Technologies to Assist New Drug Development for Combating Bacterial Infection and in Bladder Cancer Therapy- A Press Report

Printer Friendly Version WEB LINK - http://www.expresspharmaonline.com/20120315/research02.shtml Carestream Healths Research to aid in novel drug discovery, holds promise for improving bladder cancer therapy The menace of hospital acquired bacterial infection is alarmingly high in India with nearly 1,90,000 babies succumbing to it every year. Staphylococcus aureus bacteremia is one of the five most-common causes of hospital-acquired infectionsoften leading to post-surgical wound infections. Now, a cutting edge research by Carestream Health has for the first time visualised in real-time how bacterial infections are confronted by the body immune system, particularly the bladder. Such path-baking technologies will aid in novel drug discoveries, besides enhancing understanding of how the drugs perform in abating the infections. Explains Dr Rao Papineni, a distinguished scientist and Senior Principal Investigator, Research and Development, Carestream Health, S. aureus can cause a range of illnesses from minor skin infections, such as pimples, impetigo, boils (furuncles), cellulitis, folliculitis, carbuncles, scalded skin syndrome, and abscesses, to life-threatening diseases such as pneumonia, meningitis, osteomyelitis, endocarditis, toxic shock syndrome (TSS), bacteremia, and sepsis. S. aureus is also prevalent in cancer patients with abnormally low levels of neutrophils (a type of white blood cell).Methicillin-resistant S. aureus or MRSA is a greatly feared strain of S. aureus that has become resistant to most antibiotics. In ICU's in India, the rates of antibiotic resistant bacterial infection MRSA in some cases is as high as 80 per cent. And in the US, each year, some 5,00,000 patients contract the deadly MRSA infection. Says Papineni, Targeting the virulence factor (or the ability to cause disease) of bacterial infection is a promising approach for developing novel therapeutics, including treatment of cancer. A detailed understanding of the virulence factors and the resultant immune response of the human body is essential for such development. So, to assess the initial immune response to S. aureus, his group inoculated (injected) S. aureus into a laboratory mouse. The research showed real time Myeloperoxidase (MPO) enzyme activity, a part of the bodys defence system, against S. aureus bacteria. About the significance of the research, Papineni says, Besides the fact that for the first time, we have been able to visualise how bacterial infections are combated by the body immune system, we found that the bodys defense against bacteria looks similar to that of bladder cancer therapy. Such technologies will thus be valuable in developing better bladder cancer treatment.

Related Work Accepted for Presentation at American Association for cancer Research 2012.

in vivo Imaging of early inflammation response in bacterial infection

Accepted for AACR Annual Meeting 2012 in Chicago, IL Session ID: Tumor Biology 39 Session Date and Time: Tuesday Apr 3, 2012 1:00 PM - 5:00 PM E-Mail: rao.papineni1@carestreamhealth.com

Staphylococcus aureus (S. aureus) causes significant morbidity and mortality worldwide and a prime cause in hospital infections. Staphylococcus aureus bactereremia is prevalent in neutropenic cancer patients, and malignancies form a sizeable risk factor for methycillin-resistant S. aureus (MRSA) infections. Targeting the virulence products is a

promising approach for developing novel therapeutics. A detailed understanding of the virulence factors and the resultant immune response is quite essential for such development. Here, we established an athymic mice model to assess the initial immune response to S.aureus inoculation. As the polymorphonuclear neutrophils (PMN) and macrophages are a part of the early response, determination of its myeloperoxidase (MPO) activity in vivo is established. MPO is an inflammatory heme protein and utilizes hydrogen peroxide in the process of reactive oxygen species generation. 24 hrs after the intra muscular injection of the S.aureus bacterial lysate, the MPO activity was detected by i.p injection of luminal in mice. The blue luminescence resulting from the MPO activity was imaged with a commercially available multimodal imaging system. The luminescence images were overlaid on planar X-ray images for anatomical coregistration. The results show a robust MPO activity in the mouse bladder. This increase in MPO activity as a result of neutrophil activation at the bladder region was further confirmed using non-invasive X-ray contrast imaging of the bladder and co-registering the luminescence and the X-ray density signals at the bladder. The initial response shown here has similarities with the mechanism suggested recently for myobacterium bovis bacillus Calmette-Guerin (BCG) treatment of bladder cancer. Bacterial components, its structures that are involved in eliciting the robust PMN infiltration in bladder will be very valuable in the developing better bladder cancer anti-tumor treatments.