The potential price and access implications of the cost-utility and budget impact methodologies applied by NICE in England and ICER in the US for a novel gene therapy in Parkinson's disease.

: NICE in England, and ICER in the US both use cost-utility analyses (CUA) and budget impact analyses (BIA) to assess value for money and affordability, however the thresholds used differ greatly. : To perform a cross-country comparison of the results of the CUA and BIA and detail the implications for reimbursed price and volumes, for a novel gene therapy for Parkinson's disease (PD). : A Markov model was built to perform country-specific CUAs and BIAs : The US ceiling price identified through CUA is ~ 1.

Probing the function of Mycobacterium tuberculosis catalase-peroxidase by site-directed mutagenesis.

Catalase-peroxidase is a multi-functional heme-dependent enzyme which is well known for its ability to carry out both catalatic and peroxidatic reactions. Catalase-peroxidase from Mycobacterium tuberculosis(mtCP) is of particular interest because this enzyme activates the pro-antitubercular drug isoniazid. It is estimated that 2 billion people are infected with M.

Early responses to Salmonella typhimurium infection in mice occur at focal lesions in infected organs.

Salmonella typhimurium causes an invasive disease in mice that has similarities to human typhoid, with key roles for cytokines and possibly also inducible nitric oxide synthase (iNOS), in mediating host responses to infection. In this paper we demonstrate that iNOS mRNA, protein and enzyme activity is induced within spleens and livers of infected mice as early as 5 h post-infection. Immunohistochemistry and in situ hybridization indicated that iNOS expression occurs predominantly in macrophages in localized, discrete foci in the infected organs.

Identification of novel protein kinases in vascular cells.

Protein kinases play pivotal roles in almost all signal transduction pathways in eukaryotic cells (1-4) and are implicated in most major human diseases, including atherosclerosis and associated vasculoproliferative disorders of arteries such as restenosis and graft stenosis (5). Several hundred distinct kinases have already been molecularly cloned, and it is likely that as a result of new information generated through large-scale genome sequencing projects this number will increase. Despite this flood of information, and with several important exceptions, there is a relative lack of knowledge regarding the identity of kinases specifically expressed in vascular tissues or cells and more particularly, it remains unclear how the expression of kinases alters in cardiovascular disease states.