睾酮对胰岛素敏感细胞胰岛素受体底物1和葡萄糖转运载体4表达的影响

目的探讨雄激素对胰岛素敏感性影响的可能的分子机制。方法诱导3T3-L1前脂肪细胞系和C2C12成肌细胞系分别分化为3T3-L1脂肪细胞和C2C12骨骼肌细胞,然后对这两种细胞分别以10-9mol/L睾酮处理4、8、12、24及48h,并以不同浓度(10-12~10-5mol/L)的睾酮处理24h,用Western印迹的方法检测两种细胞在以两种方法处理后胰岛素受体底物1(IRS-1)和葡萄糖转运载体4(GLUT4)表达的变化。结果随着10-9mol/L浓度的睾酮处理时间的延长,IRS-1和GLUT4在两种细胞的表达逐渐增加,IRS-1于12h达峰后下降。3T3-L1脂肪细胞及C2C12骨骼肌细胞中12h峰值分别是0h对照的(1·42±0·42)倍和(1·53±0·14)倍,均P<0·05;GLUT4于24h达峰后表达下降[3T3-L1脂肪细胞及C2C12骨骼肌细胞中24h峰值分别是0h的(3·22±0·10)倍和(5·17±1·06)倍,均P<0·05]。当睾酮处理浓度从10-12mol/L逐渐增加时,IRS-1在两种细胞的表达逐渐增加,于10-9mol/L达峰值后表达逐渐下降[在3T3-L1脂肪细胞和C2C12骨骼肌细胞,10-9mol/L睾酮处理后的峰值较空白对照分别增加(4·23±0·27)倍和(3·16±0·15)倍,均P<0·05]。GLUT4在C2C12骨骼肌细胞的表达随着睾酮浓度的升高有增加的趋势[经10-7mol/L睾酮处理后的表达量是空白对照的(2·99±0·15)倍,P<0·05,于10-7mol/L后增加趋势不明显。在3T3-L1脂肪细胞中,GLUT4的表达于10-11mol/L达峰值[较空白对照增加(2·58±0·02)倍,P<0·05],然后随着睾酮浓度的升高表达下降。结论睾酮影响胰岛素信号转导分子的表达存在剂量和时间上的双向作用。     

睾酮对血管平滑肌细胞中雄激素受体mRNA表达的调控

目的观察睾酮对雄性大鼠血管平滑肌细胞中雄激素受体mRNA表达的自身调控作用.方法贴块法培养雄性 SD大鼠胸主动脉血管平滑肌细胞(VSMCs),Northern印迹分析法检测细胞中雄激素受体mRNA水平;采用细胞计3H]-胸腺嘧啶掺入法观察调控过程中细胞数量和DNA合成变化情况.结果0～4 μmol/L睾酮与静止的VSMCs作用24 h,细胞内ARmRNA表达水平呈剂量相关性增加;生理水平睾酮(40nmol/L)与静止的VSMCs作用不同时间(0～24 h),细胞内ARmRNA表达水平在24 h时方有显著增加;实验过程中细胞数量及DNA合成速率均无明显改变.结论血管平滑肌细胞中存在睾酮对雄激素受体mRNA表达的自身上调作用,调控过程中细胞活力保持稳定.提示 VSMCs中睾酮对AR表达的调控作用部分需要转录水平的参与.     

异丙酚与依托咪酯诱导对血浆皮质醇浓度的影响

目的　观察异丙酚与依托咪酯诱导对肾上腺皮质功能的影响。方法　在 2 0例择期手术麻醉的患者中分别对 2 m g/kg异丙酚与 0 .3 m g/kg依托咪酯诱导时血浆皮质醇浓度的变化进行观察。结果　异丙酚组给药后 2 h血浆皮质醇浓度由 (30 8.7± 2 7.4) nm ol/L降至 (2 6 7.7± 31.2 ) nm ol/L ,5 h后升高至 (4 0 0 .2± 2 6 .9) nm ol/L ,2 4h后恢复至给药前水平为 (30 6 .4± 35 .4) nm ol/L ;依托咪酯组给药后 2 h血浆皮质醇浓度由 (30 9.1± 36 .6 ) nm ol/L降至 (115 .9± 2 9.7) nm ol/L ,5 h时维持在 (171.1± 34.7) nm ol/L ,2 4h后恢复至给药前水平为 (311.8± 46 .2 ) nm ol/L。结论　异丙酚诱导对肾上腺皮质功能影响小 ,依托咪酯诱导则造成短暂的肾上腺皮质功能抑制。     

Annual intramuscular injection of a megadose of cholecalciferol for treatment of vitamin D deficiency: efficacy and safety data

AIM: To evaluate the efficacy and safety of an annual intramuscular injection of cholecalciferol for vitamin D deficiency. DESIGN: Prospective open-label study. PARTICIPANTS: Five men and 45 women (mean age 66.3 years) with vitamin D deficiency who were given a single therapeutic intramuscular injection of 600 000 IU (15 mg) cholecalciferol (vitamin D(3)). OUTCOME MEASURES: Serum levels of calcium, creatinine, 25-hydroxyvitamin D(3) (25OHD(3)) and parathyroid hormone, as well as early morning 2-hour urine calcium/creatinine excretion index. Specimens were collected at baseline and after 4 and 12 months of therapy. Data are reported as mean +/- 1 SD. RESULTS: Vitamin D deficiency was severe (< 12.5 nmol/L) in one participant, moderate (12.5-24 nmol/L) in 14, and mild (25-49 nmol/L) in 35. Twenty-four participants (48%) had secondary hyperparathyroidism. Following intramuscular cholecalciferol injection, serum 25OHD(3) levels normalised in all participants and remained above 50 nmol/L throughout the study. Serum 25OHD(3) levels were significantly higher at 4 months (114 +/- 35 nmol/L), and 12 months (73 +/- 13 nmol/L) compared with baseline (32 +/- 8 nmol/L) (P < 0.001), increasing by an average of 128% over the 12 months. There was a corresponding decrease in serum parathyroid hormone levels at 4 months (6 +/- 3 pmol/L) and at 12 months (5.2 +/- 3 pmol/L), with a 30% decrease at 12 months from baseline (7.4 +/- 4 pmol/L) (P < 0.01). Primary hyperparathyroidism was unmasked in one participant at 4 months and mild hypercalcaemia (serum calcium, < 2.70 mmol/L) was noted in two participants (4%) at 12 months. Serum creatinine levels remained normal in all participants throughout the study, while increases in 2-hour urine calcium/creatinine excretion index were seen in 10 participants (20%) at 12 months, three of whom had had elevated values at baseline. CONCLUSIONS: Once-yearly intramuscular cholecalciferol injection (600 000 IU) is effective therapy for vitamin D deficiency. While this therapy appears to be safe, the potential for developing hypercalciuria needs to be examined in a large randomised controlled trial.     

输精管结扎对精浆性激素的影响及意义

探讨输精管结扎对精浆中睾酮、雌二醇含量的影响及意义。方法用放射免疫法测定输精管结扎组和正常对照组精浆睾酮、雌二醇浓度。结果结扎组精浆睾酮和雌二醇浓度分别为(1.28±1.13)nmol/L，(4.49±3.82)pmol/L；正常对照组精浆睾酮、雌二醇分别为(1.40±1.30)nmol/L，(3.20±2.21)pmol/L；睾酮、雌二醇浓度在两组间无显著差别，结扎组睾酮/雌二醇比例明显低于对照组(P<0.05)。精浆睾酮与雌二醇呈显著正相关(r=0.451，P<0.01)。结论精浆中的性激素可能主要来源于前列腺和(或)精囊腺，输精管结扎后精浆睾酮/雌二醇比例降低可能是其阻遇前列腺增生的机理之一.     

The association between obesity and the diagnosis of androgen deficiency in symptomatic ageing men

OBJECTIVE: To determine the influence of obesity on the diagnosis of age-related androgen deficiency (AD) in symptomatic men according to current Australian guidelines. DESIGN, SETTING AND PARTICIPANTS: A community-based cohort of healthy ageing men with symptoms suggestive of AD was studied between May 2001 and February 2003. Men were classified as obese or non-obese according to body mass index (BMI) or waist circumference (WC). MAIN OUTCOME MEASURE: Diagnosis of AD according to Endocrine Society of Australia (ESA) guidelines. RESULTS: 223 men aged 54-86 years with mean BMI 27.3 +/- 0.2 kg/m2 (range 20.5-36.2 kg/m2) were recruited; 99 men were obese (BMI > or = 30.0 kg/m2 or WC > or = 102 cm) and 124 men were non-obese. Obese men had lower total testosterone (TT) (12.7 +/- 0.4 v 15.0 +/- 0.4 nmol/L); P < 0.001) and calculated free testosterone (275.7 +/- 7.8 v 299.3 +/- 7.4 pmol/L); P = 0.03) levels than non-obese men. TT levels < 8 nmol/L were recorded in 12% of obese men and 1% of non-obese men. Applying the ESA guidelines for the diagnosis of age-related AD, 15 obese men (15%) and 4 non-obese men (3%) were classified as being eligible for androgen therapy supported by the Pharmaceutical Benefits Scheme (PBS); the relative risk in obese men was 1.92 (95% CI, 1.44-2.55; P < 0.001). CONCLUSION: Obesity is an important determinant of serum TT levels in ageing men. Almost one in seven obese men but only one in 30 non-obese men in our study were eligible for PBS-supported androgen therapy according to Australian guidelines. Although obese men are more likely to have biochemical hypoandrogenism, the clinical implications of this remain uncertain. Studies of testosterone therapy in this group of ageing men are needed to determine whether androgen replacement is beneficial.     

瘦素、胰岛素样生长因子-1与多囊卵巢综合征高胰岛素血症的关系

目的了解瘦素、胰岛素样生长因子-1(IGF-1)与多囊卵巢综合征(PCOS)高胰岛素血症间的关系,探讨相关发病机制。方法采用病例-对照的方法,实验分为PCOS组(92例)和对照组(92例),其中PCOS组又分为PCOS-高胰岛素血症组(46例)和PCOS-非高胰岛素血症组(46例)。通过放免法检测血清瘦素、胰岛素样生长因子-1、睾酮、双氢睾酮、脱氢表雄酮、硫酸脱氢表雄酮等的水平,葡萄糖氧化酶法检测血糖水平。结果PCOS组瘦素(16.8±9.8ng/mL)、IGF-1水平(214.8±131.6ng/mL)明显高于对照组(分别为11.6±6.8ng/mL、118.0±82.9ng/mL)(P<0.05)。PCOS患者中高胰岛素组瘦素水平(19.2±10.2ng/mL)明显高于正常胰岛素组(12.5±7.6ng/mL)(P<0.05),IGF-1及空腹血糖在两组间差异无统计学意义。多元逻辑回归结果显示,在调整了体重指数、睾酮、黄体生成素/卵泡刺激素比值、双氢睾酮、脱氢表雄酮、硫酸脱氢表雄酮等因素后,瘦素、IGF-1均是PCOS的危险因素,但均不是高胰岛素血症的危险因素。结论瘦素、IGF-1可能与PCOS的发病机制有关,但与高胰岛素血症的关系有待进一步探讨。     

前药策略协同离子导入促进双氢睾酮透皮吸收

目的：加快双氢睾酮（DHT）透皮递送速率并实现速率可调,方便儿童患者个体化给药。方法合成并鉴定了水溶性离子化的前体药物双氢睾酮二甲基甘氨酸酯盐酸盐（DHT-DG）,并对其进行了物理化学性质考察;将DHT和DHT-DG制成水凝胶后,以新鲜离体猪耳皮肤作为生物屏障,考察两种凝胶在被动扩散和离子导入情况下的透皮吸收。结果2.5%DHT-DG水凝胶施加0.5 mA/cm2电流,8 h后皮肤累积透过量为（226.91±45.62）nmol/cm2,远大于单独水凝胶的被动透过量〔（10.45±3.63）nmol/cm2〕,且吸收的DHT-DG有≥80%水解为其原药DHT。离子导入DHT-DG在2 h后出现稳态流,且累积透过量可通过药物浓度和电流强度调控。结论通过合成水溶性离子化前体药物DHT-DG,并结合离子导入技术,可实现DHT快速可控地透皮递送。     

Batroxobin reduces intracellular calcium concentration and inhibits proliferation of vascular smooth muscle cells

Background Batroxobin (BX), a serine protease used in defibrinogenation and thrombolysis, also has an effect on c-fos gene and growth factor. This study attempted to determine the effects of BX on the proliferation of vascular smooth muscle cells (VSMCs) and calcium metabolism. Methods VSMCs were treated with BX at concentrations of 0.1, 0.3, or 1.0 mmol/L and cell numbers were determined at 0, 24, 48, and 72 hours. Intracellular calcium concentration (［Ca2+］i) was measured using direct fluorescence methods. Results BX was found to suppress proliferation of VSMCs in a dose-dependent fashion with inhibition rates of 18% and 31% by 48 and 72 hours, respectively. In addition, BX decreases basal ［Ca2+］i significantly. The basal level in untreated cells was 162.7±33.8 nmol/L, and decreased to 131.5±27.7 nmol/L, 128.3±28.5 nmol/L, and 125.6±34.3 nmol/L with the three concentrations of BX, respectively. Noradrenaline (NE)-induced ［Ca2+］i stimulation was also attenuated by BX (0.1 mmol/L BX, 20%±8% inhibition; 0.3 mmol/L BX, 54%±11% inhibition; 1.0 mmol/L BX, 62%±15% inhibition). The ability of NE to stimulate ［Ca2+］i was attenuated in cultures in Ca2+-free medium, as was the ability of BX to blunt NE-induced stimulation.Conclusion These findings demonstrate that BX can effectively inhibit proliferation of VSMCs, probably by blocking the release and uptake of Ca2+, thus influencing ［Ca2+］i.     

睾酮对血管平滑肌细胞中雄激素受体mRNA表达的调控

目的 观察睾酮对雄性大鼠血管平滑肌细胞中雄激素受体mRNA表达的自身调控作用。方法 贴块法培养雄性SD大鼠胸主动脉血管平滑肌细胞(VSMCs),Northern印迹分析法检测细胞中雄激素受体mRNA水平;采用细胞计数和[³H]-胸腺嘧啶掺入法观察调控过程中细胞数量和DNA合成变化情况。结果 0~4µmol/L睾酮与静止的VSMCs作用24h,细胞内AR mRNA表达水平呈剂量相关性增加;生理水平睾酮(40nmol/L)与静止的VSMCs作用不同时间(0~24 h),细胞内AR mRNA表达水平在24 h时方有显著增加;实验过程中细胞数量及DNA合成速率均无明显改变。结论 血管平滑肌细胞中存在睾酮对雄激素受体mRNA表达的自身上调作用,调控过程中细胞活力保持稳定。提示VSMCs中睾酮对AR表达的调控作用部分需要转录水平的参与。     

睾酮对体外培养小鼠卵巢颗粒细胞分泌抗苗勒管激素的影响

目的 探讨睾酮对体外培养的小鼠卵巢颗粒细胞抗苗勒管激素（anti-Mullerian hormone,AMH） 分泌的影响。方法 小鼠卵巢颗粒细胞原代培养,添加不同浓度睾酮,ELISA 法检测颗粒细胞AMH 的表达。结果 ELISA 法证实颗粒细胞中有AMH 表达,不同浓度（10-8 mmol/L、10-7 mmol/L、10-6 mmol/L） 睾酮作用24 h 可促进颗粒细胞分泌AMH,且随睾酮浓度的增加、作用时间延长,AMH 分泌明显增加（P ＜ 0.01）。结论 睾酮促进小鼠卵巢颗粒细胞分泌AMH,高浓度比低浓度作用更强。     

Transdermal fentanyl for postoperative pain management. A double-blind placebo study

A double-blind, placebo-controlled, randomized design was used to evaluate the safety and efficacy of transdermal fentanyl citrate for postoperative pain management in 42 healthy adult patients undergoing major shoulder surgery. Transdermal systems rated to deliver fentanyl citrate at a rate of 75 micrograms/h were applied to the skin immediately prior to surgery and worn for 24 hours. Patients in the active group required significantly less morphine than the placebo group during the 24-hour period that systems were in place (0.8 +/- 0.61 vs 1.3 +/- 0.64 mg/h) and for the first 12 hours after removal (0.3 +/- 0.36 vs 0.5 +/- 0.32 mg/h). The incidence of vomiting was more frequent in the active group than in the placebo group (73% vs 30%), and respiratory rate in the active group was lower than in the placebo group during the 13- to 24-hour interval of system application (14 +/- 3 vs 16 +/- 2 breaths per minute). Nevertheless, transdermal fentanyl appears to be safe and effective after orthopedic surgery in healthy adult patients.     

大庆市健康男性青少年正常青春发育时间调查

目的了解目前我国大庆市健康男性青少年正常青春发育时间及过程,帮助临床医师对青春发育异常疾病进行诊断。方法采用纵向和横向相结合的研究方法,对我国北方地区大庆市150名年龄在6—15岁的健康男性青少年学生的血促黄体生成素（LH）、促卵泡生成素（FSH）和睾酮水平以及身高、体重、青春发育的Tanner分期等人体测量学指标进行了连续4年的跟踪随访,按年龄以人次将数据资料合并分析,观察上述各项指标的变化趋势。并观察在本调查期间青春发育启动者的年龄。结果我国北方大庆市地区健康男性青少年的青春发育启动年龄为（12．0±1．6）岁;青春启动后第一年生长速度为（6．9±0．4）cm／年;血清睾酮水平为（1．0±0．3）nmol／L。结论我国北方大庆市地区健康男性青少年的青春发育启动年龄8—14岁。     

Changes in serum cardiac troponin I levels after percutaneous transluminal coronary angioplasty

OBJECTIVE: To evaluate the possible effect of percutaneous transluminal coronary (PTCA) on myocardium. METHODS: Serum cTnl and CK-MB were measured in 60 patients with coronary artery disease (CAD) who underwent PTCA before and at the 6th, 12th, 24th, 48th and 72nd hour after the interventional procedure respectively. RESULTS: The serum cTnl levels began to increase at 6 hours (9.65 +/- 6.27 micrograms/L) in 18 patients, reached the peak levels during 12-24 hours (20.43 +/- 11.28 micrograms/L, 18.52 +/- 9.52 micrograms/L), and returned to normal range till 48-72 hours (7.35 +/- 7.62 micrograms/L, 5.51 +/- 3.13 micrograms/L) after PTCA. The serum cTnl and CK-MB levels were kept normal range pre- and post-PTCA in 30 cases. The levels of cTnl in 12 cases were over baseline either before or after the procedure, while for CK-MB, only in 3 cases were over normal range after PTCA. Compared with normal cTnl group, elevated cTnl levels were related to total inflation times and dilated times (P < 0.05). CONCLUSIONS: PTCA may cause some minor damage in myocardium, serum cTnl level was more sensitive and specific for monitoring myocardial injury.     

共培养大鼠睾丸体细胞组织工程技术构建雄激素分泌组织

目的：探讨应用组织工程技术体内外构建具有一定形态和睾酮分泌功能组织的可行性。方法：雄性Wister大鼠,无菌切取双侧睾丸,制备去势及移植鼠动物模型。睾丸去包膜,剪碎,胶原酶消化,经差速贴壁或直接混合共培养方法,分别获取睾丸间质细胞（Leydig细胞）和共培养的睾丸多种体细胞,两类细胞分别与可降解生物材料聚羟基乙酸（PGA）纤维复合并进行体外培养,光、电镜观察体外组织形成过程,定期检测培养液内睾酮分泌水平。取体外培养7d细胞-材料复合物,分别移植于去势鼠睾丸鞘膜腔或大网膜内（n=6）,不同时间点取材,通过大体观察、组织学染色和免疫细胞化学方法,检测移植鼠体内雄激素分泌组织的形成过程及血睾酮水平。结果：两类细胞均与PGA具有良好的亲和性,体外可形成具有一定睾酮分泌功能的细胞-材料复合物,体内移植2个月后,两类细胞-材料复合物在大网膜和睾丸鞘膜内均可形成具有一定形态的雄激素分泌组织,再生组织具有良好的血管化。血睾酮检测及统计分析结果表明,移植6周后,单纯Leydig细胞组血睾酮水平为（0．604±0．04）μg/L,共培养细胞组血睾酮水平为（0．854±0．03）μg／L,均明显高于单纯去势鼠血睾酮水平（0．564±0．05）μg/L（P〈0．01）,两组移植鼠相比,共培养细胞移植组血睾酮水平明显高于单纯Leydig细胞移植组（P〈0．01）。结论：以共培养睾丸体细胞作为种子细胞在体内外构建雄激素分泌组织具有可行性,共培养睾丸内体细胞是雄激素分泌组织构建的良好种子细胞。     

alphastatin抑制体外内皮细胞血管生成及其作用机制的实验研究

目的探讨人纤维蛋白原α链末端的24个氨基酸片断alphastatin对人脐静脉来源内皮细胞(ECV304)血管生成抑制作用及机理。方法体外培养ECV304细胞,分别测定alphastatin对其迁移、增殖和体外管状结构形成的作用。用逆转录聚合酶链反应技术(RT-PCR)定性检测ECV304细胞中鞘氨醇激酶(SPK)mRNA的表达。分别以10、100、1000nmol/Lalphastatin处理ECV304细胞,提取细胞蛋白质,通过三磷酸腺苷(ATP)检测细胞SPK酶活性。结果不同浓度alphastatin处理组中ECV304细胞迁移的数目,分别为(103±4)个、(75±3)个、(13±1)个,低于对照组的(131±4)个,均P<0·05。alphastatin浓度为100nmol/L、1000nmol/L时,形成管状结构的面积分别为(1509±30)μm2/视野和(1301±20)μm2/视野,也明显低于对照组的(2996±31)μm2/视野,均P<0·05。alphastatin对ECV304细胞增殖的影响差异无统计学意义。RT-PCR证实ECV304细胞SPKmRNA的表达。与对照组比较,alphastatin降低ECV304细胞内1-磷酸鞘氨醇(S1P)生成量,当其浓度为100nmol/L,作用时间为12h时,效应最明显。结论体外实验证实alphastatin具有明显抑制ECV304细胞血管生成的作用,这种效应与降低细胞SPK活性、减少S1P的生成有密切关系。     

Effects of competitive and noncompetitive 5a-reductase inhibitors on serum and intra-prostatic androgens in beagle dogs

Background 5α-Reductase inhibitors (5α-RI) act by inhibiting the conversion of testosterone to dihydrotestosterone (DHT),thereby preventing DHT induced benign prostatic hyperplasia.The existing 5α-RIs ...     

创伤后应激障碍样行为异常大鼠海马Ca2+/CaM依赖性蛋白激酶表达的研究

目的探讨创伤后应激障碍(PTSD)样行为异常的神经生物学机制.方法以海马惊厥阈下电刺激方法制备PTSD大鼠模型,采用流式细胞仪、荧光标记术及Western 印迹等方法,检测PTSD样行为异常大鼠海马细胞内游离Ca2+含量与钙调素(CaM)相对活性平均通道荧光,以及海马组织总CaM、Ca2+/CaM依赖性蛋白激酶Ⅱα(CaMKⅡα)与Ⅳ(CaMKⅣ)的表达.结果电刺激停止后24 h大鼠海马细胞内游离钙浓度(nmol/L)增至顶峰(487.34±117.93,P＜0.01),72 h时仍明显增高(289.46±69.45,P＜0.05);游离CaM平均通道荧光则同步降低(24 h时为1.5±0.4,P＜0.01;72 h时为2.5±0.6,P＜0.05);而海马组织总CaM表达于电刺激停止后48 h内明显增多(P＜0.01),CaMKⅡα表达则显著降低(P＜0.01),CaMKⅣ表达于电刺激停止后24 h内明显增高(P＜0.05).结论海马细胞Ca2+-CaM-CaMKIIα/CaMKIV信号途径较长时程调控紊乱,可能是实验动物持续性PTSD样行为异常的重要病理生理基础之一.     

Recombinant human DNase inhalation in normal subjects and patients with cystic fibrosis. A phase 1 study.

OBJECTIVE--To evaluate the safety of recombinant human DNase (rhDNase) in normal subjects and in patients with cystic fibrosis. DESIGN--Nonrandomized trial in which individuals inhaled rhDNase three times a day Monday through Friday on two consecutive weeks. SETTING--The study was performed in the Clinical Research Center at the University of Washington, Seattle. Patients were recruited from the Cystic Fibrosis Center at the University of Washington. SUBJECTS AND PATIENTS--Twelve normal subjects and 14 patients with cystic fibrosis were studied (12 patients completed the protocol). The subjects and patients had to be aged 18 to 65 years and have a negative pregnancy test, if female. The normal subjects had to have a normal chest roentgenogram, be nonsmokers, and have normal pulmonary function testing. The patients with cystic fibrosis had to have a forced vital capacity greater than 40% predicted normal and have no recent exacerbation (within 2 weeks) of their lung infection or change in their medication. INTERVENTIONS--The study design was a repetitive dose escalation of aerosolized rhDNase. The subjects inhaled rhDNase three times a day, Monday through Friday, on 2 consecutive weeks and were rechallenged with a single dose 21 days after the last dose. Spirometry was measured before and 30 minutes after every rhDNase dose. MAIN OUTCOME MEASURES--Pulmonary function testing, serum DNase concentrations, and anti-DNase antibodies. Secondary outcome measures were dyspnea score and quantitative bacterial culture. MAIN RESULTS--Inhalation of rhDNase was well tolerated by all persons. There were no serious adverse reactions, and no allergic reactions were observed, even on rechallenge. No individual developed rhDNase antibodies. Improvement in both lung function and dyspnea score was observed in the adults with cystic fibrosis. Forced vital capacity was 3.2 +/- 0.3 L (mean +/- SE) on day 1 and was 3.5 +/- 0.3 L on day 12. Forced expiratory volume in 1 second was 2.1 +/- 0.2 L (mean +/- SE) on day 1 and was 2.3 +/- 0.3 L on day 12. CONCLUSIONS--Aerosolized rhDNase appears safe in normal subjects and in adults with cystic fibrosis and may improve lung function with short-term therapy.