Functional Impairment of Central Memory CD4 T Cells Is a Potential Early Prognostic Marker for Changing Viral Load in SHIV-Infected Rhesus Macaques

In HIV infection there is a paucity of literature about the degree of immune dysfunction to potentially correlate and/or predict disease progression relative to CD4+ T cells count or viral load. We assessed functional characteristics of memory T cells subsets as potential prognostic markers for changing viral loads and/or disease progression using the SHIV-infected rhesus macaque model. Relative to long-term non-progressors with low/undetectable viral loads, those with chronic plasma viremia, but clinically healthy, exhibited significantly lower numbers and functional impairment of CD4+ T cells, but not CD8+ T cells, in terms of IL-2 production by central memory subset in response to PMA and ionomycine (PMA+I) stimulation. Highly viremic animals showed impaired cytokine-production by all T cells subsets. These results suggest that functional impairment of CD4+ T cells in general, and of central memory subset in particular, may be a potential indicator/predictor of chronic infection with immune dysfunction, which could be assayed relatively easily using non-specific PMA+I stimulation

Evaluation of Leishmania donovani Protein Disulfide Isomerase as a Potential Immunogenic Protein/Vaccine Candidate against Visceral Leishmaniasis

In Leishmania species, Protein disulfide isomerase (PDI) - a redox chaperone, is reported to be involved in its virulence and survival. This protein has also been identified, through proteomics, as a Th1 stimulatory protein in the soluble lysate of a clinical isolate of Leishmania donovani (LdPDI). In the present study, the molecular characterization of LdPDI was carried out and the immunogenicity of recombinant LdPDI (rLdPDI) was assessed by lymphocyte proliferation assay (LTT), nitric oxide (NO) production, estimation of Th1 cytokines (IFN-γ and IL-12) as well as IL-10 in PBMCs of cured/endemic/infected Leishmania patients and cured L. donovani infected hamsters. A significantly higher proliferative response against rLdPDI as well as elevated levels of IFN-γ and IL-12 were observed. The level of IL-10 was found to be highly down regulated in response to rLdPDI. A significant increase in the level of NO production in stimulated hamster macrophages as well as IgG2 antibody and a low level of IgG1 in cured patient's serum was observed. Higher level of IgG2 antibody indicated its Th1 stimulatory potential. The efficacy of pcDNA-LdPDI construct was further evaluated for its prophylactic potential. Vaccination with this construct conferred remarkably good prophylactic efficacy (∼90%) and generated a robust cellular immune response with significant increases in the levels of iNOS transcript as well as TNF-α, IFN-γ and IL-12 cytokines. This was further supported by the high level of IgG2 antibody in vaccinated animals. The in vitro as well as in vivo results thus indicate that LdPDI may be exploited as a potential vaccine candidate against visceral Leishmaniasis (VL)

Modifying Provider Behavior: A Low-tech Approach to Pharmaceutical Ordering

OBJECTIVE: To determine if a clinically structured, paper-based prescription form can modify pharmaceutical prescribing behavior without restricting physician freedom to select the most appropriate medication for an individual patient. DESIGN: Uncontrolled, nonrandomized, time series design. SETTING: The urgent care clinic of a university-affiliated, county-supported hospital that provides care for underserved, vulnerable populations. PATIENTS: Patients (N = 2,189) who had a prescription written at the intervention site during the study. INTERVENTION: Four-phase interventions lasting 2 weeks each, with a washout period between each phase, consisting of: (1) collection of baseline data utilizing the traditional prescription blank, (2) introduction of the pre-formatted prescription form, (3) use of the pre-formatted prescription form with medication cost added, and (4) pre-formatted prescription form with target drug (ranitidine) removed. MEASUREMENTS AND MAIN RESULTS: Physicians were less likely to prescribe ranitidine compared to cimetidine after the introduction of the cost information (P < .01) and again after the removal of ranitidine from the pre-formatted prescription form (P < .001). CONCLUSIONS: A structured, paper-based prescription order form can shift prescribing practices without inhibiting physicians' ordering freedom

Comparison of plants used for skin and stomach problems in Trinidad and Tobago with Asian ethnomedicine

RefereedThis paper provides a preliminary evaluation of fifty-eight ethnomedicinal plants used in Trinidad and Tobago for skin problems, stomach problems, pain and internal parasites for safety and possible efficacy. Thirty respondents, ten of whom were male were interviewed from September 1996 to September 2000 on medicinal plant use for health problems. The respondents were obtained by snowball sampling, and were found in thirteen different sites, 12 in Trinidad and one in Tobago. The uses are compared to those current in Asia. Bambusa vulgaris, Bidens alba, Jatropha curcas, Neurolaena lobata, Peperomia rotundifolia and Phyllanthus urinaria are possibly efficacous for stomach problems, pain and internal parasites. Further scientific study of these plants is warranted