TLR/MyD88-mediated Innate Immunity in Intestinal Graft-versus-Host Disease

Graft-versus-host disease (GHVD) is a severe complication after allogeneic hematopoietic stem cell transplantation. The degree of inflammation in the gastrointestinal tract, a major GVHD target organ, correlates with the disease severity. Intestinal inflammation is initiated by epithelial damage caused by pre-conditioning irradiation. In combination with damages caused by donor-derived T cells, such damage disrupts the epithelial barrier and exposes innate immune cells to pathogenic and commensal intestinal bacteria, which release ligands for Toll-like receptors (TLRs). Dysbiosis of intestinal microbiota and signaling through the TLR/myeloid differentiation primary response gene 88 (MyD88) pathways contribute to the development of intestinal GVHD. Understanding the changes in the microbial flora and the roles of TLR signaling in intestinal GVHD will facilitate the development of preventative and therapeutic strategies.

Plasma Paraquat Concentration and Early Prognostic Factors in Paraquat Poisoning / 대한신장학회지

PURPOSE: Paraquat is a lethal herbicide and induces acute renal failure, hepatic dysfunction, and progressive respiratory failure. The aims of this study are to investigate the correlation between plasma paraquat concentrations and initial laboratory data at Emergency Medical Center and to investigate whether initial laboratory data is useful for predicting outcomes of paraquat-poisoned patients. METHODS: A retrospective analysis by chart review was done on 83 patients who ingested paraquat and who had presented to Emergency center of within 24 hours. Plasma paraquat concentrations, urine dithionite test and initial laboratory parameters including white blood cell count, urine pH, and AST, ALT, BUN, Creatinine, Amylase, Glucose, pH, PaCO2, PaO2, HCO3. Base Excess, Na, K, Cl were obtained at the time of Emergency Center visit. We compared urine dithionite test, plasma paraquat concentrations and Severity Index of Paraquat Pisoning (SSPI) of the survival group to those of the dead group. The patients were divided into four subgroups based on the level of plasma paraquat concentration, their initial laboratory data was compared and analyzed. RESULTS: The mean plasma paraquat concentration in the mortality group was higher than that in the survival group (88.44+/-81.56 vs. 1.32+/-1.72 microgram/mL). Among the initial laboratory data of four subgroups, WBC, Glucose, Cr, pH, HCO3, Bass excess were significantly different between the group of low level of plasma paraquat concentration and higher group. ANCOVA analysis revealed that WBC, HCO3, Bass excess correlated with the level of plasma paraquat concentration significantly. CONCLUSION: The plasma paraquat concentration and SIPP were higher in the mortality group significantly. Initial laboratory data including WBC, Glucose, Cr, pH, HCO3, Bass excess were proven to be significant prognostic factors. Especially WBC, HCO3, Bass excess can be used to predict the outcome of paraquat poisoning.