单鼻孔入路垂体腺瘤围手术期使用激素的探讨

目的探讨单鼻孔入路垂体腺瘤手术前后是否应常规使用激素的问题。方法比较37例单鼻孔入路切除垂体腺瘤患者术前及术后1、3、7d血清皮质醇浓度。结果术后第1、3d与术前比较有统计学意义,第7d与术前比较无统计学意义。除2例短期使用糖皮质激素替代治疗外,均未常规使用激素且疗效满意。随访2年无垂体功能低下表现。结论单鼻孔入路垂体腺瘤切除手术前后无常规使用激素的必要,是否使用激素应视临床症状及检验结果而定。     

Blood Pressure Responses to Prolonged Infusions of Adrenaline and Noradrenaline in Conscious Dogs

Adrenaline was infused intravenously into conscious dogs to test whether chronically elevated plasma levels can produce arterial hypertension. Adrenaline infused at 12.5 μg/kg/hr from 4 days produced no change in mean arterial pressure (+1.1 ± 2.7 mmHg) despite raising plasma adrenaline concentrations from 49 ± 20 pg/ml to 1420 ± 279 pg/ml. Myocardial tissue levels of adrenaline averaged 435 ng/g, compared to 20 ng/g in vehicle infused dogs. Longer infusions of adrenaline (11 days) at doses from 1.25 μg/kg/hr to 12.5 μg/kg/hr were also without significant effect on arterial blood pressure. In contrast, infusion of noradrenaline at 6.25 μg/kg/hr for 11 days produced sustained elevation of mean arterial pressure (11.7 ± 5.1 mmHg). Although adrenaline infusion alone did not alter arterial pressure, a small rise (5.6 ± 1.6 mmHg) was measured when the dogs were also given cortisone (50 mg twice daily). These results are therefore not in accord with the hypothesis that increased plasma levels of adrenaline may cause hypertension by activation of pre-junctional β-adrenoceptors. However simultaneous administration of adrenaline and cortisone did elevate blood pressure, indicating that increases in both adrenal cortical and medullary hormones may be required to produce hypertension.     

Pharmacokinetic–pharmacodynamic studies of the 11β-hydroxysteroid dehydrogenase type 1 inhibitor MK-0916 in healthy subjects

Aims

To characterize pharmacokinetic parameters of MK-0916 and its safety and tolerability in lean, healthy male subjects following single and multiple oral doses. To assess (by stable-isotope labelling) the in vivo inhibition of cortisone-to-cortisol conversion following oral MK-0916.

Methods

Data are presented from two randomized, controlled, double-blind, rising-dose phase I studies. In the first study, subjects received single oral doses of 0.4–100 mg MK-0916 (n = 16). In the second study, subjects received 0.2–225 mg MK-0916 followed by daily doses of 0.2–100 mg for 13 days beginning on day 2 or day 15 (n = 80). Plasma and urine drug concentrations were measured for pharmacokinetic analysis. For pharmacodynamic analysis, concentrations of plasma [¹³C₄]cortisol were measured by high-pressure liquid chromatography and tandem mass spectrometry following a single oral dose of 5 mg [¹³C₄]cortisone.

Results

Doses ≥3 mg were rapidly absorbed (time at which maximal concentration was achieved in plasma, 1.1–1.8 h). Exposure (measured as the area under the concentration–time curve from 0 to 168 h) increased approximately in proportion to dose. Values for the maximal plasma concentration and the plasma concentration at 24 h increased in excess of dose proportionality at doses <6 mg and roughly in proportion to dose at doses >6 mg. In subjects dosed with 6 mg MK-0916 once daily for 14 days, the mean trough plasma concentration was 240 nm and in vivo cortisone-to-cortisol conversion was inhibited by 84%. The relationship between plasma MK-0916 and hepatic 11β-hydroxysteroid dehydrogenase type 1 inhibition was well represented by a simple E_max model with an IC₅₀ of 70.4 nm. Exposure to MK-0916 was generally well tolerated.

Conclusions

These findings indicate that 11β-hydroxysteroid dehydrogenase type 1 is effectively inhibited in human subjects by doses of MK-0916 that are well tolerated.     

动脉粥样硬化、络气郁滞对大鼠血清皮质醇及四碘甲腺原氨酸含量水平的影响

目的观察动脉粥样硬化（AS）和络气郁滞对实验大鼠血清皮质醇（CORT）及四碘甲腺原氨酸（T4）含量水平的影响。方法采用2×2析因试验设计,将48只wistar雄性大鼠随机平均分配到正常组（NM组）、动脉粥样硬化组（AS组）、络气郁滞组（CS组）、动脉粥样硬化联合络气郁滞组（AS＋CS组）。分别连续喂养6周后,取血浆或血清,检测CORT及T4水平。结果各组CORT水平从低到高依次为NM组、AS组、AS＋CS组、CS组。各组T4水平从高到低依次为NM组、AS组、CS组、AS＋CS组。结果显示单纯AS或络气郁滞均能升高CORT水平或降低T4水平,AS联合络气郁滞对升高CORT水平或降低T4水平存在交互作用。结论单纯AS或络气郁滞均能升高CORT水平和降低T4水平。AS联合络气郁滞对升高CORT水平及降低T4水平存在交互作用。析因设计能充分利用信息。     

Activation of Spermatozoal Forward Migration in vitro by Hydrocortisone

The effects of hydrocortisone and cortisone on spermatozoal motility in vitro were tested. Hydrocortisone at concentrations of 50, 100 and 1000 nmoles/ml was effective in activating in vitro the forward migration and the motility of boar spermatozoa recovered from the cauda epididymidis. Where boar epididymal spermatozoa were incubated with hydrocortisone at concentrations of 50, 100 and 1000 nmoles/ml for between 0 and 24 h at 25°C in vitro , the spermatozoal motility was significantly higher than where no hydrocortisone was added. With ejaculated boar spermatozoa, hydrocortisone at concentrations of 100 and 1000 nmoles/ml increased the spermatozoal motility for between 0 and 2 h and at a concentration of 50 nmoles/ml increased spermatozoal motility for between 2 and 24 h at 25°C in vitro. After 4 h incubation, the effect of hydrocortisone at a concentration of 100 nmoles/ml on boar ejaculated sperm motility was not significantly different from the control. But, hydrocortisone at a concentration of 1000 nmoles/ml inhibited the forward migration of boar ejaculated sperm after it had been incubated with the sperm for 6 h. Cortisone, although structurally similar to hydrocortisone, had no significant effect in improving the motility of boar spermatozoa.
Both hydrocortisone and cortisone had no demonstrable effect on the forward migration and the motility of human spermatozoa in vitro. ,     

激素对急性胰腺炎大鼠血中细胞因子的影响及其意义

目的 :探讨激素对急性胰腺炎血中细胞因子的影响及其意义。方法 :将试验大鼠分成正常对照组、急性胰腺炎组和激素治疗组 ,观察各组大鼠血中炎症性细胞因子 (TNF α、IL 1和IL 6 )和抗炎症性细胞因子 (TGF β1和IL 10 )和血中淀粉酶的水平以及胰腺病变和胰腺湿重。结果 :①急性胰腺炎时血中炎症性细胞因子 (TNF α、IL 1和IL 6 )和抗炎症性细胞因子 (TGF β1和IL 10 )均明显升高 ,激素治疗后上述细胞因子较急性胰腺炎组均下降 ,TNF α、IL 1和IL 6在 2、 6小时时段下降最明显 (P <0 0 5 ) ,TGF β1和IL 10在 2 4小时时段明显下降(P <0 0 5 )。②急性胰腺炎组胰腺病理改变重 ,胰腺湿重较正常对照组明显增加 (P <0 0 5 ) ,经激素治疗后 ,胰腺病变明显减轻 ,胰腺湿重较急性胰腺炎组明显减少 (P <0 0 5 )。③急性胰腺炎组血中淀粉酶较正常对照组明显升高 (P <0 0 5 ) ,激素治疗后血中淀粉酶仍较正常对照组明显升高 (P <0 0 5 ) ,与胰腺炎组无统计学差异 (P >0 0 5 )。结论 :①在急性胰腺炎病程中 ,的确存在着一个免疫过激和免疫抑制的先后并存的双向免疫异常状态。②糖皮质激素可通过抑制炎症性细胞因子和抗炎症性细胞因子等对急性胰腺炎有多层面调节作用。     

高效液相梯度洗脱法测定尿中氢化可的松和可的松含量

目的测定尿中氢化可的松与可的松的比值以表达人体肾脏11β-羟化类固醇脱氢酶活性,为其研究提供一个准确、精密、重现性好的分析手段。方法HPLC-UV法,梯度洗脱,内标定量。结果尿中氢化可的松和可的松在10～100.0ng.ml     

Higher cortisol:cortisone ratios in the preovulatory follicle of completely unstimulated IVF cycles indicate oocytes with increased pregnancy potential

BACKGROUND: Conception following gonadotrophin-stimulated IVF and embryo transfer has been associated with a higher intrafollicular cortisol:cortisone ratio and decreased metabolism of cortisol to cortisone. The role of glucocorticoids in human oocyte maturation is not fully understood, but active glucocorticoid (cortisol) may be important. This study relates intrafollicular cortisol and cortisone concentrations to oocyte fertilization and embryo implantation in unstimulated cycles. METHODS: Patients aged <40 years with favourable sperm underwent unstimulated IVF-embryo transfer. Study 1 related intrafollicular cortisol levels to oocyte and IVF outcome: (i) fertilized, pregnant (n = 9); (ii) fertilized, not pregnant (n = 21); and (iii) unfertilized (n = 12). Study 2 was a case-control study of 27 patients (same outcome groups of equal size) which measured intrafollicular cortisol, cortisone and the cortisol:cortisone ratio. RESULTS: Conception cycles demonstrated higher cortisol concentrations compared with the fertilized group (study 1) [median (95% confidence interval): 299 (249-330) versus 227 nmol/l (185-261); P < 0.05] and higher cortisol:cortisone ratios when compared with the unfertilized group (study 2) [7.38 (5.23-9.19) versus 3.56 (1.75-7.46) respectively; P = 0.02]. Of the women with cortisol:cortisone ratios greater than the outcome independent mean of 5.90, 58% conceived compared with only 13% with ratios <5.90 (P < 0.02). CONCLUSION: Higher cortisol:cortisone ratios in conception cycles suggest that active glucocorticoid may be important for final oocyte maturation and embryo implantation in unstimulated cycles.     

藏药雪灵芝对炎症和免疫功能的影响

藏药雪灵芝对巴豆油引起的小鼠耳部水肿,大鼠肉芽肿以及对蛋清和角叉菜胶诱发的足肿胀急性炎症都有明显的抑制作用。对小鼠腹腔巨噬细胞的吞噬和抗体形成(血清溶血素)也有显著的抑制作用。此药毒性小,对肝、肾几无毒性,且有保肝作用。     

Interferences in the radioimmunological determination of urinary free cortisol

The magnitude of interferences arising in the radioimmunological assessment of urinary free cortisol is studied (a) by comparing cortisol immunoreactivities from crude urine, after organic solvent extraction of different selectivity and after additional chromatography by high pressure liquid chromatography (HPLC) and (b) by evaluation of the profile of immunoreactivity resulting from the fractions eluted by HPLC. Three antisera from different sources have been investigated. Values of cortisol-immunoreactivity in crude urine were about six times and values of a simple dichloromethane extract about three times higher than values obtained after HPLC. The main part of the interfering compounds arising in organic extracts have a polarity similar to cortisol, which cannot be easily eliminated by simple solvent extraction procedures. Specific estimation of urinary cortisol by radioimmunoassay requires a preceding Chromatographic technique of high efficiency, such as HPLC, which represents an adequate tool for the routine laboratory.