J Transl Med
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Relative hypovolemia is frequently found in early stages of severe sepsis and septic shock and prompt and aggressive fluid therapy has become standard of care improving tissue perfusion and patient outcome. This paper investigates the role of the nitric oxide pathway on beneficial microcirculatory effects of fluid resuscitation. ⋯ Our results suggest that the underlying mechanism of fluid therapy is the restoration of nitric oxide bioavailability, because inhibition of NOS prevented many of its beneficial effects. Nevertheless, further investigations are required in experimental models closer to conditions of human sepsis to confirm these results.
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Toll-like receptor 4 (TLR4), a lipopolysaccharide (LPS) receptor complex signal-transducing molecule, plays a crucial role in sensing LPS from gram-negative bacteria. TLR4 signaling pathway activation by LPS plays a major role in sepsis pathogenesis. A single nucleotide polymorphism, rs11536889, in the 3'-untranslated region of the TLR4 gene is thought to affect TLR4 translation. This study aimed to investigate whether organ failure in sepsis patients is related to the TLR4 rs11536889 genotype. ⋯ These results offer the first evidence that TLR4 rs11536889 is a useful marker of organ failure in patients with sepsis.
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Since first sequencing the human genome in 2003, emerging genetic/genomic technologies have ushered in a revolutionary era of medicine that purports to bridge molecular biology and clinical care. The field of translational medicine is charged with mediating this revolution. Sequencing innovations are far outpacing guidelines intended to ease their practice-based applications, including in primary care. ⋯ These ethical challenges are both philosophical and infrastructural. From a primary care perspective, the commentary further reviews the ethical, legal and social implications of the Center for Disease Control's proposed model for assessing the validity and utility of genomic testing and family health history applications. Lastly, the authors provide recommendations for future translational initiatives that aim to maximize the capacities of genomic medicine, without compromising primary care philosophies and foundations of practice.
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Remote ischemic preconditioning (RIPC) protects the heart from ischemia and reperfusion (I/R) injury. The underlying molecular mechanisms are unclear. It has been demonstrated that Connexin 43 (Cx43) is critically involved in cardioprotective interventions including classical ischemic preconditioning. In the present study we investigated the influence of RIPC on the expression patterns of Cx43 after I/R in the rat heart in vivo. ⋯ Preservation of Cx43 protein expression and phosphorylation after RIPC might protect the rat heart in vivo.
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We aim to develop a rat model of veno-arterial extracorporeal membrane oxygenation (VA-ECMO). ⋯ We have established a safe, high-throughput, economical, functioning rat model of VA-ECMO.