Consecutive Cyproterone Acetate and Estradiol Treatment in Late-Pubertal Transgender Female Adolescents

BackgroundCyproterone acetate (CA) is an antiandrogenic progestin commonly used in adult transwomen to suppress endogenous androgens, often in combination with estrogens to induce feminization.AimTo assess the (side) effects and biochemical changes of CA alone and in combination with estrogens in adolescent trans-girls.MethodsThis study was a retrospective analysis of clinical and biochemical data from 27 trans-girls who presented at Tanner stage G4 and were treated with CA monotherapy for at least 6 months (mean = 12 months) and then in combination with incremental doses of estrogens (CA + E; mean = 16 months). Statistical analysis of data included paired or unpaired Student t-test or Wilcoxon signed-ranks or Mann-Whitney U-test as appropriate.OutcomesAnthropometrics, reported beneficial and side effects, safety parameters, and hormone levels.ResultsPhysical changes included decrease of facial and non-facial hair growth. One third showed breast development under CA (Tanner stages B2–B3), which increased to Tanner stages B3 and B4 in 66.7% and 9.5% respectively, during CA + E. Reported side effects during CA and CA + E were breast tenderness, emotionality, fatigue, and flushes. No relevant weight changes were observed. Main safety parameters showed the following changes. Hemoglobin and hematocrit decreased and liver enzymes transiently and modestly increased during CA. Triglycerides and cholesterol levels slightly decreased during CA but returned to baseline during CA + E; glucose metabolism was unaffected. Relevant hormonal changes included a decrease in gonadotropins during CA + E and in total and free testosterone levels throughout treatment. Prolactin levels increased during CA and were restored during CA + E.Clinical ImplicationsCA produced modest feminizing effects in trans-girls and therefore might be a valuable alternative in situations in which gonadotropin-releasing hormone analogues are not the treatment of choice and/or are not reimbursed.Strengths and LimitationsThis is the first study to report on the effects of CA in the treatment of trans-girls and one of the few to report on the use of estrogens in this population. Limitations are the modest sample size and the retrospective nature of this study.ConclusionTreatment with CA in late-pubertal trans-girls overall was safe and well tolerated and induced mild clinical and biochemical feminizing changes. Rapid further feminization was observed with incremental doses of E.Tack LJW, Heyse R, Craen M, et al. Consecutive Cyproterone Acetate and Estradiol Treatment in Late-Pubertal Transgender Female Adolescents. J Sex Med 2017;14:747–757.     

肢体创伤后机体凝血系统改变有关指标检测的临床研究

目的　探讨肢体创伤后机体凝血系统改变的有关指标检测的临床意义。方法　将肢体创伤病人 49例分为 3组 :Ⅰ组 (n=2 2 ) :为肢体单处开放性骨折 ,未作急诊显微外科技术修复。Ⅱ组 (n =1 2 ) :肢体单处软组织缺损或肢体单处骨折伴主干血管损伤 ,需急诊行显微外科技术修复者。Ⅲ组 (n =1 5) :肢体两处以上开放性骨折伴休克或伴有头、胸、腹等处损伤。三组均检测 :血小板计数 (PLC) ,活化部分凝血活酶时间 (APTT)、凝血酶原时间 (PT)、凝血酶时间 (TT)和纤维蛋白原定量(FIB)。结果　Ⅰ、Ⅱ组各期的检测指标基本相接近 ,仅Ⅱ组中的FIB术前轻度增高 ,伤后 2 4h恢复正常。Ⅲ组与Ⅰ、Ⅱ组相比 :APTT下降 ,FIB显著增高 ,PLC尽管在正常范围内 ,但已经明显高于Ⅰ、Ⅱ组各期 ,以上三项指标差异有统计意义 (P<0 .0 5)。结论　对于一般创伤病人急诊行显微外科技术修复是可行的且是安全的 ,但对肢体严重创伤病人由于创伤后机体处于一种高凝状态 ,不适应急诊行显微外科手术 ,应采用亚急诊修复     

Acute and chronic toxicity of a lyophilised aqueous extract of Tanacetum vulgare leaves in rodents

AIM OF THE STUDY: The present investigation was carried out to evaluate the safety of an aqueous extract of tansy (Tanacetum vulgare L.) leaves by determining its potential toxicity after acute and chronic administration in rodents. MATERIALS AND METHODS: For the acute study, a lyophilized aqueous extract of tansy leaves was administered to mice in single doses of 0-13 g/kg given by gavage as well as intraperitoneal doses of 0-4.5 g/kg. General behavior adverse effects and mortality were determined for up to 14 days. In the chronic dose study, the extract was administered orally at doses of 0, 100, 300 and 600 mg/kg daily for 90 days to rats. Biochemical and hematological parameters were determined after 30 and 60 days, and then at the end of 90 days of daily administration. RESULTS: In the acute study in mice, the crude aqueous extract of tansy leaves caused dose-dependent general behavior adverse effects and mortality. The no-observed adverse effect levels (NOAEL) of the tansy extract were 7.0 g/kg and 1.0 g/kg, and the lowest-observed adverse effect levels (LOAEL) were 9.0 g/kg and 1.5 g/kg, when given by the oral and intraperitoneal routes, respectively. Mortality increased with increasing doses, with LD(50) of 9.9 g/kg and 2.8 g/kg for the oral and intraperitonal modes of administration, respectively. In the chronic study in rats, daily oral administration of the crude aqueous extract of tansy leaves for up to 90 days did not result in death or significant changes in the biological (except for hypoglycemia) and hematological parameters. CONCLUSIONS: Because of the relatively high NOAEL values in the acute study in mice, and lack of significant effect on biological and hematological parameters in rats after 90 days of daily doses, the tansy extract does not appear to have significant toxicity. In view of the dose of tansy consumed in traditional medicine, there is a wide margin of safety for the therapeutic use of the aqueous extract of Tanacetum vulgare leaves.     

Molecular cloning and characterization of a new and highly thermostable esterase from Geobacillus sp. JM6

A new lipolytic enzyme gene was cloned from a thermophile Geobacillus sp. JM6. The gene contained 750 bp and encoded a 249‐amino acid protein. The recombinant enzyme was expressed and purified from Escherichia coli BL21 (DE3) with a molecular mass of 33.6 kDa. Enzyme assays using p‐nitrophenyl esters with different acyl chain lengths as the substrates confirmed its esterase activity, yielding the highest activity with p‐nitrophenyl butyrate. When p‐nitrophenyl butyrate was used as a substrate, the optimum reaction temperature and pH for the enzyme were 60 °C and pH 7.5, respectively. Geobacillus sp. JM6 esterase showed excellent thermostability with 68% residual activity after incubation at 100 °C for 18 h. A theoretical structural model of strain JM6 esterase was developed with a monoacylglycerol lipase from Bacillus sp. H‐257 as a template. The predicted core structure exhibits an α/β hydrolase fold, and a putative catalytic triad (Ser97, Asp196, and His226) was identified. Inhibition assays with PMSF indicated that serine residue is involved in the catalytic activity of strain JM6 esterase. The recombinant esterase showed a relatively good tolerance to the detected detergents and denaturants, such as SDS, Chaps, Tween 20, Tween 80, Triton X‐100, sodium deoxycholate, urea, and guanidine hydrochloride.

     

Dutasteride Treatment Over 2 Years Delays Prostate-specific Antigen Progression in Patients with Biochemical Failure After Radical Therapy for Prostate Cancer: Results from the Randomised,Placebo-controlled Avodart After Radical Therapy for Prostate Cancer Study (ARTS)

Background

Rising prostate-specific antigen (PSA) levels after radical therapy are indicative of recurrent or residual prostate cancer (PCa). This biochemical recurrence typically predates clinically detectable metastatic disease by several years. Management of patients with biochemical recurrence is controversial.

Objective

To assess the effect of dutasteride on progression of PCa in patients with biochemical failure after radical therapy.

Design, setting, and participants

Randomised, double-blind, placebo-controlled trial in 294 men from 64 centres across 9 European countries.

Intervention

The 5α-reductase inhibitor, dutasteride.

Outcome measurements and statistical analysis

The primary end point was time to PSA doubling from start of randomised treatment, analysed by log-rank test stratified by previous therapy and investigative-site cluster. Secondary end points included time to disease progression and the proportion of subjects with disease progression.

Results and limitations

Of the 294 subjects randomised (147 in each treatment group), 187 (64%) completed 24 mo of treatment and 107 discontinued treatment prematurely (71 [48%] of the placebo group, 36 [24%] of the dutasteride group). Dutasteride significantly delayed the time to PSA doubling compared with placebo after 24 mo of treatment (p < 0.001); the relative risk (RR) reduction was 66.1% (95% confidence interval [CI], 50.35–76.90) for the overall study period. Dutasteride also significantly delayed disease progression (which included PSA- and non-PSA-related outcomes) compared with placebo (p < 0.001); the overall RR reduction in favour of dutasteride was 59% (95% CI, 32.53–75.09). The incidence of adverse events (AEs), serious AEs, and AEs leading to study withdrawal were similar between the treatment groups. A limitation was that investigators were not blinded to PSA levels during the study.

Conclusions

Dutasteride delayed the biochemical progression of PCa in patients with biochemical failure after radical therapy for clinically localised disease. The safety and tolerability of dutasteride were generally consistent with previous experience.

Clinical trial registry

ClinicalTrials.gov, NCT00558363.     

Citrin缺陷致新生儿肝内胆汁淤积症患儿生化改变研究

目的探讨citrin缺陷致新生儿肝内胆汁淤积症（NICCD）患儿生化改变特征。方法对经基因学确诊且平均月龄为3个月的26例NICCD患儿进行常规生化检查、气相色谱质谱检查及串联质谱检查并分析。结果 NICCD患儿血清总胆红素、直接胆红素、谷草转氨酶、谷丙转氨酶及乳酸水平升高均占100%,血氨及甲胎蛋白水平升高均占95.2%,胆汁酸水平升高占90.0%,低蛋白水平占84.0%,血脂水平升高占50%。半乳糖增高占78.3%,4-羟基苯乳酸增高占52.2%。C14增高占84.7%,C16增高占71.4%,瓜氨酸增高占66.7%。结论 NICCD患儿存在糖,氨基酸及脂肪酸代谢异常,以半乳糖、瓜氨酸及长链酰基肉碱增高明显。     

New evidence that serum β2-microglobulin behaves as a biological marker of bone remodelling in women

Abstract. Having observed that serum β ₂-microglobulin concentration correlates with serum tartrate-resistant acid phosphatase (TRAP) concentration in postmenopausal osteoporosis, and that metacarpal endosteal diameter is dependent on bone resorption, we correlated the two biochemical parameters with the radiographic parameter to determine if β ₂-microglobulin behaves like a biological marker of bone remodelling. In 105 women (mean age 68±4 years) consisting of 60 normal postmenopausal women and 55 osteoporotic postmenopausal women, there was a significant positive correlation between metacarpal endosteal diameter and these two biochemical values ( r = 0.66 with β ₂-microglobulin and r = 0.68 with TRAP in the osteoporotic postmenopausal women: r = 0.48 with β ₂-microglobulin and r = 0.56 with TRAP in the normal postmenopausal women: P < 0.001 for all comparisons). All three measurements were significantly higher ( P < 0.001) in the osteoporotic postmenopausal women than in the normal postmenopausal women. These findings show that serum β ₂-microglobulin behaves like a biological marker of remodelling.     

全自动生化分析仪与半自动生化分析仪在临床上的应用对比分析

目的:探讨全自动生化分析仪与半自动生化分析仪在临床应用中的对比效果,为临床诊断与治疗提供参考。方法:80例2型糖尿病患者分别使用日立7600-020型半自动生化分析仪和西门子Di-mensionRxLMax自动生化分析仪检测空腹与餐后2h静脉全血血糖。结果:全自动生化分析仪检测的空腹血糖值为(6.25±1.85)mmol/L,餐后2h血糖值为(11.52±3.30)mmol/L;而半自动生化分析仪检测的值分别为(6.32±1.56)mmol/L与(11.60±1.96)mmol/L,两种方法检测值对比无明显差异(P>0.05)。结论:全自动生化分析仪与半自动生化分析仪在临床上的应用效果均较大,对比差异不大,临床应根据患者的具体情况合理选择使用。     

Serum vitamin D status in type 2 diabetic patients from Gaza Strip

ObjectiveTo assess serum vitamin D status and its relations to other biochemical parameters in type 2 diabetic patients from Gaza Strip.Materials and methodsThis case-control study included 58 type 2 diabetic patients as well as 58 non-diabetic controls. Patients and controls were matched for age and gender. Data were obtained from questionnaire interview, and biochemical analysis of blood samples.ResultsSerum vitamin D was significantly lower in diabetic patients compared to non-diabetic controls (25.9 ± 11.0 versus 34.6 ± 13.8 ng/dl, % difference = 28.8%, P < 0.001). The number of patients having vitamin D deficient, insufficient and sufficient were 6 (10.4%), 35 (60.3%) and 17 (29.3%) compared to controls of 3 (5.2%), 16 (27.6%) and 39 (67.2%), respectively (χ² = 14.672, P < 0.001). Serum glucose, glycated hemoglobin (HbA1c), serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and triglycerides were significantly higher in patients than in controls whereas serum insulin, high density lipoprotein cholesterol (HDL-C) and calcium were significantly lower in patients. Serum vitamin D showed significant negative correlations with HbA1c (r = ? 0.186, P = 0.046), ALT (r = ? 192, P = 0.040) and AST (r = ? 0.188, P = 0.044) whereas significant positive correlations were found with HDL-C (r = 0.188, P = 0.044) and calcium (r = 0.239, P = 0.010).ConclusionThe significant negative and positive correlations of vitamin D with HbA1c and calcium, respectively suggests that vitamin D supplementation would be of potential therapeutic value in clinical settings for controlling of type 2 diabetes and more importantly its complications. However, a well-designed clinical trials are needed to define the contribution of vitamin D status and therapy in the global diabetes problem.