Members of the genus Leishmania are important intracellular pathogens that produce either cutaneous, mucocutaneous, or visceral disease in many areas of the world. In humans as well as in other mammals, the parasite is inoculated through the skin as a flagellated, extracellular promastigote by its arthropod vector, the sandfly. Once in its mammalian host, the promastigote converts to its amastigote stage, which lacks an exteriorized flagellum and is found solely within mononuclear phagocytes during established infection. In vitro, human monocyte-derived macrophages and peritoneal macrophages from several species of rodents can ingest both promastigotes and amastigotes, and they can permit intracellular multiplication of amastigotes only. Although serum factors may play a role in the pathogenesis of the disease and in protection against reinfection, the resolution of leishmaniasis is dependent primarily on cell-mediated immune responses. There appears to be a complicated interplay between cell-mediated helper and suppressor activities. The outcome of infection in each type of leishmaniasis depends on the complex and intriguing interaction of virulence factors inherent in the parasite and genetically determined host defense mechanisms.

Animals↗

PubMedDate not supplied

Reciprocal relationships between undernutrition and the parasitic disease visceral leishmaniasis.

Little is known about the interrelationship between undernutrition and parasitic infections in areas of the world where both are prevalent. The associations between undernutrition and visceral leishmaniasis, an important protozoal disease, were assessed in a study of residents of an area in Brazil with endemic leishmaniasis. Mid-arm anthropometry was used to assess fat and muscle area. Children with visceral leishmaniasis came from large families (9.6 +/- 1.1 members vs. 6.8 +/- 0.7 members in neighborhood control families), and patient housemates had fat areas that were 78% (P less than .05) those of age- and sex-matched neighborhood controls. The children with visceral leishmaniasis who were studied four months or less after diagnosis had fat areas that were 66% (P less than .05) those of age- and sex-matched household controls or 41% (P less than .01) those of neighborhood controls and muscle areas that were 81% (P less than .025) those of household controls or 75% (P less than .05) those of of neighborhood controls. It is hypothesized, on the basis of these data and other findings, that undernutrition is associated with the development of clinically apparent visceral leishmaniasis and that the disease itself has a profound effect on nutritional status, resulting in loss of both muscle and fat, effects that possibly are mediated by interleukin-1 and/or other factors produced by Leishmania donovani-infected macrophages.

Adipose Tissue↗

PubMedDate not supplied

Quinidine interactions with human atrial potassium channels: developmental aspects.

Clinical studies have suggested that quinidine is less effective when used for the treatment of atrial arrhythmias in pediatric patients compared with its clinical effectiveness in the adult patient population. Age-related changes in the cardiac actions of quinidine on action potential duration and interaction with potassium channels in several mammalian species also have been reported. We investigated the effects of postnatal development on quinidine's interaction with major repolarizing currents (Ito, IKur, Ins, and IK1) in human atrial myocytes, using the whole-cell configuration of the voltage-clamp technique. Our results indicate that there are age-related changes in both the IC50 for quinidine blockade of Ito, as well as the mechanism of quinidine unblocking. In contrast, quinidine was found to inhibit both adult and pediatric IK1 and IKur in an age-independent manner, whereas the nonselective cation current (Ins), which contributes to the sustained outward current (Isus), was insensitive to quinidine. The results from this study help to clarify the electrophysiological mechanism by which quinidine elicits its antiarrhythmic effect in the pediatric and adult human population.

Action Potentials↗