Medical principles and practice : international journal of the Kuwait University, Health Science Centre
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This review positions public health as an endeavour that requires a high order of professionalism in addressing the health of populations; this requires investment in an educational capacity that is designed to meet this need. In the global context, the field has evolved enormously over the past half century, supported by institutions such as the World Bank, the World Health Organization and the Institute of Medicine. Operational structures are formulated by strategic principles, with educational and career pathways guided by competency frameworks, all requiring modulation according to local, national and global realities. ⋯ The emergence of accreditation schemes is examined, focusing on their relative merits and legitimate international variations. The role of relevant research policies is recognized, along with the need to foster professional and institutional networks in all regions of the world. It is critically important for the health of populations that nations assess their public health human resource needs and develop their ability to deliver this capacity, and not depend on other countries to supply it.
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Based on aqueous redox chemistry and simple in vivo models of oxidative stress, Escherichia coli and Saccharomyces cerevisiae, the cationic Mn(III) N-substituted pyridylporphyrins (MnPs) have been identified as the most potent cellular redox modulators within the porphyrin class of drugs; their efficacy in animal models of diseases that have oxidative stress in common is based on their high ability to catalytically remove superoxide, peroxynitrite, carbonate anion radical, hypochlorite, nitric oxide, lipid peroxyl and alkoxyl radicals, thus suppressing the primary oxidative event. While doing so MnPs could couple with cellular reductants and redox-active proteins. Reactive species are widely accepted as regulators of cellular transcriptional activity: minute, nanomolar levels are essential for normal cell function, while submicromolar or micromolar levels impose oxidative stress, which is evidenced in increased inflammatory and immune responses. ⋯ Their accumulation in mitochondria and their ability to cross the blood-brain barrier contribute to their remarkable efficacy. We summarize herein the therapeutic effects of MnPs in cancer, central nervous system injuries, diabetes, their radioprotective action and potential for imaging. Few of the most potent modulators of cellular redox-based pathways, MnTE2-PyP5+, MnTDE-2-ImP5+, MnTnHex-2-PyP5+ and MnTnBuOE-2-PyP5+, are under preclinical and clinical development.
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Comparative analyses of the Mycobacterium tuberculosis genome with the genomes of other mycobacteria have led to the identification of several genomic regions of difference (RDs) between M. tuberculosis and M. bovis BCG. The identification of immunodominant and HLA-promiscuous antigens and peptides encoded by these RDs could be useful for diagnosis and the development of new vaccines against tuberculosis. The analysis of RD proteins and peptides by in silico methods (using computational programs to predict major and HLA-promiscuous antigenic proteins and peptides) and experimental validations (using peripheral blood mononuclear cells and sera from tuberculosis patients and BCG-vaccinated healthy subjects to assess antigen-specific cellular and humoral immune responses in vitro) identified several major antigens and peptides. ⋯ Immunizations of experimental animals with the recombinant constructs induced antigen-specific cellular responses. Further experiments showed that each of these proteins had several T and B cell epitopes scattered throughout their sequence, which confirmed their strong immunogenicity. In conclusion, the bioinformatics-based in silico identification of promiscuous antigens and peptides of M. tuberculosis is a useful approach to identify new candidates important for diagnosis and vaccine applications.