Articles: biological-models.
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Although there have been numerous advancements in burn wound management, burn injuries are still a major cause of morbidity and mortality in the United States, and novel therapeutics are still needed to improve outcomes. Poloxamer 188 (P188) is a synthetic copolymer with Food and Drug Administration (FDA) approval that has many biological applications. This study aimed to review the literature on P188 in burn injuries and its effects based on burn mechanisms. ⋯ Although its utility may be limited in radiation injuries, P188 may be helpful in delaying the initial damage caused by radiation burns. P188 therefore has the potential to be used as a therapy in both burn wound management and in the treatment of systemic injuries sustained through burns. Future studies should aim to assess the efficacy of P188 in clinical models of burn injury.
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Background : We explored the efficacy and main biological mechanism of geniposide intervention in sepsis. Methods : A sepsis model was established in male BALB/c mice through cecal ligation and puncture (CLP). Different doses of geniposide (20 or 40 mg/kg) were administered intravenously at 0 and/or 24 h after CLP surgery. ⋯ In addition, geniposide elevated the PPARγ level in monocytes ( P < 0.05). Conclusions : High-dose early-stage geniposide administration significantly improved the survival rate in a CLP mouse sepsis model by modulating the monocyte phenotype and regulating the cytokine network (IL-6/IL-10 levels). The pharmacological mechanism of geniposide action might be exerted primarily through PPARγ upregulation.
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Sepsis is associated with significant mortality and morbidity among critically ill patients admitted to intensive care units and represents a major health challenge globally. Given the significant clinical and biological heterogeneity among patients and the dynamic nature of the host immune response, identifying those at high risk of poor outcomes remains a critical challenge. Here, we performed secondary analysis of publicly available time-series gene-expression datasets from peripheral blood of patients admitted to the intensive care unit to elucidate temporally stable gene-expression markers between sepsis survivors and nonsurvivors. ⋯ Our model had robust performance in a test dataset, where patients' transcriptome was sampled at alternate time points, with an area under the curve of 0.89 (95% CI, 0.82-0.96) upon 5-fold cross-validation. We also identified 7 potential biomarkers of sepsis mortality (STAT5A, CX3CR1, LCP1, SNRPG, RPS27L, LSM5, SHCBP1) that require future validation. Pending prospective testing, our model may be used to identify sepsis patients with high risk of mortality accounting for the dynamic nature of the disease and with potential therapeutic implications.
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Curr Opin Anaesthesiol · Aug 2023
ReviewPharmacokinetic and pharmacodynamic drug display and simulation systems in anesthesia practice.
This review explores the use of tools and displays based on pharmacokinetic and pharmacodynamic (PK/PD) modelling of drugs used in anesthesia. The primary focus is on those tools designed to illustrate the interactions between two or more drugs, or classes of drugs, and in particular, their use in a real-time clinical support role. Off-line, educational tools are also explored. ⋯ PK/PD simulation is a useful tool for exposition of the relationship between drug dosing and effect. The initial promise of real-time tools has yet to be realized in routine clinical practice.