An approach to the diagnosis and treatment of cryofibrinogenemia

Cryofibrinogenemia is a rarely symptomatic disorder that is underrecognized due to the infrequency with which it causes symptoms. Although completely reversible, this disorder can be life threatening when untreated. In this review, the classification, pathophysiology, and clinical presentation of cryofibrinogenemia are described, based on case reports and prospective observational data. Diagnostic criteria are outlined, and therapies are assessed critically. This information should help clinicians in establishing a diagnosis of cryofibrinogenemia and initiating treatment.     

司坦唑醇对实验性骨质疏松大鼠骨密度和力学性能的影响

目的:探讨司坦唑醇对糖皮质激素(GC)所致大鼠骨质疏松的骨密度和力学性能影响。方法28只3月龄雄性SD大鼠,体质量(226±12)g,随机等分为基础对照(A)组、年龄对照(B)组、激素模型(C)组和司坦唑醇预防(D)组。C组和D组大鼠均喂醋酸泼尼松4.5 mg/kg·b.w.,每周2次,D组同时每天饲喂司坦唑醇0.5 mg/kg·b.w.。3月后,用双能X线吸收骨密度测量扫描仪对各组的离体双侧股骨和第5腰椎进行骨密度测定,然后用SWD-10型材料试验机行股骨干的扭转、三点弯曲和腰椎的压缩试验。结果与B组比较,C组股骨、腰椎总骨密度减少了14.64%(P<0.01);右、左股骨远段和腰椎的骨密度分别减少了21.42%(P<0.01)、19.62%(P<0.05)和23.48%(P<0.01);与C组比较,D组的BMD 均稍有增加。与B组比较,C组股骨三点弯曲的载荷减少了17.1%(P<0.05),其余的力学参数都有减少的趋势;与C组比较,司坦唑醇预防组股骨扭转角度增加了72.5%(P<0.05),其余的力学参数也都有增加的趋势。结论长期使用GC,会使大鼠股骨、腰椎的骨密度和力学性能下降;司坦唑醇则能防止GC所致骨量丢失,还能增加其力学性能。     

The effect of intramuscular stanozolol on fibrinolysis and blood lipids

The effects of a single 50 mg intramuscular injection of the anabolic steroid stanozolol (Stromba) on fibrinolysis, blood coagulation and lipids was evaluated in 12 healthy male volunteers. Significantly increased plasminogen activator levels (p < 0.05) was noted 24 hours following the injection and these remained elevated for one week. Plasminogen levels increased significantly by day two (p < 0.01) and remained elevated for three weeks. HDL cholesterol fell (p < 0.01) and both total and LDL cholesterol increased (p < 0.05) when measured one month post injection. Stanozolol appears to have therapeutic potential as an activator of the fibrinolytic system when given by intramuscular injection.     

司坦唑醇对促性腺激素释放激素拟似物处理后的青春期大鼠生长板软骨细胞IGF-1 mRNA表达及其蛋白合成、分泌的影响

目的研究司坦唑醇（stanozolol,ST）对促性腺激素释放激素拟似物（gonadotropin releasing hormone agonist,GnRHa）处理后的离体青春期大鼠生长板软骨细胞胰岛素样生长因子-1（insulin-like growth factor-1,IGF-1）mRNA表达及其蛋白合成、分泌的影响。方法将6只雌鼠的原代软骨细胞,分为时效组、量效组。根据是否用司坦唑醇干预,将时效组和量效组分为时效干预组,时效对照组;量效于预组,量效对照组,分别观察司坦唑醇的干预时限和剂量对促性腺激素释放激素拟似物处理后离体青春期大鼠生长板软骨细胞增殖的影响。采用软骨细胞增殖能力测定法（MTT）和免疫组化法检测不同剂量、不同时间点司坦唑醇处理的离体的青春期大鼠生长板软骨细胞的增殖细胞核抗原（proliferating cell nuclear antigen,PCNA）表达,荧光实时定量RT—PCR检测软骨细胞的IGF-1 mRNA表达。酶联免疫吸附法（enzyme—linked immunosorbent assay,ELISA）测定胰岛素样生长因子-1的合成。结果司坦唑醇以时效和量效作用方式,对雌激素受抑的离体青春期大鼠生长板软骨细胞增殖呈双相型影响。在合适的剂量和疗程时,软骨细胞增殖效应可达最好效果。①司坦唑醇作用2h后,软骨细胞IGF-1 mRNA表达显著增加,与时效对照组基础值相比,差异有显著意义（P〈0．05）,并存在较强的时间依赖性;作用8h时,达最高峰（为时效对照组基础值的3．8倍）。司坦唑醇的作用在（10^-10～10^-5）mol／L时,与软骨细胞的细胞核抗原增殖效应存在明显的剂量依赖性（组间比较,差异有显著意义,P〈0．05）;在10^-7mol／L时,软骨细胞的增殖细胞核抗原表达达最高峰（为基础值的5．75倍）。②司坦唑醇作用自5h起,软骨细胞胰岛素样生长因子-1蛋白合成与时间点为0组比较,差异有显著意义（P=0．042）;5h-20h时,作用存在显著时间依赖性（P〈0．05）;作用20h时,达峰值（为量效对照组基础值的3．3倍）。与量效对照组比较,司坦唑醇自10^-10mol／L组,胰岛素样生长因子-1蛋白含量开始增加,并在10^-7mol／L组达峰值（P=0．000）。结论司坦唑醇可以量效、时效的作用方式,影响和增加对促性腺激素释放激素拟似物处理后的体外培养雌激素水平,促进青春期大鼠生长板软骨细胞IGF-1 mRNA的表达和胰岛素样生长因子-1的合成、分泌,推测司坦唑醇促进生长效应机制与生长板局部胰岛素样生长因子-1的自分泌、旁分泌增加有关。     

Stanozolol treatment for successful prevention of attacks of severe primary cryofibrinogenemia

Severe essential cryofibrinogenemia is rare in childhood, and both the diagnosis and the management are challenging for pediatricians. An 11‐year‐old male, who had already lost two digits following cold exposure, was referred after multiple visits to various hospitals and subsequently diagnosed as primary cryofibrinogenemia. His history revealed unresponsiveness to calcium channel blockers, acetyl salicylic acid, pentoxifylline, dextran, and steroids. Stanozolol (2 mg/day, orally) prophylaxis was initiated and no new skin lesions developed following starting this treatment. Some of the newly formed lesions at the onset of stanozolol healed. Pediatr Blood Cancer 2010;55:174–176. © 2010 Wiley‐Liss, Inc.     

黄芪和司坦唑醇复方制剂对去卵巢大鼠肝脏和子宫的影响

目的观察黄芪和司坦唑醇复方制剂干预去卵巢模型大鼠过程中对肝脏及子宫的影响。方法取40只Whistar雌性大鼠随机分为5组，按要求行去势手术，然后分别灌胃给予生理盐水、司坦唑醇、已烯雌酚、黄芪司坦唑醇复方制剂，8周后处死，心脏取血离心，血清测定肝功能生化指标；同时，取大鼠子宫称量湿重并做病理切片，图像数字化分析子宫内膜厚度。结果黄芪和司坦唑醇复方制剂能有效地对抗单独使用司坦唑醇所引起的肝脏损伤作用；同时复方制剂干预组大鼠子宫湿重／体重比及内膜厚度与雌激素治疗组比较具有明显变化。结论黄芪和司坦唑醇复方制剂在预防骨质疏松症的同时，能有效避免司坦唑醇对肝脏的毒性损害作用，并降低去势手术及雌激素替代疗法对大鼠子宫的不良影响。     

Synchronous bilateral ductal carcinoma in situ of the male breast associated with gynecomastia in a 30-year-old patient following repeated injections of stanozolol

We report a rare case of synchronous bilateral and multifocal ductal carcinoma in situ (DCIS) in a 30-year-old patient operated on for gynecomastia following repeated injections of stanozolol, a non-aromatizable androgen. The familial medical history was negative for breast cancer and work-up of serum hormone levels was normal. The patient underwent a modified radical mastectomy without axilla dissection 6 weeks following the primary procedure and recovered uneventfully. The role of synthetic androgens in the development of male breast neoplasia warrants further scrutiny.     

Population pharmacokinetics of ciclosporin in Chinese children with aplastic anemia: effects of weight,renal function and stanozolol administration

Aim:

To develop a population pharmacokinetic model for the immunosuppressant ciclosporin in Chinese children with aplastic anemia and to identify covariates influencing ciclosporin pharmacokinetics.

Methods:

A total of 102 children with either acquired or congenital aplastic anemia aged 8.8±3.6 years (range 0.9–17.6 years) were included. Therapeutic drug monitoring (TDM) data for ciclosporin were collected. The population pharmacokinetic model of ciclosporin was described using the nonlinear mixed-effects modeling (NONMEM) VI software. The final model was validated using bootstrap and normalized prediction distribution errors.

Results:

A one-compartment model with first-order absorption and elimination was developed. The estimated CL/F was 15.1, which was lower than those of children receiving stem cell or kidney transplant reported in the West (16.9–29.3). The weight normalized CL/F was 0.45 (range: 0.27–0.70) Lh⁻¹·kg⁻¹. The covariate analysis identified body weight, serum creatinine and concomitant administration of the anabolic steroid stanozolol as individual factors influencing the CL/F of ciclosporin.

Conclusion:

Our model could be used to optimize the ciclosporin dosing regimen in Chinese children with aplastic anemia.     

Blood biochemical and oxidant/antioxidant alterations following stanozolol treatment along with resistance training in rats

This study was designed to determine the effects of anabolic steroid stanozolol (ST) in conjunction with 8 weeks of resistance training on some blood biochemical and oxidant/antioxidant profile in rats. Twenty‐four male rats were divided into four groups of six each: group 1: sedentary + placebo (physiological saline), group 2: training + placebo, group 3: training + ST (2 mg kg^?1 b.w.) and group 4: training + ST (5 mg kg^?1 b.w.). Erythrocytic activity of glutathione peroxidase was increased significantly in group 4 as compared to control group. Plasma activities of alanine aminotransferase in groups 3 and 4 and also aspartate aminotransferase in group 4 showed significant increase relative to groups 1 and 2. Moreover, alkaline phosphatase and creatine kinase activities increased significantly in groups 3 and 4 in comparison with control group. Elevated values of uric acid were significant in group 4, but not in groups 2 and 3, as compared to control group. Values of other measured parameters did not have significant alterations among experimental groups. Present findings indicate that stanozolol treatment in combination with resistance training induces some side effects especially on liver and muscle as evidenced by alterations in plasma markers of tissue damage.