New screening method for Anticancer drugs

Many researchers believe tumour growth is driven by cancerous stem cells that, for reasons not yet understood, are highly resistant to standard treatments. Chemotherapeutic agents may kill off 99 percent of the cells in a tumor, but the stem cells that remain can make the cancer recur or spread to other tissues in the body to cause new cancers.

Stem cells, unlike mature cells, can constantly renew themselves and are thought to be the source of cancers when, through mutations in their DNA, they throw off their natural restraints.
a team at the Broad Institute devised a way of screening for drugs that attack cancer stem cells but leave ordinary cells unharmed.

Cancer stem cells are hard to maintain in sufficient numbers, but the Broad Institute team devised a genetic manipulation to keep breast cancer stem cells trapped in the stem cell state.

The team, led by Piyush B. Gupta, screened some 16,000 chemicals, including all known chemotherapeutic agents approved by the FDA. The team reported in the Cell that 32 of the chemicals selectively went after cancer stem cells. The screening system proves for the first time that it is possible to single out cancer stem cells with drugs that leave ordinary cells alone. Only one of the 32 chemicals is approved as a drug for cancer.

Another approach to concentrating on cancer stem cells, based on the use of antibodies, was reported this month by OncoMed Pharmaceuticals.

The cancer stem cell theory has been thrust into the spotlight in the last five years with the discovery of stem cells in many types of solid tumors, including those of the breast, brain, prostate, colon, bladder and pancreas.

Source: http://www.nytimes.com/2009/08/14/health/research/14cancer.html?_r=1&8au&emc=au

Newer drugs for Epilepsy

Lacosamide

Lacosamide is an amino acid-related compound that has been studied in both pain syndromes and partial seizures.

Mechanism of Action: Lacosamide enhances slow inactivation of voltage-gated Na+ channels. It also binds to the collapsin-response mediator protein, CRMP-2, thereby blocking the effect of neurotrophic factors such as BDNF and NT3 on axonal and dendritic growth.

Rufinamide

Rufinamide is a new triazole derivative with little similarity to other antiseizure drugs. It is approved for use in Lennox-Gastaut syndrome and preliminary evidence suggests that it may also be useful in other difficult-to-treat epilepsy syndromes.

A Guide to the Alternatives to Animal Experimentation

Authors: Dr Syed Ziaur Rahman, MD, Dr Mohd Tariq Salman, MD
Publisher: Ibn Sina Academy of Medieval Medicine and Sciences
1st Edition: 2009, ISBN 978-81-906070-8-7

We teach animal experimentation in all science disciplines. However, since it is now not possible to sacrifice and demonstrate the effects of drugs on animals in large numbers due to ethical considerations; we in medical colleges in India are either shifting or planning to move to alternatives of these experiments. Simulations of many conventional experiments through CAL are now available. "A Guide to the Alternatives to Animal Experimentation” helps students to handle these softwares and see the effects of drugs. This is a remarkable achievement as there is still no such specific guide available in India as far as I know. In the guide, softwares including ExPharm have all been explained very well.While the book by InterNICHE entitled "From guinea pig to computer mouse" is an excellent one meant for faculty and research scientists, this particular guide by Dr Rahman (and myself as co-author) is basically aimed at undergraduate students in pharmacology to help them use the freely available downloadable softwares such as ExPharm, Ep_Dog, Organ Bath Simulation and ReMe independently and learn the effects of drugs. When the students are themselves able handle the softwares (with an instructor nearby to troubleshoot), learning becomes so easy and interesting.

To get a copy please contact me.

'Good Clinical Practices' HelpDesk

The GCP HelpDesk is a support service provided to respond to queries raised by Investigators/Physicians on Good Clinical Practice in Clinical Research. It provides a central point of contact on global GCP issues and ensures that consistent replies are provided to questions. The HelpDesk also allows the users to give their feedback, which will be continuously reviewed in order to improve its services and helps in regularly updating the list of Frequently Asked Questions (FAQs) published on its website. In this website you will find Good Clinical Practice (GCP) related information for the Clinical Research Industry professionals on request.

The GCP HelpDesk is designed to provide information for clinical research professionals with questions regarding handling, conducting and managing clinical research as per GCP, FDA and other Regulations. This HelpDesk is aimed to provide transparency from resources and expertise in the field of Clinical Research with the recent developments and changes in the guidelines for clinical research professionals.The GCP HelpDesk is a searchable website that will match the question with solution by industry experts and other dedicated sites to a specific area. Both simple and complicated questions are welcomed.

To create an account and start using the services go to: http://www.gcphelpdesk.com/index.php/component/user/?task=register

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.