Examination of rofecoxib solution decomposition under alkaline and photolytic stress conditions

Rofecoxib is a highly active and selective cyclo-oxygenase II inhibitor. A stability-indicating method for the assay of rofecoxib has been developed using reverse-phase high-performance liquid chromatography (HPLC). Stress testing of rofecoxib was conducted during the method development and validation. HPLC analysis of rofecoxib solutions stressed under alkaline and photolytic conditions revealed the presence of several degradates. Two main degradates were determined to be the cyclization product formed by photo-cyclization and the dicarboxylate formed by ring opening in the presence of base and oxygen. The identities of these degradates were confirmed by comparison of UV spectra and HPLC retention time with the independently synthesized products. The mechanistic pathways for the formation of these degradates are discussed. Further improvement of the HPLC method's ruggedness has been made based on these studies.     

Comparative assessment of in vitro release kinetics of calcitonin polypeptide from biodegradable microspheres

The objective of our study was to compare the in vitro release kinetics of a sustained-release injectable microsphere formulation of the polypeptide drug, calcitonin (CT), to optimize the characteristics of drug release from poly-(lactide-co-glycolide) (PLGA) copolymer biodegradable microspheres. A modified solvent evaporation and double emulsion technique was used to prepare the microspheres. Release kinetic studies were carried out in silanized tubes and dialysis bags, whereby microspheres were suspended and incubated in phosphate buffered saline, sampled at fixed intervals, and analyzed for drug content using a modified Lowry protein assay procedure. An initial burst was observed whereby about 50% of the total dose of the drug was released from the microspheres within 24 hr and 75% within 3 days. This was followed by a period of slow release over a period of 3 weeks in which another 10-15% of drug was released. Drug release from the dialysis bags was more gradual, and 50% CT was released only after 4 days and 75% after 12 days of release. Scanning electron micrographs revealed spherical particles with channel-like structures and a porous surface after being suspended in an aqueous solution for 5 days. Differential scanning calorimetric studies revealed that CT was present as a mix of amorphous and crystalline forms within the microspheres. Overall, these studies demonstrated that sustained release of CT from PLGA microspheres over a 3-week period is feasible and that release of drug from dialysis bags was more predictable than from tubes.     

The impact of dental appearance on the appraisal of personal characteristics

PURPOSE: The purpose of this study was to ascertain the influence of dental appearance upon subjective ratings of personal characteristics, specifically social competence, intellectual ability, and psychologic adjustment. MATERIALS AND METHODS: A cross-sectional analytic interview study was conducted with 201 undergraduates. Each participant was asked to make judgments about the personal characteristics of the subject of a single color photograph. Eight photographs of four different men were used, each with one of two degrees of dental status (visible disease, no visible disease). Outcome measures were participants' judgments of the social competence, intellectual ability, and psychologic adjustment of the subjects of the photographs. RESULTS: Participants judged subjects with less dental disease to be more socially competent, to show greater intellectual achievement, and to have better psychologic adjustment. CONCLUSION: In the absence of other information, the judgments an individual makes concerning the personal characteristics of others are influenced by dental appearance.     

Heat preconditioning prevents enterocyte mitochondrial damage induced by surgical manipulation

BACKGROUND: The small intestine is susceptible to free radical-induced damage and our earlier work has shown that surgical manipulation of the intestine results in generation of oxygen free radicals, leading to mucosal damage. Heat preconditioning has been shown to offer protection against various stresses including oxidative stress and this study looked at the effect of heat preconditioning on surgical manipulation-induced intestinal mitochondrial alterations. METHODS: Control and rats pretreated with heat were subjected to surgical manipulation by opening the abdominal wall and handling the intestine as done during laparotomy. Mitochondria were prepared from isolated enterocytes and structural and functional alterations were assessed. RESULTS: Surgical manipulation of the intestine resulted in mitochondrial alterations as seen by ultrastructural changes and altered lipid composition. Mitochondria were functionally impaired as evidenced by altered calcium flux, decreased respiratory control ratio, and increased tetrazolium dye reduction and swelling. Along with this, biochemical alterations such as increased lipid and protein oxidation were seen following surgical manipulation. Mild heat preconditioning of the animal prevented these damaging effects. CONCLUSIONS: These studies suggest that stress in the small intestine due to surgery can affect enterocyte mitochondrial structure and function and these effects can be prevented by mild whole body hyperthermia prior to surgery.     

Spectrum of MR imaging findings in spinal tuberculosis

OBJECTIVE: We describe three patients who presented with radiographic findings of a fragment on the medial side of the tibial plateau of the knee that represented an avulsion of the deep portion of the medial collateral ligament. These findings were all associated with disruption of the posterior cruciate ligament and a peripheral medial meniscal tear-the so-called reverse Segond fracture. CONCLUSION: Avulsion fracture at the tibial insertion of the deep component of the medial collateral ligament is a rare finding. When this type of injury is diagnosed, the radiologist should consider posterior cruciate ligament injury and peripheral medial meniscal tears as possible associated findings.     

A clinical profile to assess the potential risk factors for cleft lip and palate

Cleft lip and palate is one of the most common malformations in man. Although the subject of a great deal of investigation, etiologic factors contributing to these congenital deformities remain largely unknown. Various factors like race, sex, parental age at the time of conception etc. have been listed as the exogenous factors. This article strives to project any significant relationship of these factors to cleft lip and cleft palate.     

Spinal cord tethering associated with amniotic band syndrome

Amniotic band syndrome (ABS) comprises fetal morphological abnormalities that may be associated with fibrous amniotic bands that damage developing fetal parts resulting in cutaneous scars, erosions and ulcerations, digital constricting bands, craniofacial and visceral anomalies. Multiple asymmetric encephaloceles and anencephaly are neural-tube-like defects previously reported with ABS. This is the first report of spinal dysraphism with dorsal spinal cord tethering associated with ABS. We examine the pathogenetic theories of ABS in light of this report.     

Sympathetic sprouting reverses decreases in membrane-associated activity of protein kinase C following septohippocampal denervation of the rat hippocampus

Hippocampal sympathetic ingrowth (HSI), a form of neuronal plasticity, is induced by medial septal lesions and consists of the sprouting of peripheral sympathetic fibers, arising from the superior cervical ganglion, into the dentate gyrus and CA₃ region of the hippocampus. HSI has been previously shown to alter learned and spontaneous behaviors, phosphatidyl inositide hydrolysis, and the antagonist binding kinetics of both muscarinic cholinergic receptors and phorbol ester receptors. We now report that sympathetic sprouting reverses decreases in membrane-associated activity of protein kinase C (PKC) following septohippocampal denervation of the rat hippocampus. Further, no changes were found in α, β or γ PKC isoenzymes among experimental groups, suggesting that the group A PKC isoforms do not mediate the observed changes in activity and phorbol ester binding.