Role of protein kinase A in regulating steroid sulfate uptake for estrogen production in human placental choriocarcinoma cells

The purpose of this study is to assess the role of the protein kinase A (PKA) in regulating uptake of dehydroepiandrosterone sulfate (DHEAS), an estrogen precursor, by syncytiotrophoblasts. Forskolin, a PKA activator, significantly increased [³H]DHEAS uptake and the mRNA expression levels of organic anion transporter (OAT) 4 and CYP19A1 in choriocarcinoma JEG-3 cells, while other steroid sulfate transporters present in the placenta showed no change in expression level. KT5720, a PKA inhibitor, attenuated these effects of forskolin. Accordingly, the PKA pathway appears to play an important role in estrogen synthesis by cooperatively regulating OAT4 and steroidogenic enzymes in syncytiotrophoblasts.     

Factors controlling insulin secretion in vitro

Summary The development of techniques for maintaining pancreatic isletsin vitro has made it feasible to study the direct effect of various agents and metabolic changes on -cell function. Glucose has to be metabolized within the -cell to provide the signal for insulin secretion, and the importance of the Krebs' cycle is suggested by experimental results. Glucose also stimulates insulin synthesis, but independently from insulin secretion. Growth hormone and placental lactogen enhance both processes, possibly by facilitating the metabolic breakdown of glucose. The role of catecholamines and glucagon in the regulation of insulin secretion has been defined during the past few years.Original material included in this review resulted from work supported by Grant MT-1202, Medical Research Council of Canada, and by funds of the Hospital for Sick Children.     

速效抗晕胶囊质量标准研究

目的 确定速效抗晕胶囊的质量检测标准.方法 采用薄层色谱法定性鉴别干姜提取物,用高效液相色谱法测定硫酸右旋苯丙胺和茶苯海明含量.结果 薄层色谱法鉴别专属性强;高效液相色谱法中,硫酸右旋苯丙胺在244～366μg/ml范围内浓度与吸收度呈良好线性关系(r=0.9999),平均回收率为99.54%,RSD为0.81%;茶苯...     

伤椎固定结合硫酸钙椎体成形与单纯伤椎固定治疗胸腰椎爆裂骨折的对比研究

目的 对比伤椎固定结合硫酸钙椎体成形术与单纯伤椎固定治疗胸腰椎爆裂骨折的临床疗效. 方法 2005年1月- 2008年10月对61例胸腰椎爆裂骨折患者分别采用伤椎固定结合硫酸钙椎体成形(A组)与单纯伤椎固定(B组)进行治疗.A组32例,其中男22例,女10例;年龄21～ 65岁,平均36.8岁.术后随访13 ～27个月...     

椎弓根钉固定硫酸钙人工骨椎体成形术治疗胸腰椎骨折

目的探讨椎弓根钉复位内固定结合注射用硫酸钙人工骨椎体成形术治疗胸腰椎骨折的经验。方法2005年10月—2007年6月对13例胸腰椎骨折患者应用后路短节段椎弓根钉复位内固定后,在C形臂X线透视下用注射型硫酸钙人工骨(CSC)经伤椎椎弓根行椎体成形术。所有患者于术前、术后行X线和CT检查,术后随访8~16个月,平均13个月。结果13例患者手术均获成功,无神经根损伤加重或出现新的神经压迫症状,术后12周左右人工骨基本吸收,无伤椎塌陷加重,无内固定失败病例。结论后路短节段椎弓根内固定结合注射用硫酸钙椎体成形术治疗胸腰椎爆裂骨折安全性高,能减少内固定失败及椎体高度丢失等并发症。     

Glucosamine sulfate effect on the degenerated patellar cartilage: preliminary findings by pharmacokinetic magnetic resonance modeling

Normal and degenerated cartilages have different magnetic resonance (MR) capillary permeability (K^trans) and interstitial interchangeable volume (v_e). Our hypothesis was that glucosamine sulfate treatment modifies these neovascularity abnormalities in osteoarthritis. Sixteen patients with patella degeneration, randomly distributed into glucosamine or control groups, underwent two 1.5-Tesla dynamic contrast-enhanced MR imaging studies (treatment initiation and after 6 months). The pain visual analog scale (VAS) and American Knee Society (AKS) score were used. A two-compartment pharmacokinetic model was used. Percentages of variations (postreatment-pretreatment/pretreatment) were compared (t-test for independent data). In the glucosamine group, pain and functional outcomes statistically improved (VAS: 7.3 ± 1.1 to 3.6 ± 1.3, p < 0.001; AKS: 18.6 ± 6.9 to 42.9 ± 2.7, p < 0.01). Glucosamine significantly increased K^trans at 6 months (−54.4 ± 21.2% vs 126.7 ± 56.9%, p < 0.001, control vs glucosamine). In conclusion, glucosamine sulfate decreases pain while improving functional outcome in patients with cartilage degeneration. Glucosamine sulfate increases K^trans, allowing its proposal as a surrogate imaging biomarker after 6 months of treatment.     

Keratan sulfate exacerbates experimental autoimmune encephalomyelitis

Proteoglycans (PGs) are the components of extracellular matrices in the central nervous system (CNS). Keratan sulfate (KS) is a glycosaminoglycan that is included in the KSPG that acts as an inhibitory factor in nerve regeneration after CNS injury. To investigate the role of KS in immune diseases, we induced experimental autoimmune encephalomyelitis (EAE) in mice that were deficient in the N‐acetylglucosamine (GlcNAc)‐6‐O‐sulfotransferase 1 (GlcNAc6ST1) gene (KS‐KO). KS‐KO mice developed less severe EAE and showed repressed recall response in the induction phase. Furthermore, GlcNAc6ST1 might have roles in the passage of the pathogenic lymphocytes through the blood–brain barrier via adhesion molecules. Thus, modulation of KS may become a treatment for neuroimmunological diseases. © 2015 Wiley Periodicals, Inc.     

胶原蛋白硫酸肝素支架移植入猪脑后对其神经元凋亡的影响

本实验研究胶原蛋白硫酸肝素支架移植入猪脑后对其神经元凋亡的影响,测定体内试验中该支架和 猪脑组织的生物相容性。实验组通过微创手术将胶原蛋白硫酸肝素支架移植入猪的脑内。对照组行假手术。分别于术后1天、3天、7天、14天或者30天手术处死动物,取组织标本行组织学分析（包括免疫组织化学法检测Bax 和Bcl-2）。HE染色发现移植后随即出现轻度组织反应。通过末端脱氧核糖核苷酸转移酶介导的缺口末端标记分析法于术后第1、3、7、14天在两组动物脑组织中都发现小量凋亡细胞;但是Bax 和Bcl-2呈低表达。在术后3天和7天,实验组和对照组间有显著差异,但是在术后30天两组间差异不明显。该支架和猪的脑组织具有组织相容性,能作为生物学底物安全地用于中枢神经系统组织工程。     

Increased heparanase level and procoagulant activity in orthopedic surgery patients receiving prophylactic dose of enoxaparin

Background

Orthopedic hip and knee surgeries are followed by a hypercoagulable state. Heparanase is implicated in inflammation, coagulation activation and angiogenesis. Recently, heparanase was shown to directly interact with tissue factor (TF) and to enhance the generation of factor Xa (Nadir et al., Haematologica, 2010). In addition, an assay assessing heparanase procoagulant activity has been lately developed (Nadir et al., Thromb Res, 2011). In the present study heparanase level and procoagulant activity in patients undergoing orthopedic surgery were assessed.

Methods

The study group included 50 orthopedic patients. 31 patients underwent hip surgery and 19 had knee operation. 15 individuals suffered from traumatic hip fractures and 35 had osteoarthrosis of hip or knee joints. All patients received prophylactic dose of enoxaparin starting 6-8 hours post operation and lasting for 5 weeks. Plasma samples were drawn preoperatively and at 1 hour, 1 week and 1 month post operation. Samples were tested for heparanase levels by ELISA and TF/heparanase complex activity, TF activity, heparanase procoagulant activity, factor Xa and thrombin levels using chromogenic substrates.

Results

Heparanase levels were significantly higher 1 hour and 1 week post operatively compared to preoperative levels (p < 0.05, p < 0.005, respectively). The most dramatic changes were observed in heparanase procoagulant activity reaching a 2 fold increase 1 week postoperatively and 1.7 fold increase 1 month after surgery (p < 0.0001, p < 0.0001, respectively). Levels of factor Xa and thrombin did not significantly change.

Conclusions

Heparanase is involved in coagulation activation of orthopedic surgery patients. Heparanase procoagulant activity is highest 1 week postoperatively and remains high 1 month after operation. Considering extending prophylactic anticoagulant therapy or evaluating heparanase procoagulant activity may potentially prevent late thrombotic events.