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Biomedical subjects

S Solomon

Publications and source records attributed to S Solomon.

At least 505 records · Page 28Linked to original sources

HIV-1 drug resistance among untreated patients in India: Current status.

HAART has dramatically improved survival and quality of life among people living with HIV and AIDS globally. However, drug resistant mutations of HIV are a great challenge to the benefits of HAART. Antiviral resistance can be mediated either by changes in the molecular target of therapy (the primary mechanism observed in HIV-1) or in other viral proteins that indirectly interfere with a drug's activity. Drug resistant mutations easily evolve in the presence of sub-optimal adherence. With the introduction of generic HAART, there has been a steep increase in the number of patients put on HAART in India. It should also be noted that since most patients pay for medications out of their own pockets, interruptions in therapy due to monetary constraints are not uncommon. There is little information on HIV drug resistance in resource constrained settings like India where the predominant circulating HIV-1 sub-type is C. The transmissibility of drug-resistant forms of the virus is also a major concern especially when formulating treatment guidelines. This article reviews published data available on the patterns of HIV-1 drug resistance among treatment naïve in India.

Acquired Immunodeficiency Syndrome↗

Cyclic nucleotide concentrations in relation to renal growth and hypertrophy.

In rats no consistent change in the concentration of cyclic GMP or cyclic AMP concentration was found in the renal cortex between 2 hours and seven days after unilateral nephrectomy. In regenerating liver tissue, between 2 hours and seven days after removal of one-third of the liver, there were no consistent changes in cyclic GMP concentrations, but cyclic AMP concentrations were higher than in controls. During postnatal growth, no consistent changes occurred in the cyclic GMP concentration of the spleen, the testes, the kidney cortex, the renal papilla, the liver or the ventricle between two and sixty days after birth. Cyclic AMP concentration on the other hand, in all these tissues with the exception of the spleen, was depressed between the twenty-first and fortieth day after birth, i.e., at a period of rapid growth. In the spleen, the concentration of cyclic AMP increased continuously from the second to the fifth day after birth. During renal parenchymal hyperplasia induced by a large intravenous dose of folic acid two days before sacrifice, the concentration of cyclic GMP in renal cortical tissue increased consistently. A model is proposed to explain the different patterns of changes in the cyclic nucleotide concentrations found.

Animals↗

[In vitro effects of peptides of the corticostatin/defensin family on production of mitogen-induced cytokines].

Cytokines are autocrine, paracrine and endocrine glycoproteins that interact with specific cell receptors and have pleiotropic effects. Increasing evidence indicates that cytokines, immune interferon (IFN-gamma) and interleukin 6 (IL-6) among others, modulate hypothalamic-pituitary-adrenal function. Corticostatins/defensins are a family of cationic peptides recently isolated from phagocytic cells of myeloid lineage. Four peptides have been isolated from human neutrophils: HP-1, 2, 3 and 4. As defensins they participate in immunosurveillance against viruses, bacteria and fungi. Some members of the family are also able to inhibit ACTH-induced steroidogenesis. Among human peptides, only HP-4 is corticostatic. We previously demonstrated that HP-1 and HP-4 inhibit in vitro the spontaneous and cytokine-inducible natural killer activity of human peripheral blood mononuclear cells (PBMC) and potentiate cortisol-dependent inhibition. The present work was carried out to determine whether two human corticostatins/defensins, HP-1 and HP-4, were able to modulate in vitro IFN-gamma and IL-6 production by human PBMC stimulated with phytohemagglutinin or Concanavalin A. IFN-gamma was titrated using biological assay with WISH cells as indicators and vesicular stomatitis virus as the challenge virus. IL-6 was measured by means of enzyme amplified sensitivity immunoassay. Both HP-1 and HP-4 significantly reduced cytokine production. Our data indicate that HP-1 and HP-4 are novel modulators of lymphocyte functions in vitro. Their depressing properties on ACTH-induced steroidogenesis and on cytokine production add complexity to neuroendocrine-immune circuits involving hypothalamic-pituitary-adrenal function.

Anti-Bacterial Agents↗

Preventing HIV transmission: behavior and attitudes of medical house staff in a high-prevalence area.

Our objective was to evaluate human immunodeficiency virus (HIV) risk-factor assessment and counseling behavior in 86 medical house staff and to ascertain the effect of question format (closed versus open) on reported physician behaviors. We designed a cross-sectional survey using a self-report questionnaire; we received 78 returns of 86 questionnaires (91% response) from one-year and three-year medical housestaff at two general medical clinics in a university-affiliated Bronx municipal hospital. House staff reported assessing sexual behavior (51%) and intravenous drug use (81%) in new patients significantly less often than they assessed smoking (95%) or alcohol use (94%). Counseling to reduce the risk of HIV transmission among all patients occurred even less frequently (41%, all P < .05). Question format (closed versus open) significantly affected response rate; respondents to closed-format questions reported far more behaviors performed. Intravenous drug users (IVDUs) received more frequent advice than general clinic patients about reducing HIV transmission (85% versus 41%), but house staff may ignore sexual risks in IVDUs. Resident confidence that IVDUs would change sexual or drug risk behavior was equally low, 1.5 on a 4-point scale. They reported greater discomfort discussing sexuality than drug use (2.4 versus 1.7; 4-point scale, P = .003). Discomfort discussing sexuality inversely associated with sexual history-taking in multi-variate analysis. Greater involvement with HIV positive patients and fewer perceived barriers to counseling were also associated with more assessment or counseling about risks for HIV transmission. These results suggest that enhancing house staff assessment and counseling efforts to reduce risks for HIV transmission requires interventions that foster involvement with HIV positive patients, emphasize the importance of sexual transmission in IVDUs, facilitate competence in discussing sexual behavior, and address provider belief that IVDUs will not change risk behaviors. Results also demonstrate a significant effect of question format on reported physician behavior.

Attitude of Health Personnel↗

[The autocrine-paracrine modulation of natural killer activity in man by peptides of the corticostatin-defensin family].

Corticostatins (CS)-defensins are a family of peptides recently isolated from neutrophils and cells of myeloid lineage. They have been termed CS in that members of the family inhibit ACTH-induced steroidogenesis, and defensins in that they are highly effective as enhancers of intracellular killing of pathogens. Natural killer (NK) cells are an immunocyte subset whose cytotoxic activity is modulated by lymphokines and hormones. Recent evidence suggests a myeloid origin for these cells. We evaluated whether two human CS-defensins, HP-1 and HP-4, are able to modulate in vitro spontaneous NK cell activity of human peripheral blood mononuclear (PBM) cells and in vitro susceptibility to the stimulatory effect by immune interferon (IFN-gamma) or interleukin 2 (IL-2) and to the inhibitory effect of cortisol. PBM cells were incubated for 20 h with HP-1 or HP-4 and IFN-gamma or IL-2 or cortisol. NK cell activity was measured in a 4-h direct cytotoxicity assay (K562 cells as a target). We also searched for CS-defensins in NK-enriched cell preparations by means of HPLC separation of the supernatant obtained from sonicated cells. HP-1 and HP-4 significantly inhibited both spontaneous and lymphokine-inducible NK cell activity, and potentiated cortisol-dependent inhibition. Radioimmunoassay on HPLC purified fractions demonstrated the presence of HP-1 in NK-enriched cell preparations. Our data indicate that HP-1 and HP-4 are negative modulators of NK cell cytotoxicity and that autocrine/paracrine mechanisms are conceivably involved. HP-1 production by NK cells may be viewed as additional support for the thesis of the myeloid origin of these immune effectors.

Blood Proteins↗