Gp63 gene polymorphism and population structure of Leishmania donovani complex: influence of the host selection pressure?

The gp63 encoding genes were characterized by PCR-RFLP in 35 isolates representative of the Leishmania donovani complex (L. infantum, L. donovani, L. archibaldi and L. chagasi), with special attention to Mediterranean L. infantum from different geographical origins, and in separate groups from Old World Leishmania (L. major, L. tropica and L. aethiopica). The aim was to evaluate how the possible selective pressure by the host on these important surface proteins would influence structuring of our sample. Comparison was carried out with the structure obtained (i) from reported isoenzyme data, characters supposed to vary neutrally, and (ii) from PCR-RFLP analysis of gp63 inter-genic regions, containing nontranslated spacers and regulatory genes. Polymorphism within the gp63-encoding region, was much higher than in gp63 inter-genic regions. In the gp63 intra-genic dendrogram, the 4 species of L. donovani complex were discriminated and quite distinct from outgroups. Within L. infantum, geographical structuring was observed and did not overlap with the structure built-up from isoenzymes and inter-genic data. These results support the idea of a strong host-selection on gp63, at vector level but most of all at vertebrate (human or dog) immunological level. Furthermore, they illustrate how the nature of genetic characters may influence the perception of population structuring.

Efficacy and safety of single versus multiple daily doses of glibenclamide in type 2 diabetes mellitus.

Although long acting, glibenclamide is frequently given in split doses for type 2 diabetes mellitus. This may discourage compliance. It is thus appropriate to consider dosing it less frequently. We therefore studied glibenclamide effects when used once daily and when used in split doses. Our objective was to assess the feasibility of using once daily dosing as a regimen of choice. We measured plasma glucose, insulin, glibenclamide, lipids, HbAl and body mass index associated with the regimens. We also compared the number of hypoglycemic episodes occurring with them. Thirty type 2 diabetics on multiple daily glibenclamide were enrolled. Their regimens were changed over to once daily. Blood for glucose, insulin, lipids, HbAl and glibenclamide and body weight measurements were determined before and after the crossover period. We found no major difference in the sugar and insulin profiles with the two regimens. Fasting total cholesterol and triglyceride were also similar and so were plasma glibenclamide. The HbAl levels and body mass index and number of minor and major hypoglycemic episodes and hospital admissions for hypoglycemia also did not differ. We conclude that single daily dosing of glibenclamide was equivalent to multiple daily dose regimens. It can be used to an advantage to improve patient's compliance.

CD4+ T-lymphocyte measures in the treatment of individuals infected with human immunodeficiency virus type 1. A review for clinical practitioners.

The CD4+ lymphocyte is a major target of the human immunodeficiency virus type 1 (HIV-1). CD4+ T-lymphocyte measures have been used to predict the risk of HIV-1-related complications in diverse populations, to guide management decisions, and to define cases of the acquired immunodeficiency syndrome (AIDS). To examine the role of CD4+ measures in the management and epidemiologic monitoring of HIV-1 infection, we evaluated current literature regarding the accuracy and precision of CD4+ measures and the use of these and other prognostic measures in the care of HIV-1-infected persons. Several studies have reported wide intraindividual and interindividual variability in the absolute CD4+ count, which can detract from its clinical usefulness. Approaches to address this variability include the following: drawing specimens at a similar time of the day; monitoring CD4+ percent that has less variability; following a meticulous laboratory technique; using serial tests to guide management decisions; and retesting after efforts to eliminate transient treatment and clinical factors that can affect the CD4+ count. The expense and limited availability of CD4+ measures also present barriers to widespread use. Other laboratory and clinical factors offer additional prognostic information and have an evolving role in management decisions. CD4+ measures have an important role in HIV-1 clinical care, research, and disease surveillance, but strategies are required to address problems with variability, expense, and availability.

Use of recombinant DNA probes for species identification of Old World Leishmania isolates.

Recombinant DNA probes from a genomic Leishmania major library were screened for their potential to distinguish among Old World Leishmania taxa by Southern blot analysis. A probe, pDK10, was selected and tested on a panel of 58 Old World Leishmania strains that had already been typed isoenzymatically; these strains belong to the different species described so far and had been isolated from various hosts and vectors in 14 countries. In the present study, 45 zymodemes were represented. Using the pDK10 probe, we were able to differentiate between the different phenetic complexes. No variations in hybridization patterns were found within these complexes. In addition, there was a good concordance between identification based on DNA hybridization with the pDK10 probe and that based on isoenzyme typing. The probe has been applied in identifying Leishmania strains that were isolated in Tunisia from humans, animals, or insects. Our results show that the application of the pDK10 probe, in combination with a Pst I digestion of Leishmania DNA, could be a possible alternative to isoenzyme analysis for the identification of Leishmania strains.

Mercury determination in hair of Malaysian fishermen by neutron activation analysis.

Fish has been known as a source of nonoccupational mercury exposure to fish-consuming population groups. In this study, hair samples collected from fishermen and their families residing in an industrialized area in Penang and a nonindustrialized area in Terengganu were analyzed for mercury by neutron activation. The range, arithmetic mean, geometric mean, and median of the mercury concentrations for the groups in Penang and in Terengganu were 0.45-16.68, 3.61, 3.49, and 2.96 and 6.79-18.31, 12.08, 11.69, and 12.05 mg/kg, respectively. Somewhat lower values than from the Penang group were found in a group from Selangor consisting mainly of office workers. The group in Penang took about 40-100 g of fish/d, whereas the group in Terengganu consumed twice as much. This shows that hair mercury levels depend on a fish consumption pattern, and not on the location of the population. The levels of mercury found in this study were similar to those reported by other workers for fish-consuming population groups worldwide.