TRPV1 Contributes to Cerebral Malaria Severity and Mortality by Regulating Brain Inflammation.

Transient receptor potential vanilloid 1 (TRPV1) is a Ca+2-permeable channel expressed on neuronal and nonneuronal cells, known as an oxidative stress sensor. It plays a protective role in bacterial infection, and recent findings indicate that this receptor modulates monocyte populations in mice with malaria; however, its role in cerebral malaria progression and outcome is unclear. By using TRPV1 wild-type (WT) and knockout (KO) mice, the importance of TRPV1 to this cerebral syndrome was investigated. Infection with Plasmodium berghei ANKA decreased TRPV1 expression in the brain. Mice lacking TRPV1 were protected against Plasmodium-induced mortality and morbidity, a response that was associated with less cerebral swelling, modulation of the brain expression of endothelial tight-junction markers (junctional adhesion molecule A and claudin-5), increased oxidative stress (via inhibition of catalase activity and increased levels of H2O2, nitrotyrosine, and carbonyl residues), and diminished production of cytokines. Plasmodium load was not significantly affected by TRPV1 ablation. Repeated subcutaneous administration of the selective TRPV1 antagonist SB366791 after malaria induction increased TRPV1 expression in the brain tissue and enhanced mouse survival. These data indicate that TRPV1 channels contribute to the development and outcome of cerebral malaria.

Probiotics, mechanisms of action, and clinical perspectives for diarrhea management in children.

Infectious diarrhea is the second most common cause of morbidity and mortality in children under 5 years of age in the underdeveloped areas of the world. Conventional treatment consists of rehydration, which may be coupled with antimicrobial agents in more severe bacterial infections or with antiprotozoal agents. In the last few decades, research on the use of probiotic strains, such as Lactobacillus rhamnosus GG ATCC 53013 (LGG), Lactobacillus reuteri DSM 17938 and Saccharomyces boulardii, has gained much attention to prevent and treat diarrheal diseases. However, they are rarely used in the clinical routine, perhaps because there are still gaps in the knowledge about the effective benefit to the patient in terms of the reduction of the duration of diarrhea and its prevention. Furthermore, only a few probiotic strains are safely indicated for usage in pediatric practice. This review summarizes the current knowledge on the antimicrobial mechanisms of probiotics on distinct enteropathogens and their role in stimulating host defense mechanisms against intestinal infections. In addition, we highlight the potential of probiotics for the treatment and prevention of diarrhea in children. We conclude that the use of probiotics is beneficial for both the treatment and prevention of diarrhea in children and that the identification of other candidate probiotics might represent an important advance to a greater reduction in hospital stays and to prevent infectious diarrhea in a larger portion of this population.