Sublingual immunotherapy with Dermatophagoides monomeric allergoid down-regulates allergen-specific immunoglobulin E and increases both interferon-γ- and interleukin-10-production

BACKGROUND: The clinical efficacy and safety of sublingual immunotherapy (SLIT) for aeroallergens has been demonstrated in several trials, whereas the immunological changes induced by this treatment, which may account for the clinical improvement, are still unclear. OBJECTIVE: To investigate the effects of a successful SLIT on the in vitro allergen-driven T cell response and cytokine secretion as well as on the serum levels of chemokines and of IgE, IgG1 and IgG4 antibodies (Abs). MATERIALS AND METHODS: Twenty-five Dermatophagoides pteronyssinus (Dp)-sensitive patients with perennial rhinitic and/or rhinitic and asthmatic symptoms were randomized into two groups (13 untreated (UT) and 12 SLIT-treated) for a 1 year and half study. The proliferative response of peripheral blood mononuclear cell (PBMC) to purified Der p1 allergen, their cytokines (IFN-gamma, IL-4, IL-10 and TGF-beta) production and serum levels of chemokines associated with T helper type 1 (Th1) (CXCL10) or T helper type 2 (Th2) (CCL22) responses and of Dp-specific IgE, IgG1 and IgG4 Abs were evaluated before and after 6 months of treatment. RESULTS: SLIT induced a significant reduction of symptom medication scores after 6, 12 and 18 months of treatment in comparison with UT patients. SLIT-treated patients showed a significant decrease in serum levels of DP-specific IgE Abs, whereas total IgE, and specific IgG1 and IgG4 Abs remained unchanged. The proliferative response of allergen-specific T cells to Der p1 in vitro after 6 months of treatment was reduced, while no effect was observed on T cell proliferation to recall antigen (streptokinase). Moreover, Der p1-driven IFN-gamma and IL-10 were significantly increased in culture supernatants of PBMC from 6 month-treated patients in comparison with those detected at the beginning of therapy. CONCLUSIONS: These data suggest that the allergen-driven enhancement of IL-10- and IFN-gamma-producing T cells precedes and associates with SLIT-induced down-regulation of specific IgE, thus providing a rationale to explain the clinical benefit of SLIT in allergic patients.     

Pharmacokinetics of different routes of administration of misoprostol

BACKGROUND: The pharmacokinetic parameters of four different routes of administration of a single dose of 400 microg of misoprostol were studied. METHODS: A total of 40 women undergoing termination of pregnancy by suction evacuation was randomized by computer model to receive 400 microg of misoprostol by one of four routes: (i) sublingual (ii) oral (iii) vaginal and (iv) vaginal with addition of water. Venous blood samples were taken at 0, 1, 2, 5, 10, 20, 30, 45, 60, 120, 240 and 360 min after the administration of misoprostol. Misoprostol acid (MPA) was determined in serum samples using gas chromatography/tandem mass spectrometry. RESULTS: Sublingual misoprostol achieved the highest serum peak concentration (Cmax) (574.8 +/- 250.7 pg/ml) of MPA and this was significantly higher than those in the other groups [Oral: 287.6 +/- 144.3 pg/ml (P < 0.01), vaginal: 125.2 +/- 53.8 pg/ml (P < 0.001) and vaginal with water: 162.8 +/- 57.1 pg/ml (P < 0.001)]. The time to peak concentration (Tmax) was similar in both the sublingual (26.0 +/- 11.5 min) and oral groups (27.5 +/- 14.8 min) and was significantly shorter than those in both vaginal groups. The area under the MPA concentration versus time curve up to 360 min in the sublingual group (743.7 +/- 291.2 pg.h/ml) was significantly greater than those in oral (402.8 +/- 151.6 pg.h/ml, P < 0.05) and vaginal (433.7 +/- 182.6 pg.h/ml, P < 0.05) groups, but no significant difference was found between sublingual and vaginal administration if water (649.3 +/- 333.8 pg.h/ml) was added. CONCLUSION: The new sublingual route of administration of misoprostol demonstrated a great potential to be developed into a method of medical abortion.     

Sumatriptan succinate sublingual fast dissolving thin films: formulation and in vitro/in vivo evaluation

Sumatriptan succinate (SS) is a 5-HT1 receptor agonist used in the treatment of migraine having poor bioavailability (15%) due to its extensive first-pass effect. The aim of this work was to prepare SS sublingual fast dissolving thin films (SFDTFs) allowing the drug to directly enter the systemic circulation and bypassing the first-pass metabolism. Plain thin films were prepared using solvent casting technique adopting 2³?×?3 factorial design to study the effect of polymer and plasticizer type and concentration on mechanical properties and in vitro disintegration time of the plain prepared films using Design-Expert®. Medicated films were prepared after addition of 35?mg SS to each of the two selected plain formulae (F6 and F7) having desirability values above 0.9 showing the values of: 0.038, 0.039?kgf/mm² and 156.24, 164.16% and 0.0248, 0.0240?kgf/mm² as tensile strength, percent elongation and elastic modulus, respectively. PVP K30 was efficient as crystallization inhibitor in retarding SS crystallization. Pharmacokinetic study of the optimum formula F7 (PVP K30:SS (1:1 w/w)) in healthy human volunteers using LC/MS/MS revealed a shorter t_max (0.25?h) compared to Imitrex® tablet 25?mg (2?h) which is considered promising especially for the rapid relief of acute migraine attacks.     

粉尘螨滴剂舌下免疫治疗哮喘伴过敏性鼻炎患儿的临床疗效及安全性

目的:观察粉尘螨滴剂舌下免疫治疗哮喘伴过敏性鼻炎患儿的临床疗效及安全性。方法:观察分析接受粉尘螨滴剂舌下免疫治疗的哮喘伴过敏性鼻炎患儿72例,根据免疫治疗疗程分为1年组、2年组、3年组,随访评估治疗前后患儿哮喘症状（日间和夜间症状）评分、鼻炎症状评分、总症状评分（哮喘和鼻炎症状评分总和）、药物使用评分、哮喘和鼻炎的视觉模拟评分（VAS评分）。结果:1年组、2年组和3年组患儿治疗后哮喘症状评分、鼻炎症状评分、总症状评分、药物使用评分、哮喘和鼻炎的VAS评分较治疗前均显著下降（P＜0.05）,治疗3年组和2年组药物使用评分显著低于1年组（P＜0.05）,2年组和3年组之间药物使用评分未见显著差异。各治疗组未发现不良反应。结论:粉尘螨滴剂舌下免疫不同治疗组均具有较好的临床疗效且安全性好,治疗2年以上的患儿临床疗效更好。     

舌下腺舌神经鞘瘤临床病例报告及分析

本文通过对经诊治的1例左侧舌下腺舌神经鞘瘤患者进行临床病例报告及分析。发现对于神经鞘瘤这种生长缓慢、包膜完整的良性肿瘤,沿包膜外完整切除,术后3个月复诊创口愈合良好,舌感觉及运动无异常,未见复发。所以在对于舌下腺肿瘤的临床诊断及治疗时,舌神经鞘瘤应予以鉴别诊断。