The maraviroc expanded access program — safety and efficacy data from an open-label study

Purpose:

The maraviroc (MVC) expanded access program (EAP) was initiated to increase MVC availability to patients with limited treatment options. Darunavir (DRV), raltegravir (RAL), and etravirine (ETV) were either recently approved or under regulatory review at study initiation and available for coadministration with MVC. Thus, the safety of MVC in combination with new antiretroviral therapies (ARVs) could be assessed. This open-label safety study of MVC was conducted at 262 sites worldwide in 1032 R5 HIV-positive treatment-experienced patients with limited/no therapeutic options.

Methods:

Study visits included screening, baseline, end of study or early discontinuation, and follow-up 30?days after last dose. Interim visits for HIV-1 RNA and CD4 cell counts occurred according to local HIV infection management guidelines. Safety data were analyzed overall and by subgroup based on ARV combination [MVC+optimized background therapy (OBT), MVC?±?OBT+DRV/r, MVC?±?OBT+RAL, MVC?±?OBT+RAL+DRV/r, MVC?±?OBT+RAL+ETV?±?DRV/r].

Results:

Most (90.3%) adverse events (AEs) were of mild or moderate severity with few grade 3/4 events, discontinuations, or temporary discontinuations/dose reductions due to AEs or serious AEs. Similar results were observed across subgroups. Of treated patients, 79.9% and 50% had HIV-1 RNA Conclusion:

MVC was well tolerated with virologic suppression observed in most patients.     

Angio-Suppressive Effect of Partially Purified Lectin-like Protein from Musa acuminata pseudostem by Inhibition of VEGF-Mediated Neovascularization and Induces Apoptosis Both In Vitro and In Vivo

Lifestyle and nutritional changes have contributed much to the somatic genetic changes which have concurrently led to an increase cancer in humans. Hence the plant-based and nutritional involvements block oncogenic transformation are in good demand. We evaluate Phloem exudates of the dietary plant, Musa acuminate pseudostem, the initial domesticated plant species with the effective lectin activity for its functional role against the tumor development and its mechanism of action. Our experimental data exhibit that Musa acuminata Lectin Protein (MALP) shows a promising cytotoxic effect against the various human cancer cell lines. Supporting this, we evaluate the in vivo anti-tumor and anti-angiogenic activity of MALP in Ehrlich Ascites Carcinoma mice model (EAC). MALP treatment resulted in tumor growth inhibition and increased the lifespan of the EAC-bearing mice without showing any side effects on normal mice, as revealed by histological parameters. Further, a significant decrease in the ascites vascular endothelial growth factor (VEGF) secretion and microvessel density supports the anti-angiogenic property of the MALP. Apoptosis-inducing activity of MALP was revealed by DNA fragmentation assay, Caspase-3 inhibitor assay and cellular morphology were studied by fluorescence staining methods. Our study delivers the real evidence that MALP with a promising an anticancer potential expressively degenerates the tumor development by affecting angiogenesis and apoptosis.     

Effect of Sirolimus Withdrawal in Patients with Deteriorating Renal Function

Sirolimus has been an important addition to immunosuppressive regimens utilized in kidney transplantation. However, sirolimus can potentiate calcineurin inhibitor (CNI) nephrotoxicity by some still uncertain mechanisms. Studies have demonstrated that withdrawal of a CNI under sirolimus immunosuppression can improve renal function. However, it has yet to be demonstrated that withdrawal of sirolimus from such a regimen can also improve renal function and reverse progressive functional deterioration. We studied 17 patients who developed deterioration of renal function while on a CNI and sirolimus. Once an established deterioration in renal function was noted, sirolimus was withdrawn from the regimen and replaced with mycophenolate mofetil. Out of 17 patients with a negative slope in 1/cr, 15 demonstrated a positive treatment effect (change to a positive slope). On aggregate, renal function improved by 18% (creatinine 2.75-2.24 mg/dL), LDL cholesterol improved, as did hematocrit values after withdrawal. The majority of patients on a CNI and sirolimus regimen who experience deterioration in renal function demonstrate improvement in renal function after withdrawal of sirolimus. This strategy may be particularly useful in those patients where CNI withdrawal is considered to be of high immunologic or metabolic risk.     

An unusual combination of idiopathic generalized short-root anomaly associated with microdontia, taurodontia, multiple dens invaginatus, obliterated pulp chambers and infected cyst: a case report

Generalized diminished root formation is a rare condition leading to early loss of teeth. This report describes an unusual case of generalized short roots associated with microdontia, taurodontism of posterior teeth, and multiple dens invaginatus along with short stature in a 20-year-old man, who had lost several teeth because of spontaneous exfoliation.