Metronidazole loaded pectin microspheres for colon targeting

A multiparticulate system having pH-sensitive property and specific enzyme biodegradability for colon-targeted delivery of metronidazole was developed. Pectin microspheres were prepared using emulsion-dehydration technique. These microspheres were coated with Eudragit® S-100 using oil-in-oil solvent evaporation method. The SEM was used to characterize the surface of these microspheres and a distinct coating over microspheres could be seen. The in vitro drug release studies exhibited no drug release at gastric pH, however continuous release of drug was observed from the formulation at colonic pH. Further, the release of drug from formulation was found to be higher in the presence of rat caecal contents, indicating the effect of colonic enzymes on the pectin microspheres. The in vivo studies were also performed by assessing the drug concentration in various parts of the GIT at different time intervals which exhibited the potentiality of formulation for colon targeting. Hence, it can be concluded that Eudragit coated pectin microspheres can be used for the colon specific delivery of drug. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:4229–4236, 2009     

Involvement of adipokines in rimonabant‐mediated insulin sensitivity in ob/ob mice

Objectives It has been recently reported that blockade of type 1 cannabinoid (CB1) receptors by specific antagonists or genetic manipulation alleviates dyslipidaemia, hyperglycaemia and insulin resistance in animal models of obesity and type 2 diabetes. However, the precise role of adipokines in the insulin‐sensitising effects of the CB1 antagonist rimonabant is not clear. Methods ob/ob mice were treated with different doses of rimonabant and then subjected to an oral glucose tolerance test. The expression of different adipokines in white adipose tissue was analysed by quantitative real‐time PCR. Key findings Rimonabant (30 mg/kg) significantly inhibited body weight and fat pad weight gain (P < 0.05) and improved glucose tolerance. Gene expression analysis indicated that tumour necrosis factor‐α, visfatin and retinol binding protein‐4 were downregulated in the adipose tissue of ob/ob mice treated with rimonabant compared with controls, whereas adiponectin was significantly upregulated. Conclusions Rimonabant‐mediated alteration of adipokines in white adipose tissues may play a role in improving insulin sensitivity in obese animals.     

PapA1 and PapA2 are acyltransferases essential for the biosynthesis of the Mycobacterium tuberculosis virulence factor sulfolipid-1

Mycobacterium tuberculosis produces numerous exotic lipids that have been implicated as virulence determinants. One such glycolipid, Sulfolipid-1 (SL-1), consists of a trehalose-2-sulfate (T2S) core acylated with four lipid moieties. A diacylated intermediate in SL-1 biosynthesis, SL(1278), has been shown to activate the adaptive immune response in human patients. Although several proteins involved in SL-1 biosynthesis have been identified, the enzymes that acylate the T2S core to form SL(1278) and SL-1, and the biosynthetic order of these acylation reactions, are unknown. Here we demonstrate that PapA2 and PapA1 are responsible for the sequential acylation of T2S to form SL(1278) and are essential for SL-1 biosynthesis. In vitro, recombinant PapA2 converts T2S to 2'-palmitoyl T2S, and PapA1 further elaborates this newly identified SL-1 intermediate to an analog of SL(1278). Disruption of papA2 and papA1 in M. tuberculosis confirmed their essential role in SL-1 biosynthesis and their order of action. Finally, the Delta papA2 and Delta papA1 mutants were screened for virulence defects in a mouse model of infection. The loss of SL-1 (and SL(1278)) did not appear to affect bacterial replication or trafficking, suggesting that the functions of SL-1 are specific to human infection.     

Metabolic syndrome: an evolving threat in the genesis of coronary artery disease

Cardiovascular disease is an escalating worldwide health problem. Effective tools to predict and prevent its development and progression are needed. Correctly diagnosing the metabolic syndrome, which identifies people at higher risk for developing diabetes mellitus and cardiovascular disease, may be valuable in guiding treatment and prevention of these major disorders. Several important definitions of the metabolic syndrome have been proposed. The authors discuss these definitions and how they vary in terms of their relationship to incident cardiovascular disease, type 2 diabetes mellitus, and surrogate markers of atherosclerosis. Establishing clarity on what is meant by the metabolic syndrome and agreement as to its underlying basis is needed to reach consensus between the many different definitions that have been proposed. This is particularly the case if it is to become a useful adjunct in clinical practice to identify those who may benefit from more intensive lifestyle interventions and more detailed short-term risk assessments.     

Comorbidities play a larger role in predicting health-related quality of life compared to having an ostomy

BACKGROUND: Previous research suggests an ostomy worsens health-related quality of life (HR-QOL), but comorbidities also can affect HR-QOL. METHODS: Eligible patients had abdominal operation with ostomy (cases) or similar procedure without ostomy (controls). Patients were recruited for this case-control study from 3 Veterans Affairs hospital medical and pharmacy records. Comorbidities were assessed with Charlson-Deyo Comorbidity Index. Multinomial logistic regression evaluated the impact of comorbidities and having an ostomy on HR-QOL, measured using the Medical Outcomes Study Short Form 36 for Veterans. RESULTS: A total of 237 ostomates (cases) and 268 controls were studied. Average age was 69 years; 64% of cases had colostomy, 36% ileostomy. Twenty-nine percent of patients had a high level of comorbidities. Cases and controls were similar except for reasons for undergoing surgery. High comorbidity was a significant predictor of low HR-QOL in 6 domains of the Short Form 36 for Veterans; having an ostomy was a significant predictor in 4. CONCLUSIONS: High comorbidity significantly influences low HR-QOL and impacted more domains than having an ostomy.     

Localized pericardial constriction resulting in a "dumbbell" heart

We describe an unusual case of a young man presenting with calcific constrictive pericarditis. The patient had a history of restrictive cardiomyopathy and pericardial effusion during infancy and received antituberculous treatment. Investigations revealed the presence of thickened pericardium and a thickened calcific constrictive band around the atrioventricular groove posteriorly and over the infundibulum anteriorly. Intraoperatively, the band caused the heart to have a "dumbbell" appearance. A pericardiectomy was performed along with excision of the constricting band. The patient had an uneventful recovery.     

Downregulation of Inflammatory Responses by Novel Caffeic Acid Ester Derivative by Inhibiting NF-kappa B

Introduction  Considering anti-tumorigenic activity of caffeic acid phenyl ester, synthesis of several esterified form of caffeic acid is a novel approach in designing for potent drugs. Results  Our study demonstrates that esterified caffeic acid with methyl vanillate, termed as caffeic acid methyl vanillate ester (CAMVE), blocked inflammatory stimuli-induced inflammatory responses. It decreased amounts of iNOS, Cox-2, and ICAM1 by inhibiting NF-κB through inhibition of IKK activity, IκBα degradation, and p65 nuclear translocation. Conclusion  Overall, our data suggest that novel caffeic acid ester down-regulates inflammatory responses through inhibition of NF-κB and dependent several gene expressions, further suggesting its efficacy as a promising therapeutic agent.