Preparation of polylactide-co-glycolide and chitosan hybrid microcapsules of amifostine using coaxial ultrasonic atomizer with solvent evaporation

The objective of this study was to evaluate the effect of various processing and formulation factors on the characteristics of amifostine hybrid microcapsules. Amifostine-loaded hybrid microcapsules were prepared using PLGA and chitosan. In short, amifostine powder was dissolved in de-aerated water with or without chitosan. The amifostine solution was later emulsified into PLGA solution in dichloromethane containing phosphatidylcholine. The resultant emulsion was fed through the inner capillary of a coaxial ultrasonic atomizer. The liquid fed through the coaxial outer capillary was either water or chitosan solution. The atomized droplets were collected into PVA solution and the droplets formed microcapsules immediately. The hybrid microcapsules prepared with chitosan solution only as an outer layer liquid showed the maximum efficiency of encapsulation (30%). The median sizes of all three formulations were 33-44 microm. These formulations with chitosan showed positive zeta-potential and sustained drug release with 13-45% amifostine released in 24 h. When chitosan was incorporated into inner as well as outer liquid layers, the drug release increased significantly, 45% (compared with other formulations) released in 24 h and almost 100% released in 11 days. Hybrid microcapsules of amifostine showed moderately high efficiency of encapsulation. The cationic charge (due to the presence of chitosan) of these particles is expected to favour oral absorption and thus overall bioavailability of orally administered amifostine.     

Exploring the challenges for clinical pharmacists in Sudan

Background Clinical pharmacy practice in hospitals is a new role for pharmacists in Sudan. Pharmacists have to face the challenge of moving from their traditional roles within the pharmacy premises to new roles on the wards with direct contact with patients and other healthcare professionals. Objectives To explore the role and challenges facing the clinical pharmacists of Sudan. Settings Two of the main government hospitals in Sudan and an online survey. Method This study applied a two phase mixed method, a focus group discussion and a survey. A FGD was conducted with the clinical pharmacists in two of the main government hospitals in Sudan. This was followed by an on-line survey among the clinical pharmacists of Sudan. Main outcome measure The role of the clinical pharmacists of Sudan and the challenges facing clinical pharmacy practice. Results Four pharmacists participated in the focus group and 51 out of 140 pharmacists (34%) completed the on-line survey. The roles that were perceived by the majority of pharmacists as part of their duties in hospitals in Sudan were identifying drug-related problems (100%, n = 51), providing drug-related information to healthcare professionals by (96%, n = 47), and educating patients about their medicines (96%, n = 48). The pharmacists identified a number of obstacles that hindered their progress in practice. These obstacles were related to the pharmacists themselves, the lack of senior clinical pharmacists for leadership, the environment they were working in and the training they had received in clinical pharmacy. Conclusion The new clinical pharmacists in Sudan faced several challenges that need to be overcome in order to move forward in their clinical practice. To do so they will require support from pharmacy educational institutions, other healthcare professionals and the healthcare institutions they are working within.     

Awakening the sleeping kidney in a dialysis-dependent patient with fibromuscular dysplasia: A case report and review of literature

Renal artery stenosis is a common cause of secondary hypertension and chronic kidney disease. We present here a case of fibromuscular dysplasia that was treated with surgical revascularization, resulting in recovery of kidney function with eventual cessation of chronic dialysis. The case involves a 25-year-old female with coincidentally discovered hypertension, who underwent further investigations revealing a diagnosis of renal artery stenosis due to fibromuscular dysplasia. She subsequently developed two episodes of malignant hypertension, with flash pulmonary oedema and worsening renal failure that resulted in dialysis dependence. After evidence was obtained that the right kidney was still viable, a revascularization procedure was performed, improving blood pressure control and restoring kidney function, thereby allowing dialysis to be stopped. This case highlights the importance of evaluating patients with renal artery stenosis for revascularization before committing them to a life of chronic dialysis.     

External Validation of the European Association of Urology Biochemical Recurrence Risk Groups to Predict Metastasis and Mortality After Radical Prostatectomy in a European Cohort

The impact of biochemical recurrence (BCR) after radical treatment of prostate cancer on oncological outcomes remains unclear. A new European Association of Urology BCR risk stratification (low and high risk) has been proposed. To validate these risk groups, we retrospectively analyzed data for 1125 post-radical prostatectomy (RP) BCR patients (surgery between 1992 and 2006). Univariable Kaplan-Meier plots and multivariable Cox regression models with time-dependent covariates were used to test the independent predictor status of the risk grouping on metastatic progression (MP) and prostate cancer-specific mortality (PCSM). The 5-yr MP-free and PCSM-free survival rates were significantly higher among patients with low BCR risk compared to their high-risk counterparts. In multivariable analyses, the BCR risk grouping reached independent predictor status for MP (hazard ratio [HR] 3.46; p < 0.001) and PCSM (HR 5.12; p < 0.001). Salvage radiation therapy, especially when delivered at prostate-specific antigen <0.5 ng/ml, was highly protective. Our findings corroborate the validity of this novel BCR risk grouping, which is easily applicable in daily practice and could be valuable in decision-making for salvage therapy and clinical trials.Patient summaryThe European Association of Urology grouping for the risk of biochemical recurrence of prostate cancer after radical prostatectomy was valid when applied in a European study cohort.     

Potential Risk Factors for Breast Cancer in Pakistani Women

Background: Breast cancer is the most common female malignancy worldwide and its incidence is on the rise in Pakistan. The aim of this case-control study was to quantify the association of various risk factors with breast cancer risk among Pakistani women. Materials and Methods: A total of 2,246 women were studied, including 1,238 women with histologically confirmed breast cancer patients and age matched control subjects (N1008) without breast cancer and other chronic diseases. Subjects were interviewed using a specifically designed questionnaire. Unconditional logistic regression was applied. Subsequent disease-specific mortality was also measured. Results: In this study, majority of the breast cancer patients (69.59%) were in age ranges of 40s and 50s. BMI greater than 25kg/m2 (OR1.57; 95%CI, 1.26-1.90 and OR1.60; 95%CI, 1.26-2.03), marital status of unmarried (OR2.03; 95%CI, 1.69-2.44), lack of breast feeding, smoking (current or ever), lack of physical activity and post-menopausal status were found to have significant positive associations with breast cancer. It was also observed that increased parity reduced the disease risk. A larger number of cases (58.1%) had their right breast affected while 22.8% had other complications as well. Conclusions: This exploratory analysis indicated a number of risk factors to be associated with increased risk of breast cancer. It was also observed that mean age at diagnosis is a decade earlier than in western countries. It is hoped that our findings will facilitate establishment of adequate evidence-based awareness and preventive measures for Pakistani women.     

4-[18F]fluoroglutamic acid (BAY 85-8050), a new amino acid radiotracer for PET imaging of tumors: synthesis and in vitro characterization

There is a high demand for tumor specific PET tracers in oncology imaging. Besides glucose, certain amino acids also serve as energy sources and anabolic precursors for tumors. Therefore, (18)F-labeled amino acids are interesting probes for tumor specific PET imaging. As glutamine and glutamate play a key role in the adapted intermediary metabolism of tumors, the radiosynthesis of 4-[(18)F]fluoro l-glutamic acid (BAY 85-8050) as a new specific PET tracer was established. Cell-uptake studies revealed specific tumor cell accumulation.     

Special focus on the role of α(1D)-adrenoreceptors in the assessment of renal tubular sodium re-absorptive responses in spontaneously hypertensive rats subjected to high sodium diet

α(1D)-adrenoceptors are involved in the genesis/maintenance of hypertension in spontaneously hypertensive rats (SHR). This study aims to investigate the role of α(1D)-adrenoceptors in the antinatriuretic and antidiuretic responses in SHR subjected to high sodium (SHRHNa) and normal sodium (SHRNNa) intake for six weeks. Renal inulin clearance study was performed in which the antinatriuretic and antidiuretic responses to phenylephrine were examined in the presence and absence of α(?D)-adrenoceptors blocker BMY7378. Data, mean±S.E.M. were subjected to ANOVA with significance at p<0.05. Results show that feeding SHR for six weeks with high salt did not cause any change in blood pressure. SHRHNa had higher (all p<0.05) urine flow rate (UFR), fractional and absolute excretion of sodium (FE(Na) and U(Na)V) compared to SHRNNa. Phenylephrine infusion produced significant reduction in UFR, FE(Na) and U(Na)V in both SHRHNa and SHRNNa. The antidiuretic and antinatriuretic responses to phenylephrine in both groups were attenuated in the presence of BMY7378. Moreover, the antidiuretic and antinatriuretic responses to phenylephrine and BMY7378 were independent on any significant changes in renal and glomerular hemodynamics in both groups. Thus we conclude that high sodium intake did not bring any further increase in blood pressure of SHR, however, it results in exaggerated natriuresis and diuresis in SHRHNa. Irrespective of dietary sodium changes, α?-adrenoceptors are involved in mediating the antinatriuretic and antidiuretic responses to phenylephrine in SHR. Further, high sodium intake did not significantly influence the functionality of α(?D)-adrenoceptors in mediating the adrenergically induced antinatriuresis and antidiuresis.