氢化可的松乳膏含量测定方法改进

目的改进氢化可的松乳膏现有质量标准的含量测定方法。方法通过改进供试品的提取处理过程,优化操作步骤。结果改进方法的氢化可的松平均回收率为98.57%,RSD=1.17%(n=9),测定结果与药典方法结果比较没有明显差别,可代替原提取方法。结论该方法准确度高、操作简便,适用于医院制剂的快速检验。     

吸入布地奈德治疗毛细支气管炎

目的探讨吸入布地奈德混悬液在治疗毛细支气管炎中的地位。方法将103例轻中症毛细支气管炎患儿随机分为治疗组53例,对照组50例,在常规治疗基础上,治疗组吸入布地奈德混悬液,对照组同样吸人布地奈德混悬液,另外静滴琥珀酸氢考,观察哮鸣音减少、消失及住院时间。结果两组间比较哮鸣音减少、消失及住院时间,差异无统计学意义（P〉0．05）。结论吸入布地奈德在治疗轻中症毛细支气管炎中效果肯定,同时静滴琥珀酸氢考不能获得更好的疗效。     

氢化可的松洗剂的制备及质量控制

目的:制备氢化可的松洗剂并建立其质量控制方法。方法:以氢化可的松为主药制备洗剂;采用紫外分光光度法测定其中主药的含量,同时考察制剂稳定性及皮肤刺激性。结果:所制制剂为无色澄明液体,检查符合2005年版《中国药典》中相关规定;氢化可的松检测浓度在5～30μg.mL-1范围内呈良好的线性关系(r=0.9990),平均回收率为100.09%(RSD=0.17%);制剂放置3、6个月各项指标均无明显变化,刺激性实验结果皮肤无红斑、水肿等不良反应。结论:本制剂制备工艺简便可行,质量稳定可控。     

Risk of death does not alter the efficacy of hydrocortisone therapy in a mouse E. coli pneumonia model

BACKGROUND: Risk of death may influence the efficacy of anti-inflammatory agents in sepsis. "Physiologic" dose corticosteroids, while improving survival in earlier trials with higher control mortality rates (>50%), were not beneficial in the recent CORTICUS trial with lower control mortality (31%). We investigated whether risk of death altered the effects of hydrocortisone in a mouse pneumonia model. METHODS: Mice (n=637) challenged with high, medium or low intratracheal E. coli doses were randomized to receive one of three hydrocortisone doses (5, 25 or 125 mg/kg) or normal saline (NS) only (control) for 4 days. All animals were treated with similar volumes of ceftriaxone and NS support following E. coli and were observed for 168 h. RESULTS: Decreasing E. coli doses reduced control mortality rates (from 94 to 12%). In similar patterns (not significant) each hydrocortisone dose increased the odds ratio (OR) of survival (95% confidence interval) with each E. coli dose (ORs ranging from 1.2 [0.4, 3.7] to 6.1 [0.6, 61.0]). The effect of hydrocortisone on the OR was not related to control mortality rate (r=-0.13, p=0.29) and overall was highly significant (2.04 [1.37, 3.03], p=0.0004). In randomly selected animals 48 h after the highest E. coli dose, compared with the control, hydrocortisone (125 mg/kg) significantly decreased IL-6, INFgamma, and nitric oxide levels. CONCLUSIONS: In this mouse model the beneficial effects of hydrocortisone were independent of risk of death. These findings suggest that factors other than risk of death may underlie the differing effects of corticosteroids in recent sepsis trials.     

Stress doses of hydrocortisone in septic shock: beneficial effects on opsonization-dependent neutrophil functions

Objective To assess the effects of stress doses of hydrocortisone (HC) on clinical parameters and neutrophil functions in patients with septic shock. Design Prospective, double-blind, randomized, placebo-controlled study. Setting Intensive care units of a university hospital. Patients and participants 30 adult patients with septic shock. Interventions Patients were allocated to receive either HC (intravenous bolus of 100 mg preceding a continuous infusion 10 mg/h, n = 15) or placebo (n = 15), respectively. The effects of HC were assessed at baseline and after 24 h. Measurements and results As compared with placebo-treated patients, administration of HC significantly decreased norepinephrine requirements (from 1.5 to 0.8 mg/h; p < 0.001), interleukin-6 serum concentrations (from 388.8 to 88.8 pg/ml; p < 0.02), and the spontaneous release of hydrogen peroxide (H₂O₂) by neutrophils (−33.0%; p < 0.05). Additionally, HC treatment preserved the autologous plasma-induced amplification of phagocytosis of zymosan particles [factor of opsonin-induced amplification of phagocytosis of unopsonized particles: 1.80 for placebo vs. 1.75 for HC at baseline (not significant between groups) and 0.50 for placebo vs. 1.75 for HC after 24 h of treatment (p < 0.05)]. These effects were paralleled by respective changes in the phagocytosis-associated H₂O₂ production. Conclusions In patients with septic shock stress doses of HC exert beneficial effects in terms of improvements in hemodynamics, decrease in pro-inflammatory mediators, and oxidative stress without the compromise of opsonization-dependent phagocytic neutrophil functions; thus, HC treatment does not aggravate non-specific immunosuppression but instead improves innate immunity in the early stage of septic shock.     

Elevated alpha-amylase but not cortisol in generalized social anxiety disorder

Stress-system dysregulation is thought to increase the risk for anxiety disorders. Here we describe both hypothalamic pituitary adrenal (HPA) axis and autonomic nervous system (ANS) activity in basal non-challenging conditions and after 0.5 mg dexamethasone in generalized social anxiety disorder (gSAD) patients. To ensure stress-free sampling we collected saliva and determined cortisol and alpha-amylase (sAA), the latter a relative new marker of autonomic activity.Forty-three untreated gSAD patients without comorbidity were compared with 43 age and gender matched controls in non-stressed conditions on sAA and cortisol after awakening, during the day (including late evening), and after a low dose (0.5 mg) of dexamethasone. Cortisol and sAA were analyzed with mixed models. Additional analyses were done with paired t-tests. Apart from the assessments in the morning, gSAD patients had significantly higher diurnal and post-dexamethasone 1600 h sAA levels. No differences between gSAD and controls in any cortisol measurements were found.In conclusion, in gSAD in basal, non-stimulated conditions and after dexamethasone, we found hyperactivity of the ANS, as measured with sAA, but not of the HPA-axis. This suggests a relative increased activity of the ANS as compared to the HPA-axis, in line with the observed hyperarousal in gSAD.     

氢化可的松和胰岛素对兔软骨细胞生长的影响

目的：观察胰岛素和氢化可的松对兔软骨细胞生长的影响，方法：取新西兰兔膝关节软骨细胞，分别加入胰岛素，氢化可的松或二者的复合物的培养液中培养，用MTT法测定其对软骨细胞的增殖的影响。结果：单独使用胰岛素0．035μg/ml即可显著促进软骨细胞增殖（P＜0．01），当浓度增至0．35μg/ml时，其促进作用达到最大值（P＜0．01）。氢化可的松10μg/ml时对软骨增殖的抑制作用明显（P＜0．05）。随着氢化可的松浓度的增大，抑制作用更显著，当浓度增至100μg/ml时，软骨细胞几乎全部死亡（P＜0．01）。当胰岛素0．35μg/ml与氢化可的松50μg/ml联合使用时，氢化可的松可以拮抗胰岛素的作用，结论：低浓度胰岛素对软骨细胞的生长有促进作用，氢化可的松对软骨细胞的生长有抑制作用，二者联合使用时，氢化可的松可以拮抗胰岛素的作用。     

Recombinant streptokinase vs hydrocortisone suppositories in acute hemorrhoids: A randomized controlled trial

AIM: To compare the efficacy and safety of recombinant streptokinase(rSK) vs hydrocortisone acetate-based suppositories in acute hemorrhoidal disease.METHODS: A multicenter(11 sites), randomized(1:1:1), open, controlled trial with parallel groups was performed. All participating patients gave their written,informed consent. After inclusion, patients with acute symptoms of hemorrhoids were centrally randomized to receive, as outpatients, by the rectal route, suppositories of rSK 200000 IU of one unit every 8 h(first 3 units)and afterwards every 12 h until 8 administrations were completed(schedule A), one unit every 8 h until 6 units were completed(schedule B), or 25 mg hydrocortisone acetate once every 8 h up to a maximum of 24 administrations. Evaluations were performed at 3, 5,and 10 d post-inclusion. The main end-point was the 5thday response(disappearance of pain and bleeding, and≥ 70% reduction of the lesion size). Time to response and need for thrombectomy were secondary efficacy variables. Adverse events were also evaluated.RESULTS: Groups were homogeneous with regards to demographic and baseline characteristics. Fifth day complete response rates were 156/170(91.8%; 95%CI:87.3-96.2), 155/170(91.2%; 95%CI: 86.6%-95.7%),and 46/170(27.1%; 95%CI: 20.1%-34.0%) with rSK(schedule A and B) and hydrocortisone acetate suppositories, respectively. These 64.6% and 63.9%differences(95%CI: 56.7%-72.2% and 55.7%-72.0%)were highly significant(P 0.001). This advantage was detected since the early 3rd day evaluation(68.8% and64.1% vs 7.1% for the rSK and active control groups,respectively; P 0.001) and was maintained even at the late 10 th day assessment(97.1% and 93.5% vs67.1% for rSK and hydrocortisone acetate, respectively;P 0.001). Time to response was 3 d(95%CI: 2.9-3.1)for both rSK groups and 10 d(95%CI: 9.3-10.7) in the hydrocortisone acetate group. This difference was highly significant(P 0.001). All subgroup stratified analyses(with or without thrombosis and hemorrhoid classification) showed a statistically significant advantage for the rSK groups. Thrombectomy was necessary in4/251 and 14/133 patients with baseline thrombosis in the rSK and hydrocortisone acetate groups, respectively(P 0.001). There were no adverse events attributable to the experimental treatment.CONCLUSION: rSK suppositories showed a significant advantage over a widely-used over-the-counter hydrocortisone acetate preparation for the treatment of acute hemorrhoidal illness, as well as having an adequate safety profile.     

氢化可的松增强白细胞介素-1对离体大鼠胰岛β细胞的抑制作用

本文测定了新生大鼠胰岛在有或无白细胞介素-1(IL-1)、氢化可的松(HC)的培养液中孵育时的胰岛素释放率及胰岛素含量。IL-1(500ng/L)于孵育的第1～3天内引起胰岛素释放减少,但第4～7天部分恢复。HC(10~(-7)及10~(-6)mol/L)似能防止IL-1(500ng/L)所诱致的在孵育第1～3天内的胰岛素释放减少,但在第4～7天却使胰岛素释放减少更为明显;7天后胰岛的胰岛素含量降低也极明显。结果提示HC能增强IL-1对离体新生大鼠胰岛β细胞功能的抑制作用。     

异氟醚麻醉对大鼠血皮质醇及海马脑源性神经营养因子和神经生长因子的影响

目的 探讨异氟醚麻醉对大鼠血皮质醇及海马脑源性神经营养因子(BDNF)和神经生长因子(NGF)的影响.方法 成年SD雄性大鼠36只,10周龄,体重250～280 g,采用随机数字表法,将其随机分为6组:正常对照组(C组,n=6)、O2组(O组,n=6)和异氟醚组(I组,n=24).I组通入2％异氟醚2h,纯氧流量3 L/min,O组仅通入纯氧.O组于停止通入纯氧后进行水迷宫实验,Ⅰ组分别于停止给药后2h、1、7、14 d取6只大鼠、进行水迷宫实验,定位航行实验中记录逃避潜伏期和游泳总路程,空间探索实验中记录穿越平台次数和游泳总路程.每个时点水迷宫实验结束后,取眼眶血,测定血浆皮质醇浓度;取海马组织,测定BDNF和NGF的含量.结果 与C组比较,O组空间探索实验中穿越平台次数减少,游泳总路程缩短,血浆皮质醇浓度降低,Ⅰ组于停止给药后1d时定位航行实验中逃避潜伏期和游泳总路程均延长,空间探索实验中穿越平台次数减少,游泳总路程缩短、海马BDNF含量降低(p＜0.05或0.01).结论 异氟醚麻醉对大鼠认知功能短期内有一过性抑制作用,其机制与促进皮质醇释放与海马BDNF合成有关,而与海马NGF合成无关.