Researchers at Massachusetts General Hospital (MGH) are investigating a new way to block replication of hepatitis C virus “HCV” by targeting not the virus itself, but the genes that the virus exploits during its life cycle.

HCV has a high rate of replication that it can replicate a trillion particles per day. Also, due to its high rate of mutation, it can escape our immune system.

HCV replicates mainly within hepatocytes in liver by binding to receptors on the surface of the liver “CD81″ and human scavenger receptor class B1 “SR-BI”. Then it utilizes the intracellular machinery necessary for its replication.

Transmission occurs by blood to blood contact, where it causes chronic liver infection in about 70-80% of patients & long term infections can cause liver failure or liver cancer.

HCV infection is usually treated with a six to eleven month regimen combining peginterferon and the antiviral drug ribavirin, but unfortunately, treatment is not successful in many patients and has serious side effects that some cannot tolerate.

Many drugs target viral enzymes, but due to the great ability of HCV to mutate, such approach lead to the emergence of resistant strains.

Recently, a new strategy has developed, which is to block human genes, which act as a cofactors for HCV infection. Using small interfering RNAs (siRNAs), researchers examined blocking of approximately 21,000 predicted messenger RNA transcripts in the human genome.

The siRNA scan found 96 genes that appear to have a role in viral replication, one gene codes for an enzyme called PI4KA, which is believed to be involved in the formation of membrane structures within the cell. Another group of genes contribute to formation of the coat.

So, by blocking these genes, HCV replication is stopped. At this time, these tested agents might not be suitable for therapeutic use.

Source & Image credits : Harvard Science.

 

Tags: blood contact, CD81, HCV, hepatocytes, Massachusetts General Hospital, peginterferon, PI4KA, ribavirin, siRNAs, SR-BI

Seriously, these days, no matter where I turn to, there is somebody contracting some form of bacterial infection that turns out to be pretty serious. At the beginning of the new year, a 20-year-old perfectly fit Brazilian model died of what appeared to be a Pseudomonas aeruginosa infection. As far as I know, polymyxins should work like a charm. Sadly, her life ended after enduring the amputation of her limbs and a nephroectomy procedure in an attempt to save her. And now again, rumor has it that Michael Jackson contracted a MRSA infection following a nose job.

Where did the antibiotics go? Is the bacterial resistance way ahead of us that we can’t even keep up? In a field study conducted amongst fellow neighbors & relatives, many did infact admit that they go rushing to their local pharmacies demanding a prescription of antibiotics for a mild flu or a fever of 38 degrees. Not that that is worse enough, they don’t comply to the pharmacist’s orders “if he did infact give an order” to administer it for the full course of the medication.

This should be a warning sign…an alarm triggering off right about now. Developed countries are already facing these problems, we shouldn’t be lingering around. Public awareness campaigns, maybe similar to those concerning the bird flu being aired these days, ought to be held. Our community is in desperate need of our expertise to guide, inform, and advise them about the consequences and potential threats at stake here.

“The window is closing and we’re coming to the end of the antibiotic era,” said J. Glenn Morris Jr., M.D., who heads the division of hospital epidemiology at the University of Maryland School of Medicine, College Park, MD. This was in 1999.

Can we really beat antibiotic resistance? or are bacteria getting the best of us?

Tags: bacterial resistance, brazilian model, c8bcf5c0dc8cfaa24f17995e7625c2b0, michael jackson, MRSA, pseudomonas

Despite great advances in cancer therapy, conventional therapies are still implementing drawbacks and dilemmas that drives cancer research to consider other strategies to overcome the drawbacks implicated by conventional cancer therapy. The  cancer treatment using  anticancer agents possesses many adverse events related to bone marrow suppression and death  of other rapidly proliferating cells is resulting from the either of the two following reasons:

• The narrow therapeutic index of anticancer agents that is in many cases hard to adjust with the inter-individual Pharmacokinetic &/or pharmacogenetic variation among  cancer patients.
• The lack of specificity in most of anticancer agents systemically administered where anticancer agents kill both tumor cells and healthy cells.

Both of the above facts driven cancer therapy research in to many different aspects in the hope of optimizing the therapy & providing new techniques to get over the drawbacks of conventional therapy; The pharmacokinetics & /or pharmacogenetics, gene therapy  in addition to the targeting therapy including the nanotherapy.

Professor Mostafa El Sayed  was awarded the 2007 US National Medal of Science for his huge contribution in the field of nanotherapy in cancer  as a molecular targeting approach that overcomes side effects of conventional cancer therapy. The idea lies in two main aspects: The first is molecular targeting & the second is photothermal destruction of malignant cells. The technique encompasses injecting gold nanoparticles conjugated with anti- Epidermal Growth Factor Receptor “anti -EGFR”  monoclonal antibody , where the anti-EGFR is responsible for the the specific targeting which is molecularly based on the fact that epithelial carcinoma cells, particularly over-expresses “EGFR”. Regarding the tumor cidal effect it is mainly dependent on the  photothermal destruction which is the role of the laser beam & gold nanoparticles, where particular nano size of gold makes it able to absorb light in Near Infra Red Region , which is the region where optical penetration is optimal &  scatter laser beam and convert the light energy to thermal energy that is able to damage cell membrane and release the digestive enzymes and hence the death of cancer cells.

Image credit: www.gatech.edu

The choice of the laser light is a matter of  the cancer location , where in case of cancer under the skin,  Near Infra Red “NIR” laser light is recommended for its larger penetration depth. Gold particles are especially used because  they are easily bioconjugated & they served as photoabsorbers due to overlap of absorption band of their specific nanosize with with argon laser beam. The gold nanoparticles are having a silica core and a gold shell & their absorption in the NIR is tuned by adjusting gold layer thickness as well as the size of silica core.

The pioneering success of the technique has been proved effective upon accumulation of Anti-EGFR antibody conjugated gold nanoparticles selectively in carcinoma cells and survival of benign cells as demonstrated by microscopic pictures of both  benign & cancer cells as follows:

Gold nanoparticles are concentrated in cancer cells. “Pic 1”
Image credit: www.gatech.edu

Gold nanoparticles are not retained in benign cells. “Pic 2”
Image credit: www.gatech.edu

References:

• Ivan H. El Sayed, Xiaohua Huang, Mostafa A. El Sayed, ” Selective laser Photo-thermal therapy of epithelial carcinoma  using anti-EGFR antibody conjugated gold nanoparticles”, Cancer Letters 239 (2006) 129-135.
• Erin B. Dickerson, Erick C. Dreaden, Xiaohua Huang, Ivan H. El Sayed,Hunghao Chu, Sujatha Pushpanketh, John F. Mcdonald, Mostafa A. El Sayed, ” Gold nano assiated near-infrared Plasmonic Phototheramal Therapy (PPTT) of squamos cell carcinoma in mice”, Cancer Letters 269 ( 2008) 57- 66.

Tags: adverse events, anticancer, argon laser, bone marrow suppression, cancer, Epithelial Carcinoma, Gene Therapy, laser, Molecular targetting, monoclonal antibody, nanotherapy, narrow therapeutic index, Pharmackinetic, pharmacogenetic, Photo-Thermal Destruction, Professor Mostafa El Sayed