Anesthesiology
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Volatile anesthetics (VAs) alter the function of key central nervous system proteins but it is not clear which, if any, of these targets mediates the immobility produced by VAs in the face of noxious stimulation. A leading candidate is the glycine receptor, a ligand-gated ion channel important for spinal physiology. VAs variously enhance such function, and blockade of spinal glycine receptors with strychnine affects the minimal alveolar concentration (an anesthetic EC50) in proportion to the degree of enhancement. ⋯ Taken together, these results indicate that glycine receptors containing the α1 subunit are not likely to be crucial for the action of isoflurane and other VAs.
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Anesthetic preconditioning protects cardiomyocytes from oxidative stress-induced injury, but it is ineffective in patients with diabetes mellitus. To address the role of hyperglycemia in the inability of diabetic individuals to be preconditioned, we used human cardiomyocytes differentiated from induced pluripotent stem cells generated from patients with or without type 2 diabetes mellitus (DM-iPSC- and N-iPSC-CMs, respectively) to investigate the efficacy of preconditioning in varying glucose conditions (5, 11, and 25 mM). ⋯ The opening of mitochondrial adenosine 5'-triphosphate-sensitive potassium channels are disrupted in DM-iPSC-CMs in 11 mM and 25 mM glucose and in N-iPSC-CMs in 25 mM glucose. Cardiomyocytes derived from healthy donors and patients with a specific disease, such as diabetes in this study, open possibilities in studying genotype- and phenotype-related pathologies in a human-relevant model.
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Physiologic instability is a common clinical problem in the critically ill. Many natural feedback systems are nonlinear, and seemingly random fluctuations may result from the amplification of external perturbations or even arise de novo as a consequence of their underlying dynamics. Characterization of the underlying nonlinear state may be of clinical importance, providing a technique to monitor complex physiology in real-time, guiding patient care and improving outcomes. ⋯ Hypotension leads to a reduction in dominant Hölder exponents for mean arterial pressure, demonstrating an increasing signal complexity consistent with the activation of important homeokinetic processes. Conversely, pharmacological interventions may also alter the underlying dynamics. Pharmacological restoration of homeostasis leads to system decomplexification, suggesting that homeokinetic mechanisms are derecruited as homeostasis is restored.
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Patients with peritoneal carcinomatosis often report abdominal pain, which is relatively refractory to morphine. It has been considered that a new animal model is required to investigate the mechanism of abdominal pain for the development of optimal treatments for this type of pain. ⋯ Both the up-regulation of substance P and down-regulation of μ-opioid receptor seen in the dorsal root ganglia may be, at least in part, responsible for the abdominal pain-like state associated with peritoneal carcinomatosis.
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The understanding of how general anesthetics act on individual cells and on global brain function has increased significantly during the last decade. What remains poorly understood is how anesthetics act at intermediate scales. Several major theories emphasize the importance of neuronal groups, sets of strongly connected neurons that fire in a time-locked fashion, in all aspects of brain function, particularly as a necessary substrate of consciousness. The authors have undertaken computer modeling to determine how ã-aminobutyric acid receptor type A (GABAA) receptor potentiating agents such as propofol may influence the dynamics of neuronal group formation and ongoing activity. ⋯ GABAA facilitation both directly and indirectly inhibits the ability of neurons to form groups spontaneously. A lack of group formation is consistent with some theories of anesthetic-induced loss of memory formation and consciousness.