelial barrier function by upregulating the mRNA transcript levels of mucin 2 (MUC2), and ZO-1 and occludin tight junction proteins. The results suggest that the ATV anti-inflammatory and protective effects on 5-FU-induced mice mucositis involve the inhibition of the TLR4/MYD88/NPRL3/NF-κB, iNos, and caspase 3.

Pegylated LyeTx I-b peptide is effective against carbapenem-resistant Acinetobacter baumannii in an in vivo model of pneumonia and shows reduced toxicity.

The World Health Organization (WHO) has been warning about the importance of developing new drugs against superbugs. Antimicrobial peptides are an alternative in this context, most of them being involved in innate immunity, acting in various ways, and some even showing synergism with commercial antimicrobial agents. LyeTx I-b is a synthetic peptide derived from native LyeTx I, originally isolated from Lycosa erythrognatha spider venom. Although LyeTx I-b is active against several multidrug-resistant bacteria, it shows some hemolytic and cytotoxic effects. To overcome this hindrance, in the present study we PEGylated LyeTx I-b and evaluated its toxicity and in vitro and in vivo activities on pneumonia caused by multi-resistant Acinetobacter baumannii. PEGylated LyeTx I-b (LyeTx I-bPEG) maintained the same MIC value as the non- PEGylated peptide, showed anti-biofilm activity, synergistic effect with commercial antimicrobial agents, and did not induce resistance. Moreover, in vivo experiments showed its activity against pneumonia. Additionally, LyeTx I-bPEG reduced hemolysis up to 10 times, was approximately 2 times less cytotoxic to HEK-293 cells and 4 times less toxic to mice in acute toxicity models, compared to LyeTx I-b. Our results show LyeTx I-bPEG as a promising antimicrobial candidate, significantly active against pneumonia caused by multidrug-resistant A. baumannii.

Effect of spleen surgeries on Escherichia coli distribution on the mononuclear phagocytic system.

OBJECTIVE: To avoid asplenic state, many approaches preserving the spleen have been proposed in the literature: splenorraphy, partial splenectomy with or without preservation of hilar vessels and splenic tissue auto-implants. Subtotal splenectomy, preserving the upper spleen pole nourished only by splenogastric vessels is an alternative when the splenic pedicle must be ligated. The purpose of this study was to evaluate the influence of partial, subtotal and total splenectomies on the distribution of Escherichia coli in the mononuclear phagocytic system. METHOD: Thirty-two rats divided into four groups were studied: sham operation (total spleen preservation), partial splenectomy, subtotal splenectomy and total splenectomy. Five weeks after surgeries, an aliquot of E. coli marked with tecnetium-99m was injected intravenously. The animals were killed 20min later and the spleen, lungs and liver were removed in order to determine the distribution of labeled bacteria. RESULTS: The amount of E. coli in the splenic tissue was greater in the intact spleen group than in the partial or subtotal splenectomy groups. Phagocytosis through the spleen did not differ between the partial and subtotal splenectomy groups. The amount of bacteria in the lungs was greater in the partial than in the subtotal splenectomy group. The distribution of labeled bacteria was greater in the liver of animals submitted to subtotal splenectomy than in the other groups. CONCLUSION: The upper splenic pole, supplied only by splenogastric vessels, has the ability to remove live bacteria from the blood stream, showing that effective blood clearance occurs even without vascularization through the splenic pedicle. Thus, the distribution of E. coli through the mononuclear phagocytic system shows different behavior depending on the type of splenectomy to which the animals are submitted.

Effect of gamma irradiation on the inactivation of aflatoxin B1 and fungal flora in peanut

The effect of gamma irradiation on aflatoxin B1 levels and fungal infection were investigated in peanut samples, Tatu Vermelho cultivar. At a radiation dose of 10 KGy, growth of molds was completely inhibited. Doses of 15, 20, 25 and 30 KGy were sufficient for destruction of aflatoxin B1 by 55-74%. The results suggested that the decontamination of molds by irradiation, before production of aflatoxin B1, is the most acceptable method in the preservation of peanut.

O efeito da irradiação gama nos níveis de aflatoxina B1 e na infecção fúngica foram investigadas em amostras de amendoim, cultivar Tatu Vermelho. Dose de irradiação gama (60Co) de 10 KGy inibiu completamente o crescimento de fungos. Doses de 15, 20, 25 e 30 KGy foram suficientes para destruição de aflatoxina B1 de 55 a 74%. Pode-se concluir do presente trabalho, que a descontaminação de fungos por irradiação gama antes da produção de aflatoxina B1 é o método apropriado na preservação de amendoim.