丙酸氟替卡松联合沙美特罗吸入治疗支气管哮喘

目的观察糖皮质激素与长效β2受体激动剂联合吸入治疗支气管哮喘的疗效。方法对47例诊断为支气管哮喘中重度持续的患儿予丙酸氟替卡松及沙美特罗联合吸入治疗。观察病人治疗前、治疗1周及治疗1个月时PEF值、哮喘症状计分、治疗第1周及第4周使用短效β2受体激动剂的天数、患儿对治疗的主观感受(或家长的评价)及治疗过程中的不良事件。结果治疗1周时PEF值、哮喘症状计分与治疗前相比显著缩短(P<0.01),治疗1个月时症状及肺功能均进一步改善。治疗第4周使用短效β2受体激动剂的天数与第1周相比有显著缩短(P<0.01)。结论糖皮质激素与长效β2受体激动剂有互补作用.对于中重度哮喘患儿,两者联合吸入治疗,有显著疗效。     

针刺对小鼠实验性前列腺增生的防治作用

目的：探讨针刺治疗前列腺增生症的作用机理。方法：采用丙酸睾丸素皮下注射造成小鼠前列腺增生模型，通过针刺白环俞、会阴旁、委阳和三阴交穴，观察针刺对前列腺湿重、组织形态、血清睾丸酮、雌二醇、酸性磷酸酶含量的影响。结果：针刺对丙酸睾丸素引起的小鼠前列腺增生有显著的抑制作用，可使增生的前列腺重量明显减轻，腺上皮细胞增生明显减少，并能降低血清睾丸酮含量，抑制酸性磷酸酶活性，升高雌二醇含量。结论：针刺治疗前列腺增生症的作用机理与降低血清睾丸酮含量，升高雌二醇含量，抑制酸性磷酸酶的活性有关。     

Effects of short-term exposure to high-dose inhaled corticosteroids on novel markers of bone metabolism

Objectives: Novel assays have been developed for markers of type 1 collagen turnover. The aim of this study was to evaluate the effect of short-term exposure to inhaled corticosteroids on both the novel and conventional markers of bone metabolism. Methods: Nine healthy subjects received 2 weeks treatment with inhaled budesonide 800 μg per day in week 1, and 1600 μg per day in week 2, or fluticasone 750 μg per day in week 1 and 1500 μg per day in week 2, with a 1-week washout in between. Measurement of carboxy-terminal propeptide of type 1 collagen (PICP), carboxy-terminal telopeptide of type 1 collagen (ICTP), plasma alkaline phosphatase bone isoenzyme, and 24-h urinary calcium excretion were made at baseline and at the end of each 2-week treatment period. Results: ICTP was significantly reduced following treatment with budesonide but not fluticasone compared with baseline: baseline 4.2 μg⋅1⁻¹ budesonide 3.0 μg⋅1⁻¹, fluticasone 3.6 μg⋅1⁻¹. There were no significant changes in PICP compared with baseline after treatment with budesonide or fluticasone. The ratio of PICP:ICTP increased significantly after treatment with both budesonide and fluticasone compared with baseline: baseline 27.4, budesonide 43.7, t 42.6. There were no significant differences between the two treatments for any of the measured parameters. Conclusions: Thus, when using sensitive markers of collagen turnover, short-term inhaled corticosteroid therapy was found paradoxically to reduced bone resorption. Received: 26 June 1995/Accepted in revised form: 14 November 1995     

Transplacental effect of diethylstilbestrol in female rats.

The effect of diethylstilbestrol propionate (DES; 1 mg/kg body wt. was studied in the female offspring of rats exposed subcutaneously on the 19th day of gestation. Examination of vaginal smears showed persistent estrus in adult rats treated prenatally with DES. Compensatory ovarian hypertrophy (COH) induced by hemicastration of these rats was not suppressed by estrogens. A per oral test for glucose-tolerance revealed decreased utilization of glucose in the offspring of DES-treated rats. Preliminary observations demonstrated that tumors developed in 14 of 18 (77.8%) progeny transplacentally expoed to DES and in 9 of 34 (26.5%) intact control rats. Tumors of the ovary and the endometrium were found only in the rats treated prenatally with DES; no tumors of the uterine cervix or vagina were observed in either experimental or control groups. It is suggested that a transplacental effect of DES in the female is impairment of the sex differentiation of the hypothalamus. The resulting hormonal and metabolic shifts might promote tumorigenesis.     

Pseudopregnancy in female rats: Effects of hormonal manipulations of the male

The stimulus determinants of pseudopregnancy were examined by mating female rats to castrated males maintained on estradiol benzoate (EB) or testosterone propionate (TP), or to intact males. Females were mated for five intromissions (5I), one ejaculatory series (1E), or three ejaculatory series (3E). Copulatory behavior was quite similar for males of all groups. Overall, females that copulated with EB males became pseudopregnant significantly less often than those females mated to TP or intact males. The amount of copulation (5I vs. 1E vs. 3E) received by females from functionally intact males influenced their probability of becoming pseudopregnant or pregnant. EB males had significantly lower body, penile, and seminal vesicle weights in addition to a greatly reduced complement of penile spines than either TP or intact males; adrenal weights did not differ. TP and intact males did not differ on any weight measure. These results indicate that some factor influenced by male hormonal status, possibly penile morphology, plays a role in the initiation of the functional luteal phase in laboratory rats.     

Bioavailability of fluticasone propionate and mometasone furoate aqueous nasal sprays

Objectives To compare the systemic exposure for intranasal mometasone furoate (MF) and fluticasone propionate (FP) aqueous nasal sprays (ANS) in terms of serum and urinary cortisol parameters and plasma pharmacokinetics.Methods Twelve healthy subjects completed this three-way, cross-over study. They received FPANS (50 g/spray), MFANS (50 g/spray) or placebo ANS, eight sprays per nostril every 8 h for 4 days. Cortisol measurements were made at baseline and day 4. FP and MF plasma concentrations were also measured on day 4.Results MFANS produced similar mean plasma AUC (123 pmol/l h) to FPANS (112 pmol/l h). Despite the use of high doses, necessary to generate adequate pharmacokinetic data, only minor reductions in cortisol parameters were found, with no difference between FPANS and MFANS.Conclusions FP and MF have similar and very low systemic bioavailability when administered intranasally using a high-dose regimen. It is therefore unlikely that therapeutic doses of intranasal FP or MF will produce dissimilar or significant degrees of systemic exposure or systemic effects.     

Developmental toxicity of estrogenic chemicals on rodents and other species

ABSTRACT  Antenatal sex-hormone exposure induces lesions in mouse reproductive organs, which are similar to those in humans exposed in utero to a synthetic estrogen, diethylstilbestrol. The developing organisms including rodents, fish and amphibians are particularly sensitive to exposure to estrogenic chemicals during a critical window. Exposure to estrogens during the critical period induces long-term changes in reproductive as well as non-reproductive organs, including persistent molecular alterations. The antenatal mouse model can be utilized as an indicator of possible long-term consequences of exposure to exogenous estrogenic compounds including possible environmental endocrine disrupters. Many chemicals released into the environment potentially disrupt the endocrine system in wildlife and humans, some of which exhibit estrogenic activity by binding to the estrogen receptors. Estrogen responsive genes, therefore, need to be identified to understand the molecular basis of estrogenic actions. In order to understand molecular mechanisms of estrogenic chemicals on developing organisms, we are identifying estrogen responsive genes using cDNA microarray, quantitative RT-PCR, and differential display methods, and genes related to the estrogen-independent vaginal changes in mice induced by estrogens during the critical window. In this review, discussion of our own findings related to endocrine distuptor issue will be provided.     

The effects of topical agents of fluticasone propionate, oxymetazoline, and 3% and 0.9% sodium chloride solutions on mucociliary clearance in the therapy of acute bacterial rhinosinusitis in vivo

OBJECTIVES: The aims of the study were to determine: 1) how mucociliary activity in acute bacterial rhinosinusitis is affected; 2) how this activity is changed by therapy; 3) the effects of topical agents on mucociliary clearance, and 4) the most appropriate topical agent(s) to be used in the therapy of sinusitis. STUDY DESIGN: Five groups of patients with acute bacterial rhinosinusitis were studied prospectively. METHODS: All patients had 500 mg oral amoxicillin and 125 mg oral clavulanic acid preparations given three times daily for 3 weeks. According to the topical agent applications, these groups included: group I (n = 12), no topical treatment was given; group II (n = 14), two puffs for each nostril once daily of 50 microg/100 mL fluticasone propionate was given; group III (n = 9), one puff for each nostril three times daily of 0.05% oxymetazoline was given; group IV (n =12), 3% sodium chloride (NaCl) (buffered to pH 6.5-7 at room temperature) was given; and group V (n =13), 10-mL solutions of 0.9% NaCl (buffered to pH 6.5--7 at room temperature) were given for nasal irrigations three times daily. All patients had medication for 3 weeks and were controlled each week. The saccharin method was used to measure nasal mucociliary clearance. To investigate the early effects of the topical agents for groups II to V, an additional test was repeated 20 minutes after the basal mucociliary clearance recordings. The test was repeated in the first, second, and third weeks of the treatment. RESULTS: The mucociliary clearance was significantly slower in the acute bacterial rhinosinusitis group than in the control group. There was no significant difference between the basal mucociliary clearance and the 20th minute mucociliary clearance of the fluticasone propionate and 0.9% NaCl solution groups. The mean values of the basal and the 20 minute's mucociliary clearance of the oxymetazoline group were 24.72 +/- 6.16 and 15.5 +/- 7.45 minutes, respectively, which were statistically significant. The mean values of the basal and the 20th minute mucociliary clearance of the 3% NaCl solution groups were 19.45 +/- 9.35 and 15.45 +/- 8.20 minutes, respectively, which were also statistically significant. In the first group (without topical treatment), the basal mucociliary clearance became significantly shorter after the second week of treatment. In the first and second weeks of the treatment of the oxymetazoline group, the mucociliary clearance did not change significantly, but after the third week the mucociliary clearance was significantly shorter. In the 3% NaCl solution group, significant improvement began from the first week and continued through the third week. Comparing the basal and the third weeks' mucociliary clearance values among the groups, the oxymetazoline and 3% NaCl solution groups revealed more significant improvement than the other groups, but this improvement was not different from the improvement of group I. There was still a statistically significant difference in the mucociliary clearance of the post-treatment sinusitis groups from the control group. CONCLUSIONS: The oxymetazoline and 3% NaCl solution groups seemed to be more effective in mucociliary clearance, but there was no significant difference in improvement among the groups. The improvement of acute bacterial rhinosinusitis takes more than 3 weeks, according to the mucociliary clearance values of the groups.     

Systemic bioavailability of fluticasone propionate administered as nasal drops and aqueous nasal spray formulations

AIMS: To measure and compare the systemic bioavailability of fluticasone propionate aqueous nasal spray and a new nasal drop formulation, using a sensitive analytical method and high dose regimen. METHODS: Volunteers received four 800 microg doses of fluticasone propionate as a nasal spray or drops over 2 days, separated by an 8 h dose interval. On day 2, blood samples were collected for assay of fluticasone propionate plasma concentrations. RESULTS: The mean systemic exposure, for both formulations was 8.5 pg x ml(-1) x h (drops) and 67.5 pg x ml(-1) x h (spray). Mean absolute bioavailabilities were estimated to be 0.06% (drops) and 0.51% (spray), by reference to historical intravenous data. CONCLUSIONS: Both formulations exhibited low systemic bioavailability, even at 12 times the normal daily dose. The bioavailability from the nasal drops was approximately eight times lower than from the nasal spray.     

吸人沙美特罗/丙酸氟替卡松治疗稳定期慢性阻塞性肺疾病疗效分析

目的:比较吸入沙美特罗/丙酸氟替卡松(SM/FP)治疗稳定期慢性阻塞性肺疾病(COPD)的疗效.方法:采用随机平行对照实验方法,将60例29～76岁肺功能Ⅱ～Ⅲ级的COPD患者随机分为治疗组(30例)和对照组(30例).治疗组患者吸入SM/FP(50μg/250μg);对照组常规治疗.比较分析2组患者肺功能及住院次数变化.结果:经6个月的治疗,治疗组与对照组肺功能变化差异有统计学意义(P＜0.05).治疗组半年住院次数(3人次)少于对照组(7人次).结论:长期联合吸入糖皮质激素和β2-受体激动剂治疗稳定期COPD的疗效优于非吸人治疗.