Rapid and Selective Access to Three Distinct Sets of Indole-Based Heterocycles From a Single Set of Ugi-Adducts Under Microwave Heating.

Rapid and selective access to three distinct sets of indole-based heterocycles from a single set of Ugi-adducts under microwave heating.

Chem Commun (Camb). 2013 Mar 1;
Zhang L, Zhao F, Zheng M, Zhai Y, Liu H

Three distinct sets of indole-based heterocycles were rapidly and selectively synthesized from the same set of Ugi-adducts under microwave heating in a reaction-condition-controlled manner. Notably, an unprecedented metal-free intramolecular sp3-hybridized C-H arylation using only cesium carbonate was discovered. HubMed – drug


Valproic acid-induced hyperammonemic encephalopathy – a potentially fatal adverse drug reaction.

Springerplus. 2013 Dec; 2(1): 13
Sousa C

A patient with an early diagnosed epilepsy Valproic acid is one of the most widely used antiepileptic drugs. Hyperammonemic encephalopathy is a rare, but potentially fatal, adverse drug reaction to valproic acid.A patient with an early diagnosed epilepsy, treated with valproic acid, experienced an altered mental state after 10?days of treatment. Valproic acid serum levels were within limits, hepatic function tests were normal but ammonia levels were above the normal range. Valproic acid was stopped and the hyperammonemic encephalopathy was treated with lactulose 15?ml twice daily, metronidazole 250?mg four times daily and L-carnitine 1?g twice daily.Monitoring liver function and ammonia levels should be recommended in patients taking valproic acid. The constraints of the pharmaceutical market had to be taken into consideration and limited the pharmacological options for this patient’s treatment.Idiosyncratic symptomatic hyperammonemic encephalopathy is completely reversible, but can induce coma and even death, if not timely detected. Clinical pharmacists can help detecting adverse drug reactions and provide evidence based information for the treatment. HubMed – drug


Equipping Residents to Address Alcohol and Drug Abuse: The National SBIRT Residency Training Project.

J Grad Med Educ. 2012 Mar; 4(1): 58-63
Pringle JL, Kowalchuk A, Meyers JA, Seale JP

The Screening, Brief Intervention and Referral to Treatment (SBIRT) service for unhealthy alcohol use has been shown to be one of the most cost-effective medical preventive services and has been associated with long-term reductions in alcohol use and health care utilization. Recent studies also indicate that SBIRT reduces illicit drug use. In 2008 and 2009, the Substance Abuse Mental Health Service Administration funded 17 grantees to develop and implement medical residency training programs that teach residents how to provide SBIRT services for individuals with alcohol and drug misuse conditions. This paper presents the curricular activities associated with this initiative.We used an online survey delivery application (Qualtrics) to e-mail a survey instrument developed by the project directors of 4 SBIRT residency programs to each residency grantee’s director. The survey included both quantitative and qualitative data.All 17 (100%) grantees responded. Respondents encompassed residency programs in emergency medicine, family medicine, pediatrics, obstetrics-gynecology, psychiatry, surgery, and preventive medicine. Thirteen of 17 (76%) grantee programs used both online and in-person approaches to deliver the curriculum. All 17 grantees incorporated motivational interviewing and validated screening instruments in the curriculum. As of June 2011, 2867 residents had been trained, and project directors reported all residents were incorporating SBIRT into their practices. Consistently mentioned challenges in implementing an SBIRT curriculum included finding time in residents’ schedules for the modules and the need for trained faculty to verify resident competence.The SBIRT initiative has resulted in rapid development of educational programs and a cohort of residents who utilize SBIRT in practice. Skills verification, program dissemination, and sustainability after grant funding ends remain ongoing challenges. HubMed – drug


GPR158, an Orphan Member of G Protein-Coupled Receptor Family C: Glucocorticoid-Stimulated Expression and Novel Nuclear Role.

PLoS One. 2013; 8(2): e57843
Patel N, Itakura T, Gonzalez JM, Schwartz SG, Fini ME

Members of the large G protein-coupled receptor (GPCR) clan are implicated in many physiological and disease processes, making them important therapeutic drug targets. In the present study, we follow up on results of a pilot study suggesting a functional relationship between glucocorticoid (GC)-induced ocular hypertension and GPR158, one of three orphan members of the GPCR Family C. GC treatment increases levels of GPR158 mRNA and protein through transcriptional mechanisms, in cultured trabecular meshwork (TBM) cells derived from the eye’s aqueous outflow pathway. Like treatment with GCs, transient overexpression of GPR158 stimulates cell proliferation, while siRNA knockdown of endogenous GPR158 has the opposite effect. Both endogenous and overexpressed GPR158 show an unusual subcellular localization pattern, being found almost entirely in the nucleus. However, when cells are treated with inhibitors of clathrin-mediated endocytosis, GPR158 is shifted to the plasma membrane. Mutation of a bipartite nuclear localization signal (NLS) in the 8 helix also shifts GPR158 out of the nucleus, but in this case the protein is found in vesicles localized in the cytoplasm. These results suggest that newly synthesized GPR158 first traffics to the plasma membrane, where it rapidly undergoes endocytosis and translocation to the nucleus. Significantly, mutation of the NLS abrogates GPR158-mediated enhancement of cell proliferation, indicating a functional requirement for nuclear localization. GPR158 overexpression upregulates levels of the cell cycle regulator cyclin D1, but mutation of the NLS reverses this. Overexpression of GPR158 enhances the barrier function of a TBM cell monolayer, which is associated with an increase in the levels of tight junction proteins ZO-1 and occludin, similar to reported studies on GC treatment. Regulated paracellular permeability controls aqueous outflow facility . Since GCs stimulate GPR158 expression, the result is consistent with a role for elevation of GPR158 expression in GC-induced ocular hypertension. HubMed – drug