Antileishmanial polyphenols from Garcinia vieillardii

Seven xanthones, the new vieillardiixanthones B and C (1) and (7), pancixanthones A (2), B (3), 1,6-dihydroxyxanthone (6), pyranojacareubin and 5,6-O-dimethyl-2-deprenylrheediaxanthone together with two benzophenones, clusiachromene (4) and 3-geranyl-2,4,6-trihydroxybenzophenone (5) were isolated from the stem bark of the neocaledonian Garcinia vieillardii. 2, 5 and 6 showed a significant antileishmanial activity against the promastigote forms of Leishmania mexicana and L. infantum and against the amastigote forms of L. infantum

Interlaboratory evaluation of an ELISA performed using a robotic automatic workstation versus manually testing for screening of Salmonella Typhimurium and Salmonella Choleraesuis antibodies in pig serum

An enzyme-linked immunosorbent assay (ELISA) was developed to detect antibodies directed against Salmonella spp. in porcine serum. This assay is based on the Exiqon VetScreen TM Salmonella Covalent Mix-ELISA 96-well microtiter plates (Jauho et al, 2000). These microtiter plates are photochemically coated with Salmonella typhimurium and Salmonella choleraesuis PS- antigens 1,4,5,6,7, and 12 using the ExiqonDs patented photochemical method for covalent coupling of ligands to polymer surfaces (Wiuff et al, 2000). The assay was developed using an automatic robotic workstation. The Exiqon VetScreen TM Salmonella Covalent Mix-ELISA plates do not require any blocking steps. The developed assay showed 30 minutes incubation time for porcine serum samples as optimal, thereby giving a total assay time of two hours. In order to evaluate the assay, a comparison study between the FSD, Canada; Exiqon, Copenhagen Denmark was performed. A panel of positive and negative porcine serum samples was tested. The tests were carried out using a robotic automatic workstation and using a manually performed assay in three different laboratories (Exiqon and Danish Veterinary Lab, Denmark; Svanova, Sweden).The developed assay showed high specificity, sensitivity and excellent reproducibility. The interlaboratory study gave results of substantial agreement. No difference between manual and robotized performance could be identified. The automated ELISA can be used in high throughput screening of swine Salmonella spp. antibodies in seroprevalence studies

Efficient ortho-formylation in vitamin E series, application to the semi-synthesis of natural 5- and 7-formyl-δ-tocotrienols revealing an unprecedented 5-bromo-7-formyl exchange

Semi-synthesis of 5- and 7-formyltocopherols and tocotrienols has been developed by ortho-formylation of C-5 or C-7-unsubstituted vitamin E derivatives (14 examples) up to 90% yield, through heating in the presence of respectively 10-10-15 equivalents of MgCl2-Et3N-(CH2O)n. Formylation of 5-bromo-δ-tocotrienol revealed an unprecedented 5-bromo/7-formyl exchange and yielded 7-bromo-5-formyl-δ-tocotrienol as major product. The minor 5-bromo-7-formyl-δ-tocotrienol led in three steps to 7-formyl-δ-tocotrienol previously isolated from the stem bark of Garcinia virgata

Modified-release hydrocortisone to provide circadian cortisol profiles

Context: Cortisol has a distinct circadian rhythm regulated by the brain's central pacemaker. Loss of this rhythm is associated with metabolic abnormalities, fatigue, and poor quality of life. Conventional glucocorticoid replacement cannot replicate this rhythm. Objectives: Our objectives were to define key variables of physiological cortisol rhythm, and by pharmacokinetic modeling test whether modified-release hydrocortisone (MR-HC) can provide circadian cortisol profiles. Setting: The study was performed at a Clinical Research Facility. Design and Methods: Using data from a cross-sectional study in healthy reference subjects (n = 33), we defined parameters for the cortisol rhythm. We then tested MR-HC against immediate-release hydrocortisone in healthy volunteers (n = 28) in an open-label, randomized, single-dose, cross-over study. We compared profiles with physiological cortisol levels, and modeled an optimal treatment regimen. Results: The key variables in the physiological cortisol profile included: peak 15.5 mu g/dl (95% reference range 11.7-20.6), acrophase 0832 h(95% confidence interval 0759-0905), nadir less than 2 mu g/dl (95% reference range 1.5-2.5), time of nadir 0018 h (95% confidence interval 2339-0058), and quiescent phase (below the mesor) 1943-0531 h. MR-HC 15 mg demonstrated delayed and sustained release with a mean (SEM) maximum observed concentration of 16.6 (1.4) mu g/dl at 7.41 (0.57) h after drug. Bioavailability of MR-HC 5, 10, and 15 mg was 100, 79, and 86% that of immediate-release hydrocortisone. Modeling suggested that MR-HC 15-20 mg at 2300 h and 10 mg at 0700 h could reproduce physiological cortisol levels. Conclusion: By defining circadian rhythms and using modern formulation technology, it is possible to allow a more physiological circadian replacement of cortisol. (J Clin Endocrinol Metab 94: 1548-1554, 2009

SLC11A1 (NRAMP1) Polymorphisms and Tuberculosis Susceptibility: Updated Systematic Review and Meta-Analysis

Background: Natural resistance associated macrophage protein 1 (NRAMP1), encoded by the SLC11A1 gene, has been described to regulate macrophage activation and be associated with infectious and autoimmune diseases. The relation between SLC11A1 polymorphisms and tuberculosis susceptibility has been studied in different populations. Methods: We systematically reviewed published studies on SLC11A1 polymorphisms and tuberculosis susceptibility until September 15, 2010 and quantitatively summarized associations of the most widely studied polymorphisms using metaanalysis. Results: In total, 36 eligible articles were included in this review. In Meta-analysis, significant associations were observed between tuberculosis risk and widely studied SLC11A1 polymorphisms with summarized odds ratio of 1.35 (95%CI, 1.17– 1.54), 1.25 (95 % CI, 1.04–1.50), 1.23 (95 % CI, 1.04–1.44), 1.31 (95%CI, 1.08–1.59) for 39 UTR, D543N, INT4, and 59 (GT)n, respectively. Heterogeneity between studies was not pronounced, and the associations did not remarkably vary in the stratified analysis with respect to study population and study base. Conclusions: The association between SLC11A1 polymorphisms and tuberculosis susceptibility observed in our analyses supports the hypothesis that NRAMP1 might play an important role in the host defense to the development of tuberculosis