Effects of inhaled fluticasone propionate on CTLA-4-positive CD4+CD25+ cells in induced sputum in mild asthmatics

Background and objective: Cytotoxic T-lymphocyte antigen 4 (CTLA-4) signalling of regulatory T cells regulates mucosal lymphocyte tolerance and differentiation, and may therefore have a beneficial effect in allergic diseases such as asthma. The aim of this study was to evaluate the effects of fluticasone propionate (FP) on CD4+CD25+ T cell co-expression of CTLA-4 in the sputum of mild asthmatic subjects. Methods: Eleven mild, stable asthmatic subjects completed a double-blind, randomized, cross-over, placebo-controlled study to compare the effects of 14 days 200 µg twice daily FP and placebo. Before and after treatment, airway hyperresponsiveness was measured, and sputum was induced for measurements of CTLA-4+CD4+CD25+ cells, eosinophils and levels of IL-10, IL-13 and transforming growth factor (TGF)-β Results: FP treatment increased co-expression of CTLA-4 on sputum CD4+CD25+ cells from a mean (SEM) of 7.9% (1.8) to 12.7% (3.3) after 14 days treatment (P < 0.05) compared with placebo. FP treatment also significantly increased IL-10 levels, reduced per cent sputum eosinophils, and reduced airway hyperresponsiveness (P < 0.05). There was a significant negative correlation between the change in airway hyperresponsiveness and per cent sputum eosinophils (P < 0.01), but no correlation with changes in CTLA-4+CD4+CD25+ cells (P > 0.05). There was no change in the levels of sputum IL-13 or TGF-β Conclusions: The percentage of airway CTLA-4+CD4+CD25+ cells increased after FP treatment, coincident with improvements in airway inflammation and hyperresponsiveness. Whether improved asthma assessments are related to the increase in CTLA-4+CD4+CD25+ cells and thus improved regulation of T-cell tolerance and differentiation will require a larger sample size to determine. The normalization of CTLA-4+CD4+CD25+ cells in asthma may contribute to the management of this disease.     

Depigmentation – a rare side effect to intra-articular glucocorticoid treatment

Intra-articular glucocorticoid injections are often used in patients with rheumatoid arthritis, either as bridging therapy or in periods with increased disease activity. We present a case of local skin depigmentation that occurred at the site of injection in a dark-skinned patient. Depigmentation is a rare complication of such therapy but may have important implications for dark-skinned patients.Abbreviations DMARD Disease-modifying anti-rheumatic drugs - RA Rheumatoid arthritis     

Successful use of intravenous clomipramine in depressive–catatonic state associated with corticosteroid treatment

We report two female patients who deteriorated to depressive–catatonic state after interepisode recovery from a hypomanic episode induced by corticosteroid treatment. Their symptoms developed during maintenance treatment with a low dose of prednisolone in Case 1 and after discontinuation of betamethasone in Case 2. Intravenous clomipramine successfully relieved their symptoms including reduction in contact and reactivity, immobility and mutism. These two patients showed no schizophrenic symptoms such as hallucinations and delusions. Corticosteroid-induced mood disorder can deteriorate into depressive stupor, severe depressive episode with catatonic features in DSM-IV. Clomipramine, a tricyclic antidepressant with relatively stronger serotonin reuptake inhibition, is one of the useful treatment options for corticosteroid-induced depression even in severe cases.     

Benign Mucinous Cystadenoma of the Appendix Report of 3 Cases. Review of the Literature

Backgrounds/Aims: Inflammation during the early phase of anastomotic wound healing is an essential cellular response and is suppressed by corticosteroids. The anti-inflammatory effect of corticosteroids is largely responsible for its impairment of wound healing in bowel anastomosis. Beta-D-glucan, a commonly used macrophage activator, has been shown to improve anastomotic wound healing under normal conditions. In the present study, we have investigated the effects of beta-D-glucan on anastomotic wound healing in rats treated with long-term corticosteroid. Methodology: 92 male Sprague-Dawley rats were randomized into four groups. 1: control, 2: control + beta-D-glu-can, 3: steroid, 4: steroid + beta-D-glucan. Methylprednisolone (5mg/kg) was injected IM daily for 14 days in groups 3 and 4. After 14 days, following anaesthesia and laparotomy, colonic anastomosis was performed 3 cm away from the peritoneal reflection of rectum. In groups 2 and 4, 100mg/kg beta-D-glucan was administered orally for 7 days before laparotomy. On postoperative day 3, relaparotomies were performed and bursting pressures, hydroxyproline levels and histopathological specimens were studied.

Results: The mean values of bursting pressures groups were 50.8 (95% CI 46.99-56.50), 58.2 (95% CI 54.49-61.90), 32.0 (95% CI 29.21-34.98), 45.9 (95% CI 43.09-48.80) respectively. The differences of the mean values of the groups between group 1 and 2 and also 3 were significant (p = 0.002, p < 0.001). The mean values of hydroxyproline of the groups were 3.8 (95% CI 3.56-4.06), 4.7 (95% CI 4.50-5.04), 2.9 (95% CI 2.73-3.20), 3.9 (95% CI 3.65-4.22) respectively. The differences of the values of the groups between control (group1) and group 2 and also group 3 were significant (p = 0.001, p < 0.001). In histopathological examination, increased macrophages and fibroblast population were observed in specimens from beta-D-glucan-treated animals.

Conclusion: The results indicate that in rat model, oral administration of beta-D-glucan causes a significant improvement in the healing of anastomotic wound impaired by long-term corticosteroid administration.     

Effects of Neurotensin on the Healing of Experimental Anastomosis of the Colon

The leakage of colonic anastomoses increases perioperative morbidity significantly. The purpose of the study was to investigate the influence of neurotensin, an intestinal trophic peptide, on the healing of colonic anastomosis. Forty-two Wistar-albino rats were separated into three equal groups: Group 1 (control group) — segmental resection of the left colon and end-to-end anastomosis; Group 2 (dexamethasone group) — resection and anastomosis, plus 0.1 mg/kg/day of dexamethasone; Group 3 (neurotensin group) — same surgical procedure plus 300 pg/kg/day of neurotensin. Bursting pressure and tissue hydroxyproline content were determined as parameters of the anastomosis strength and healing on the 3^rd and 7^th days postoperatively. On the 3^rd day, mean bursting pressures were 141.4, 146.7 and 73.1 (p = 0.0001) cm of water in the control group, dexamethasone and neurotensin groups respectively. On the 7^th day, bursting pressures were measured as 237.4, 100.6 (p = 0.0001) and 72.7(p = 10^-6) cm of water, in the control group, dexamethasone and neurotensin groups respectively. Between the 3^rd and 7^th days, bursting pressures were increased significantly in the control group (p = 0.0001), decreased in the dexamethasone (p = 0.048), and maintained their lowest values in the neurotensin (p = 0.96) groups. On the 7^th day, mean hydroxyproline levels were measured as 9.20, 3.30 (p = 0.007), 2.86 (p = 0.007) pg, in the control group, dexamethasone, and neurotensin groups respectively. Between the 3^rd and 7^th days, tissue hydroxyproline levels were increased significantly in the control group (p = 0.004), decreased in the dexamethasone (p = 0.03), and maintained their lowest values in the neurotensin (p = 0.87) groups. The anastomosis resistance to intraluminal pressure was weak, tissue collagen content was insufficient, and healing was inadequate in the dexamethasone and neurotensin groups in respect to the control group. We concluded that neurotensin impaired the healing, and affected the strength of the colonic anastomosis.