Osteoporosis in children and young adults

Osteoporosis is a major public health problem with serious long-term complications. In children, the definition of osteoporosis is not only based on densitometric criteria but also takes into account vertebral and long bone fragility fractures. Several factors, such as long-term high-dose steroids, chronic inflammation, malnutrition, immobility, lack of sex steroids, and medication can reduce bone density and increase the risk for fragility fractures when left untreated. Also, genetic conditions can predispose to primary bone fragility disorders, with osteogenesis imperfecta being the most common. Furthermore, since the growing skeleton is at an increased rate of bone remodeling, the ability to heal long bone fractures and reshape vertebral fractures differentiates children from adults. The scope of this chapter is to review the risk factors of osteoporosis and fragility fractures and describe the commonest causes of primary and secondary osteoporosis and their management in children and young adults.     

Eosinophilic gastroenteritis with severe protein-losing enteropathy: Successful treatment with budesonide

We report the clinical, laboratory, endoscopic and histopathological findings in a 40-year-old woman with watery diarrhoea and hypoproteinaemia. Elevated alpha(1)-antitrypsin clearance confirmed massive protein-losing enteropathy. Gastroscopic and colonoscopic biopsies showed abundant infiltration of the small bowel wall with eosinophils in proximal duodenum and terminal ileum, respectively. These findings established the diagnosis of eosinophilic gastroenteritis. Both the inflammatory alterations and the severe intestinal protein loss were successfully treated with budesonide, a topically active corticosteroid preparation with controlled small bowel release. The case report illustrates that remission of protein-losing enteropathy secondary to eosinophilic gastroenteritis can be achieved with budesonide, thus supporting its use for this uncommon disease characterised by inflammatory intestinal lesions.     

siRNA沉默MIF基因对糖皮质激素抑制脂质炎症介质释放的影响及其机制

 目的： 研究小干扰RNA（siRNA）阻断巨噬细胞移动抑制因子（macrophage migration-inhibitory factor,MIF）基因表达对糖皮质激素抑制脂质炎症介质释放的影响及其细胞内机制。方法：体外培养小鼠巨噬细胞系RAW2647,采用免疫荧光法观测siRNA转染效率,RT-PCR检测MIF mRNA的表达,Western blotting检测MIF蛋白的表达;RAW2647细胞转染MIF siRNA后观察地塞米松（Dex）抗炎作用的变化,用ELISA检测细胞上清中前列腺素E2(PGE2)和白三烯B4(LTB4)的含量,Western blotting检测胞浆膜联蛋白Annexin 1和下游胞浆磷酸酯酶A2α（cPLA2α）的蛋白表达变化。结果：与阴性对照相比,MIF siRNA能有效阻断细胞内源性MIF蛋白的表达,增强RAW2647细胞对Dex作用的敏感性;明显增强Dex抑制PGE2和LTB4产生的效应,增加胞浆蛋白Annexin 1的表达,抑制cPLA2α的磷酸化。结论：MIF siRNA能增强糖皮质激素抑制脂质炎症介质PGE2和LTB4的释放,且可能是通过影响Annexin 1-cPLA2α信号通路实现的。阻断内源性MIF蛋白的表达可显著增强RAW2647细胞对糖皮质激素抗炎作用的敏感性。     

Restraint stress and ethanol consumption in two mouse strains

Background: This study examined the interaction between restraint stress and ethanol drinking in mice that consume low and high amounts of ethanol. Methods: Two strains of mice (129SVEV and C57BL/6J) underwent 1 hour of restraint stress twice per day for 4 days in the presence of a CRF‐1 receptor antagonist, a glucocorticoid receptor antagonist or vehicle. Ethanol preference and consumption were assessed using a two bottle choice design. In another study, mice were implanted with pellets containing corticosterone; ethanol preference and consumption were assessed using a two bottle choice design. Results: Restraint stress significantly increased ethanol preference and consumption in 129SVEV mice but not in C57BL/6J mice. Then 129SVEV mice underwent the identical stress procedure; however, mice received either the CRF‐1 receptor antagonist, R121919 (15 or 20 mg/kg, ip) or vehicle 30 minutes prior to stress. R121919 did not block the stress‐induced change in ethanol preference despite causing a significant blunting in the HPA axis. Negative results were also obtained using the CRF‐1 receptor antagonist, Antalarmin (20 mg/kg, ip). In another study, 129SVEV mice were administered either the glucocorticoid receptor antagonist Mifepristone (25, 50 or 100 μg/kg, ip) or vehicle under the same procedure. Mifepristone did not alter ethanol preference. Moreover, the three receptor antagonist did not alter nonstress ethanol consumption either. In the last study, both mouse strains underwent active or sham adrenalectomy, then pellets containing corticosterone or placebo were implanted and preference for ethanol versus water was tested. Corticosterone administration decreased ethanol consumption in a strain‐dependent manner. Conclusion: These data show the restraint model for stress can modestly increase ethanol consumption in 129SVEV mice but not in C57BL/6J mice. Pharmacologic manipulation of CRF and corticosterone did not blunt baseline or stress‐induced change in ethanol preference nor did administration of corticosterone mimic the effects of restraint stress on ethanol consumption. These findings suggest the mechanism responsible for increasing ethanol consumption in this model is independent of the HPA axis and extra‐hypothalamic CRF.     

雷公藤多甙联合糖皮质激素治疗肾病综合征效果观察

目的：研究雷公藤多甙联合糖皮质激素对肾病综合征患者的疗效及安全性。方法将40例肾病综合征患者随机分为研究组和对照组,每组20例,均给予常规治疗。研究组在此基础上,予以雷公藤多甙片联合泼尼松治疗;对照组给予泼尼松治疗。治疗前与治疗后3、6、12个月,观查患者血压、尿常规、24 h尿蛋白、血肌酐、尿素氮、血浆白蛋白、肝功能、血常规、不良反应等情况,并判断疗效。结果治疗3个月后,与对照组比较,研究组Scr、BUN、24 h尿蛋白下降,血浆白蛋白上升,差异有统计学意义(P<0．05)。研究组治疗总有效率为85．00%,显著高于对照组,差异有统计学意义(χ2=4．285,P=0．038)。随访12个月,研究组复发率为11．80%,明显低于对照组,差异有统计学意义(χ2=4．043,P=0．044)。研究组不良反应发生率为10．00%,显著低于对照组,差异有统计学意义(χ2=4．800,P=0．028)。结论雷公藤多甙联合糖皮质激素治疗具有改善肾病综合征患者临床症状,减少复发,副作用少的特点。     

Barriers in the management of glucocorticoid‐induced osteoporosis

Objective

To determine present practice for the management of glucocorticoid‐induced osteoporosis (GIOP) in veterans; to characterize provider knowledge, beliefs, and practice behaviors regarding management of GIOP; and to identify potential barriers and interventions in the management of GIOP.

Methods

To characterize current management of GIOP in an academic veterans administration medical center, we conducted a retrospective chart review of 100 patients who were prescribed a 90‐day supply of prednisone. To assess clinicians' knowledge of GIOP clinical guidelines and perceptions of GIOP management, primary care clinicians and subspecialists completed a questionnaire and participated in focus groups.

Results

Chart review revealed that only 32 of 100 patients receiving long‐term glucocorticoid treatment underwent bone mineral density testing, and only 32 patients were prescribed the recommended calcium supplements. Of the 23 providers who completed the questionnaire and participated in the focus groups, 4 correctly identified both the dose and duration of glucocorticoid use at which GIOP prevention measures should be instituted. Common GIOP management barriers cited by participants were lack of knowledge, having limited time during the clinic visit to address all problems, patient nonadherence, and system problems. The most commonly mentioned potential interventions were the use of computerized clinical reminders and patient education.

Conclusion

Clinicians frequently do not follow recommended guidelines for the management of GIOP. Improving the management of GIOP will likely require a fundamental redesigning of care processes for this disorder in order to overcome provider, patient‐related, and system barriers.     

氟美松对正常大鼠膈肌的影响

利用氟美松制备的大鼠类固醇肌病模型，研究了氟美松对大鼠膈肌的重量、收缩特性、肌纤维的横断面积、氧化酶活性、糖原和超微结构的影响。结果发现：（１）氟美松的使用可使大鼠膈肌明显萎缩，以Ⅱａ、Ⅱｂ型纤维萎缩为著；（２）在１００Ｈｚ电刺激下，膈肌的张力明显下降，膈肌耐疲劳的能力（１／２ＲＴ）显著提高；（３）膈肌中Ⅰ型、Ⅱｂ型纤维中ＡＴＰ酶、琥珀酸脱氢酶（ＳＤＨ）的活性均下降，膈肌中糖原含量增加。电镜观察发现氟美松可以导致膈肌线粒体增生、空泡样变性及部分肌丝局灶性破坏。氟美松导致的上述各种改变，可能直接或间接地影响膈肌物质能量代谢而导致其收缩性能的改变。     

糖皮质激素治疗对急性呼吸窘迫综合征患者预后的影响

目的：探讨早期应用糖皮质激素（GC）治疗对急性呼吸窘迫综合征（ARDS）患者预后的影响。方法回顾性分析成都军区总医院2008年1月至2011年12月收治的所有ARDS病例的临床资料,选择符合2012年柏林ARDS诊断标准的成人患者,根据是否采用过GC治疗将患者分为GC组与非GC组。GC组患者均在ARDS发生48 h内开始静脉使用低剂量GC（＜5 mg·kg-1·d-1,均换算为氢化可的松的剂量）治疗,激素种类为甲泼尼松龙、地塞米松,疗程为7～21 d;而非GC组为ARDS发生后未使用GC治疗。比较两组患者机械通气时间、重症加强治疗病房（ICU）住院时间、总住院时间、医疗费用和28 d生存率的差异。结果共纳入ARDS患者117例,其中GC组56例（占47.86%）,非GC组61例（占52.14%）。与非GC组比较,GC组机械通气时间明显缩短〔d：0（0,2.50）比2.00（0,2.50）,Z＝2.015,P＝0.044〕,28 d生存率明显升高〔71.43%（40/56）比50.82%（31/61）,χ2＝5.198,P＝0.023〕,ICU住院时间〔d：7.50（2.00,11.00）比4.00（1.00,9.00）,Z＝1.879, P＝0.060〕和总住院时间〔d：16.00（10.00,27.75）比15.00（7.00,28.00）,Z＝0.592,P＝0.552〕差异无统计学意义,但非GC组患者的医疗费用显著低于GC组〔万元：3.15（1.51,5.78）比4.39（1.66,10.88）,Z＝2.204,P＝0.028〕。结论早期使用GC治疗ADRS患者可改善预后,特别是28 d生存率。     

α7nAChR参与生理浓度糖皮质激素的抗炎作用*

 目的： 探讨α7烟碱型乙酰胆碱受体（α7nAChR）在生理浓度糖皮质激素（GCs）抗炎过程中的作用。方法: MTT法检测不同浓度氢化可的松对小胶质细胞BV-2活性的影响;在建立LPS刺激的BV-2细胞炎症模型基础上,实验分组如下：(1) 空白对照组;(2) LPS组;(3) GCs＋LPS组;(4) α7nAChR阻断剂甲基牛扁亭碱（MLA）＋GCs＋LPS组,ELISA法测定细胞上清中TNF-α和IL-1β的含量。结果: 2 000 和1 000 nmol/L 氢化可的松可分别使细胞存活率降低至(76.9±5.5)%和(90.8±7.3)%,表现出超生理剂量GCs的细胞损伤作用。LPS明显刺激BV-2细胞释放TNF-α和IL-1β,并呈现时间和剂量依赖性。生理浓度（500和250 nmol/L）的氢化可的松均可减少LPS诱导BV-2细胞释放TNF-α和IL-1β,10 nmol/L MLA预处理BV-2细胞能拮抗GCs抑制炎症因子释放的作用。结论: α7nAChR参与了生理浓度GCs的抗炎作用。