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Highly active antiretroviral therapy dysregulates proliferation and differentiation of human pre-adipocytes

World Journal of Virology 2017年第3期6卷 53-58页

作者： Eyone Jones Pavel Mazirka Margaret A McNurlan frank darras Marie C Gelato Giuseppe Caso Department of Surgery Rutgers Robert Wood Johnson Medical School Department of Surgery Stony Brook University Medical Center Department of Urology Stony Brook University Medical Center Department of Medicine Stony Brook Uni-versity Medical Center

AIM To investigate the mechanism(s) by which potential effects of multi-drug highly-active antiretroviral therapy contributes to lipodystrophy syndrome. METHODS Preadipocytes from healthy donors were assessed for proliferation and differentiation in the presence of nucleoside reverse transcriptase inhibitors(NRTIs), nonnucleoside reverse transcriptase inhibitors(NNRTIs), and protease inhibitors(PIs) individually and in combination. Effects on proliferation were assessed with a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide assay and effects on differentiation were assessed from glycerol-3-phosphate dehydrogenase(GPDH) activity and quantitation of Oil Red O staining for intracellular lipid. Data were analyzed with a randomized block ANOVA with post-hoc Fisher's Least Significant Difference test. RESULTS Preadipocyte proliferation was inhibited by a combination of NNRTI + NRTI(14% at 48 h, P < 0.001) and PI + NRTI(19% at 48 h, P < 0.001) with additional suppression when ritonavir(RTV) was added(26% at 48 h). The drug combination of atazanavir(ATV) + RTV + emtricitabine(FTC) + tenofovir(TDF) had the greatest inhibitory effect on proliferation at 48 h. Preadipocyte differentiation was most significantly reduced by the efavirenz + FTC + TDF assessed either by GPDH activity(64%) or lipid accumulation(39%), P < 0.001. Combining NRTIs with a PI(ATV + FTC + TDF) significantly suppressed differentiation(GPDH activity reduced 29%, lipid accumulation reduced by 19%, P < 0.01). This effect was slightly greater when a boosting amount of RTV was added(ATV + FTC + TDF + RTV, P < 0.001). CONCLUSION Although combination antiretroviral therapy is clinically more efficacious than single drug regimens, it also has a much greater inhibitory effect on preadipocyte proliferation and differentiation.

关键词： Nucleoside reverse transcriptase inhibitors Non-nucleoside reverse transcriptase inhibitors Protease inhibitors Pre-adipocytes Highly active antiretroviral therapy Lipodystrophy

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Emphysematous Pyelonephritis in a Renal Transplant Patient

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Open Journal of Nephrology 2014年第2期4卷 86-91页

作者： Kashif J. Piracha frank darras Edward P. Nord Nand K. Wadhwa Division of Nephrology Department of Medicine Stony Brook Medicine Stony Brook USA Transplantation Services Stony Brook Medicine Stony Brook USA

Emphysematous pyelonephritis (EPN) is a necrotizing bacterial infection of the kidney that is caused by gas-forming organisms. We report a case of a 58-year-old man with a renal transplant who presented to the emergency room with nausea, vomiting and right lower quadrant abdominal pain. At the time of presentation, he was hemodynamically stable, and the abdominal examination was significant for tenderness over the allograft. Urinalysis was positive for large amounts of leukocyte esterase and white blood cells. He received empiric antibiotic coverage with piperacillin/tazobactam. Over the following 24 hours, the patient developed septic shock manifested by hemodynamic instability. A non-contrast CT scan of the abdomen and pelvis elucidated a heterogeneous gas containing collection in the allograft. Emergent transplant nephrectomy was performed. Postoperatively, the patient rapidly recovered and was subsequently discharged home to commence outpatient hemodialysis. A review of the literature suggests that early recognition of the severity of EPN as manifested by hemodynamic instability dictates emergent transplant nephrectomy as the treatment of choice.

关键词： Emphysematous Pyelonephritis Kidney Allograft Transplant

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