STS 557, a new orally active progestin with antiprogestational and contragestational properties in rabbits

STS 557 (17α-cyanomethyl-17β-hydroxy-estra-4,9(10)-diene-3-one) is a potent progestin. This compound was 10 times as potent as the standard levonorgestrel as judged by the classic Clauberg-McPhail Assay. The antiprogestational response is significant when STS 557 treatment starts 2 days before progesterone administration. It does not disturb the priming activity of estradiol. This compound alone is adequate for endometrial priming. Early pregnancy is maintained in ovariectomized does. Administration on day 1 of pregnancy reduces the number of implantations. In comparison with chlormadinone acetate and d-norgestrel, only STS 557 treatment causes complete inhibition of egg fertilization.     

Effect of STS 557 on semen composition, fertility and sexual behaviour of male rabbits

Fertility control of male rabbits was achieved by daily oral administration of STS 557 (17-cyanomethyl-17β-hydroxy-estra-4.9(10)-diene-3-one) over a period of 8 weeks. In doses of 10 and 20 mg STS 557 per animal per day, fertility inhibition was accompanied by a decrease of mean number of mounts and ejaculations. Furthermore, semen volume, number of sperm per ejaculate, and sperm motility were reduced. At a dose of 5 mg STS 557 per day, male sterility was associated with reduction of sperm motility and semen fructose content. Libido, semen volume, sperm number, and sialic acid content in semen remained unaffected. Development of male contraceptives on the basis of chronic progestin treatment without concomitant androgen supplement may thus be possible.     

STS 557 as an interceptive in rodents and baboons

Studies with mice, rats, guinea pigs and baboons were undertaken to define the interceptive action of the new progestin STS 557 (17α -cyanomethyl-17β-hydroxy-estra-4.9(10)-diene-3-one) and to compare it with other progestins used in oral contraceptives. STS 557, norethindrone and norethindrone acetate reduced deciduoma formation as well as the number of implantations in mice and rats. Chlormadinone acetate and levonorgestrel when administered at the appropriate dose could not prevent early pregnancy or deciduoma formation. But in contrast to STS 557, levonorgestrel maintained early pregnancy in ovariectomized rats. On the other hand, STS 557 was ineffective as a postcoital agent in guinea pigs. When 0.4 mg STS 557 was orally administered to 37 female baboons 3 or 6 h after the mating period, only one pregnancy occurred in a total of 60 cycles investigated (controls: 11 pregnancies in 12 cycles investigated). The results are discussed in view of the development of an interceptive method based on STS 557.     

Contraceptive potentiality of STS-557--a feasibility study in male bonnet monkey (Macaca radiata)

STS-557 (17 alpha-cyanomethyl-17 beta-hydroxy-estra-4, 9(10)-diene-3-one) was administered (i.m.) to two groups (4 in each group) of adult male bonnet monkeys at a daily dose of 10 mg/monkey for 12 weeks (first group) and 5 mg/monkey for 14 weeks (second group). Treatment with the 10 mg dose resulted in a significant decline in the count, motility, acrosin and hyaluronidase activities and the fertilizing ability (zona-free hamster egg penetration assay) of spermatozoa by the 6th week of initiation of treatment. The circulating level of STS-557 was low after one week and increased from the 2nd week of treatment when the serum level of testosterone was significantly reduced. Complete recovery was observed by the 11th week after withdrawal of treatment. The treatment with the 5 mg dose had minor and inconsistent effect on the motility, hyaluronidase and acrosin activity, and the fertilizing ability of spermatozoa in addition to the blood level of testosterone. STS-557 may have the potentiality to be used as a chemical contraceptive in the male but compensation for the reduced level of blood testosterone may be necessary.     

Effects of STS-557 and 20 Aet-1 on sperm functions and serum level of testosterone in bonnet monkey (Macaca radiata).

Treatment of adult male bonnet monkeys with STS-557 (17 alpha-cyanomethyl 17 beta-hydroxy estra-4, 9(10)-dien-3-one; 12 mg/monkey daily for 15 weeks; i.m.) reduced the sperm count from the 9th week, leading close to azoospermia on the 2nd post-treatment week which persisted until the 10th post-treatment week and normalcy was restored on the 13th post-treatment week. The sperm motility was reduced from the 9th week of treatment to 8th post-treatment week. The fertilizing ability of spermatozoa (formation of swollen sperm head or pronuclei in zona-free hamster eggs) was abolished from the 8th week of treatment to the 7th post-treatment week. The serum level of testosterone was reduced from the 2nd to 12th week of treatment (data on subsequent weeks were not collected). When 20 Aet-1 (testosterone-trans-4-n butyl cyclohexyl carboxylate; 40 mg/monkey, single; i.m.) was administered on the first day of STS-557 treatment, the sperm count was reduced from the 10th week, with near azoospermia ensuing on the 13th week which continued until the 8th post-treatment week; recovery was observed on the 12th post-treatment week. The motility was low from the 8th week of treatment to 6th week after withdrawal of treatment. The fertilizing ability of spermatozoa was abolished from the 8th week to the 12th week of treatment (data on last week of treatment were not collected). The serum level of testosterone was maintained within normal range except on the 2nd, 6th and 12th week of treatment. 20 Aet-1 alone had no significant effect on these parameters.(ABSTRACT TRUNCATED AT 250 WORDS)     

心理干预辅助治疗产后抑郁的疗效观察

目的探讨心理干预对产后抑郁患者的辅助治疗效果。方法40例产后抑郁患者随机分为研究组、对照组各20例，研究组除了给予药物治疗外，同时实施家庭干预及合理情绪疗法，对照组单用药物治疗。治疗前和治疗后第4、6、8周及3个月随访分别用汉密尔顿抑郁量表（HAMD17）评定。结果两组治疗后第4、6周末，疗效未见统计学差异；治疗后第8周和3个月后随访，两组疗效差异有显著统计学意义。结论心理干预辅助治疗产后抑郁有更好的远期效果。     

恩替卡韦治疗慢性乙型肝炎患者免疫功能变化的研究

目的 研究恩替卡韦(ETV)治疗慢性乙型肝炎过程中患者免疫功能的变化.方法 在应用ETV治疗的不同时间点抽取HBV感染患者及健康对照者静脉血.对HBV表面标志物、HBV DNA、ALT水平进行检测;分离血清及外周血单核细胞(PMBC),检测并对比治疗前后血清细胞因子、经CD3/CD28细胞和HBV核心抗原(HBcAg)...     

Evaluation of STS-557 as an oral contraceptive in male rat

To examine the nature and site of post-testicular antifertility action of STS-557 (17 alpha-cyanomethyl-17 beta-hydroxy-estra-4,9-dien-3-one), male rats were given the steroid orally daily for 60 days. In doses of 1 and 5 mg per animal per day it had no effect on fertility at the end of 3 weeks of treatment. When the treatment was extended for 60 days, spermatogenic arrest and loss of libido were evident in animals treated with 5 mg dose; animals receiving 1 mg dose of steroid showed no decrease of spermatogenesis or sexual activity and their fertility remained unaffected. In 35-day-old growing rats the steroid produced inconsistent effects on spermatogenesis after a 15-day treatment period at 1 and 5 mg doses. Both in adult and in growing rats the steroid caused a significant reduction in the weights and secretory function of the epididymis and other accessory sex organs; a dose-dependent response was seen in all the sex organs. Evaluation in castrated rat model revealed that STS-557 is a weak anti-androgen. Although this steroid is a potent inhibitor of spermatogenesis, its inhibitory effect on Leydig cell function is a contraindication for its use as a male oral contraceptive.     

Chemical synthesis and evaluation of 17α-alkylated derivatives of estradiol as inhibitors of steroid sulfatase

Steroid sulfatase (STS) controls the levels of 3-hydroxysteroids available from circulating steroid sulfates in several normal and malignant tissues. This and the known involvement of active estrogens and androgens in diseases such as breast and prostate cancers thus make STS an interesting therapeutic target. Here we describe the chemical synthesis and characterization of an extended series of 17α-derivatives of estradiol (E2) using different strategies. A variant of the samarium-Barbier reaction with stoichiometric samarium metal and catalytic Kagan reagent formation was used for introducing low reactive benzyl substrates in position 17 of estrone (E1) whereas heterocyclic substrates were metalated and reacted with either the carbonyl or the 17-oxirane of E1. In vitro evaluation of the inhibitory potency of the new compounds against STS identified new inhibitors and allowed a more complete structure-activity relationship study of this family of 17α-derivatives of E2.     

不同n-6/n-3多不饱和脂肪酸构成比对高脂饲料喂养大鼠脂联素和糖脂代谢及抗氧化能力的影响

目的探讨高脂饲料喂养条件下,不同n-6/n-3多不饱和脂肪酸(polyunsaturated fatty acid,PUFA)构成比对大鼠脂联素和糖脂代谢及抗氧化能力的影响。方法50只雄性Wistar大鼠按体重随机分为5组:1个普通饲料组(脂肪供能比17%,n-6/n-3PUFA=5∶1)和4个高脂饲料组(脂肪供能比均为42%,n-6/n-3 PUFA构成比分别为1∶1、5∶1、10∶1、20∶1)。喂养12周后检测大鼠血糖和血脂(0、4、8和12周)、血清抗氧化指标(0和12周)以及睾周脂肪组织脂联素mRNA、蛋白表达和血清脂联素水平(12周)。结果大鼠各指标初始值组间差异均无统计学意义(P>0.05)。12周时,n-6/n-3PUFA 10∶1、20∶1组血糖显著高于对照组(P<0.05),4个高脂组血清总胆固醇(total cholesterol,TC)、甘油三酯(triglyceride,TG)显著高于对照组(P<0.01),其中20∶1组TG显著高于其余3组(P<0.01);4个高脂组谷胱甘肽过氧化物酶和超氧化物歧化酶含量显著低于对照组(P<0.05),其中20∶1组下降最明显,丙二醛含量显著高于对照组(P<0.05),其中10∶1组上升最明显;20∶1组脂联素mRNA表达显著低于对照组、1∶1组和5∶1组(P<0.05),5∶1组脂联素蛋白表达水平显著高于其余高脂组(P<0.05),而20∶1组表达水平最低(P<0.05)。结论较低的n-6/n-3 PUFA构成比(1∶1和5∶1),有助于改善高脂饲料条件下大鼠糖脂代谢及抗氧化能力,提高脂联素表达。     

Exercise treatment for depression: efficacy and dose response

BACKGROUND: This study, conducted between 1998 and 2001 and analyzed in 2002 and 2003, was designed to test (1) whether exercise is an efficacious treatment for mild to moderate major depressive disorder (MDD), and (2) the dose-response relation of exercise and reduction in depressive symptoms. DESIGN: The study was a randomized 2x2 factorial design, plus placebo control. SETTING/PARTICIPANTS: All exercise was performed in a supervised laboratory setting with adults (n =80) aged 20 to 45 years diagnosed with mild to moderate MDD. INTERVENTION: Participants were randomized to one of four aerobic exercise treatment groups that varied total energy expenditure (7.0 kcal/kg/week or 17.5 kcal/kg/week) and frequency (3 days/week or 5 days/week) or to exercise placebo control (3 days/week flexibility exercise). The 17.5-kcal/kg/week dose is consistent with public health recommendations for physical activity and was termed "public health dose" (PHD). The 7.0-kcal/kg/week dose was termed "low dose" (LD). MAIN OUTCOME MEASURES: The primary outcome was the score on the 17-item Hamilton Rating Scale for Depression (HRSD(17)). RESULTS: The main effect of energy expenditure in reducing HRSD(17) scores at 12 weeks was significant. Adjusted mean HRSD(17) scores at 12 weeks were reduced 47% from baseline for PHD, compared with 30% for LD and 29% for control. There was no main effect of exercise frequency at 12 weeks. CONCLUSIONS: Aerobic exercise at a dose consistent with public health recommendations is an effective treatment for MDD of mild to moderate severity. A lower dose is comparable to placebo effect.     

Case-control study on occupational risk factors for soft-tissue sarcoma

OBJECTIVE: The main objective of this study was to investigate potential association between development of soft-tissue sarcoma (STS) and occupational exposures related to farming and the agricultural industry in Canada. METHODOLOGY: A population-based case-control study of STS was conducted among Canadian men stratified by province of residence and age group. Conditional logistic regression was used to fit multivariable statistical models. RESULTS: The following variables were positively associated with the incidence of STS: machinist, chicken farming, pulp and paper industry worker, and apartment complex worker. Mixed farming and exposure to chlorine were negatively associated with STS. CONCLUSION: The higher risk of developing STS may be associated with longest-held job as a machinist, short-term jobs as chicken farm worker, pulp and paper industry worker, and apartment complex worker.     

Elicitation of health state utilities in soft tissue sarcoma

Purpose

Soft tissue sarcomas (STS) are uncommon tumours with varying histological subtypes. There is a paucity of available data concerning the quality-of-life (QoL) impact of STS which could be used to support economic evaluation of future treatments. This study aimed to elicit societal utility values for health states that depict the impact of STS and its treatment.

Methods

Following the development of eight health state vignettes, a sample of 100 members of the UK general public participated in a valuation exercise to elicit utility values using the time trade-off procedure.

Results

The treatment response state was valued as the least burdensome by participants followed by the prospect of stable disease (mean utility value: 0.736 SD 0.21). Serious adverse events were associated with a range of disutilities from ?0.236 for grade III/IV pain to ?0.357 for grade III/IV nausea/vomiting. Progressive disease was deemed the least desirable outcome and was associated with a substantial decline in utility (?0.473).

Conclusions

Findings suggest advanced STS are associated with significant burden for individuals. Treatment-related adverse events were seen as debilitating, however, progression represents an enormous challenge to QoL. This illustrates the significant value to individuals of extending the progression free survival period.     

Chemopreventive effect of raw and cooked lentils (Lens culinaris L) and soybeans (Glycine max) against azoxymethane-induced aberrant crypt foci

Although lentils (Lens culinaris L) contain several bioactive compounds that have been linked to the prevention of cancer, the in vivo chemopreventive ability of lentils against chemically induced colorectal cancer has not been examined. Our present study examined the hypothesis that lentils could suppress the early carcinogenesis in vivo by virtue of their bioactive micro- and macroconstituents and that culinary thermal treatment could affect their chemopreventive potential. To accomplish this goal, we used raw whole lentils (RWL), raw split lentils (RSL), cooked whole lentils (CWL), and cooked split lentils (CSL). Raw soybeans (RSB; Glycine max) were used for the purpose of comparison with a well-studied chemopreventive agent. Sixty weanling Fischer 344 male rats, 4 to 5 weeks of age, were randomly assigned to 6 groups (10 rats/group): the control group (C) received AIN-93G diet, and treatment leguminous groups of RWL, CWL, RSL, CSL, and RSB received the treatment diets containing AIN-93G+5% of the above-mentioned legumes. After acclimatization for 1 week (at 5th to 6th week of age), all animals were put on the control and treatment diets separately for 5 weeks (from 6th to 11th week of age). At the end of the 5th week of feeding (end of 11th week of age), all rats received 2 subcutaneous injections of azoxymethane carcinogen at 15 mg/kg rat body weight per dose once a week for 2 consecutive weeks. After 17 weeks of the last azoxymethane injection (from 12th to 29th week of age), all rats were euthanized. Chemopreventive ability was assessed using colonic aberrant crypt foci and activity of hepatic glutathione-S-transferases. Significant reductions (P < .05) were found in total aberrant crypt foci number (mean ± SEM) for RSB (27.33 ± 4.32), CWL (33.44 ± 4.56), and RSL (37.00 ± 6.02) in comparison with the C group (58.33 ± 8.46). Hepatic glutathione-S-transferases activities increased significantly (P < .05) in rats fed all treatment diets (from 51.38 ± 3.66 to 67.94 ± 2.01 μmol mg⁻¹ min⁻¹) when compared with control (C) diet (26.13 ± 1.01 μmol mg⁻¹ min⁻¹). Our findings indicate that consumption of lentils might be protective against colon carcinogenesis and that hydrothermal treatment resulted in an improvement in the chemopreventive potential for the whole lentils.     

2008—2010年西双版纳州手足口病流行病学特征分析

目的了解西双版纳州2008—2010年手足口病的发病率、流行高峰、人群分布及病原构成。方法对2008—2010年疾病监测信息系统报告的手足口病病例进行流行病学特征分析。结果①2008年西双版纳州报告手足口病病例511例,发病率48.21/10万;无重症及死亡病例。2009年报告723例,发病率67.74/10万;重症1例,重症率为0.14%。2010年报告1 013例,发病率94.25/10万;重症3例,重症率0.30%。②2009年流行呈单峰分布,高峰在第16～23周,最高峰在第17周。2010年流行高峰则出现在第37～45周,最高峰在第40周,高峰期明显推后。③2008—2010年病例的年龄分布特点相似,主要集中在3岁以下儿童,占发病总数的64.05%,其中,以1岁年龄组发病率最高。3岁以下发病率为218.96/10万,3～10岁发病率为22.04/10万。发病率之间差异存在统计学意义(χ2=4 100.65,P0.01)。3岁以下发病率高于3～10岁的发病率。④2010年报告的1 013例病例中,采集标本60份,其中咽拭子52份,粪便标本6份,血清标本2份。使用中国广州安达公司生产的试剂盒进行检测,EV71阳性14例,阳性率23.33%,CoxA16阳性8例,阳性率13.33%。结论 2008—2010年间,2010年手足口病流行强度最强,3岁以下儿童发病率高于3岁以上。EV71流行是导致2010年疫情上升和重症增加的原因。预防控制以农村为重点,采取三级预防模式,包括卫生条件的改善、健康教育、易感人群保护和手足口病疫苗研制等;同时应重视二、三级预防,通过新的检测技术和手段早期发现患者,并给予及时的治疗,以预防和减少并发症的发生。     

Population-based reference values for the 1-min sit-to-stand test

Objectives

To determine reference values for the 1-min sit-to-stand (STS) test in an adult population.

Methods

Cross-sectional study nested within a nationwide health promotion campaign in Switzerland. Adults performed the STS test and completed questions on demographics and health behavior.

Results

6,926 out of 7,753 (89.3 %) adults were able to complete the STS test. The median number of repetitions ranged from 50/min (25–75th percentile 41–57/min) in young men and 47/min (39–55/min) in young women aged 20–24 years to 30/min (25–37/min) in older men and 27/min (22–30/min) in older women aged 75–79 years.

Conclusions

The reference values support the interpretation of 1-min STS test performance and identification of subjects with decreased lower body muscular strength and endurance.     

不同剂量辛伐他汀治疗老年高脂血症疗效及安全性观察

目的：观察辛伐他汀（舒降之）20mg与40mg不同剂量对老年高脂血症患者的降血脂疗效及安全性的影响。方法：70例老年高脂血症患者以抽签法随机分为舒降之200mg组（A组，n=40）及舒降之40mg组（B组，n=30).观察用药4周，8周，12周患者的血清总胆固醇（TCH），低密度脂蛋白固醇（LDL－C），高密度脂蛋白胆固醇（HDL－C）及甘油三酯（TG）变化。并观察两组患者服药前后肝肾功能，血糖及心肌酶学的变化。结果：服用舒降之20mg/d4周，8周及12周可分别使患者血清TCH降低32．1％，32．1％、36．0％，TG降低35．1％、49．6％、52．9％，LDL降低39．3％、37．3％、35．2％，HDL－C升高2．0％、0．8％、8．3％，服用舒降之40mg/d4周，8周及12周可分别使患者血清TCH降低41．8％，48．0％、51．0％，TG降低18．4％，32．3％、38．4％，LDL降低42．4％，47．5％，50．8％，HDL－C升高1．0％，2．0％、13．0％，两种剂量药物治疗前后肝肾功能，血糖及心肌酶学无显著性差异。结论：每日口服舒降之20mg与40mg比较疗效基本相同，且安全性一致。     

三氯乙烯亚急性毒作用研究

[目的]探讨静式吸入三氯乙烯(TCE)对SD清洁级雄性大鼠的亚急性毒作用。[方法]将TCE分4个浓度组0 (对照组)、1、5、10g/m3 ,每组2 5只,SD雄性大鼠,对其进行静式吸入染毒,2h/d ,5d/周,连续4周,染毒结束后,再继续饲养1周。于每星期三染毒后每组各随机抽取5只大鼠,收集2 4h尿液,分析其三氯乙酸(TCA)含量作为TCE接触指标,并做尿常规;尿液收集完后采血检测生化指标,同时进行大鼠肝、肾、肺等脏器的病理检查。[结果]各剂量组大鼠4周内均无死亡,体重增长无显著性差异;第3周中、高剂量组和第4、5周高剂量组的肝脏脏器系数变大,与对照组相比,差异有显著性(P <0 .0 5 ) ;第5周高剂量组肾脏脏器系数变大,与对照组相比,其差异有显著性(P <0 .0 5 )。血液生化功能检测未见异常;病理组织学检查发现:染毒组与对照组相比,1～4周肺、肝、肾各脏器病变差异无显著性,第5周高剂量组肺部炎浸(支气管炎)及肾小管内蛋白管型明显增多;1～5周对照组大鼠尿液中均未检测到TCA ;第1、3、4周的中、高剂量组和第2周高剂量组尿中TCA含量增加,和低剂量组相比,差异均有显著性(P <0 .0 5 ) ;同时也发现,1～4周各剂量组大鼠尿中TCA含量随着TCE染毒用量的增加而增加,有一定的线性趋势,各剂量组脱离接触TCE 1周后尿中皆未检测到TCA ;在染毒4周     

地牡宁神口服液治疗3~6岁多动症患儿有效性、安全性

目的探究地牡宁神口服液治疗3~6岁多动症患儿临床疗效及安全性,为证实中医药治疗儿童多动症有效性及安全性提供临床依据。方法文章采用自身对照研究,2014年3月-2018年9月,将符合入组标准的3~6岁多动症儿童31人作为研究对象,疗程为24周,以Conners父母用症状问卷(parent symptom questionnaire,PSQ)、中医证候量表及韦氏智力量表评估其疗效,以血生化、血常规、心电图及不良反应发生率评价其安全性。结果在第24周,患儿PSQ在第24周末与治疗前相比,PSQ中各维度评分均较治疗前降低,且除心身障碍维度外[治疗前(0.37±0.29)分,第24周(0.26±0.21)分,Z=-1.490,P=0.140],余差异均具有统计学意义(P<0.05)。中医症候疗效:在第8周、16周、24周,中医证候主、次症积分及总积分均低于治疗前(P<0.05),且总有效率分别为61.29%、80.65%、83.87%。第24周时,韦氏幼儿智力结果显示:总智商,知觉推理、工作记忆、加工速度得分,皆高于基线分,差异具有统计学意义(P<0.05)。血常规、血生化差异皆无统计学意义(P>0.05),治疗前后心电图检查均未有异常发现,不良反应发生率为约13%。结论地牡宁神口服液治疗小儿多动症疗效确切,且不良反应少,安全性高。     

舍曲林早期干预对急性卒中后抑郁及血中5-羟色胺水平的影响

目的 观察舍曲林早期干预对急性卒中后抑郁(PSD)及血中5-羟色胺(5-HT)水平的影响.方法 130例PSD患者随机分为两组,每组各65例.舍曲林治疗组给予舍曲林联合心理干预治疗12周,常规治疗组仅行心理干预治疗12周,所有患者在治疗前后均进行汉密尔顿抑郁量表(HRSD)评分、Zung抑郁白评量表(SDS)评分、血浆及血小板5-HT测定.结果 舍曲林治疗组治疗4、8周时HRSD、SDS评分较治疗前减分明显(P<0.05或<0.01).舍曲林治疗组HRSD、SDS评分变化治疗4、8周时优于或明显优于常规治疗组(P<0.05或<0.01);两组减分率(治疗前至治疗8周)比较差异有统计学意义(P均<0.01);两组血浆5-HT水平治疗前后比较差异无统计学意义(P>0.05);舍曲林治疗组治疗4、8周时血小板5-HT水平明显低于治疗前水平(P<0.01),而常规治疗组治疗前后比较差异无统计学意义(P>0.05).结论 早期应用舍曲林治疗可减轻PSD症状、促进神经功能康复;血浆5-HT检测结果无显著临床意义,舍曲林治疗可引起PSD患者血小板5-HT水平明显降低.