6623 research outputs found
Sort by
Treatment outcome and prognostic factors of tonsillectomy for palmoplantar pustulosis and pustulotic arthro‐osteitis: A retrospective subjective and objective quantitative analysis of 138 patients
Get PDFPustulosis palmaris et plantaris (PPP) and pustulotic arthro-osteitis (PAO) are tonsil-related diseases. Treatment outcome of tonsillectomy and prognostic factors influencing the outcome have not been analyzed quantitatively. We evaluated those using the Palmoplantar Pustulosis Area and Severity Index (PPPASI). At 1, 3, 6, 12, 24 and more than 24 months post-tonsillectomy, 20 (31%), 34 (48%), 70 (60%), 57 (80%), 36 (95%) and 23 (96%) patients realized 80% or more improvement of PPP skin lesions, respectively, and eight (17%), 23 (36%), 30 (50%), 38 (79%), 12 (100%) and four (100%) patients showed 80% or more improvement of PPPASI (i.e. PPPASI% ≥ 80%), respectively. At 1, 3, 6, 12 and more than 12 months post-tonsillectomy, 19 (73%), 21 (66%), 27 (73%), 19 (79%) and 15 (83%) patients realized a disappearance of PAO-induced arthralgia, respectively. Kaplan-Meier analysis of 80 patients with PPP revealed that, at 12 and 24 months post-tonsillectomy, lesions disappeared (i.e. PPPASI = 0) in 38% and 66% of patients, respectively, and lesions improved by 80% or more (i.e. PPPASI% ≥ 80%) in 71% and 95% of patients, respectively. The log-rank test and univariate and multivariate analyses showed that smoking cessation post-tonsillectomy and PAO were significant predictive factors for the early disappearance of skin lesions. This report is the first demonstrating objective evidence of the great efficacy of tonsillectomy to improve PPP skin lesions. Even post-tonsillectomy, smoking inhibited the early disappearance of the lesions
Altered colonic sensory and barrier functions by CRF: roles of TLR4 and IL-1
Get PDFVisceral allodynia and increased colonic permeability are considered to be crucial pathophysiology of irritable bowel syndrome (IBS). Corticotropin-releasing factor (CRF) and immune-mediated mechanisms have been proposed to contribute to these changes in IBS, but the precise roles have not been determined. We explored these issues in rats in vivo. The threshold of visceromotor response, i.e., abdominal muscle contractions induced by colonic balloon distention was electrophysiologically measured. Colonic permeability was estimated by quantifying the absorbed Evans blue in colonic tissue. Intraperitoneal injection of CRF increased the permeability, which was blocked by astressin, a non-selective CRF receptor antagonist, but astressin2-B, a selective CRF receptor subtype 2 (CRF2) antagonist did not modify it. Urocortin 2, a selective CRF2 agonist inhibited the increased permeability by CRF. Eritoran, a toll-like receptor 4 (TLR4) antagonist or anakinra, an interleukin-1 receptor antagonist blocked the visceral allodynia and the increased gut permeability induced by CRF. Subcutaneous injection of lipopolysaccharide (immune stress) or repeated water avoidance stress (WAS, psychological stress), 1 h daily for 3 days induced visceral allodynia and increased gut permeability (animal IBS models), which were also blocked by astressin, eritoran or anakinra. In conclusion, stress-induced visceral allodynia and increased colonic permeability were mediated via peripheral CRF receptors. CRF induced these visceral changes via TLR4 and cytokine system, which were CRF1 dependent, and activation of CRF2 inhibited these CRF1-triggered responses. CRF may modulate immune system to alter visceral changes, which are considered to be pivotal pathophysiology of IBS
Paraquat toxicity is attenuated by 4-phenylbutyrate-induced phosphorylation of ERK2 via PI3K in A549 cells
Get PDFParaquat (PQ) is a widely used herbicide in the world despite being highly toxic to humans. PQ causes fatal damage to multiple organs, especially the lungs. While oxidative stress is the main toxic mechanism of PQ, there is no established standard therapy for PQ poisoning. In this study, we investigated the cytoprotective effect of 4-phenylbutyrate (4PBA) on PQ toxicity in human lung adenocarcinoma A549 cells. Phosphorylation levels of major survival signaling kinases Akt and ERK, as well as expression levels of antioxidant enzymes catalase and superoxide dismutase 2 (SOD2) were examined. The cytoprotective mechanism of 4PBA against PQ was compared with the antioxidant reagent trolox. We demonstrated that both 4PBA and trolox attenuated PQ toxicity, but their mechanisms were different. 4PBA increased ERK2 phosphorylation levels, which could be inhibited by the PI3K inhibitor LY294002. The cytoprotective effect of 4PBA was also inhibited by LY294002. Catalase expression levels were increased by 4PBA, although this increase was not inhibited by LY294002. 4PBA did not increase SOD2 expression. Trolox did not affect phosphorylation of Akt or ERK, or the expression of antioxidant enzymes. These results suggest that 4PBA attenuated PQ cytotoxicity by ERK2 activation via PI3K. Our study may provide new findings for understanding the molecular mechanism underlying cytoprotection by 4PBA, as well as new therapeutic targets for PQ poisoning.博士（医学）旭川医科大