Articles: function.
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Critical care medicine · Jan 2017
Suppression of T Cell Autophagy Results in Decreased Viability and Function of T Cells Through Accelerated Apoptosis in a Murine Sepsis Model.
While type 1 programmed cell death (apoptosis) of T cells leads to immunosuppression in sepsis, a crosstalk between apoptosis and autophagy (type 2 programmed cell death) has not been shown. The aim of this study is to elucidate the details of the interaction between autophagy and immunosuppression. ⋯ We demonstrated that blocking autophagy accelerated apoptosis and increased mortality in concordance with the insufficient autophagy process in CD4 T cells in the murine sepsis model, suggesting that T cell autophagy plays a protective role against apoptosis and immunosuppression in sepsis.
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Background The Nav1.7 subtype of voltage-gated sodium channels is specifically expressed in sensory and sympathetic ganglia neurons where it plays an important role in the generation and transmission of information related to pain sensation. Human loss or gain-of-function mutations in the gene encoding Nav1.7 channels (SCN9A) are associated with either absence of pain, as reported for congenital insensitivity to pain, or with exacerbation of pain, as reported for primary erythromelalgia and paroxysmal extreme pain disorder. Based on this important human genetic evidence, numerous drug discovery efforts are ongoing in search for Nav1.7 blockers as a novel therapeutic strategy to treat pain conditions. ⋯ The results obtained in the live cell imaging assay were supported by patch-clamp studies as well as by quantitative PCR and Western blotting experiments that confirmed the presence of Nav1.7 mRNA and protein in dorsal root ganglia but not in embryonic hippocampal neurons. Conclusions The findings presented here point to a selective effect of Protoxin-II in sensory neurons and helped to validate a new method for investigating and comparing Nav1.7 pharmacology in sensory versus central nervous system neurons. This will help in the characterisation of the selectivity of novel Nav1.7 modulators using native ion channels and will provide the basis for the development of higher throughput models for enabling pain-relevant phenotypic screening.
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[This corrects the article on p. 107 in vol. 21, PMID: 28250784.].
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Knowledge of how alterations in pharmacogenomics and pharmacogenetics may affect drug therapy in the intensive care unit (ICU) has received little study. We review the clinically relevant application of pharmacogenetics and pharmacogenomics to drugs and conditions encountered in the ICU. ⋯ Application of pharmacogenetics and pharmacogenomics has seen improvements in drug therapy. Ongoing study and incorporation of these concepts into clinical decision making in the ICU has the potential to affect patient outcomes.
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Critical care medicine · Jan 2017
Multicenter Study Observational StudyChronic Kidney Disease After Acute Kidney Injury Requiring Continuous Renal Replacement Therapy and Its Impact on Long-Term Outcomes: A Multicenter Retrospective Cohort Study in Korea.
Severe acute kidney injury requiring continuous renal replacement therapy is associated with a high risk of early mortality. Our objectives were to identify a cohort of early survivors and to follow their renal progress and long-term mortality. ⋯ Renal functional assessment at 3 months after continuous renal replacement therapy initiation can be useful in predicting progression to end-stage renal disease and long-term mortality. Furthermore, continuous close monitoring and management of acute kidney injury patients requiring continuous renal replacement therapy are required, even in those with recovered renal function.