Objective: Aging people living with HIV (PLWH), especially post-menopausal women may be at higher risk of comorbidities associated with HIV, ART, hypogonadism and at-risk alcohol use. Our studies in simian immunodeficiency virus (SIV)-infected male macaques demonstrated that chronic binge alcohol (CBA) reduced acute insulin response to glucose (AIRG), and at-risk alcohol use decreased HOMA-β in PLWH. The objective of this study was to examine the impact of ovariectomy (OVX), on glucose-insulin dynamics and integrity of pancreatic endocrine function in CBA/SIV-infected female macaques. Methods: Female macaques were administered CBA (12-15 g/kg/week) or isovolumetric water (VEH) intragastrically. Three months after initiation of CBA/VEH administration, all macaques were infected with SIVmac251, and initiated on anti-retroviral therapy (ART) 2.5 months post-infection. After one month of ART, macaques were randomized to OVX or sham surgeries (N=7-8/group), and euthanized 8 months post-OVX (study endpoint). Frequently sampled intravenous glucose tolerance tests (FSIVGTT) were performed at selected timepoints. Pancreatic gene expression and islet morphology were determined at study endpoint. Results: There was a main effect of CBA to decrease AIRG at Pre-SIV and study endpoint. There were no statistically significant OVX effects on AIRG (p=0.06). CBA and OVX decreased expression of pancreatic markers of insulin docking and release. OVX increased endoplasmic stress markers. Conclusions: CBA but not OVX impaired glucose-insulin expression dynamics in SIV-infected female macaques. Both CBA and OVX altered integrity of pancreatic endocrine function. These findings suggest increased vulnerability of PLWH to overt metabolic dysfunction, that may be exacerbated by alcohol use and ovarian hormone loss.
Benznidazole (Bz) is the recommended drug for the treatment of Chagas disease; however, its efficacy may vary according to the sensitivity of Trypanosoma cruzi strains to the drug and host immune background. The study evaluated the immune response of peripheral blood mononuclear cells (PBMC) that were infected in vitro with the Colombian strain (Col) and treated with Bz. The co‐cultures were incubated for 24 h, 5 and 10 days, where cytokine dosage was performed in the supernatant and evaluation of the cells for CD28+ and CTLA‐4+ molecules in CD4+ and CD8+ lymphocytes, and CD80+, CD86+ and HLA‐DR+ in CD14+ cells. The results showed that Col induced a strong inflammatory response, with an increase in IFN‐γ and TNF early in the infection (24 h), however, from 5 days of infection on, TNF production declined, and IL‐10 production increased, which may be associated with a control mechanism of the exacerbated inflammatory response. The Bz treatment did not significantly alter the frequencies of the phenotypes evaluated both T cell subsets and CD14+ cells. Therefore, this study reinforces the need for typing the patient's strain to guide therapy and promote individualized treatment protocols due to the heterogeneous genetic background among T. cruzi strains.
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