Journal of critical care
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The effective treatment of sepsis and septic shock has remained elusive despite intense research efforts. The tools of molecular biology have been applied to the problem of sepsis in an attempt to design more rational, directed therapy. Cellular interactions with invading microorganisms begin a series of stimulation events within the cell. ⋯ The measurement of cytokines is critically important to our understanding of their role in health and disease. Cytokines may be measured by either immunologic methods or biological assays. Molecular biology has made important contributions to our understanding of sepsis by precisely identifying some of the mediators and providing reagents for therapeutic use.
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The high mortality associated with sepsis syndrome and multiple organ dysfunction syndrome has persisted despite extraordinary research efforts in the laboratory and the intensive care unit. These syndromes produce systemic tissue damage that is likely to result from widespread inflammation and subsequent endothelial injury. ⋯ As a result of systemic inflammation and nonmetabolic oxygen use, oxidative stress may occur both outside and inside the cell. The consequences of these oxidative processes during sepsis may be ongoing cell damage mediated by reactive oxygen and nitrogen oxide species that culminates in multisystem organ failure.
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Recent advances in the field of molecular biology have revolutionized our understanding of the functioning of living organisms and facilitated the development of robust tools for both diagnosis and treatment of diseases. With particular reference to the field of critical care medicine, development of molecular biology techniques have aided in the following: (1) rapid and highly specific detection of pathogenic infectious agents (eg, Mycobacterium tuberculosis, Pneumocystis carinii, cytomegalovirus, Legionella); (2) development of assays for measurement of circulating cytokines such as tumor necrosis factor (TNF) and interleukin (IL)-1 that has helped our understanding of the pathogenesis of the sepsis syndrome; (3) administration of antibodies or soluble receptors to attempt to prevent untoward effects of cytokines such as TNF or IL-1; and (4) the administration of recombinant deoxyribonucleic acid (DNA) or proteins to patients in an attempt to alter the course of a disease such as antioxidant enzymes (superoxide dismutase). The rapidity of progress in this field has been staggering, which necessitates frequent updating of our knowledge for clinicians to put these molecular tools to their best use. This brief review attempts to explain the basic principles of commonly used techniques in molecular biology including recombinant DNA, polymerase chain reaction, DNA libraries, gene therapy, and protein biochemistry in a manner that is understandable to those without an in-depth knowledge of the field.
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Journal of critical care · Jun 1995
ReviewMolecular mechanisms of sepsis: molecular biology of the cell.
Complex and interrelated biological processes are at work in the expression of the host response to sepsis. To a large degree, these processes reflect drastic changes in the molecular workings of cells of the body. The protean nature of sepsis reflects this molecular adaptation. ⋯ It uses the process of endotoxin-induced cellular activation as its model and highlights important aspects of DNA promoter and enhancer processes in this activation. Specific examples of known promoter genes and genomic translation are described. This review serves as a "primer" for the subsequent three review articles in this series that will follow it in preceding issues.