Gastro-retentive dosage form for improving bioavailability of Cefpodoxime proxetil in rats

Cefpodoxime proxetil (CP) is a prodrug with poor oral bioavailability because of its metabolism to Cefpodoxime acid (CA) in luminal contents and intestinal epithelial cells. In the present investigation, regional variability in different segments of the gastrointestinal tract vis-à-vis solubility and metabolism were investigated, and the results indicated potential for a gastro retentive (GR) dosage form. Suitability of a GR dosage from for CP and finally in vivo efficacy were investigated. Thereafter, an effervescent floating GR dosage form was developed for CP and evaluated in rats. The GR dosage form improved the oral bioavailability of CP significantly by about 75%, hence providing a proof-of-concept. The Tmax value increased to 1.43+/-0.24 h from 0.91+/-0.23 h of pure drug, while Cmax values of 4735+/-802 ng/ml and 3094+/-567 ng/ml were obtained for the GR dosage form and pure drug respectively.     

Metabolomic profiling reveals potential markers and bioprocesses altered in bladder cancer progression

Although alterations in xenobiotic metabolism are considered causal in the development of bladder cancer, the precise mechanisms involved are poorly understood. In this study, we used high-throughput mass spectrometry to measure over 2,000 compounds in 58 clinical specimens, identifying 35 metabolites which exhibited significant changes in bladder cancer. This metabolic signature distinguished both normal and benign bladder from bladder cancer. Exploratory analyses of this metabolomic signature in urine showed promise in distinguishing bladder cancer from controls and also nonmuscle from muscle-invasive bladder cancer. Subsequent enrichment-based bioprocess mapping revealed alterations in phase I/II metabolism and suggested a possible role for DNA methylation in perturbing xenobiotic metabolism in bladder cancer. In particular, we validated tumor-associated hypermethylation in the cytochrome P450 1A1 (CYP1A1) and cytochrome P450 1B1 (CYP1B1) promoters of bladder cancer tissues by bisulfite sequence analysis and methylation-specific PCR and also by in vitro treatment of T-24 bladder cancer cell line with the DNA demethylating agent 5-aza-2'-deoxycytidine. Furthermore, we showed that expression of CYP1A1 and CYP1B1 was reduced significantly in an independent cohort of bladder cancer specimens compared with matched benign adjacent tissues. In summary, our findings identified candidate diagnostic and prognostic markers and highlighted mechanisms associated with the silencing of xenobiotic metabolism. The metabolomic signature we describe offers potential as a urinary biomarker for early detection and staging of bladder cancer, highlighting the utility of evaluating metabolomic profiles of cancer to gain insights into bioprocesses perturbed during tumor development and progression.     

Prevalence of obstructive lung disease in HIV population: a cross sectional study

Background

Observational studies have suggested an association between HIV infection and emphysema.

Aims

The primary aim of this study was to estimate the prevalence of obstructive lung disease in HIV-infected patients seen in an outpatient infectious disease clinic. The secondary aim was to estimate the prevalence of Obstructive Lung Disease (OLD) in smokers and non smokers in this population.

Methods

This was a prospective cross-sectional study. Consecutive patients who were seen for routine HIV care underwent spirometry and answered the St. George’s Respiratory Questionnaire (SGRQ). Further, we collected information from the charts on demographics, co-morbidities, CD4 cell count, and HIV viral load (current, baseline, etc).

Results

This study included 98 HIV-infected patients with mean age of 45 years, (SD: 11) and 84% male. They were seen from November 2008 to May 2009 at Thomas Jefferson University in Philadelphia. According to established criteria, spirometry results were classified as normal in 69% and obstructive in 16.3%. Among those who never smoked, the prevalence of obstructive lung disease on spirometry was 13.6%. The prevalence of obstruction in HIV patients with a history of smoking was 18.5%. Current and ever smokers comprised 21.4% and 55% of the patients respectively. The mean SGRQ total score was 7. The mean SGRQ score in active smokers was 17 and 15 in those subjects with a prior history of smoking. The mean SGRQ score among patients with obstruction in spiromerty was 27.7 in patients with obstruction on spirometry.

Conclusion

This urban population of HIV-infected persons has a relatively high prevalence of obstructive lung disease as assessed by spirometry. Furthermore, the high prevalence of obstructive lung disease in never smokers may suggest a possible association between HIV infection and emphysema. In addition the SGRQ total score was comparatively higher in patients with obstruction on spirometry. Our data suggests that potentially all patients with HIV should be screened a for OLD.     

Psychological Profile of Taiwanese Female Cosmetic Surgery Candidates: Understanding Their Motivation for Cosmetic Surgery

Background  

Psychological processes consisting of body image and self-esteem are considered key to the motivation for cosmetic surgery (CS). The current study aimed to investigate such processes as well as social support, perception of other people’s opinion, and sex life satisfaction of Taiwanese female CS candidates. Further analyses were conducted to identify which processes predicted motivation for CS.     

2-Amino-5-thiazolyl motif: a novel scaffold for designing anti-inflammatory agents of diverse structures

Substituted thiazoles with different structural features were synthesized and screened for their anti-inflammatory activity in acute carrageenin induced rat paw edema model and chronic formalin induced rat paw edema model. The compounds 1-5 showed 83, 30, 63, 69 and 73% protection, respectively, in acute carrageenin induced rat paw edema model. In 5-day chronic formalin induced rat paw edema model on the fifth day 1 and 5 gave 66 and 41% protection. Both studies were carried out at a dose of 100mg/kg body weight. The activity was compared with that of Ibuprofen, Rofecoxib, and Dexamethasone both in acute and chronic anti-inflammatory models. Compound 1 without COX-1 and COX-2 inhibitory activity showed good activity profile almost mimicking the gold standard Dexamethasone in terms of efficacy. A 7-day study in rats at dose of 100mg/kg showed that this compound does not have any ulcerogenic activity and toxicity. The activity of 5 shows that incorporating two pharmacophoric features in one molecule can be a good drug designing strategy. 2,4-Diaminothiazoles with an aliphatic oxime esters attached via a ketone bridge to the 5th position of thiazole was identified as a novel scaffold for designing anti-inflammatory agents.     

Neurothekeoma of the eyelid: a case report

The purpose of this article is to describe a rare benign tumor of nerve sheath origin arising from the eyelid in an elderly male. Local excision was done and histopathological examination revealed a neurothekeoma. Six months later the patient was doing well with no recurrence. The case was unique in that the patient was an elderly male while neurothekeoma is commonly seen on the face of young adults, especially females.     

Retrograde Parotidectomy and facial nerve outcomes: A case series of 44 patients

Purpose

The most common surgical method to remove benign parotid tumors remains the prograde approach. We examined if a retrograde surgical technique offers better outcomes than historical prograde controls.