Ministry of Health clinical practice guidelines: depression.

The Ministry of Health (MOH) have updated the clinical practice guidelines on Depression to provide doctors and patients in Singapore with evidence-based treatment for depression. This article reproduces the introduction and executive summary (with recommendations from the guidelines) from the MOH clinical practice guidelines on Depression, for the information of readers of the Singapore Medical Journal. Chapters and page numbers mentioned in the reproduced extract refer to the full text of the guidelines, which are available from the Ministry of Health website: http://www.moh.gov.sg/content/moh_web/home/Publications/guidelines/cpg/2012/depression.html. The recommendations should be used with reference to the full text of the guidelines. Following this article are multiple choice questions based on the full text of the guidelines.

Ministry of Health clinical practice guidelines: schizophrenia.

The Ministry of Health (MOH) has updated the clinical practice guidelines on Schizophrenia to provide doctors and patients in Singapore with evidence-based treatment for schizophrenia. This article reproduces the introduction and executive summary (with recommendations from the guidelines) from the MOH clinical practice guidelines on Schizophrenia, for the information of readers of the Singapore Medical Journal. Chapters and page numbers mentioned in the reproduced extract refer to the full text of the guidelines, which are available from the Ministry of Health website: http://www.moh.gov. sg/mohcorp/publications.aspx?id=26138. The recommendations should be used with reference to the full text of the guidelines. Following this article are multiple choice questions based on the full text of the guidelines.

Fourth-order algorithms for solving the multivariable Langevin equation and the Kramers equation.

We develop a fourth-order simulation algorithm for solving the stochastic Langevin equation. The method consists of identifying solvable operators in the Fokker-Planck equation, factorizing the evolution operator for small time steps to fourth order, and implementing the factorization process numerically. A key contribution of this paper is to show how certain double commutators in the factorization process can be simulated in practice. The method is general, applicable to the multivariable case, and systematic, with known procedures for doing fourth-order factorizations. The fourth-order convergence of the resulting algorithm allowed very large time steps to be used. In simulating the Brownian dynamics of 121 Yukawa particles in two dimensions, the converged result of a first-order algorithm can be obtained by using time steps 50 times as large. To further demonstrate the versatility of our method, we derive two new classes of fourth-order algorithms for solving the simpler Kramers equation without requiring the derivative of the force. The convergence of many fourth-order algorithms for solving this equation are compared.

Inhibitors of arachidonoyl ethanolamide hydrolysis.

Arachidonoyl ethanolamide (anandamide) is a naturally occurring brain constituent that binds to a specific brain cannabinoid receptor (CBR1). An amidase activity (anandamide amidase) in membrane fractions of brain and in cultured neuroblastoma cells rapidly degrades anandamide to arachidonic acid (Deutsch, D. G., and Chin, S. (1993) Biochem. Pharmacol. 46, 791-796). In the current study, analogs of anandamide representing three classes of putative transition-state inhibitor (trifluoromethyl ketones, alpha-keto esters, and alpha-keto amides) were synthesized and tested as inhibitors of anandamide hydrolysis in vitro and as ligands for CBR1. The trifluoromethyl ketones and alpha-keto esters showed nearly 100% inhibition of anandamide hydrolysis in vitro at 7.5 microM inhibitor and 27.7 microM anandamide. Arachidonyl trifluoromethyl ketone was the only synthetic compound in the series of fatty acid derivatives able to displace [3H]CP-55940 binding to CBR1 with a Ki of 0.65 microM. It was also the most effective inhibitor in intact neuroblastoma cells, leading to a 12-fold increase of cellular anandamide levels at 12 microM. From the action of these inhibitors on this hydrolytic enzyme, it seems likely that anandamide is cleaved by a mechanism that involves an active-site serine hydroxyl group. These inhibitors may serve as useful tools to elucidate the role anandamide plays in vivo.

Enzymatic synthesis and degradation of anandamide, a cannabinoid receptor agonist.

Enzymatic activities have been identified which catalyze both the hydrolysis and synthesis of arachidonylethanolamide (anandamide). Anandamide was taken up by neuroblastoma and glioma cells in culture, but it did not accumulate since it was rapidly degraded by an amidase activity that resided mainly in the membrane fractions. This amidase activity was expressed in brain and the majority of cells and tissues tested. Phenylmethylsulfonyl fluoride (PMSF) was found to be a potent inhibitor of this amidase. A catalytic activity for the biosynthesis of anandamide from ethanolamine and arachidonic acid was readily apparent in incubations of rat brain homogenates. The stability of anandamide in serum and its rapid breakdown in cells and tissues are consistent with the observation that it is active when administered systemically, and its duration of action will be regulated by its rate of degradation in cells.

Captopril does not protect against renal oxidative injury.

The free thiol group of captopril is important in the action and metabolism of this drug. It has been postulated that the thiol group may allow captopril to act in a manner similar to glutathione and protect against oxidative injury. This study investigated the ability of captopril, enalaprilat, and N-acetylcysteine to prevent tertbutyl hydroperoxide induced oxidative injury in rat renal homogenates. Lipid peroxidation was significantly increased in homogenates from captopril-treated animals (p < 0.05), and following glutathione depletion this was further enhanced (p < 0.001). Renal glutathione content was significantly reduced by captopril treatment (p < 0.01). These results suggest that captopril does not act as an alternate source of reducing equivalents to glutathione and does not protect against renal oxidative injury in this model.