Traumatic brain injury affects over a million Americans annually, but pharmacological therapy remains limited. Current standards of care in acute, subacute and chronic phases of injury are primarily supportive. This review discusses pharmacological strategies and future directions in patient treatment emphasizing pleiotropic agents targeting inflammation, oxidative damage, and glutamate excitotoxicity.
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Impact of attaining an aggressive PK/PD target with continuous infusion beta-lactams on the clinical efficacy of targeted therapy of early post-transplant Gram-negative infections in critically ill OLT recipients. An interim analysis of a 3-year prospective, observational, study.
J Infect Dis
January 2025
Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Italy.
Background: To assess the impact of attaining aggressive beta-lactam pharmacokinetic/pharmacodynamic (PK/PD) targets on clinical efficacy in critical orthotopic liver transplant (OLT) recipients with documented early Gram-negative infections.
Methods: OLT recipients admitted to the post-transplant ICU between June 2021 and May 2024 having documented Gram-negative infections treated with targeted therapy continuous infusion (CI) beta-lactams, and undergoing therapeutic drug monitoring (TDM)-guided beta-lactam dosing adjustment in the first 72 hours were prospectively enrolled. Free steady-state concentrations (fCss) of beta-lactams (BL) and/or of beta-lactamase inhibitors (BLI) were calculated, and aggressive PK/PD target attainment was measured.
Low regulatory T-cells frequency is associated with graft rejection after small bowel transplantation: Clinical and experimental evidence.
PLoS One
January 2025
Transplant Group, La Paz University Hospital Health Research Institute (IdiPAZ), Madrid, Spain.
Background: Intestinal transplantation (ITx) represents the only curative option for patients with irreversible intestinal failure. Nevertheless, its rejection rate surpasses that of other solid organ transplants due to the heightened immunological load of the gut. Regulatory T-cells (Tregs) are key players in the induction and maintenance of peripheral tolerance, suggesting their potential involvement in modulating host vs.
View Article and Find Full Text PDFExploring effector protein dynamics and natural fungicidal potential in rice blast pathogen Magnaporthe oryzae.
PLoS One
January 2025
Department of Computer Science and Engineering, University of Chittagong, Chattogram, Bangladesh.
Rice blast, caused by Magnaporthe oryzae, is one of the most destructive fungal diseases in rice, resulting in major economic losses worldwide. Genetic and genomic studies have identified key genes and proteins, such as AvrPik variants and MAX proteins, that are crucial for the pathogen's virulence. These effector proteins interact with specific alleles of the Pik gene family on rice chromosome 11, modulating the host's immune response.
View Article and Find Full Text PDFStructure-guided engineering of a mutation-tolerant inhibitor peptide against variable SARS-CoV-2 spikes.
Proc Natl Acad Sci U S A
January 2025
Cellular and Structural Physiology Laboratory, Advanced Research Initiative, Institute of Integrated Research, Institute of Science Tokyo, Bunkyo-ku, Tokyo 113-8510, Japan.
Pathogen mutations present an inevitable and challenging problem for therapeutics and the development of mutation-tolerant anti-infective drugs to strengthen global health and combat evolving pathogens is urgently needed. While spike proteins on viral surfaces are attractive targets for preventing viral entry, they mutate frequently, making it difficult to develop effective therapeutics. Here, we used a structure-guided strategy to engineer an inhibitor peptide against the SARS-CoV-2 spike, called CeSPIACE, with mutation-tolerant and potent binding ability against all variants to enhance affinity for the invariant architecture of the receptor-binding domain (RBD).
View Article and Find Full Text PDFProtective effects of neutrophil serine protease inhibition against ischemia-reperfusion injury in lung or heart transplantation.
FEBS J
January 2025
INSERM UMR-1100, "Research Center for Respiratory Diseases (CEPR)", Tours, France.
Transplanted organs are inevitably exposed to ischemia-reperfusion (IR) injury, which is known to cause graft dysfunction. Functional and structural changes that follow IR tissue injury are mediated by neutrophils through the production of oxygen-derived free radicals, as well as from degranulation which entails the release of proteases and other pro-inflammatory mediators. Neutrophil serine proteases (NSPs) are believed to be the principal triggers of post-ischemic reperfusion damage.
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