The emancipation of testosterone from niche hormone to multi-system player

It is no exaggeration to say that our conceptualization of the (patho-) physiological functions of testosterone has undergone a revolutionary development over the last three decades. The traditional thinking was that the biological functions of testosterone were restricted mainly to the area of reproduction and male sexuality. However, scientific research has clearly demonstrated that testosterone is a multi-system hormone serving a wide range of hitherto unsuspected biological functions.In line with this, it will be argued in this contribution that the physiological role of testosterone has been underestimated, while the risks of testosterone administration have been overstated. Space does not permit to elaborate extensively on all new insights of the role of testosterone in the biology of the male. Three areas will be addressed: (1) the role that testosterone can play in body weight management of hypogonadal men; (2) the role of testosterone in inflammatory processes; (3) the strategy required to let patients benefit from the recent insights that testosterone is a multi-system hormone whose use should not be limited to reproductive/sexual medicine.     

多种血管新生指标在肝细胞肝癌中的表达及敏感性比较

目的　探讨血管新生指标CD34、CD31、vWF、Ⅳ型胶原纤维及层粘连蛋白在肝细胞肝癌(HCC)中的表达及意义 ,同时比较上述几种血管新生因子与增殖细胞核抗原 (PCNA)、病理指标及预后的相关性 ,以便筛选出有效的临床预后指标。方法　采用免疫组化方法 ,对 5 3例肝细胞肝癌的标本进行CD31、CD34、vWF、Ⅳ型胶原纤维及层粘连蛋白的染色、计数 ,并用检测数据与患者的临床资料进行统计分析。结果　统计染色的血管面积后发现 ,CD34与多种临床病理指标无相关性 ;CD31与肝内门静脉浸润相关 ;vWF与肿瘤的TNM分期及肝内门静脉浸润呈正相关 ;CollⅣ与肝内门静脉浸润呈正相关、与术后生存期呈负相关 ;Lam与肝硬化及术中出血量呈负相关、与术后生存期呈正相关。PCNA与肿瘤TNM分期有关。结论　在HCC中 ,CollⅣ、vWF、及CD31为肝细胞肝癌的有效血管新生及预后指标 ;Lam则与肝硬化及术中出血相关 ;PCNA指数肿瘤分期有关 ;CD34不能用作血管新生或预后指标     

Progressive hemolytic anemia due to delayed recognition of a Beall mitral valve prosthesis

In addition to a working knowledge of general complications such as thromboembolism and infective endocarditis, optimal care of the patient with a prosthetic valve requires specific knowledge concerning the characteristics of a given patient's prosthesis. This may need to include the ability to identify the valve roentgenographically when history and records are unavailable. A 53-year-old woman with mitral stenosis secondary to rheumatic heart disease and status post a reported Bjork-Shiley mitral valve (MV) replacement 17 years prior to hospital admission was referred for evaluation of severe hemolytic anemia. Previous cinefluoroscopy in 1986 at the time of a cerebrovascular accident revealed a normally functioning caged disc prosthesis and not the tilting disc of a Bjork-Shiley prosthetic valve. The valve was not further characterized and she continued receiving warfarin therapy until May 1989 when she presented with laboratory findings showing a marked hemolytic anemia with a hemoglobin of 6.5 mg/dl and lactate dehydrogenase (LDH) value of 2100 IU. Echocardiography revealed normal valvular function without evidence of perivalvular leak. The patient was referred for further evaluation with chest roentgenogram at the time of hospital admission revealing a valve configuration characteristic of the Beall model 103/104 series that has been found to manifest progressive disc variance with a high degree of hemolytic anemia (despite normal noninvasive evaluation of MV function), disc tilting with intermittent regurgitation, and catastrophic disc embolization in extreme cases. The precise identification of valvular prosthesis in patients after valve replacement is crucial for optimal management. As in our case, the mere identification of a particular valve may necessitate certain management and therapy based on the natural history of that valve. In the absence of reliable history and/or records, the roentgenographic examination should lead to the precise identification.     

THE PITUITARY-LEYDIG CELL AXIS IN MEN WITH SEVERE DAMAGE TO THE GERMINAL EPITHELIUM

Eighteen men (mean age 27, range 18-30 years) treated for Hodgkin's disease with 6-8 courses of MVPP (Mustine, Vinblastine, Procarbazine and Prednisolone) have had Leydig cell function assessed by their steroidogenic responses to stimulation by a single bolus dose of HCG (1000 units intramuscularly). Normal age-matched men (n = 16) acted as controls. Baseline immunoreactive FSH was markedly raised in the patients (mean 18.1 +/- SD 6.9 vs 2.0 +/- 1.5 IU/l, P less than 0.0001) reflecting damage to the germinal epithelium. Immunoreactive LH was also greater in patients (10.3 +/- 3.9 IU/l) than in controls (3.9 +/- 1.9 IU/l, P less than 0.0001). There were no differences between the baseline testosterone, androstenedione, oestradiol, oestrone and sex hormone binding globulin (SHBG) concentrations. The testosterone/SHBG ratios were similar in the two groups and there was no correlation between baseline LH and testosterone concentrations or testosterone/SHBG ratios. Testosterone, androstenedione, oestradiol and oestrone secretion in response to HCG stimulation were similar at 24 h and 96 h in both groups. In order to explain the paradox of elevated immunoreactive LH in the face of normal testicular steroidogenesis in such patients, LH biological activity (B) as well as LH immunoreactivity (I) and FSH and testosterone were estimated in a second similar group of patients (n = 17, mean age 27, range 17-43 years) and in a further age-matched control group (n = 17). Bioactive and immunoreactive LH levels were significantly increased (P less than 0.005 and P less than 0.001, respectively) in the patient group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Membrane flow within the myelin sheath in IDPN neuropathy

This report describes some aspects of beta,beta'-iminodipropionitrile (IDPN) neuropathy in rats as observed by ultrastructural methods and X-ray diffraction. Light microscopy shows gross swelling of the axons in proximal lumbar spinal roots 8 days after intraperitoneal injection of IDPN. Mean axon cross-sectional area and mean axon perimeter increased to 280% and 160% of their control values, respectively. At the same time, myelin membrane packing was not visibly disturbed. In addition, X-ray diffraction patterns, recorded under physiological conditions, demonstrate that the myelin lipid bilayer thickness and widths of the aqueous spaces between bilayers did not change. Related observations are made on posterior tibial nerve (PNS myelin) and ventral spinal cord (CNS myelin). The various observations together are interpreted in terms of a fluid myelin membrane. It is proposed that the myelin membrane flows during axon swelling even though normal membrane-membrane contacts are maintained within the sheath. Membrane flow and slippage between membranes are explained in terms of a molecular model of the myelin multilayer.     

Structure-activity relationship in the gastric cytoprotective effect of several sesquiterpene lactones.

The structural requirements for the gastric cytoprotective activity of several sesquiterpene lactones are reported. A theoretical-experimental study on the potentially active centers is carried out. The biological evaluation of reduced analogues and the simulation of the molecular interactions between these compounds and an endogenous cysteine residue suggest that the presence of a non sterically hindered Michael acceptor seems to be an essential structural requirement for the cytoprotective activity in this family of compounds. This observation suggests that cytoprotection is mediated through a Michael reaction between the sulfhydryl-containing peptides of the mucosa and Michael acceptors present in the molecules under study. This mechanism of action is in addition to and distinct from the one proposed in our previous paper, namely, that these sesquiterpenes stimulate endogenous synthesis of prostaglandins.