Single daily poly-pill for HIV

In a prospective, randomized trial, a single daily tablet containing efavirenz, emtricitabine, and tenofovir (Atripla; Bristol Myers Squibb & Gilead Sciences LLC) maintained viral suppression in HIV-1 infected patients as well as the standard multiple-pill regimen.

The report of the study, published in the Journal of the Acquired Immune Deficiency Syndrome, notes that at baseline, all 300 participants were on stable antiretroviral therapy (ART) regimens, with viral loads of less than 200 copies/mL for at least 3 months. Their mean CD4 count was 540 cells/�L, and 96% of subjects had HIV-1 RNA <50>

On randomization, 203 were assigned to the Atripla regimen while 97 remained on their baseline regimen. The entire 48-week study was completed by 266 patients.

In the intent-to-treat analysis, it was found that at 48 weeks, the primary endpoint -- HIV-1 RNA below 200 copies/mL -- had been achieved by 89% of the patients in the single-tablet group versus 88% of those on unmodified antiretroviral regimens, "indicating noninferiority" of the newer approach.

Similarly, there was no significant difference between groups in maintenance of viral load below 50 copies/mL and no significant changes in CD4 cell counts within or between the two arms of the study.

Discontinuation rates were similar between the groups, but more patients in the single-tablet group discontinued due to adverse events, "most commonly for nervous system symptoms," according to the investigators.

Three patients in the single-tablet group and one in the control group had virologic failure.

"In summary," the researchers conclude, "patients who were stable and virologically suppressed while receiving a wide array of non-nucleoside reverse transcriptase inhibitor- and protease inhibitor-based antiretroviral regimens and had their treatment simplified to a single-tablet regimen of efavirenz, emtricitabine, and tenofovir maintained high rates of virologic suppression compared to those who continued their regimen unmodified."

Source: J Acquir Immune Defic Syndr 2009;51:163-174.

Web 2.0 tools for Teaching

For teachers who are net-savvy, want to be on the cuttiong edge of new teaching methodologies and collaborative learning and are enthisiastic about developing their teaching skills in a new and dramatic way, this blog gines a description of Web 2.0 websites and webtools which have potential for use college and university teaching.
http://web20teach.blogspot.com/

Ceftobiprole: first cephalosporin with activity against MRSA

Ceftobiprole is the first member of a new series of advanced cephalosporins with activity against methicillin-resistant Staphylococcus aureus (MRSA). The drug received a letter of approval from the United States Food and Drug Administration (FDA) in March 2008 for the treatment of complicated skin and skin structure infections including diabetic foot infections. Ceftobiprole exerts its antibacterial activity by inhibiting the penicillin-binding proteins (PBPs) involved in cell wall synthesis. It is stable against hydrolysis by many gram-positive beta-lactamases and a has higher affinity for various PBPs (such as PBP2a of MRSA or PBP2x of Streptococcus pneumoniae), which leads to a wider spectrum of activity compared with older beta-lactams. Ceftobiprole activity does not cover extended-spectrum beta-lactamase-producing Enterobacteriaceae and some other pathogens, including Enterococcus faecium or Acinetobacter baumanii.
Generally well tolerated, with nausea and taste disturbance being the most common adverse events, ceftobiprole appeared noninferior to empiric therapy in several clinical trials. Several precautions regarding hypersensitivity and drug incompatibility are reported.
Ceftobiprole is available only for i.v. administration. Dosage recommendations are 500 mg as a 1-hour intravenous infusion every 12 hours for the treatment of complicated skin and skin structure infections caused by certain gram-positive pathogens, and 500 mg as a 2-hour infusion every 8 hours when susceptible gram-negative or both gram-positive and susceptible gram-negative pathogens are involved. Dosage adjustments are indicated for patients with moderate or severe renal impairment, and dosage recommendations are expected to be 500 or 250 mg, respectively, as a 2-hour infusion every 12 hours.
Ceftobiprole represents a promising option for the treatment of mono- and polymicrobial infections caused by multidrug-resistant gram-positive and susceptible gram-negative pathogens, but further toxicity and safety studies are warranted.

Database of Receptors and Channels

The following two sites give updated and detailed description of all known Receptors and ion Channels.:
1) IUPHAR Database of G Protein-Coupled Receptors and the IUPHAR Database of Voltage-Gated and Ligand-Gated Ion Channels.
2) Guide to Receptors and Channels (GRAC), 3rd edition published by British Pharmacological society.

A Study of Nigella sativa Linn. seeds for antimicrobial activity against multidrug resistant clinical strains of Pseudomonas aeruginosa.

A Study of Nigella sativa Linn. seeds for antimicrobial activity against multidrug resistant clinical strains of Pseudomonas aeruginosa. Hippocratic Journal of Unani Medicine. 4(4). 2009. 95-104.
Authors: Mohd T Salman(1),*, Rahat A Khan(1), Indu Shukla(2)
Address: (1)Department of Pharmacology, (2)Department of Microbiology, Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh, India. 202002.
*Corresponding Author: Present address- Department of Pharmacology, Era’s Lucknow Medical College, Sarfarazganj, Hardoi Road, Lucknow. India. 202003.
Abstract
Nigella sativa (black cumin) seed oil and extracts were tested in varying dilutions against strains of Pseudomonas aeruginosa resistant to a number of clinically used antibiotics isolated from patients attending JN Medical College Hospital, Aligarh, using disc agar diffusion technique on inoculated Muellar Hinton agar plates under standard laboratory conditions. Both the oil and Methanolic extract showed remarkable dose dependant antibacterial activity against the tested strains upto a dilution of 1:50 as evident from the zones of inhibition. No cross resistance was noticed with any of the tested antibiotics.

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Circumcision

Published Online First: 15 December 2008. doi:10.1136/sti.2008.032334
Sexually Transmitted Infections 2009;85:116-120

Copyright © 2009 by the BMJ Publishing Group Ltd.

EPIDEMIOLOGY

Male circumcision and Neisseria gonorrhoeae, Chlamydia trachomatis and Trichomonas vaginalis: observations after a randomised controlled trial for HIV prevention

J Sobngwi–Tambekou¹, D Taljaard², M Nieuwoudt³, P Lissouba¹, A Puren³ and B Auvert⁴

¹ INSERM U687, Hôpital Paul Brousse, Villejuif, France
² Progressus, Johannesburg, South Africa
³ National Institute for Communicable Diseases, Johannesburg, South Africa
⁴ INSERM U687, Assistance Publique-Hôpitaux de Paris, University of Versailles, France

Correspondence to:
Dr Bertran Auvert, INSERM U687, 12 avenue Paul Vaillant-Couturier, 94804 Villejuif Cedex, France; bertran.auvert@uvsq.fr

Objective: To assess the association between male circumcision and Neisseria gonorrhoeae, Chlamydia trachomatis and Trichomonas vaginalis using data from a male circumcision randomised controlled trial.

Methods: We used data collected during the male circumcision trial conducted in Orange Farm (South Africa) among men aged 18–24 years. Altogether, 1767 urine samples collected during the final follow-up visit were analysed using PCR. Prevalence of N gonorrhoeae, C trachomatis and T vaginalis was assessed as a function of male circumcision using odds ratios (OR) given by univariate and multivariate logistic regression.

Results: In an intention-to-treat analysis, prevalence of N gonorrhoeae, C trachomatis and T vaginalis among intervention and control groups were 10.0% versus 10.3% (OR 0.97; p = 0.84), 2.1% versus 3.6% (OR 0.58; p = 0.065) and 1.7% versus 3.1% (OR 0.54; p = 0.062), respectively. The association between T vaginalis and male circumcision remained borderline when controlling for age, ethnic group, number of lifetime partners, marital status, condom use and HIV status (AOR 0.48; p = 0.069). In the as-treated analysis, this association became significant (OR 0.49, p = 0.030; AOR 0.41, p = 0.030).

Conclusions: This study demonstrates for the first time that male circumcision reduces T vaginalis infection among men. This finding explains why women with circumcised partners are less at risk for T vaginalis infection than other women. The protective effect on T vaginalis is an additional argument to recommend male circumcision in Africa where it is acceptable.

Trial registration number: NCT00122525.

Some new drug approvals in June 2009

Simponi
Pharmacological class: TNF blocker.
Active Ingredient: Golimumab 50mg/0.5mL; soln for SC inj; preservative-free.
Indication: Moderately to severely active rheumatoid arthritis (RA), in combination with methotrexate (MTX). Active psoriatic arthritis (PsA), alone or with MTX. Active ankylosing spondylitis (AS).
Company: Centocor Ortho Biotech, Inc.

Axert approved for migraine treatment in adolescents

The FDA has approved Axert (almotriptan malate tablets, from Ortho-McNeil Janssen), a selective 5-HT1B/1D receptor agonist, for the acute treatment of migraine headache in adolescents 12-17 years of age with a history of migraine attacks lasting ≥4 hours.

Reclast approved for biennial dosing regimen to prevent female osteoporosis

The FDA has approved Reclast (zoledronic acid, from Novartis) injection for the prevention of osteoporosis in women for two years with a single dose.

Lamictal XR approved for treatment of epilepsy

GlaxoSmithKline announced that the FDA has approved Lamictal XR (lamotrigine extended-release tablets) as a once-a-day add-on therapy for epilepsy patients ≥13 years of age with partial onset seizures.

Nuvigil launched for excessive sleepiness

Nuvigil (armodafinil tablets) is now available from Cephalon in 50mg, 150mg, and 250mg dosage strengths.

Vyvanse approved for pediatric ADHD control 13 hours post-dose

Shire Pharmaceuticals has received FDA approval for a labeling change for its once-daily Attention Deficit Hyperactivity Disorder (ADHD) treatment Vyvanse (lisdexamfetamine dimesylate capsules).

Cycloset -a new antidiabetic

The U.S. FDA approved Cycloset, a new quick-release oral formulation of bromocriptine mesylateis, which is the first therapy directly targeting the body’s dopamine activity to improve glycemic control. It is also the only drug to be approved subsequent to the FDA's guidelines that require studies demonstrating that diabetes drugs do not increase cardiovascular risk.

Preclinical studies indicate that while an increase in dopamine activity leads to improvements in diabetes, the time of day of the increased dopamine activity is also important. Studies in diabetic animals have shown that increased dopaminergic activity at a particular time of day is most effective in “resetting” the biological clock neurochemistry to a physiology that improves diabetic dysmetabolism. Taken orally, once-a-day, in the morning, Cycloset provides a single brief pulse of dopamine agonist activity shortly after its administration. Morning Cycloset improves post-prandial (after-meal) glucose without increasing plasma insulin concentrations, and the beneficial effects of Cycloset on post-meal glycemic control in patients with Type 2 diabetes are demonstrable many hours after the drug has been substantially cleared from the circulation, for example at lunch and dinner.

Mechanism: Bromocriptine mesylate, an ergot derivative, is a sympatholytic dopamine D2 agonist that exerts inhibitory effects on serotonin turnover in the central nervous system. It has been proposed that bromocriptine can reverse many of the metabolic alterations associated with obesity by resetting central (hypothalamic) circadian organization of monoamine neuronal activitties. Indeed, bromocriptine, if administered systemically or into the cerebral ventricle during the early hours of the light cycle, prevents or reverses seasonal fattening, insulin resistance, and decreased endogenous (hepatic) glucose production in mammals. Moreover, timed bromocriptine treatment decreased body weight and improved glucose tolerance in obese individuals who were instructed to follow a hypocaloric diet . Bromocriptine has also been shown to reduce mean daylong plasma glucose, triglyceride, and free fatty acid (FFA) levels in the absence of a change in body weight in obese nondiabetic women.