粉尘螨滴剂对3～14岁支气管哮喘和过敏性鼻炎的疗效及安全性分析

目的评估舌下特异性免疫治疗药物＂粉尘螨滴剂＂治疗3～14岁过敏性哮喘及变应性鼻炎患儿的疗效和安全性。方法对78例3～14岁由粉尘螨过敏引起的过敏性哮喘和（或）变应性鼻炎患儿进行为期25周的脱敏治疗,记录治疗前后患儿的哮喘症状评分和鼻炎症状评分,统计分析疗效及安全性。结果治疗后患儿的哮喘症状评分和鼻炎症状评分较治疗前均显著下降,差异具有统计学意义（P〈0.01）。治疗期间出现7例次局部不良反应,1例次全身不良反应,未出现严重全身不良反应。结论舌下特异性免疫治疗粉尘螨滴剂是治疗儿童过敏性哮喘和变应性鼻炎的一种安全、有效的治疗方法。     

舌下脱敏治疗儿童间歇性变应性鼻炎、支气管哮喘50例疗效分析

目的：评估舌下含服粉尘螨滴剂治疗尘螨致敏的间歇性过敏性哮喘、变应性鼻炎患儿的临床疗效;观察单一脱敏对单一粉尘螨过敏和双螨过敏的疗效。方法：收集2012年6月至2013年6月到我院儿科确诊的螨过敏间歇性变应性鼻炎（AR）和过敏性哮喘（AS）患儿50例,按皮肤点刺试验（SPT）结果将患儿分为粉尘螨组27例和双螨组23例。记录所有患儿治疗前和治疗12个月后的症状评分、用药情况评分和视觉模拟评分（VAS）。用酶联免疫吸附（ELISA）法检测部分患儿的血清特异性免疫球蛋白G亚型4（sIgG4）水平。结果：①舌下脱敏治疗12个月后,患儿的症状评分、用药评分和VAS评分均有显著性降低,和舌下脱敏治疗前比较差异有统计学意义（P<0.01）;患儿的血清sIgG4水平脱敏治疗前为（79.21±78.13）,脱敏治疗12个月后为（137.95±92.01）,治疗前后比较差异具有统计学意义（P<0.01）。②单一粉尘螨舌下脱敏治疗单一粉尘螨和双螨过敏患者12个月后,患儿的症状评分、用药评分和VAS评分均显著性降低,且和治疗前相比差异具有统计学意义（P<0.01）;治疗12个月后,粉尘螨组和双螨组的症状评分、用药评分和VAS评分比较差异无统计学意义（P>0.05）。结论：舌下脱敏治疗螨过敏引起的间歇性哮喘鼻炎患儿具有显著效果,单一粉尘螨脱敏治疗单一粉尘螨过敏和双螨过敏患儿的疗效相当。     

粉尘螨滴剂舌下含服治疗儿童支气管哮喘伴过敏性鼻炎的临床疗效

目的评估粉尘螨滴剂治疗儿童支气管哮喘伴过敏性鼻炎的临床疗效。方法将94例5～14岁粉尘螨过敏的患儿分常规组和脱敏组,分别采用常规治疗和粉尘螨舌下含服脱敏治疗,定期随访,记录患儿的哮喘症状和鼻炎症状,用药情况,并在治疗2 a后复查粉尘螨皮肤点刺。结果脱敏组和常规组治疗前哮喘症状评分分别为(2.55±0.52)和(2.60±0.49)分,治疗2 a均明显降低,分别为(0.30±0.59)和(0.85±0.87)分;鼻炎评分治疗前分别为(5.86±2.61)和(5.72±2.41)分,治疗2 a明显降低分别为(1.34±0.79)和(3.66±1.87)分;用药评分治疗前分别为(5.21±1.13)和(5.02±1.26)分,治疗2 a也明显降低,分别为(0.17±0.43)和(0.77±0.92)分。粉尘螨点刺结果分级评分治疗前(3.63±0.48)和(3.56±0.50)分,治疗2 a分别为(2.43±0.43)和(3.39±0.60)分。各项评分免疫组与常规组比较差异有高度统计学意义(P<0.001)。均未见严重的不良反应。结论粉尘螨滴剂吞下含服治疗儿童支气管哮喘伴过敏性鼻炎安全、有效。     

儿童变应性鼻炎103例舌下脱敏疗法治疗效果的临床评价

目的 探讨舌下含服标准化粉尘螨变应原疫苗治疗儿童变应性鼻炎的有效性和应用价值.方法 103例粉尘螨过敏的变应性鼻炎患儿治疗前及治疗1年后进行鼻炎症状、体征、药物应用及视觉模拟量表（VAS）评分,并统计不良反应发生率.结果 治疗前患儿鼻部各症状评分分别为（2.71±0.70）、（1.69±0.79）、（1.97±0.99）、（1.93±0.83）分,体征、用药、VAS评分分别为（1.85±0.84）、（2.13±0.83）、（7.43±1.33）分;治疗后鼻部各症状评分分别为（0.42±0.55）、（0.25±0.44）、（0.32±0.56）、（0.41±0.51）分,体征、用药、VAS评分分别为（0.24±0.43）、（0.24±0.47）、（1.25±0.71）分.各指标比较的差异均有统计学意义（P＜0.01）.结论 舌下含服标准化粉尘螨变应原疫苗是一种治疗儿童变应性鼻炎的有效方法.     

粉尘螨滴剂治疗儿童变应性鼻炎的疗效及安全性

目的：评价舌下含服标准化粉尘螨滴剂治疗儿童变应性鼻炎2年疗效及其安全性。方法螨过敏变应性鼻炎儿童240例随机分为观察组和对照组,各120例,对照组氯雷他定或／和康酸莫米松药物治疗,观察组加用舌下含服粉尘螨滴剂,疗程2年,评价治疗前后症状评分和药物评分及安全性。结果2年后,观察组患儿症状评分和药物评分为（3.46±0.85）,（0.28±0.43）分,较治疗前的（10.76±1.08）,（1.28±0.68）分均明显减少（P均＜0.05）,较对照组治疗后的（9.76±1.14）,（1.09±0.35）分均明显减少（P均＜0.05）。观察组随访期间出现皮疹、鼻咽痒等11例,对照组出现鼻腔出血,乏力、嗜睡等10例,均未出现过敏性休克等严重全身不良反应。结论舌下含服标准化尘螨滴剂治疗尘螨引起的儿童变应性鼻炎有效,并有较好的安全性。     

粉尘螨滴剂治疗儿童过敏性鼻炎伴哮喘50例的临床疗效观察

目的：观察粉尘螨滴剂治疗儿童过敏性鼻炎伴哮喘的临床疗效。方法将过敏原监测试验尘螨（＋＋＋）~（＋＋＋＋）的哮喘合并鼻炎的98例患儿随机分为治疗组50例和对照组48例,对照组给予常规治疗,治疗组在常规治疗基础上,同时给予为期一年的舌下 SLIT 治疗,比较治疗6、12月临床疗效。结果哮喘、鼻炎症状评分较对照组显著下降（P 均＜0.01）。结论粉尘螨滴剂联合常规治疗可提高儿童过敏性鼻炎伴哮喘的临床疗效。     

粉尘螨性变应性鼻炎患者舌下免疫治疗的疗效

目的 评价舌下免疫治疗粉尘螨性变应性鼻炎的疗效.方法 对69例粉尘螨性变应性鼻炎患者用粉尘螨滴剂舌下含服进行免疫治疗,持续2年,观察治疗效果.结果 与治疗前比较,治疗后3个月患者的症状明显改善,治疗后6个月症状改善更加明显(P＜0.01),此后症状改善维持在一个较稳定的水平.结论 舌下免疫治疗粉尘螨性变应性鼻炎是一种安全、有效的针对病因的治疗方法.     

舌下含服粉尘螨滴剂治疗86例变应性鼻炎疗效观察

目的评价舌下含服粉尘螨滴剂变应原疫苗治疗变应性鼻炎的疗效。方法将粉尘螨过敏为主的变应性鼻炎患者156例,分为实验组和对照组,实验组进行舌下含服粉尘螨滴剂治疗2年,观察治疗前及治疗后1年的各项临床症状评分,并进行综合评价。结果两组在治疗后1年在鼻部症状、体征、视觉模拟量表评分(VAS评分)及药物评分几方面有差异,均有统计学意义(P值均<0.01)。治疗期间无严重不良反应病例发生。结论经舌下含服粉尘螨滴剂治疗变应性鼻炎是一种安全有效的方法。     

影响粉尘螨滴剂治疗过敏性鼻炎疗效的相关因素分析

目的 探讨影响粉尘螨滴剂治疗过敏性鼻炎疗效的相关因素。方法 采用回顾性方法分析2012年1月~2014年6月在本院门诊就诊的过敏原为尘螨的过敏性鼻炎患者326例,采用粉尘螨滴剂舌下含服脱敏治疗,根据患者鼻炎症状、体征进行评分,采用单因素及多因素方法进行统计学分析。结果 年龄、多重过敏原、病程、对症药物治疗、规则用药、伴发鼻窦炎、疗程为粉尘螨滴剂治疗过敏性鼻炎疗效的影响因素(P<0.05),年龄、规则用药、疗程是影响粉尘螨滴剂治疗过敏性鼻炎疗效的独立因素(P<0.05)。结论 应用粉尘螨滴剂治疗过敏性鼻炎应尽早、规则、足够疗程用药,同时对症治疗过敏性鼻炎、鼻窦炎等症状,均能提高脱敏治疗的效果。     

舌下含服粉尘螨滴剂治疗儿童过敏性鼻结膜炎的疗效分析

目的 探讨舌下含服粉尘螨滴剂治疗儿童过敏性鼻结膜炎的疗效。方法 选择2019年5月至2020年5月本院收治的过敏性鼻结膜炎患儿400例,随机分为对照组和研究组各200例。对照组予以常规抗过敏药物或糖皮质激素对症治疗,研究组予以粉尘螨滴剂舌下脱敏治疗,比较两组鼻部症状评分、鼻部体征评分、眼部症状评分、鼻炎用药评分、结膜炎用药评分及不良反应发生率。结果 研究组治疗0.5年、1年、2年后的鼻部症状评分、鼻部体征评分、眼部症状评分、鼻炎用药评分、结膜炎用药评分均低于对照组(P<0.05);两组治疗过程中均未出现严重不良反应且总发生率比较差异无统计学意义(P>0.05)。结论 粉尘螨滴剂舌下脱敏疗法对过敏性鼻结膜炎患儿临床症状改善效果明显,抗过敏药物用量更少,可获得理想的远期疗效,且安全性高,值得推广。     

Quantitative in vivo and in vitro sex differences in artemisinin metabolism in rat

1. The pharmacokinetics of the antimalarial compound artemisinin were compared in the male and female Sprague-Dawley rat after single dose i.v. (20 mg.kg) or i.p. (50 mg.kg) administration of an emulsion formulation. 2. Plasma clearance of artemisinin was 12.0 (95% confidence interval: 10.4, 13.0) l.h. kg in the male rat and 10.6 (95% CI: 7.5, 15.0) l.h. kg in the female rat suggesting high hepatic extraction in combination with erythrocyte uptake or clearance. Artemisinin half-life was 0.5 h after both routes of administration in both sexes. Values for plasma clearance and half-lives did not statistically differ between the sexes. 3. After i.p. administration artemisinin AUCs were 2-fold higher in the female compared with male rat (p 0.001). Artemisinin disappearance was 3.9-fold greater in microsomes from male compared with female livers and it was inhibited in male microsomes by goat or rabbit serum containing antibodies against CYP2C11 and CYP3A2 but not CYP2B1 or CYP2E1. 4. The unbound fraction of artemisinin in plasma was lower (p 0.001) in plasma obtained from the male (8.8 2.0%) compared with the female rat (11.7 2.2%). 5. The possibility of a marked sex difference, dependent on the route of administration, has to be taken into account in the design and interpretation of toxicological studies of artemisinin in this species.     

Quantitative in vivo and in vitro sex differences in artemisinin metabolism in rat

1. The pharmacokinetics of the antimalarial compound artemisinin were compared in the male and female Sprague-Dawley rat after single dose i.v. (20 mg x kg(-1)) or i.p. (50 mg x kg(-1)) administration of an emulsion formulation. 2. Plasma clearance of artemisinin was 12.0 (95% confidence interval: 10.4, 13.0) 1 x h(-1) x kg(-1) in the male rat and 10.6 (95% CI: 7.5, 15.0) 1 x h(-1) x kg(-1) in the female rat suggesting high hepatic extraction in combination with erythrocyte uptake or clearance. Artemisinin half-life was approximately 0.5 h after both routes of administration in both sexes. Values for plasma clearance and half-lives did not statistically differ between the sexes. 3. After i.p. administration artemisinin AUCs were 2-fold higher in the female compared with male rat (p < 0.001). Artemisinin disappearance was 3.9-fold greater in microsomes from male compared with female livers and it was inhibited in male microsomes by goat or rabbit serum containing antibodies against CYP2C11 and CYP3A2 but not CYP2B1 or CYP2E1. 4. The unbound fraction of artemisinin in plasma was lower (p < 0.001) in plasma obtained from the male (8.8 +/- 2.0%) compared with the female rat (11.7 +/- 2.2%). 5. The possibility of a marked sex difference, dependent on the route of administration, has to be taken into account in the design and interpretation of toxicological studies of artemisinin in this species.     

休克时血中氧自由基的变化

本实验测定10名休克患者血浆和红细胞的丙二醛(MDA)、血浆总抗的氧化活性(AOA)的含量。结果表明:休克病人红细胞膜和血浆 MDA 含量(4.298±0.722;5.348±0.834)与对照组(3.235±0.682;4.356±1.081)比较明显增高(P<0.05);血浆 AOA(39.65±7.858)与对照组(48.21±10.81)比较明显降低(P<0.01)。提示:休克时,患者机体内自由基反应增强是引起组织细胞损伤的原因之一。     

Interindividual variability in metabolic activation in humans in vivo

In assessing interindividual variability in metabolic activation, the toxic metabolite is often too unstable for conventional analysis. Possible alternatives include a stable product of the reactive metabolite e.g. cysteinyl derivatives of N-acetyl-4-benzoquinoneimine, the toxic metabolite of paracetamol, adducts with DNA or protein, and indirect measurement of the activity of the enzyme(s) producing the active metabolite. An example of the last approach is the use of furafylline, a highly specific inhibitor of human CYP1A2, to determine the extent of the metabolic activation of the cooked food mutagens PhIP and MeIQx. The extent of inhibition, determined from levels of unchanged amine in urine, is an indirect measure of the activity of the activation pathway. Further refinement of this approach, allied to improved measures of the biological process of interest should prove of value in evaluating interindividual variability and its role in the risk assessment process.     

Theophylline kinetics in peripheral tissues in vivo in humans

Several biochemical and cellular effects have been described for methylxanthines under in vitro conditions. However, it is unknown, whether threshold concentrations required to exert these effects are attained in target tissues in vivo. We therefore employed the microdialysis technique for measuring theophylline concentrations in peripheral tissues under in vivo conditions.Following in vitro and in vivo calibration, microdialysis probes were inserted into the medial vastus muscle and into the periumbilical subcutaneous adipose layer of healthy volunteers. Following single oral dose administration of 300 mg or i.v. infusion of 240 mg theophylline, in vivo time courses of theophylline concentrations were monitored in tissues and plasma. Major pharmacokinetic parameters (c_max, t_max, AUC) were calculated for plasma and tissue time courses. The mean AUC_tissue /AUC_plasma-ratio was 0.56 (p.o.) and 0.55 (i.v.) for muscle and 0.55 (p.o.) and 0.72 (i.v.) for subcutaneous adipose tissue.We conclude that microdialysis provides important information on the distribution and the tissue pharmacokinetics of theophylline.Abbreviations FPIA Fluorescence polarisation immuno assay - AUC Area under the curve - t_max Time to peak concentration - c_max Peak concentration     

Changes in angiopoietin expression in glomeruli involved in glomerulosclerosis in rats with daunorubicin-induced nephrosis

AIM: To study the potential pathological role of endogenous angiopoietins in daunorubicin-induced progressive glomerulosclerosis in rats. METHODS: Seventy male Wistar rats were allocated randomly into a daunorubicin group (DRB; n=40) or a control group (n=30). The rats in the DRB group were injected with DRB (15 mg/kg), in their tails. Subsequently, at intervals of 1, 2, 4, 6, 8, and 12 weeks, 5 male Wistar rats in each group were chosen randomly for 24 h urinary protein quantitative measurements (24 h UPQM), and determination of plasma tumor necrosis factor alpha (TNF-alpha), angiopoietin-1 (Ang1), and angiopoietin-2 (Ang2) levels. Kidney sections were examined by electron microscopy, Periodic Acid Schiff (PAS) staining, immunohistochemical staining and in situ hybridization histochemistry. RESULTS: As glomerulosclerosis progressed in the DRB group, expression of Ang1 mRNA and protein in glomeruli decreased and expression of TNF-alpha protein, Ang2 mRNA and protein in glomeruli increased. Expression of Ang1 mRNA and protein in glomeruli were negatively correlated with 24 h UPQM, Fn protein expression, and mean area of extracellular matrix (MAECM). In comparison, expression of Ang2 mRNA and protein in glomeruli were positively correlated with 24 h UPQM, Fn protein expression and MAECM; furthermore, there was a positive correlation between plasma Ang2 and 24 h UPQM. Plasma TNF-alpha and expression of TNF-alpha in glomeruli were positively correlated with expression of Ang2 mRNA and protein in glomeruli. There was a negative correlation between Ang1 protein expression and Ang2 protein expression in glomeruli. CONCLUSION: During DRB-induced glomerulosclerosis, podocyte injury led to a shift in the balance of Ang1 and Ang2 in glomeruli. Increased TNF-alpha in plasma and glomeruli may upregulate Ang2 expression in glomeruli. Elevated Ang2 in both plasma and glomeruli may mediate protein permeability through the glomerular filtration barrier. Moreover, local expression of Ang2 may facilitate the progress of glomerulosclerosis by upregulating a component expression of extracellular matrix.