Articles: sepsis.
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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 in vivo efficacy of three cell wall-active antibiotics, imipenem, meropenem, and ceftazidime, was compared in mice rendered hypersusceptible to the pathophysiologic effects of lipopolysaccharide by treatment with D-galactosamine. When CF-1 mice were administered Escherichia coli, D-galactosamine, and saline intraperitoneally, an LD50 was achieved at an inoculum of approximately 2 x 10(4) cfu. ⋯ When the dose of antibiotic was decreased to 2 mg/kg, neither meropenem nor ceftazidime could provide measurable protection, whereas imipenem was almost fully protective (P < .002). These differences in protective efficacy were also noted with experimental Pseudomonas aeruginosa but not Staphylococcus aureus infection.
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Traditionally, sepsis is defined as a systemic inflammatory reaction of the organism to Gram-negative bacterial leading to septic shock--characterized by hemodynamic derangements--and eventually to septic multi-organ malfunction. Sepsis syndrome is diagnosed when fever and other abnormalities of vital signs are present along with abnormalities of one or more organ systems that are not the site of infection and trauma (but with an identifiable locus of infection), and is associated with a range of 30% to 50% mortality. In the United States, one of the most frequent and serious problems confronting clinicians is the management of a serious infection and the systemic response to the infection, such as sepsis. ⋯ Calcium plays vital roles in the intracellular regulation of a variety of cellular responses (for example, contraction, secretion, cell-cell communication, cell proliferation) under physiologic conditions in various cell-types. Alterations in intracellular Ca2+ regulation leading to elevated cytosolic Ca2+ concentration could not only interfere with the cellular responses but also activate lytic enzymes such as proteinases and phospholipases. The objective of this article is to discuss the experimental findings that indicates relationship between alterations in cellular signaling and protein metabolic derangements in non-immune cells (skeletal muscle or liver) during sepsis and inflammation.