Transcriptomic responses provide a new mechanistic basis for the chemopreventive effects of folic acid and tributyrin in rat liver carcinogenesis.

The steady increase in the incidence and mortality of hepatocellular carcinoma (HCC) signifies a crucial need to understand better its pathogenesis to improve clinical management and prevention of the disease. The aim of this study was to investigate molecular mechanisms for the chemopreventive effects of folic acid and tributyrin alone or in combination on rat hepatocarcinogenesis. Male Wistar rats were subjected to a classic "resistant hepatocyte" model of liver carcinogenesis and treated with folic acid and tributyrin alone or in combination for 5 weeks during promotion stage. Treatment with folic acid and tributyrin alone or in combination strongly inhibited the development of glutathione-S-transferase placental form (GSTP)-positive foci. Microarray analysis showed significant changes in gene expression. A total of 498, 655 and 940 of differentially expressed genes, involved in cell cycle, p53-signaling, angiogenesis and Wnt pathways, was identified in the livers of rats treated with folic acid, tributyrin or folic acid and tributyrin. A detailed analysis of these differentially expressed genes revealed that treatments inhibited angiogenesis in the preneoplastic livers. This was evidenced by the fact that 30 out of 77 differentially expressed genes common to all three treatments are involved in the regulation of the angiogenesis pathway. The inhibition of angiogenesis was confirmed by reduced levels of CD34 protein. In conclusion, the tumor-suppressing activity of folic acid and tributyrin is associated with inhibition of angiogenesis at early stages of rat liver carcinogenesis. Importantly, the combination of folic acid and tributyrin has stronger chemopreventive effect than each of the compounds alone.

In vitro hemolytic activity of Lonomia obliqua caterpillar bristle extract on human and Wistar rat erythrocytes.

Human accidental envenomation caused by skin contact with the bristles of Lonomia obliqua caterpillar causes coagulation and fibrinolysis disorders. Alterations of hematologic parameters are observed only in severe cases of envenomation, but with no clinical evidence of intravascular hemolysis. However, since we have observed intravascular hemolysis in preliminary studies using Wistar rats as an experimental model for investigating L. obliqua envenomation, the objective of the present study was to investigate the in vitro hemolytic activity of the bristle extract of L. obliqua caterpillars on human and rat erythrocytes. Our results showed that the bristle extract has indirect and direct hemolytic activity on human and rat erythrocytes, although direct hemolytic activity was only observed at higher bristle extract concentrations. We also observed that the bristle extract has a proteolytic activity on band 3 of human and rat erythrocyte membranes. Thus, crude L. obliqua bristle extract was found to contain at least two components with hemolytic activity on erythrocytes, a phospholipase enzyme and another protein with a direct activity on the erythrocyte membrane.

Folato, vitamina B12 e ferritina sérica e defeitos do tubo neural / Folate, vitamin B12, serum ferritin and defects of the neural tube

Objetivo: verificar os níveis de folatos, vitamina B12 e ferritina em pacientes cujos fetos apresentaram defeitos de tubo neural (DTN). O folato sangüíneo e a vitamina B12 atuam como cofatores para as enzimas envolvidas na biossíntese do DNA. A interrupção deste processo pode impedir o fechamento do tubo neural. A suplementação vitamínica contendo folato pode reduzir as taxas de ocorrência de defeitos de tubo neural, embora exista a preocupação de que esta prevenção possa mascarar a deficiência de vitamina B12. Métodos: dosagens de vitamina B12 e ferritina pelo método de enzimaimunoensaio com micropartículas e a dosagens de ácido fólico pelo método de captura iônica (IMx ABBOTT). Resultados: a porcentagem de gestantes com deficiência de vitamina B12 (níveis séricos < 150 pg/ml) foi de 11,8 por cento. Não houve nenhum caso de deficiência de folato (níveis séricos < 3,0 ng/ml). A prevalência de gestantes com deficiência nos estoques de ferro foi de 47,1 por cento (níveis séricos < 12 ng/ml). Conclusões: com os resultados encontrados neste estudo (prevalência de 11,8 por cento de deficientes em vitamina B12 e 0 por cento de deficiência de folato), sugerimos que a suplementação se realize após a determinação da vitamina B12 sérica.

Purpose: to determine folate, vitamin B12 and ferritin levels in patients whose fetuses presented neural-tube defects (NTD). Blood folate and vitamin B12 act as cofactors of enzymes involved in DNA biosynthesis. Interruption of this process may block neural-tube closing. Vitamin supplementation with folate may reduce occurrence rates and recurrence of NTD, although there is concern about the fact that this prevention may mask vitamin B12 deficiency. Methods: vitamin B12 and ferritin determinations by enzyme immunoassay with microparticles and folic acid determination using the ion capture method (IMx ABBOTT). Results: the percentage of pregnant women with vitamin B12 deficirncy (serum levels < 150 pg/ml) was 11.8 percent. There was no case of folate deficiency (serum levels < 3.0 ng/ml) and prevalence of pregnant women with iron store deficiency was 47.1 percent (serum levels < ng/mg). Conclusions: occording to the results obtained in this study (prevalence of 11.8 percent of vitamin B12 and 0 percent of folate deficient pregnant women) we suggest that supplementation should be administered after serum vitamin B12 determination.

Folato e ferritina na gestação / Folate and Ferritin in pregnancy

As deficiências de folato e de ferritina sérica acarretam anemia em gestantes (considerada mundialmente um problema de Saúde Pública). O objetivo do trabalho foi estudar os níveis de folato e de ferritina séricos em gestantes. Foram determinadas as dosagens de folato e de ferritina e o eritograma de 90 gestantes, usuárias dos serviços de Pré-Natal do Hospital e Maternidade Vila Nova Cachoeirinha e do Hospital Universitário da USP. Das gestantes , 22,2(per cent) eram anêmicas e 2,2(per cent) eram deficientes de acido fólico; 18,8(per cent) eram deficientes de ferritina e anêmicas ao mesmo tempo. A média dos níveis de folato sérico foi de 7,42ng/ml com dp ñ 3,49. A média dos níveis de ferritina sérica foi 47,22 ng/ml com dp ñ 44,02. Analisando os prontuários das pacientes após o parto, observamos que cinco abortaram; houve um caso de cardiopatia congênita e nunhuma delas teve concepto afetado por defeito de tibo neural (au)