Cortical bone mineralization differences between hip-fractured females and controls. A microradiographic study

The strength of bone depends on both bone quantity and bone quality. One determinant of bone quality is the degree of mineralization of bone tissue (DMB). To assess the role for DMB in osteoporotic hip fractures, we compared the degree of mineralization in femoral neck cortex from 23 women with hip fractures (age, 65–96 years) and 14 female controls (age, 75–103 years) using quantitative microradiography calibrated with an aluminum step wedge.Variables were DMB in osteons (oDMB_Almean) and interstitial tissue (exDMB_Almean). Wilcoxon signed-rank tests were used to compare oDMB_Almean to exDMB_Almean in each group, and Mann–Whitney tests to compare oDMB_Almean and exDMB_Almean between hip-fracture patients and controls.DMB was significantly lower in the osteons than in the interstitial tissue in both groups (hip-fracture group, P = 0.000; control group, P = 0.001). DMB values in osteons and interstitial tissue were significantly greater in the hip-fracture patients than in the controls (P = 0.007 and P = 0.005, respectively).These cross-sectional data suggest that bone fragility may be related to a higher degree of tissue mineralization.     

An augmented aging process in brain white matter in HIV

Objective

HIV infection and aging are both associated with neurodegeneration. However, whether the aging process alone or other factors associated with advanced age account for the progression of neurodegeneration in the aging HIV‐positive (HIV+) population remains unclear. Methods: HIV+ (n = 70) and HIV‐negative (HIV?, n = 34) participants underwent diffusion tensor imaging (DTI) and metrics of microstructural properties were extracted from regions of interest (ROIs). A support vector regression model was trained on two independent datasets of healthy adults across the adult life‐span (n = 765, Cam‐CAN = 588; UiO = 177) to predict participant age from DTI metrics, and applied to the HIV dataset. Predicted brain age gap (BAG) was computed as the difference between predicted age and chronological age, and statistically compared between HIV groups. Regressions assessed the relationship between BAG and HIV severity/medical comorbidities. Finally, correlation analyses tested for associations between BAG and cognitive performance. Results: BAG was significantly higher in the HIV+ group than the HIV? group F (1, 103) = 12.408, p = .001). HIV RNA viral load was significantly associated with BAG, particularly in older HIV+ individuals (R² = 0.29, F(7, 70) = 2.66, p = .021). Further, BAG was negatively correlated with domain‐level cognitive function (learning: r = ?0.26, p = .008; memory: r = ?0.21, p = .034). Conclusions: HIV infection is associated with augmented white matter aging, and greater brain aging is associated with worse cognitive performance in multiple domains.

     

激素性股骨头坏死大鼠C-反应蛋白水平及藻酸双酯钠干预后的骨重建效应

目的:观察激素性股骨头坏死发生时C-反应蛋白水平的变化及藻酸双酯钠的干预作用。方法:实验于2006-03/11在吉林大学基础医学院病理教研室实验室完成。①50只健康Wistar大鼠随机分成5组,正常对照组、激素模型组、藻酸双酯钠组、阿仑膦酸钠 乐力组、藻酸双酯钠 阿仑膦酸钠 乐力组,每组各10只。②给药:除正常组外,所有动物按24.5mg/kg予醋酸泼尼松龙臀肌注射,1次/周。藻酸双酯钠组予藻酸双酯钠50mg/d灌服。阿仑膦酸钠组予阿仑膦酸钠2.5mg/d和乐力50mg/d灌服。藻酸双酯钠 阿仑膦酸钠 乐力组予藻酸双酯钠50mg/d、阿仑膦酸钠2.5mg/d和乐力50mg/d灌服。所有动物间断强迫立位4h/d,青霉素钠5万u/周肌注预防感染。于实验第2,3,4,5,6周末,每组选取动物2只,抽取2mL血液用免疫比浊法检测C-反应蛋白,取股骨头进行组织形态学观察。结果:①各组C-反应蛋白水平的变化:实验开始第2周,除正常对照组外,各组C-反应蛋白水平明显增高,与正常对照组比较均差异显著。第3周开始激素模型组与阿仑膦酸钠 乐力组逐渐增高,波动在15～20mg/L之间,与其他各组差异显著;藻酸双酯钠组和藻酸双酯钠 阿仑膦酸钠 乐力组逐渐下降至正常。②各组大鼠股骨头组织形态学观察结果:正常对照组:骨小梁结构清晰、粗大、排列规则,脂肪细胞少见,偶见空骨陷窝,髓腔内红细胞丰富。激素模型组:第4周骨小梁明显稀疏、变细,甚至断裂,结构模糊,髓腔内脂肪细胞增多、肥大,红细胞数量减少,空骨陷窝数量逐渐增多,第6周更显著。藻酸双酯钠组和阿仑膦酸钠 乐力组介于正常对照组和激素模型组之间。藻酸双酯钠 阿仑膦酸钠 乐力组接近于正常对照组。结论:C-反应蛋白在激素性股骨头坏死中起着重要作用,它可以作为激素性股骨头坏死早期预测的指标,藻酸双酯钠对C-反应蛋白水平有干预作用。     

肥大细胞、巨噬细胞及转化生长因子在IgA肾病患者肾组织中的浸润及意义

目的:观察肥大细胞、巨噬细胞、转化生长因子β1在IgA肾病患者肾组织中的浸润表达,并分析其意义。方法:①收集2004-06/2006-02青岛大学医学院附属医院肾内科收治的26例IgA肾病住院患者的肾活检标本,均经肾活检确诊肾小球系膜区存在以IgA为主的免疫复合物,并经临床及实验室检查排除紫癜性肾炎、狼疮性肾炎等继发性IgA肾病,临床资料及病理资料完整,患者全部签署肾穿刺知情同意书。另取5例配型不合的移植肾或肾穿刺后病理结果正常的肾组织(捐献者均签署捐献协议)作为正常对照组。②两组标本均行常规组织化学染色及特染,采用免疫组织化学技术检测肥大细胞、巨噬细胞在肾组织中的浸润及转化生长因子β1的表达,肥大细胞与巨噬细胞阳性呈黄褐色,转化生长因子β1阳性呈深黄色。③IgA肾病活动性指标包括每系膜区系膜细胞增生数、间质炎性细胞浸润细胞性新月体占肾小球面积的百分比3项。慢性化指标包括纤维性新月体占肾小球面积、局灶性节段性硬化占肾小球面积、肾小管萎缩占肾小管间质面积、间质纤维化程度占肾小管间质面积4项。④单盲法分析肥大细胞、巨噬细胞及转化生长因子β1的相关性及其与IgA肾病活动性指标、慢性化指标、血肌酐、尿蛋白之间的关系。结果:①肥大细胞、巨噬细胞的浸润及转化生长因子β1的表达:正常肾组织中偶见或无肥大细胞、巨噬细胞和转化生长因子β1的表达,而患肾中肥大细胞、巨噬细胞的浸润数量和转化生长因子β1的表达均明显增强(t=3.82～7.27,P<0.01)。②肥大细胞、巨噬细胞、转化生长因子β1与临床指标的相关性:相应部位肥大细胞、巨噬细胞的浸润数量及转化生长因子β1的表达呈显著正相关(r=0.51～0.91,P均<0.01)。肥大细胞数量与慢性化指标、血肌酐呈显著正相关(r=0.87,0.69,P均<0.01),与活动性指标和尿蛋白定量无明显相关性(r=0.30,0.21,P均>0.05);巨噬细胞数量和转化生长因子β1与活动性指标、慢性化指标、血肌酐、尿蛋白定量均呈显著正相关(r=0.39～0.90,P均<0.01;r=0.34～0.68,P<0.01或0.05)结论:①肥大细胞可能是IgA肾病肾间质纤维化的重要参与者,其数量增加可能预示着IgA肾病的慢性化和预后不良。②巨噬细胞可能是IgA肾病发生发展过程的全程参与者,它的浸润可能是肥大细胞在肾间质中浸润的前提条件之一。③转化生长因子β1不仅是贯穿始终的重要的致纤维化因子,而且可能是巨噬细胞和肥大细胞的重要趋化因子,并能促进它们的增殖、活化、发挥生物学作用。     

复方大承气汤保留灌肠治疗食管/贲门癌术后胃瘫

目的:食管/贲门癌术后发生的胃瘫综合征,通常持续时间较长,严重影响了患者术后机体的功能恢复。观察复方大承气汤保留灌肠对治疗食管/贲门癌术后胃瘫的可行性及其临床价值。方法:选择2004-09/2006-04于南京中医药大学附属医院胸心外科行食管/贲门癌手术且术后出现胃瘫的患者共11例,男6例,女5例,平均(62.3±10.8)岁。复方大承气汤组方药物由大黄后下10g,芒硝冲5g,枳实10g,厚朴20g,桃仁10,赤芍10g,炒莱菔子30g组成。盐酸甲氧氯普胺注射液(胃复安)由上海禾丰制药有限公司生产(批准文号:国药准字H31021522,生产批号为:5A08006)。电脑将患者随机分为实验组和对照组。实验组6例,男女各半,平均年龄(60.1±10.8)岁。对照组5例,男3例,女2例,平均年龄(68.6±5.1)岁。两组患者年龄及性别构成比具有可比性,无统计学差异(χ2性别=0.1103,P=0.7398;χ2年龄=3.0359,P=0.0814,P均>0.05)。食管癌5例,其中上段癌1例,中段癌2例,下段癌2例;贲门癌6例。纳入标准:①已行食管/贲门癌手术的患者。②符合1994年3月第3届国际内镜及胃肠病学术研究会制定胃瘫的诊断标准。③已签署知情同意书者。④一般体质情况尚可。⑤未应用影响平滑肌收缩的药物,如654-2、阿托品等。排除标准:①不能耐受灌肠者。②不合作者。③患有糖尿病、结缔组织病或甲状腺功能减退者。④合并心、脑、肾及其他严重疾病。两均进行基础治疗。实验组用复方大承气汤100mL保留灌肠,2次/d;对照组用盐酸甲氧氯普胺注射液10mg肌注,2次/d。两组其他治疗措施相同。治疗前及治疗结束后检测患者血清胃泌素,记录肠鸣音的次数,评价患者治疗前后临床症状改善的程度及临床疗效。结果:11例患者均进入结果分析。①两组治疗前血清胃泌素、临床症状、肠鸣音次数无统计学差异(P>0.05)。②两组治疗后临床症状评分与治疗前相比,差异显著(Z=-10.5,P<0.05)。③实验组治疗后肠鸣音次数与治疗前比较,差异显著(Z=10.5,P<0.05)。④两组临床疗效比较,差异显著(实验组:痊愈:83.3%,好转:16.7%,无效:0;对照组:痊愈:20%,好转:40%,无效:40%,Z=4.49,P<0.05)。结论:复方大承气汤保留灌肠可治疗食管/贲门癌术后胃瘫,能有效地提高临床疗效,治疗效果优于胃复安。     

人心脏微血管内皮细胞血管细胞黏附分子1及核因子κB在缺氧再复氧损伤后的表达与黄芪多糖的干预

目的:前期对整体动物的研究发现,黄芪多糖具有抗心肌缺血再灌注损伤的作用。此次主要定量测定人心脏微血管内皮细胞血管细胞黏附分子1及核因子κB mRNA的表达,探讨黄芪多糖治疗心肌缺血再灌注损伤的机制。方法:实验于2007-01/03在北京中医药大学东直门医院中医内科学教育部重点实验室完成。①实验材料:原代人心脏微血管内皮细胞(ScienCell公司:从人心肌组织中分离后立即冻存)。②实验过程及分组:以体外缺氧再复氧复制缺血再灌注损伤模型。将细胞分为4组:正常对照组、再灌注损伤组、黄芪多糖组(分为100,50,25mg/L3个亚组,在缺氧/复氧的同时加入相应浓度的药物)及吡咯烷二硫代氨基甲酸组(50μmol/L,于缺氧前加入,预处理30min后吸弃)。③实验评估:应用实时荧光定量聚合酶链反应检测血管细胞黏附分子1和核因子κB mRNA表达的变化。结果:①人心脏微血管内皮细胞的培养:复苏16h细胞散在分布,胞体肥厚、透明,呈菱形或多角形;36h形成多个小岛样克隆;48～72h细胞约85%融合,呈铺路石样生长。②实时荧光定量聚合酶链反应:扩增动力曲线平滑,每条曲线均有较明显的指数扩增期;扩增回归曲线的回归系数均>0.990,起始模版浓度与Ct值之间呈良好的线性关系。与正常对照组比,缺氧再复氧可明显增加人心脏微血管内皮细胞中血管细胞黏附分子1和核因子κB mRNA的表达(P<0.05,P<0.01)。黄芪多糖各剂量组均明显抑制缺氧再复氧后人心脏微血管内皮细胞上血管细胞黏附分子1mRNA的表达(P<0.01);核因子κB mRNA的表达在黄芪多糖50mg/L剂量组中降低(P<0.05)。结论:黄芪多糖能够抑制再灌注损伤的人心脏微血管内皮细胞中血管细胞黏附分子1及核因子κB mRNA的表达,从而减轻内皮细胞的炎症反应及黏附作用,改善心肌缺血再灌注损伤。     

Definitions for warning signs and signs of severe dengue according to the WHO 2009 classification: Systematic review of literature

Since warning signs and signs of severe dengue are defined differently between studies, we conducted a systematic review on how researchers defined these signs. We conducted an electronic search in Scopus to identify relevant articles, using key words including dengue, “warning signs,” “severe dengue,” and “classification.” A total of 491 articles were identified through this search strategy and were subsequently screened by 2 independent reviewers for definitions of any of the warning or severe signs in the 2009 WHO dengue classification. We included all original articles published in English after 2009, classifying dengue by the 2009 WHO classification or providing the additional definition or criterion of warning signs and severity (besides the information of 2009 WHO). Analysis of the extracted data from 44 articles showed wide variations among definitions and cutoff values used by physicians to classify patients diagnosed with dengue infection. The establishment of clear definitions for warning signs and severity is essential to prevent unnecessary hospitalization and harmonizing the interpretation and comparability of epidemiological studies dedicated to dengue infection.     

Modulation of adherence, invasion, and tumor necrosis factor alpha secretion during the early stages of infection by Streptococcus pneumoniae ClpL

Heat shock proteins (HSPs) play a pivotal role as chaperones in the folding of native and denatured proteins and can help pathogens penetrate host defenses. However, the underlying mechanism(s) of modulation of virulence by HSPs has not been fully determined. In this study, the role of the chaperone ClpL in the pathogenicity of Streptococcus pneumoniae was assessed. A clpL mutant adhered to and invaded nasopharyngeal or lung cells much more efficiently than the wild type adhered to and invaded these cells in vitro, as well as in vivo, although it produced the same amount of capsular polysaccharide. However, the level of secretion of tumor necrosis factor alpha (TNF-alpha) from macrophages infected with the clpL mutant was significantly lower than the level of secretion elicited by the wild type during the early stages of infection. Interestingly, treatment of the human lung epithelial carcinoma A549 and murine macrophage RAW 264.7 cell lines with cytochalasin D, an inhibitor of actin polymerization, increased adherence of the mutant to the host cells. In contrast, cytochalasin D treatment of RAW 264.7 cells decreased TNF-alpha secretion after infection with either the wild type or the mutant. However, pretreatment of cell lines with the actin polymerization activator jasplakinolide reversed these phenotypes. These findings indicate, for the first time, that the ClpL chaperone represses adherence of S. pneumoniae to host cells and induces secretion of TNF-alpha via a mechanism dependent upon actin polymerization during the initial infection stage.