ABSTRACT
Elevated substance P can be utilized to predict early mortality during the first week of cerebral infarction. Whether aprepitant, a substance P receptor blocker could be utilized to alleviate poststroke pneumonia which is investigated in this study. Intraluminal monofilament model of middle cerebral artery occlusion (MCAO) was constructed in C57BL/6J male mice, and the relative expression of substance P was detected in collected bronchoalveolar lavage fluid (BALF) and lung tissue homogenate at 24 hours, 48 hours, and 72 hours poststroke. On the other hand, different concentrations of aprepitant (0.5, 1, and 2 mg/kg) were atomized and inhaled into MCAO mice. Inflammation cytokines and bacterial load were detected in collected BALF and lung tissue homogenate at 72-hour poststroke, and lung injury was revealed by histological examination. Aprepitant administration decreased total proteins, total cells, neutrophils, and macrophages in BALF. The concentrations of interleukin (IL)-6, IL-1ß, tumor necrosis factor-α, interferon γ, monocyte chemoattractant protein-1, and IL-10 in lung tissue homogenates were also diminished by the administration of aprepitant. In conclusion, aprepitant could attenuate poststroke pneumonia in mice suggesting its potential therapeutic use in the clinic.
Subject(s)
Aprepitant , Bronchoalveolar Lavage Fluid , Cytokines , Disease Models, Animal , Infarction, Middle Cerebral Artery , Mice, Inbred C57BL , Pneumonia , Animals , Aprepitant/pharmacology , Aprepitant/therapeutic use , Male , Infarction, Middle Cerebral Artery/complications , Infarction, Middle Cerebral Artery/drug therapy , Pneumonia/drug therapy , Pneumonia/complications , Pneumonia/pathology , Bronchoalveolar Lavage Fluid/chemistry , Cytokines/metabolism , Stroke/drug therapy , Stroke/complications , Stroke/pathology , Substance P/metabolism , Lung/pathology , Lung/drug effects , Mice , Morpholines/pharmacology , Morpholines/therapeutic useABSTRACT
PURPOSE: There is a limited evidence of durable effect of parathyroidectomy (PTX) on the quality of life (QoL) in dialysis populations. We aimed to investigate this concern by comparing the QoL scores in the pre- and post-PTX periods in a cohort of dialysis patients. PATIENTS AND METHODS: A total of 212 dialysis patients were enrolled in a hospital-facilitated dialysis center in China between July 1, 2016 and June 30, 2021. The mean age was 46.4 years; the male:female ratio was 96:116; hemodialysis 191, peritoneal dialysis 21. Informative data relating to demographics and dialysis were recorded for comparison. QoL was measured using the Chinese version of the Kidney Disease Quality of Life-36 (KDQOL-36™) and compared subscale scores between the pre-and post-PTX period. Appropriate statistical methods and Pearson's correlation test were used for statistical analysis. RESULTS: Nutritional markers, including hemoglobin and albumin, significantly increased post-PTX than pre-PTX. KDQOL-36 domain scale scores, including Symptoms and Problems of Kidney Disease, Burden of Kidney Disease, Effects of Kidney Disease (EKD), Physical Component Summary (PCS) score, and Mental Component Summary score, significantly increased post-PTX than pre-PTX. All patients were further stratified into three groups based on the PTX duration-0-2 years, >2-<5 years, and ≥5 years-and all KDQOL-36 domain scale scores increased in individual PTX durations. The PTX duration showed a significant negative correlation between PCS subscale scores and a positive correlation between EKD subscale scores. CONCLUSION: PTX could improve QoL in dialysis patients with medically refractory secondary hyperparathyroidism. The durable effects should be studied using a larger sample.
