药物防治激素性股骨头坏死的研究进展

随着激素性股骨头坏死发病机制研究的深入，使药物防治激素性股骨头坏死成为可能。本文回顾了近年来一些国内外学者根据其发病机制进行的药物预防激素性股骨头坏死的研究，提出降脂、抗凝药联用不能完全预防激素性股骨头坏死的发生，激素性股骨头坏死是以脂肪代谢紊乱和血管内凝血为主要发病机制，其他一些病理机制共同作用的结果。     

激素性股骨头坏死发病机制的研究进展

股骨头坏死为骨科常见疾病,其病因可分为创伤性和非创伤性。其中长期或大剂量应用皮质激素已成为非创伤性股骨头坏死的首位发病因素,但其确切发病机制尚不明确。目前有多种学说,包括：血管内凝血学说、脂肪代谢紊乱及骨内高压学说、动脉血管炎学说等。近年来,随着细胞生物学、分子生物学、干细胞等在激素性股骨头坏死研究中的不断深入,细胞凋亡、骨髓基质干细胞脂肪分化、基因多态性等被认为与激素性股骨头坏死的发生发展有密切联系,为其发病机制的研究开辟了新的方向。     

CYP450基因多态性对非创伤性股骨头坏死的影响

酒精和激素是引起非创伤性股骨头坏死的常见原因,随着非创伤性股骨头坏死发病机制研究的逐渐深入,部分研究认为酒精和激素可影响肝酶的代谢,从而对非创伤性股骨头坏死的发生、发展产生重要影响。细胞色素450酶(cytochrome P450,CYP450)作为肝酶常见的一种类型,其作用机制的研究逐渐得到医学研究者的青睐。随着CYP450研究深入,部分研究认为CYP450易感基因位点的变化可能是非创伤性股骨头坏死的发病机制,本文通过综述CYP450相关基因的多态性研究进展,对临床以及实验研究非创伤性股骨头坏死作用机制提供一定的参考和借鉴。     

激素性股骨头坏死发病机制的研究进展

正1953年,Pietrogrande首次报道应用糖皮质激素与股骨头坏死相关~([1])。多年以来,对激素导致股骨头坏死的研究不断深入。目前,长期或大量应用激素已成为股骨头缺血坏死的首位发病因素。激素性股骨头坏死恢复比较困难,致残率高,且部分患者需要长期服用激素,随着病程的发展,造成股骨头不可逆损害,严重影响患者的生活质量,已受到世界范围内骨科领域的广泛关注。探究激素性股骨头坏死的发病机制对股骨头坏死     

激素性股骨头坏死载脂蛋白基因多态性与中医证候的研究进展

激素性股骨头坏死(steroid-induced osteonecrosis of thefemoral head,SONFH)是指由于糖皮质激素(简称激素)使用不当(长期小剂量或短期大剂量使用),破坏了股骨头的血液供应,从而引起股骨头局部区域骨小梁和骨髓坏死为特征的疾病。随着激素在临床的广泛应用,激素引起的股骨头坏死(osteonecrosis of the femoral head,ONFH)已成为非创伤性股骨头坏死的主要原因。但确切的发病机理尚未完全明了,因此有效的早期干预仍在探索。近年来国内外许多学者从脂肪代谢的基因水平对其发病机理方面进行了深入研究,本文就这些研究进展进行综述。     

预测早期激素性股骨头坏死的生物标志物研究进展

激素性股骨头坏死是一种进展性疾病，往往发生较为隐匿且进展迅速，如若不及时进行早期干预通常会进展为股骨头坏死和进一步塌陷，最终导致全髋关节置换，严重影响患者的生活质量。目前，虽然对激素性股骨头坏死的病因、发病机制、诊断和治疗已进行广泛地研究，但仍未找到理想的诊疗措施来治愈该疾病，关于激素性股骨头坏死的早期诊断和预防仍是当前面临的一个具有挑战性的问题。本文将近年来可能预测激素性股骨头坏死发生的潜在生物标志物进行综述，为临床激素性股骨头坏死的早期诊断和预防提供新思路。     

激素性股骨头缺血坏死发病机理及其研究进展

目的：总结激素性股骨头缺血坏死发病机理及其进展,为临床防治提供理论依据。方法：对近４６年来相关激素性股骨头缺血坏死的基础及临床研究主要文献进行归纳、分析、总结。结果：激素性股骨头缺血坏死存在如下发病机理,脂肪代谢紊乱;骨内压增加;骨质疏松及激素的毒性作用。血管炎、前凝血状况及血管内凝血结论：激素性股骨头缺不死存在复杂的病理生理学过程,在前凝血状况下应用激素及其血管内凝血发病机理理论被认为很可能是激     

系统性红斑狼疮并发无菌性股骨头坏死的相关因素分析

目的 对系统性红斑狼疮(SLE)并发无菌性股骨头坏死(ONF)的相关因素进行分析,提高SLE合并无菌性股骨头坏死的认识.方法 对32例SLE合并无菌性股骨头坏死的患者进行回顾性分析,并抽取同期年龄、性别匹配的SLE患者作对照,分为股骨头坏死组和非股骨头坏死组,收集整理其临床资料及有关实验室检查,分析其发病情况、临床脏器累及、实验室检查及其治疗等特点.结果 合并有ONF的SLE患者比无ONF组在临床上以网状青斑与雷诺现象更常见,而抗心磷脂抗体阳性率明显高于对照组;激素的起始剂量、每日最高剂量、累积用量与ONF发病无明显相关,而大剂量激素冲击治疗与ONF的发病密切相关;此外,血脂水平、SLEDAI积分、有无使用免疫抑制剂等均与ONF发生无相关性.结论 SLE患者以血管炎为主要临床表现者或凝血功能障碍者,其脉管系统对激素敏感性增加,大剂量激素冲击治疗容易并发ONF.     

破骨细胞在激素性股骨头坏死发展中的作用

 激素性股骨头坏死(osteonecrosis of femoral head, ONFH)是由于长期使用激素类药物, 以股骨头血供受损, 骨细胞及骨髓成份死亡及随后修复, 继而导致股骨头结构改变、股骨 头塌陷、关节功能障碍为特征的代谢性疾病。目前, 对ONFH 发病机制的研究较多, 包括骨内高压学说、凝血机制改变学说、脂肪栓塞学说、骨质疏松学说、骨细胞凋亡学说等。虽然这些研究均有一些临床和实验研究依据, 但均不能完全解释股骨头坏死的全部病理过程。其中, 骨细胞活性改变是上述多种学说的中间作用环节, 因此很多学者认为成骨细胞分化障碍及其脂肪变导致髓腔的压力增高和破骨细胞的骨吸收活性增强可能在股骨头发生坏死的过程中起关键的作用。本文对破骨细胞在激素性股骨头坏死发展中的作用作一综述。     

国内股骨头无菌性坏死动物实验研究近况

下面，仅就1985～1997年国内有关股骨头无菌性坏死动物实验研究的24篇论文作一分析。1．股骨头无茵性坏死实验研究的关键之一是动物模型的制做。自Pietrogrand和Mastromarinel[1]首先报导长期大剂量肾上腺皮质激素引起的股骨头无菌性坏死之后，人们开始注意激素与股骨头坏死的关系。此后，相继有人使用皮质激素类药物制做股骨头无菌性坏死动物模型。近年来，国内使用这类模型研究其发病机理及治疗方法者更加广泛。使用的兹物多为：醋酸氢化考的松8mg／kg，每周一次肌注；醋酸氢化泼尼松7．5mg／kg，每周1～2次肌注；强的松龙8mg或12．25mg…     

维生素D在糖尿病及其常见并发症中的研究进展

维生素D作为一类类固醇类激素原，可通过其代谢产物调节细胞代谢以控制多种生物功能。越来越多的研究表明，维生素D通过多种方式影响着糖尿病发生和发展，补充维生素D不仅可用于预防和控制糖尿病，还能预防或减轻糖尿病相关并发症的发生。本文将对维生素D在糖尿病及其常见并发症中的研究进展进行综述。     

雌激素硫酸转移酶和甾体硫酸酯酶在子宫内膜癌中的作用

子宫内膜癌是雌激素依赖性肿瘤。雌激素硫酸转移酶、甾体硫酸酯酶在体内雌激素合成与代谢中发挥着重要作用。本文对雌激素硫酸转移酶、甾体硫酸酯酶在子宫内膜癌中的作用作一综述。     

Steroid metabolism and morphologic features of the human testis

Serum FSH, LH, and testosterone were studied in 114 infertile men with poor sperm production. Testicular biopsies were taken and classified morphologically. In 90 specimens, the pattern of conversion of progesterone was determined in vitro and expressed as the ratio of 20 alpha-hydroxy-4-pregnene-3-one to 17 alpha-hydroxyprogesterone. An excess of the former metabolite indicates a prepubertal type of steroid metabolism. The normal limit of this ratio is given. The collected data indicate that the prepubertal type of steroid metabolic pattern is related to the thickness of the lamina propria of the seminiferous tubules only, and not to peripheral hormone levels. In particular, the presence of hyaline deposits in the lamina propria seems to determine the metabolic pattern. It is suggested that the character of the lamina propria separating the tubular and interstitial compartments of the testis is of crucial importance for the functional interrelationship between these compartments. This supports the concept of an intratesticular regulatory mechanism of both steroid metabolism and spermatogenesis.     

Impaired Leydig Cell Function In Vitro in Testicular Tissue from Human Males with "Sertoli Cell Only" Syndrome

Testicular histopathology in patients with "Sertoli Cell Only" Syndrome is characterized by absence of germinal cells. Some of these patients have high levels of LH in their peripheral blood as well as subnormal serum testosterone levels. This indicates a possible correlation between the lack of germinal cells and an impairment of Leydig cell steroidogenic activity. It has previously been shown that in vitro conversion of tritiated steroid precursors within testicular tissue indicates the Leydig cell steroidogenic activity. In this study we have investigated whether or not testicular tubular cell disorder with lack of germinal cells is related to impairment of the intratesticular steroid metabolism in vitro. Ten patients with testicular histopathology characteristic of "Sertoli cell only" syndrome were investigated and their steroid metabolism patterns were compared with those of 22 control patients. Leydig cell dysfunction was found in the group of patients with SOS; 17 alpha-hydroxylation was significantly lower and the production of 20 alpha-dihydroprogesterone was significantly higher, as compared to the control patients. The Leydig cell impairment may be due to a disturbed influence from the damaged tubules.     

基于CT三维重建的激素性股骨头坏死患者股骨头坏死组织分布研究

目的利用CT三维重建观察激素性股骨头坏死患者股骨头坏死组织体积及分布情况。方法以2016年9月-2018年12月收治并符合选择标准的25例激素性股骨头坏死患者为研究对象。男22例,女3例;年龄20~63岁,平均38.8岁。股骨头坏死均为国际骨循环研究会(ARCO)Ⅱ期;病程3~18个月,平均9.2个月。首先行髋关节CT扫描,采用Mimics Research 21.0软件三维重建股骨头并识别坏死组织;然后利用3-matic Research 13.0软件将重建的股骨头分割为8个区域,测算股骨头、坏死组织体积,坏死组织体积比,以及不同区域坏死组织分布情况。结果股骨头三维数字模型显示坏死组织主要位于股骨头前上方,坏死组织区域主要呈穹窿状。股骨头分区显示坏死组织主要集中于前上内区、前上外区与后上内区。25例患者股骨头体积为(48399.52±9408.90)mm^3,坏死组织体积为(20917.08±6566.94)mm^3,坏死组织体积比为44.75%±15.72%。不同区域坏死组织体积及体积比不一致,其中前上内区、前上外区和后上内区较大。结论基于CT三维重建能快速直观地评估股骨头坏死组织体积及分布情况。     

Cholinesterase Its significance in anaesthetic practice

Plasma cholinesterase is an enzyme which has importance to the anaesthetist primarily for its rôle in the metabolism of suxamethonium, although other anaesthetic related drugs that this enzyme metabolises are also increasingly important. In this article we review current thoughts on the function, profile and chemistry of plasma cholinesterase. Causes of variations in the activity of the enzyme are described and the basis of genetic variations is explained.     

Cross sectional investigation of the effects of inhaled corticosteroids on bone density and bone metabolism in patients with asthma

BACKGROUND: Bone mineral density has been reduced in patients with asthma taking inhaled corticosteroids in some cross sectional studies and this could be important if treatment is continued for several decades. The possibility of confounding by age, menopausal status, physical activity and, especially, past oral steroid use has not been excluded in most studies. The present study was designed to assess the magnitude of any reduction in bone mineral density in relation to inhaled steroid use after adjusting for these factors. METHODS: Bone mineral density (BMD), vertebral fractures, and markers of bone metabolism (serum osteocalcin, procollagen peptide I, bone-specific alkaline phosphatase, and urinary deoxypyridinoline cross links) were measured in 81 patients with asthma age 20-40 years; 34 patients (19 men) who had never had inhaled or systemic steroids and 47 (19 men) who had taken inhaled steroids for at least five years with limited exposure to systemic steroids in the past. Data relating to past medication use, physical activity, smoking, and other confounding factors were collected by questionnaire. The relation between inhaled steroid dose and duration and BMD was assessed by linear regression analysis, accounting for potential confounders including weight, exercise, and oral steroid use. RESULTS: The 47 patients taking an inhaled steroid had a mean current dose of 620 micrograms/day (range 100-3000 micrograms), a mean duration of use of 7.8 years, and had had a mean of 0.85 courses of prednisolone in the past. There was no significant difference in mean BMD values between those who were and those who were not on inhaled steroids in men or women. However, on multivariate analysis, cumulative inhaled steroid dose was associated with a reduction in posterior-anterior (P-A) and lateral lumbar spine bone mineral density in women, equivalent to a 0.11 standard deviation reduction in bone density per 1000 micrograms/day inhaled steroid per year after adjustment for potential confounding factors (95% CI for P-A spine 0.01 to 0.22; for lateral spine 0.02 to 0.21). Previous oral steroid use was not an important confounding factor in these patients. Inhaled steroid use was not related to BMD at the wrist or hip in women or at any skeletal site in men. Women taking an inhaled steroid had lower levels of serum osteocalcin than those not taking them, although this was not dose related. Inhaled steroid use was not associated with differences in other markers of bone metabolism in men or women or with the presence of vertebral fractures. CONCLUSIONS: Although an effect of confounding factors cannot be excluded entirely in a cross sectional study, our findings are in keeping with an effect of inhaled steroid therapy in reducing bone density in the spine in women and provide an estimate of the magnitude of this effect.


     

骨质疏松分子生物学研究的昨天与今天

骨质疏松的发病过程受遗传和环境的共同影响,与基因、受体、细胞因子密切相关。本文综述了近年来骨质疏松研究领域的热点话题,梳理了骨质疏松主要候选基因钙磷代谢调节激素及其受体基因、性激素及其受体基因、细胞因子及其受体基因、I型胶原蛋白基因在基础研究和临床研究中的应用。为骨质疏松早期预防、早期治疗及抗骨质疏松药物研发提供分子生物学参考。     

Prolactin effect on the permeability of human benign hyperplastic prostate to testosterone

While it has been known for over 30 years that prolactin (Prl) synergizes with androgen in the support and stimulation of prostatic growth and metabolism, the evidence that this is accomplished through increasing access of the steroid to the cellular machinery of the gland has arisen only since about 1970. There is widespread uncertainty as to how the Prl effect takes place: by 1) increasing the free steroid concentration in the blood; 2) facilitating the uptake of protein-bound androgen; 3) increasing, by metabolism or receptor-binding, the concentration gradient that can support passive diffusion of the steroid across the plasma membrane; or 4) modification of the fluidity of the membrane itself to increase the solubility of the steroid in the lipoprotein and, thus, the ease of penetration of the cell. The present study attempted to learn if Prl is an effective stimulus of androgen uptake when the first three options are not operative. Using an equilibrium exchange procedure to track the uptake of [17 alpha-3H]-testosterone ([17 alpha-3H]-T) into minced benign hyperplastic human prostate tissue and the irreversible metabolism of the entering steroid to [17 alpha-3H]-dihydrotestosterone [17 alpha-3H]-DHT, it was found that the rate of production of the 5 alpha-reduced metabolite, during a 1-hr incubation in vitro, was directly proportional to the concentration of ovine Prl over the dose range of 0-160 ng/ml. The clinical significance of Prl mediation of steroid uptake is discussed, and suggestions are made as to how the Prl might alter the permeability of the plasma membrane.