{beta}2-Microglobulin Kinetics During Haemofiltration

To study the kinetics of ß₂-microglobulin during haemofiltration,seven patients with end-stage renal failure were treated withthe AN 69 (acrylonitrile), Duo-Flux (cellulose acetate) andF 60 (polysulphone) haemofilter. Low ß₂-microglobulinsieving coefficients and a highly negative filter mass balanceerror were observed during the initial phase of treatment withAN 69 but not with Duo-Flux or F 60, indicating a high degreeof ß₂-microglobulin adsorption by AN 69. Total removalof ß₂-microglobulin was calculated by addition ofthe total amount adsorbed by the membrane and the total amountrecovered in the collected ultrafiltrate. With AN 69 and F 60,total removal of ß₂-microglobulin amounted to 393±135(SD) and 316±35mg per treatment, while total removalwith Duo-Flux was 242±79 mg per treatment. Thus, highlypermeable membranes such as AN 69 or F 60 used in a haemofiltrationmode may nearly balance the presumed generation of ß₂-microglobulinin uraemic patients. During treatment, an increase of the calculatedß₂-microglobulin distribution volume occurred withall three membranes, probably representing extra-to-intracellularwater shifts. The water shifts occurring during haemofiltrationreduce the value of precision of ß₂-microglobulinkinetics and limit the value of the plasma level decrease asan index of ß₂-microglobulin removal.     

泼尼松及其醋酸酯片剂的生物利用度比较研究

本文报道了体外溶出速度有显著差异的泼尼松与醋酸泼尼松片剂的体内比较试验。结果表明:醋酸泼尼松片剂之间及泼尼松与醋酸泼尼松片剂之间均无体内外相关关系。由于三个样品体内血峰浓度、曲线下面积、峰时均表示有相等的生物利用度,因此,作者认为目前采用的泼尼松片溶出速度技术一般地还不能用来充分预示体内生物利用度参数。     

Inhibition of spermatogenesis in men using various combinations of oral progestagens and percutaneous or oral androgens

Eight men (experiment 1) requesting male contraception received a daily oral dose of 20 mg medroxyprogesterone acetate (MPA) combined with 125 mg percutaneous dihydrotestosterone (DHT). Three months later the mean sperm count was only diminished slightly; the replacement of DHT for four men by percutaneous testosterone at the same concentration led to a dramatic fall in sperm count. For 6-18 months all men were treated with MPA plus percutaneous testosterone (250 mg daily). The latter dose restored physiological levels of plasma testosterone. Follicle-stimulating hormone levels were inhibited more severely than in the DHT-treated group, whereas LH levels were variable. Azoospermia was achieved and maintained in six cases; two men were oligozoospermic and in one case a moderate secondary rise in the sperm count was observed. Twelve volunteers (experiment 2) received a daily oral dose of either 5 or 10 mg norethisterone acetate plus percutaneous testosterone (250 mg daily). All of them achieved azoospermia within 2 months, but two subjects later exhibited a partial restoration in sperm count. Follicle-stimulating hormone and LH levels were inhibited more severely than in the first experiment. The sperm count and gonadotrophin levels returned to initial values within 6 months after cessation of the treatment in both experiments. No side-effects were noted concerning blood parameters, libido or body weight. However, several female partners had elevated levels of plasma testosterone. In experiment 3 (13 volunteers), percutaneous testosterone was replaced by oral testosterone undecanoate (160 mg daily). Only seven men were azoospermic and most of them had lowered levels of plasma testosterone. Thus, the combination of percutaneous testosterone and oral progestagens appears to be the most convenient for male hormonal contraception.     

Relationship of anesthetic activity of alkyl acetates to hydrophobicity and in vivo effect on membrane fluidity in mice

In vivo anesthetic activity of alkyl acetates in mice was studied in relation to hydrophobicity and the in vivo effect on membrane fluidity. The anesthetic potency (AD₅₀) of alkyl acetates was determined; AD₅₀ shows the i.p. dose required to anesthetize 50% of mice from the treated group. We used log P (n-octanol/water partition coefficient) as an operational definition of hydrophobicity. Membrane fluidity was determined using 1,6-diphenyl-1,3,5-hexatriene (DPH) as fluorescence probe. Log (1/AD₅₀) was a parabolic function of log P, and the value of log P that corresponds to the minimum AD₅₀ was estimated to be 2.08. Brain synaptosomal membranes were prepared from mice 30 min after dosing with each of the three alkyl acetates applied at 1.5-fold AD₅₀: n-butyl, n-amyl, and n-hexyl acetate. In each alkyl acetate group, most of the animals were anesthetized (>68%). Decreased membrane fluidity was observed for the animals that were anesthetized while no change in the fluidity was seen for the animals that were not anesthetized. The results suggest an involvement of decreased DPH fluidity in alkyl acetate-induced anesthesia. Received: 24 March 1997 / Accepted: 27 May 1997     

Elevated salt appetite and brain binding of angiotensin II in mineralocorticoid-treated rats

Angiotensin II (Ang II) and aldosterone levels increase with sodium deficiency, promoting sodium conservation and arousing a salt appetite in rats. The mechanism(s), by which these two hormones interact to produce salt appetite is not known. The experiments reported here tested the possibility that increased mineralocorticoids change the number and/or affinity of Ang receptors in the brain. Rats were given a series of deoxycorticosterone acetate (DOCA) injections (500 micrograms/day, s.c., for 4 days) which are known to produce a salt appetite when given in conjunction with an intracerebroventricular injection of Ang. The binding of 125I-Ang II to membranes prepared from the septal-anteroventral third ventricular region was then examined. DOCA treatment resulted in a significant increase in the number of Ang binding sites (Bmax) with no change in binding affinity (Kd). The binding of 125I-Ang II was then investigated in membranes prepared from 12 other brain regions as well as the pituitary and adrenal gland, showing that the increase in binding capacity occurred in only a few specific brain regions. A third experiment verified that the DOCA treatment used here was sufficient to arouse a salt appetite when combined with a single intracerebroventricular injection of Ang II. The mechanism that underlies the production of salt appetite by aldosterone and Ang II may at least partially consist of mineralocorticoid-induced increases in the number of Ang receptors in discrete brain regions.     

Endocrine, seminal and peripheral effects of depot medroxyprogesterone acetate and testosterone enanthate in men

Depot medroxyprogesterone acetate (D-MPA, 250 mg) and testosterone enanthate (TE, 200 mg) were administered twice with a 4-week interval to nine healthy men, and the levels in blood of steroids, gonadotrophins, lipoproteins, sex hormone binding globulin (SHBG) and prostaglandins (PGs) were measured, as well as steroid levels in semen and the sperm count and motility. The hormones analysed were: MPA, testosterone, androstenedione (A), dihydrotestosterone (DHT), oestradiol (E2), cortisol (C), luteinizing hormone (LH), follicle stimulating hormone (FSH) and the sulphoconjugated forms (-S) of testosterone, DHT, pregnenolone (5-P) and dehydroepiandrosterone (DHEA). Peak values of MPA (10.2 +/- 4.6 nmol/l) and testosterone (28.0 +/- 10.0) were found in the first blood samples 2 days after each injection. Thereafter the levels of MPA decreased gradually and reached the limit of detection 18-20 weeks after the second injection. Blood levels of testosterone fell sharply from the peak values and were grossly subnormal 2 weeks after each injection; levels did not return to pretreatment values during 24 weeks of follow-up. The pattern of change of DHT, A, E2 and sulphonated androgens was similar to that of testosterone. These data suggest that D-MPA and TE are absorbed at similar rates, and that the TE is metabolized rapidly. The subsequent reduction in the levels of A, testosterone-S and DHT-S was less marked and reached pretreatment values earlier than did the testosterone levels. No obvious changes were found in the levels of C, 5-P-S and DHEA-S or in the seminal plasma levels of the various steroids studied. The blood levels of LH and FSH fell precipitously 2 days after the first injection, then started to increase 4 weeks after the second injection to reach pretreatment values 12 weeks later. Of the lipoproteins studied only the levels of HDL-cholesterol and SHBG were found suppressed after treatment. Severe oligozoospermia and the complete absence of progressively motile sperm, in at least one semen sample, was observed in all subjects at 3-7 and at 5-16 weeks, respectively, after the last injection, suggesting that the men were infertile for at least 1 month after treatment. A spurious increase in the PG content of semen was also observed. In spite of the low blood testosterone levels, no subject reported changes in sexual behaviour or other signs of anabolic imbalance during or after the study. However, the increase in levels of E2 in some individuals should be kept in mind as a possible cause of side-effects.(ABSTRACT TRUNCATED AT 400 WORDS)     

Effects of tibolone on the breast

Objective: to evaluate the effect of hormone replacement therapy and tibolone on the breast. Study design: prospective, controlled, randomized study. Setting: Outpatient Menopause Clinic of the Second University of Naples. Participants: forty four women in spontaneous menopause without any risk factor for breast cancer were randomly allocated to three groups: 15 patients (group A) were treated with transdermal oestrogens 50 μg, 2 patches/week for 3 weeks per month, plus acetate nomegestrolo per os 5 mg/die for 12 days per cycle, 17 patients (group B) were treated with tibolone 2.5 mg/die. Twelve patients not given any medication represented the control group (group C). Methods: at the time of recruitment and after at least 12 months of therapy the patients were subjected to a questionnaire aimed at quantifying the slight, moderate or severe presence of the tension/mastodynia symptoms and to a mammographic test to assess the parenchymal pattern according to a quantitative method: type 1 (less than 25% of mammary gland covered by dense tissue), type 2 (from 25% to 75% of total glandular area covered by dense tissue), type 3 (more than 75% of mammary parenchyma covered by dense tissue). Statistical analysis was carried out by means of Fisher's exact test. Results: after at least 12 months of treatment in Group A 5 out of 15 patients (33%) showed a trend of increase in mammographic density not statistically significant (P=0.22) when compared with group B in which one patient showed a swift from type 1 to type 2 and another from type 2 to type 3. The analysis of tension/mastodynia symptoms revealed a significantly difference between the two groups (P=0.02): in group A mastodynia appeared in three previously asymptomatic women and increased in five women, with a total increase in the symptomatology in 8 out of 15 patients (53.3%), in group B only in one case (5%) mastodynia turned from slight to moderate. Conclusion: in postmenopausal women oestroprogestogenic replacement therapy may be associated with an increase in mammographic density and with the onset or increase in mastodynia. On the contrary tibolone does not seem to affect normostructured mammas and may be considered a first-rate replacement therapy in case of mammas showing particular density or benign mastopathies.     

长效氯醚避孕针对家兔慢性毒性的实验研究

研究结果表明:①氯醚避孕针长期使用对家兔体重增长无影响。②各组动物实验前后血常规检查,结果均在正常值范围内,未见外周血中白细胞总数及其分类的异常改变。③各项生化指标检查,可见给药组血清GPT活性在9个月以内有升高(P<0.01),但随继续用药逐渐恢复正常,肝脏排泄机能、肾功能及血糖、血清蛋白、血脂等无明显影响。④各组动物尿常规检查未见异常改变。以上结果提示,长效氯醚避孕针长期应用,对家兔重要器官的机能无明显毒性作用。     

三取代乙酸酯类化合物的合成

许多具有解痉作用的化合物亦有不同程度的镇痛作用。如早已在临床应用的杜冷丁,就是在合成哌啶类解痉剂中发现的,它既有解痉作用,又具镇痛作用。