Design, Synthesis, Antiviral Activity, and Pre-Formulation Development of Poly-L-Arginine-Fatty Acyl Derivatives of Nucleoside Reverse Transcriptase Inhibitors

The objective of this work was to design conjugates of anti-HIV nucleosides conjugated with fatty acids and cell-penetrating poly-L-arginine (polyArg) peptides. Three conjugates of polyArg cell-penetrating peptides with fatty acyl derivatives of alovudine (FLT), lamivudine (3TC), and emtricitabine (FTC) were synthesized. In general, the compounds exhibited anti-HIV activity against X4 and R5 cell-free virus with EC50 values of 1.5–16.6 μM. FLT-CO-(CH2)12-CO-(Arg)7 exhibited EC50 values of 2.9 μM and 3.1 μM against X4 and R5 cell-free virus, respectively. The FLT conjugate was selected for further preformulation studies by determination of solution state degradation and lipid solubility. The compound was found to be stable in neutral and oxidative conditions and moderately stable in heated conditions. [Refer to PDF for graph

Primary Hyperparathyroidism in Pregnancy—A Rare Cause of Life-Threatening Hypercalcemia: Case Report and Literature Review

Objective. To report a case of primary hyperparathyroidism in a pregnant patient, report the obstetric and neonatal outcomes, and review the relevant literature. Results. A 29-year-old primigravida was successfully treated for PHP with minimally invasive resection of a parathyroid adenoma in the second trimester of pregnancy. A healthy baby girl was delivered at 37-week gestation with an unremarkable neonatal course. To the best of our knowledge, this is the second case report in the literature utilizing intraoperative PTH during a parathyroidectomy in a pregnant woman. Conclusions. Primary hyperparathyroidism is a rare life-threatening condition that can present during pregnancy. The diagnosis can be difficult to establish during pregnancy, given the nonspecific symptoms related to hypercalcemia. However, a better understanding of the condition, improved diagnostic studies, and well-organized multidisciplinary management decisions can significantly reduce the morbidity and mortality associated with the disease during pregnancy. This case report is presented to highlight the value of early diagnosis and appropriate management of PHP during pregnancy