Decoupling the Contribution of Surface Energy and Surface Area on the Cohesion of Pharmaceutical Powders

Pharmaceutical Research - Surface area and surface energy of pharmaceutical powders are affected by milling and may influence formulation, performance and handling. This study aims to decouple the...     

The pharmacological treatment and management of obesity

Obesity is a pandemic with many complications that increase the societal disease burden and cost of health care, and decrease longevity and quality of life. Currently, 1 in 3 adults in the United States is obese. Physicians must therefore regularly confront obesity and its consequent diseases, and develop strategies for effective treatment and management. This article summarizes current lifestyle modifications, pharmacological treatment, and surgical options for the management of obesity and discusses the benefits, limitations, and risks of each. As insights are gained into the pathophysiology of a gut-brain neurochemical feedback axis governing satiety and feeding behavior, targets for new pharmacotherapies are being developed. In particular, gut hormone analogs are an attractive antiobesity therapy because they appear to lack the adverse effects historically associated with central nervous system-acting agents.     

Using Reminder Letters to Improve Adherence to Routine Hemoglobin A1C Testing in Adults with Diabetes

The American Diabetes Association (ADA) recommends hemoglobin A1C (A1C) goals of < 7% for most non-pregnant adults and < 8% for adult patients with extensive or life-limiting comorbidities. A1C testing is indicated every 3-months for patients not meeting goals to assess glycemic control, adjust medications, suggest lifestyle changes, and offer counseling. However, many patients do not adhere to routine testing. A clinic-wide quality improvement (QI) pilot project was implemented using mailed reminder letters to improve patient adherence to routine A1C testing in patients with hemoglobin A1C . 8%. Sixty-eight patients were identified for this letter intervention. Of these, 14 patients (20%) were historically adherent to 3-month interval testing, 31 patients (46%) were historically non-adherent, and 23 (34%) had historical A1C test intervals of less than 3-months because of provider orders. The primary outcome was improvement in A1C testing adherence rates of those who were previously non-adherent. There was a 58% increase overall and a 103% increase in testing rates among women. Statistical significance was not observed at the P = .05 level. However, improvement in adherence rates among women reached the P = .10 significance level. Mailed reminder letters may be useful in improving adherence to routine A1C testing in patients with diabetes. Further study of this intervention in larger groups is needed to provide timely data for the management of diabetes care.     

Evaluation of antifungal susceptibility and clinical characteristics in fungal keratitis in a tertiary care center in North India

Purpose:To study the antifungal susceptibility of common corneal pathogenic fungi to antifungal agents in the North Indian population.Methods:Prospective study of the antifungal sensitivity testing (natamycin, amphotericin B, voriconazole, itraconazole, fluconazole, posaconazole, caspofungin, micafungin) of fungal isolates from 50 cases of culture positive fungal keratitis by using E test method. Details noted included demographic data, visual acuity, clinical details, grade of keratitis, healing time, and success in medical management.Results:Of 50 patients with fungal keratitis (mean age: 40.28 ± 16.77 years), 12 eyes healed within 3 weeks, 14 had a delayed healing response, and 24 had chronic keratitis. Among the 15 cases of Fusarium isolates, 93.3% were sensitive to natamycin, while 40% to amphotericin B; 66.6% to voriconazole, 13.4% to itraconazole and fluconazole each. 80% of Fusarium cases (n = 12) showed susceptibility to posaconazole. Among Aspergillus flavus isolates, 53.4% (n = 8) were sensitive to natamycin, with only 40% (n = 7) showing sensitivity to amphotericin B and good susceptibility to azoles. MIC against susceptible Fusarium spp. for natamycin was 3–16 µg/mL, amphotericin B: 1–8 µg/mL, voriconazole: 0.5–1.5 µg/mL, itraconazole: 0.5–12 µg/mL, posaconazole: 0.094–1.5 µg/mL. MIC against Aspergillus flavus was natamycin: 8–32 µg/mL, amphotericin B: 0.5–16 µg/mL, voriconazole: 0.025–4 µg/mL, itraconazole: 0.125–8 µg/mL, posaconazole: 0.047–0.25 µg/mL; against Aspergillus niger isolates, to natamycin was 6 µg/mL (n=1), amphotericin B 8–12 µg/mL (n = 3), voriconazole: 0.125–0.19 µg/mL (n = 3), itraconazole: 0.38–0.75 µg/mL, posaconazole: 0.064–0.19 µg/mL and against Aspergillus fumigatus (n = 1), was natamycin4 µg/mL, amphotericin B - 8 µg/mL, voriconazole 0.25 µg/mL, itraconazole 1 µg/mL, and posaconazole 0.19 µg/mL. MIC against susceptible Acremonium spp. for natamycin was 1.5–16 µg/mL, amphotericin B: 0.5–8 µg/mL, voriconazole: 0.19–3 µg/mL, itraconazole: 0.125 µg/mL, posaconazole: 0.125–0.5 µg/mL and against susceptible Curvularia was natamycin 0.75–4 µg/mL, amphotericin B 0.5–1 µg/mL, voriconazole 0.125–0.19 µg/mL, itraconazole 0.047–0.094 µg/mL, posaconazole 0.047–0.094 µg/mL. MIC against Mucor spp.+ Rhizopus spp. (n = 1) was natamycin: 8 µg/mL, amphotericin B: 0.75 µg/mL, posaconazole: 1.5 µg/mL. MIC against of Alternaria (n = 1) was voriconazole: 0.19 µg/mL, posaconazole: 0.094 µg/mL. MIC against Penicillium (n=1) was natamycin: 8 µg/mL, voriconazole: 0.25 µg/mL, itraconazole: 0.5 µg/mL, and Posaconazole: 0.125 µg/mL.Conclusion:Our observations highlight the variations in susceptibility to antifungal agents. Posaconazole seems to be effective with low MIC against common corneal pathogenic fungal isolates.     

Vitamin D and Systems Biology

The biological actions of the vitamin D receptor (VDR) have been investigated intensively for over 100 years and has led to the identification of significant insights into the repertoire of its biological actions. These were initially established to be centered on the regulation of calcium transport in the colon and deposition in bone. Beyond these well-known calcemic roles, other roles have emerged in the regulation of cell differentiation processes and have an impact on metabolism. The purpose of the current review is to consider where applying systems biology (SB) approaches may begin to generate a more precise understanding of where the VDR is, and is not, biologically impactful. Two SB approaches have been developed and begun to reveal insight into VDR biological functions. In a top-down SB approach genome-wide scale data are statistically analyzed, and from which a role for the VDR emerges in terms of being a hub in a biological network. Such approaches have confirmed significant roles, for example, in myeloid differentiation and the control of inflammation and innate immunity. In a bottom-up SB approach, current biological understanding is built into a kinetic model which is then applied to existing biological data to explain the function and identify unknown behavior. To date, this has not been applied to the VDR, but has to the related ERα and identified previously unknown mechanisms of control. One arena where applying top-down and bottom-up SB approaches may be informative is in the setting of prostate cancer health disparities.