Low plasma DHEA-S increases mortality risk among male hemodialysis patients

Objective

The incidence of chronic kidney disease (CKD) is on the rise. CKD patients are at high risk of cardiovascular (CVD) and all-cause mortality. CKD patients have several endocrine disorders, including low levels of dehydroepiandrosterone sulfate (DHEA-S). In the general population, low levels of DHEA-S are associated with high CVD and all-cause mortality. The aim of this study was to analyze the prognostic value of plasma DHEA-S on the survival of CKD patients on hemodialysis.

Method

This was a single-center prospective cohort study on two hundred CKD patients on hemodialysis, which assessed the prognostic value of plasma DHEA-S on their survival.

Result

We found that plasma DHEA-S levels were negatively associated with age, and positively associated with dialysis duration and plasma creatinine, albumin, and phosphate levels in hemodialysis men. Elderly patients with co-morbidities (i.e. diabetes mellitus, congestive heart failure, and chronic obstructive pulmonary disease), poorer fluid control which was evaluated by higher cardiothoracic ratio, and low plasma creatinine and albumin levels seemed to have poor prognosis in hemodialysis men. Furthermore, low plasma DHEA-S levels were significantly associated with CVD-related [hazard ratio (HR) = 3.877; P = 0.021], non-CVD-related (HR = 3.522; P = 0.016), and all-cause mortality (HR = 3.667; P = 0.001) in hemodialysis men. But low plasma DHEA-S levels were not significantly associated with CVD-related, non-CVD-related, and all-cause mortality in hemodialysis women. Multivariate Cox regression analysis suggested that low plasma DHEA-S levels are significantly and independently associated with all-cause mortality in hemodialysis men (HR = 2.933; P = 0.033).

Conclusion

The study suggested that low plasma DHEA-S was independently and significantly associated with all-cause mortality in CKD hemodialysis men.     

硫酸沙丁胺醇丙卡特罗治疗小儿支气管哮喘的临床对照研究

目的评价高选择行β2受体激动剂硫酸沙丁胺醇治疗小儿急性轻中度支气管哮喘是否差于丙卡特罗。方法93例诊断为小儿轻中度急性支气管哮喘患儿,随机分为硫酸沙丁胺醇组(实验组)42例,丙卡特罗组(对照组)51例。分别记录患儿用药前和用药后第3,7,10,14 d的肺功能。结果用药后实验组和对照肺功能指标(FEV1%,PEF%)与治疗前相比均有显著改善(P<0.05);实验组与对照组相比,患儿用药后第3,7,10,14 d肺功能指标FEV1%(P=0.36,0.72,0.52,0.63)和PEP%(P=0.50,0.59,0.62,0.83)差别无统计学意义。结论硫酸沙丁胺醇治疗小儿急性轻中度支气管哮喘在改善肺功能方面并不差于丙卡特罗。     

重度支气管哮喘硫酸镁治疗疗效分析

目的探讨重度支气管哮喘应用硫酸镁治疗疗效与安全性。方法将2009年11月～2011年4月于我院诊治的支气管哮喘重度患者81例分为两组。对照组39例均给予吸氧、平喘等常规治疗;观察组42例在对照组治疗外另给予硫酸镁治疗。结果观察组42例患者显效34例,有效7例,无效1例,总有效率97.62%,显著高于对照组(χ2=12.85,P<0.01)。两组患者均无不良反应。结论对重度支气管哮喘患者在常规治疗外静脉滴注硫酸镁治疗,疗效显著。     

载三联抗结核药硫酸钙/氨基酸聚合物人工骨体内缓释实验研究

目的:观察载异烟肼、利福平、吡嗪酰胺三联抗结核药硫酸钙/氨基酸聚合物人工骨在大鼠体内的缓释效果.方法:取6～7周龄SD大鼠80只,随机分为实验组与对照组,实验组载三联抗结核药人工骨植入大鼠骶脊肌内,40只;对照组植入空白未载药人工骨于大鼠骶脊肌内,40只;术后1d、3d、1周、2周、4周、6周、8周、12周处死大鼠,每次处死实验组、对照组大鼠各5只,应用高效液相色谱法检测大鼠植入人工骨局部周边组织及血液中三种药物浓度,2周及6周时HE染色观察大鼠肝、肾病理组织学变化.结果:植入载三联抗痨药人工骨局部周边1cm肌肉组织中,术后1d、3d、1周、2周、4周、6周、8周、12周时,高效液相色谱法检测异烟肼为4.09 ±0.56μg/ml、2.45 ±1.33μg/ml、2.12±1.56μg/ml、1.58 ±4.12μg/ml、2.09 ±2.35μg/ml、2.31 ±1.44μg/ml、4.26±2.17 μg/ml、3.79 ±0.49 μg/ml;利福平为4.02±1.14 μg/ml、1.90±0.11 μg/ml、1.88±0.90μg/ml、0.79±1.08 μg/ml、0.86±0.44μ g/ml、0.89±0.98μg/ml、3.92± 1.09μ g/ml、3.57±0.22μg/ml;吡嗪酰胺为460.87±1.41 μg/ml、440.91±1.69 μg/ml、430.21 ±0.86μg/ml、340.73± 1.45μg/ml 、320.85±2.0μg/ml、270.61±1.0μg/ml、230.38±0.48μg/ml;12周时植骨块局部组织,周边1cm肌肉组织异烟肼、利福平、吡嗪酰胺能达到10倍最低抑菌浓度,静脉血三种药物平均浓度为2.79μg/ml、2.02μg/ml、4.38 μg/ml低于植骨块局部周边浓度;肝、肾组织组织病理学检查未见损伤.结论:载三联抗结核药硫酸钙/氨基酸聚合物人工骨体内释放平稳,可实现体内局部用药缓释;其可直接植入体内,对肝、肾组织无明显药物损伤.     

Local insulin therapy affects fracture healing in a rat model

A significant number of lower extremity fractures result in mal‐union necessitating effective treatments to restore ambulation. Prior research in diabetic animal fracture models demonstrated improved healing following local insulin application to the fracture site and indicated that local insulin therapy can aid bone regeneration, at least within an insulin‐dependent diabetic animal model. This study tested whether local insulin therapy could accelerate femur fracture repair in normal, non‐diabetic rats. High (20 units) and low (10 units) doses of insulin were delivered in a calcium sulfate carrier which provided sustained release of the exogenous insulin for 7 days after fracture. Histomorphometry, radiographic scoring, and torsional mechanical testing were used to measure fracture healing. The fracture calluses from rats treated with high‐dose insulin had significantly more cartilage than untreated rats after 7 and 14 days of healing. After 4 weeks of healing, femurs from rats treated with low‐dose insulin had significantly higher radiographic scores and mechanical strength (p < 0.05), compared to the no treatment control groups. The results of this study suggest that locally delivered insulin is a potential therapeutic agent for treating bone fractures. Further studies are necessary, such as large animal proof of concepts, prior to the clinical use of insulin for bone fracture treatment. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 776–782, 2013     

Effect of chondroitinase ABC on adhesion and behavior of synovial membrane‐derived mesenchymal stem cells in rabbit partial‐thickness chondral defects

Transplanted cells may have difficulty attaching to the surface of partial‐thickness chondral lesions because of the anti‐adhesive properties of the proteoglycan rich matrix. Therefore, the current study attempts to evaluate the effect of chondroitinase ABC (chABC) on the adhesion and behavior of transplanted synovial membrane‐derived mesenchymal stem cells (SDSCs) in rabbit partial‐thickness chondral defects. In ex vivo adhesion experiments, chABC treatment (0.1 U/ml) was increased in SDSC attachment to the cartilage explants, and significantly diminished by pretreatment with neutralizing antibody against fibronectin. In the in vivo experiments, 1 day and 4 weeks after the chABC treatment (0.1 and 1 U/ml), the immunoreactivity (IR) against CS‐56 (intact chondroitin sulfate antibody) was markedly decreased; however, the IR of 2B6 (stub of the chondroitin 4‐sulfate chain), 3B3 (stub of the chondroitin 6‐sulfate chain), and fibronectin was increased. At 12 weeks, this IR returned to normal except in the high‐dose chABC‐treated group (1 U/ml). Furthermore, the attachment of SDSCs to the chondral defects after chABC treatment was increased at 7 days compared with that in the chondral defects pretreated with saline. However, the tissue repaired by SDSCs was negatively stained for type II collagen at 12 weeks. In conclusion, these results showed that the exposure to fibronectin by chABC treatment enhances the attachment of SDSCs to partial‐thickness chondral defects. However, the tissue regenerated by SDSCs showed lack of hyaline cartilage regeneration. Thus, to understand the fate of transplanted MSCs in cartilage defect is very important for successful cell therapies. © 2013 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 31:1293–1301, 2013     

Low Plasma Dehydroepiandrosterone Sulfate Level and its Relationship to Adiponectin in Hemodialysis Patients

The aim of the present study was to assess the relationship between plasma DHEA-S and adiponectin concentrations in hemodialyses patients (HD). Plasma adiponectin, DHEA-S, cholesterol, and albumin levels were estimated in 94 HD and 46 healthy subjects (HS). In HD, a significantly lower plasma DHEA-S concentration (2.5±0.2 vs. 4.7±0.4 μmol/L respectively; p?=?0.002) but significantly higher plasma adiponectin level (15.0±0.7 vs. 8.7±0.8 μg/mL respectively; p?=?0.004) than in HS were found. Only in uremic patients was a significant negative correlation found between plasma adiponectin and DHEA-S concentrations (tau?=?–0.210; p?=?0.001). Decreased plasma DHEA-S level is associated with increased adiponectinemia in uremic patients.     

Critical role of microvasculature basal lamina in ischemic brain injury

Cerebral vascular system can be divided into two categories: the macrovessels and microvessels. The microvessels consist of arterioles, capillaries and venules. There are three basic components in the microvasculature: endothelial cells, basal lamina and end-feet of astrocytes. The basal lamina is situated between the endothelial cells and the end-feet of astrocytes, and connects these two layers together. Damage to the basal lamina causes the dismantlement of microvascular wall structures, which in turn results in increase of microvascular permeability, hemorrhagic transformation, brain edema and compromise of the microcirculation. The present article reviews microvascular changes during ischemic brain injury, with emphasis on basal lamina damage.     

Bottom-Up and Top-Down Approaches to Explore Sodium Dodecyl Sulfate and Soluplus on the Crystallization Inhibition and Dissolution of Felodipine Extrudates

The objectives of this study were to explore sodium dodecyl sulfate (SDS) and Soluplus on the crystallization inhibition and dissolution of felodipine (FLDP) extrudates by bottom-up and top-down approaches. FLDP extrudates with Soluplus and SDS were prepared by hot melt extrusion, and characterized by polarized light microscopy, differential scanning calorimetry, and fourier transform infrared spectroscopy. Results indicated that Soluplus inhibited FLDP crystallization, and the whole amorphous solid dispersions (ASDs) were binary FLDP-Soluplus (1:3) and ternary FLDP-Soluplus-SDS (1:2:0.15～0.3 and 1:3:0.2～0.4) extrudates. Internal SDS (5%-10%) decreased glass transition temperatures of FLDP-Soluplus-SDS ternary ASDs without presenting molecular interactions with FLDP or Soluplus. The enhanced dissolution rate of binary or ternary Soluplus-rich ASDs in the nonsink condition of 0.05% SDS was achieved. Bottom-up approach indicated that Soluplus was a much stronger crystal inhibitor to the supersaturated FLDP in solutions than SDS. Top-down approach demonstrated that SDS enhanced the dissolution of Soluplus-rich ASDs via wettability and complexation with Soluplus to accelerate the medium uptake and erosion kinetics of extrudates, but induced FLDP recrystallization and resulted in incomplete dissolution of FLDP-rich extrudates. In conclusion, top-down approach is a promising strategy to explore the mechanisms of ASDs' dissolution, and small amount of SDS enhances the dissolution rate of polymer-rich ASDs in the nonsink condition.