Prevalence of peripheral neuropathy among type 2 diabetes mellitus patients in a rural health centre in South India

International Journal of Diabetes in Developing Countries - There is a huge burden of diabetes-related complications, both microvascular and macrovascular, in India. With the rising prevalence of...     

Regulatory Actions of Toll-Like Receptor 2 (TLR2) and TLR4 in Leishmania donovani Infection in the Liver

In livers of susceptible but self-curing C57BL/6 mice, intracellular Leishmania donovani infection enhanced Toll-like receptor 4 (TLR4) and TLR2 gene expression. In the liver, infected TLR4^−/− mice showed reduced gamma interferon (IFN-γ), tumor necrosis factor (TNF), and inducible nitric oxide synthase (iNOS) mRNA expression, higher-level and slowly resolving infection, delayed granuloma formation, and little response to low-dose chemotherapy; in serum, the ratio of IFN-γ to interleukin 10 (IL-10) activity was decreased by 50%. In contrast, in TLR2^−/− mice, control of liver infection, parasite killing, and granuloma assembly were accelerated and chemotherapy''s efficacy enhanced. In livers of infected TLR2^−/− mice, mRNA expression was not increased for inflammatory cytokines or iNOS or decreased for IL-10; however, the serum IFN-γ/IL-10 ratio was increased 6.5-fold and minimal responses to IL-10 receptor blockade suggested downregulated IL-10. In established infection in wild-type mice, blockading TLR2 induced parasite killing and triggering TLR4 strengthened resistance and promoted chemotherapy''s effect. Thus, in experimental L. donovani infection in the liver, TLR4 signaling upregulates and TLR2 signaling downregulates macrophage antileishmanial activity, making both receptors potential therapeutic targets in visceral leishmaniasis for engagement (TLR4) or blockade (TLR2).     

Expression of glial antigens in mouse astrocytes: Species differences and regulation in vitro

Expression of developmentally regulated antigens was used to characterize glial cells in cultures from embryonic mouse cerebral cortex. Over 90% of the cells had a flat morphology, and about 50% of these flat cells also expressed the ganglioside GD3. Up to 40% of all the GD3 expressing cells also expressed A2B5 antigen. Flat cells expressing either glial fibrillary acidic protein (GFAP), or GD3 or both were present at all times in vitro. These three populations of flat cells could not be further distinguished on the basis of NG2 or fibronectin expression, or with respect to their responses to the mitogens FGF-2, PDGF, or EGF. The glial cultures also contain a small number ( ∼5%) of process bearing cells with the morphological and immunocytochemical characteristics of oligodendrocyte precursors. The expression of GD3 by flat cells changed with time in culture as the fraction of flat cells expressing only GD3 declined and the fraction of cells expressing GFAP (with or without GD3) increased. The data are consistent with those flat cells expressing only GD3 being astrocyte precursors. Furthermore, between 1 and 3 weeks in vitro GD3/GFAP cells lose GD3 while retaining GFAP. Cells expressing only GFAP could be induced to express GD3 and A2B5 by treatment with FGF-2. The widespread and regulated expression of GD3 and A2B5 by murine glia is different from the restricted pattern of expression previously reported for these antigens in rat brain cell cultures. These results demonstrate that expression of GD3 and A2B5 by murine astrocytes depends on both culture age and extracellular signals and that these gangliosides are not markers for cell lineage in the mouse. © 1996 Wiley-Liss, Inc.     

Epidemiological studies on pulmonary pathogens in HIV-positive and -negative subjects with or without community-acquired pneumonia with special emphasis on Mycoplasma pneumoniae

The prevalence of Mycoplasma pneumoniae among HIV-positive patients with community-acquired pneumonia (CAP) remains unclear. We investigated 300 HIV-positive adults (200 with CAP and 100 with no respiratory illness) and 75 HIV-negative adults with CAP for the prevalence of respiratory pathogens using culture and serology. A growth inhibition test was employed to confirm the isolates of M. pneumoniae using species-specific typing sera. The prevalence of M. pneumoniae in HIV-positive subjects was 17% by induced sputum and 11.3% by throat swab culture. The seroprevalence of anti-M. pneumoniae IgM was 11.7% by ELISA and 14.3% by the gelatin microparticle agglutination test. The prevalence of M. pneumoniae among HIV-negative cases was relatively low. Streptococcus pneumoniae was predominant (28%) among subjects with lower respiratory disease, whereas Staphylococcus aureus (15%) was common among upper respiratory symptomatic cases. Rales (P=0.001), pharyngeal erythema (P=0.02), cervical adenopathy (P=0.004), skin rash (P=0.001), and crepitations (P=0.001) were each significantly related to M. pneumoniae positivity. Statistical significance was observed in relation to total lymphocyte count (P=0.02) and erythrocyte sedimentation rate (P=0.04), as well as M. pneumoniae positivity. This study shows that the prevalence of M. pneumoniae in HIV-positive subjects is comparatively higher than in HIV-negative subjects with pulmonary symptoms, and concords with previous pilot studies carried out in Chennai, South India.     

Pharmacokinetic interaction between ethinyl estradiol, norethindrone and darunavir with low-dose ritonavir in healthy women

BACKGROUND: An open-label, randomized, crossover study was performed to investigate the effect of multiple doses of darunavir co-administered with low-dose ritonavir (DRV/r) on the steady-state pharmacokinetics of the oral contraceptives ethinyl estradiol (EE) and norethindrone (NE) (commercial name of the combined drug Ortho-Novum 1/35) in 19 HIV-negative healthy women. METHODS: In session 1, participants received 35 microg EE and 1.0 mg NE from days 1 to 21. In session 2, participants received the same oral contraceptive treatment as in session 1 on days 1 to 21 plus DRV/r (600 mg/100 mg twice daily) on days 1 to 14. Pharmacokinetic assessments were performed on day 14 for each session. RESULTS: Steady-state systemic exposure to EE and NE decreased when DRV/r was co-administered, based on the ratio of least square means of the minimum plasma concentration (Cmin), the maximum plasma concentration (Cmax), and the area under the curve (AUC24h) of EE (which decreased by 62%, 32% and 44%, respectively) and NE (which decreased by 30%, 10% and 14%, respectively) compared with administration of EE and NE alone. Five participants discontinued the study due to grade 2 cutaneous events, as required per protocol, during treatment with EE and NE in combination with DRV/r. There were no clinically relevant findings for laboratory and cardiovascular parameters. CONCLUSIONS: The pharmacokinetic interaction observed here is considered to be clinically relevant as EE concentrations are considerably reduced when DRV/r is co-administered with EE and NE. Alternative or additional contraceptive measures should be used when oestrogen-based contraceptives are co-administered with DRV/r.     

Immune reconstitution inflammatory syndrome in association with HIV/AIDS and tuberculosis: Views over hidden possibilities

Background  

CD4+ T lymphocyte (CD4) cell count testing is the standard method for determining eligibility for antiretroviral therapy (ART), but is not widely available in sub-Saharan Africa. Total lymphocyte counts (TLCs) have not proven sufficiently accurate in identifying subjects with low CD4 counts. We developed clinical algorithms using TLCs, hemoglobin (Hb), and body mass index (BMI) to identify patients who require ART.     

Evidence That Alpha-9 Human Papillomavirus Infections are a Major Etiologic Factor for Oropharyngeal Carcinoma in Black South Africans

Human papillomavirus (HPV) infection, most commonly genotype 16 of the alpha-9 family, is implicated in the etiology of a subset of oropharyngeal squamous cell carcinomas (OPSC) worldwide. Data are scarce regarding OPSC in South Africans, and three prior studies suggest no significant etiologic role for HPV. We aimed to investigate for evidence of HPV etiology in OPSCs from black South Africans by polymerase chain reaction (PCR) methodologies with determination of HPV subtype by sequencing, in situ hybridization (ISH), and p16^INK4a immunohistochemistry (IHC), as a surrogate marker for an HPV-driven tumor. It was hypothesized that HPV-driven tumors would be positive by PCR plus IHC and/or ISH whereas OPSCs with HPV background infections (HPV-passenger) would be positive by PCR alone. Formalin-fixed, paraffin-embedded tissues from 51 OPSCs collected between 2005 and 2010 from 41 patients were analyzed for HPV by GP5+6+ PCR (targeting the HPV L1 region), pU-1M/pU-2R PCR (targeting the HPV E6/E7 region) and HPV-31 specific PCR (targeting the E5 region), chromogenic ISH, and p16^INK4a IHC. All cases positive by PCR were subject to sequencing to determine HPV genotype. The patient mean age was 58.0 years and 88 % were male. Of the 51 evaluable tumors, 48 (94.1 %) were positive for HPV DNA by PCR: 25 (49.1 %) met criteria for an HPV-driven tumor, 23 (45.1 %) for HPV-passenger, and 3 (5.9 %) were HPV-unrelated. Sequencing of the PCR-positive cases revealed the following genotypes: combined HPV-16 and 31 (41.7 %), HPV-31 (25.0 %), HPV-16 (22.9 %), combined HPV-16 and 18 (6.3 %), and a single case each of HPV 18 and HPV 33. Studies via ISH were negative in all cases. In accordance with worldwide trends but contrary to prior South African data, HPV likely plays an etiologic role in a significant subset (at least 49.1 %) of OPSC in black South Africans. We found that the alpha-9 HPV family, particularly HPV-16 and 31 either in combination or separately, to predominate in our sample tumors. The use of multiple PCR primers increased sensitivity of viral detection, and a HPV-31 specific primer confirmed the presence of this genotype in many samples. Further studies including HPV E6/E7 mRNA assays are needed to better elucidate the pathogenic role of HPV in black South African OPSCs.