Drug and Alcohol Rehabilitation: Targeting the Androgen Receptor in the Management of Castration-Resistant Prostate Cancer: Rationale, Progress, and Future Directions.

Targeting the androgen receptor in the management of castration-resistant prostate cancer: rationale, progress, and future directions.

Filed under: Drug and Alcohol Rehabilitation

Curr Oncol. 2012 Dec; 19(Suppl 3): S22-31
Leibowitz-Amit R, Joshua AM

Since the year 2000, tremendous progress has been made in the understanding of castration-resistant prostate cancer (crpc), a disease state now recognized to retain androgen receptor (ar)-dependency in most cases. That understanding led to the rational design of novel therapeutic agents targeting hormonal pathways in metastatic crpc. Two new drugs-the CYP17 inhibitor abiraterone acetate and the potent ar antagonist enzalutamide-were recently shown to prolong overall survival after chemotherapy treatment in patients with metastatic disease, with the former agent also demonstrating impressive activity in the pre-chemotherapy setting. Other new drugs targeting the ar-as well as drugs targeting heat shock proteins that protect cytoplasmic ar from degradation-are currently undergoing clinical development.This review briefly describes the molecular mechanisms underlying castration resistance and hormonal dependence in prostate tumours and summarizes the current ongoing and completed clinical trials that are targeting hormonal pathways in metastatic crpc. Potential mechanisms of resistance to these novel hormonal agents are reviewed. Finally, future research directions, including questions about drug sequencing and combination, are discussed.
HubMed – drug


Design, physicochemical characterization, and optimization of organic solution advanced spray-dried inhalable dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylethanolamine poly(ethylene glycol) (DPPE-PEG) microparticles and nanoparticles for targeted respiratory nanomedicine delivery as dry powder inhalation aerosols.

Filed under: Drug and Alcohol Rehabilitation

Int J Nanomedicine. 2013; 8: 275-93
Meenach SA, Vogt FG, Anderson KW, Hilt JZ, McGarry RC, Mansour HM

Novel advanced spray-dried and co-spray-dried inhalable lung surfactant-mimic phospholipid and poly(ethylene glycol) (PEG)ylated lipopolymers as microparticulate/nanoparticulate dry powders of biodegradable biocompatible lipopolymers were rationally formulated via an organic solution advanced spray-drying process in closed mode using various phospholipid formulations and rationally chosen spray-drying pump rates. Ratios of dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylethanolamine PEG (DPPE-PEG) with varying PEG lengths were mixed in a dilute methanol solution. Scanning electron microscopy images showed the smooth, spherical particle morphology of the inhalable particles. The size of the particles was statistically analyzed using the scanning electron micrographs and SigmaScan(®) software and were determined to be 600 nm to 1.2 ?m in diameter, which is optimal for deep-lung alveolar penetration. Differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) were performed to analyze solid-state transitions and long-range molecular order, respectively, and allowed for the confirmation of the presence of phospholipid bilayers in the solid state of the particles. The residual water content of the particles was very low, as quantified analytically via Karl Fischer titration. The composition of the particles was confirmed using attenuated total-reflectance Fourier-transform infrared (ATR-FTIR) spectroscopy and confocal Raman microscopy (CRM), and chemical imaging confirmed the chemical homogeneity of the particles. The dry powder aerosol dispersion properties were evaluated using the Next Generation Impactor™ (NGI™) coupled with the HandiHaler(®) dry powder inhaler device, where the mass median aerodynamic diameter from 2.6 to 4.3 ?m with excellent aerosol dispersion performance, as exemplified by high values of emitted dose, fine particle fraction, and respirable fraction. Overall, it was determined that the pump rates defined in the spray-drying process had a significant effect on the solid-state particle properties and that a higher pump rate produced the most optimal system. Advanced dry powder inhalers of inhalable lipopolymers for targeted dry powder inhalation delivery were successfully achieved.
HubMed – drug


Management of chronic pain in elderly, frail patients: finding a suitable, personalized method of control.

Filed under: Drug and Alcohol Rehabilitation

Clin Interv Aging. 2013; 8: 37-46
Rastogi R, Meek BD

The elderly population is projected to make up 20% of the total United States population by the year 2030. In addition, epidemiological data suggests increasing prevalence of chronic pain and frailty with advancing age. Pain, being a subjective symptom, is challenging to manage effectively. This is more so in elderly populations with age-specific physiological changes that affect drug action and metabolism. Elderly patients are also more likely to have multiple chronic health pathologies, declining function, and frailty. The barriers present for patients, providers, and health systems also negatively impact efficient and effective pain control. These factors result in disproportionate utilization of health resources by the older population group. The scientific literature is lagging behind in age-specific studies for the elderly population. As a result, there is a lack of age-specific standardized management guidelines for various health problems, including chronic pain. Increasing efforts are now being directed to studies on pain control in the elderly. However, pain management remains inconsistent and suboptimal. This article is an attempt to suggest an informed, comprehensive guide to achieve effective pain control in the presence of these limitations.
HubMed – drug


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