• 【DPP-4抑制剂linagliptin可以抵消正常和糖尿病小鼠大脑中的卒中:与格列美脲比较。】 复制标题 收藏 收藏
    DOI:10.2337/db12-0988 复制DOI
    作者列表:Darsalia V,Ortsäter H,Olverling A,Darlöf E,Wolbert P,Nyström T,Klein T,Sjöholm Å,Patrone C
    BACKGROUND & AIMS: :Type 2 diabetes is a strong risk factor for stroke. Linagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor in clinical use against type 2 diabetes. The aim of this study was to determine the potential antistroke efficacy of linagliptin in type 2 diabetic mice. To understand whether efficacy was mediated by glycemia regulation, a comparison with the sulfonylurea glimepiride was done. To determine whether linagliptin-mediated efficacy was dependent on a diabetic background, experiments in nondiabetic mice were performed. Type 2 diabetes was induced by feeding the mice a high-fat diet for 32 weeks. Mice were treated with linagliptin/glimepiride for 7 weeks. Stroke was induced at 4 weeks into the treatment by transient middle cerebral artery occlusion. Blood DPP-4 activity, glucagon-like peptide-1 (GLP-1) levels, glucose, body weight, and food intake were assessed throughout the experiments. Ischemic brain damage was measured by determining stroke volume and by stereologic quantifications of surviving neurons in the striatum/cortex. We show pronounced antistroke efficacy of linagliptin in type 2 diabetic and normal mice, whereas glimepiride proved efficacious against stroke in normal mice only. These results indicate a linagliptin-mediated neuroprotection that is glucose-independent and likely involves GLP-1. The findings may provide an impetus for the development of DPP-4 inhibitors for the prevention and treatment of stroke in diabetic patients.
    背景与目标: :2型糖尿病是中风的重要危险因素。 Linagliptin是临床上用于治疗2型糖尿病的二肽基肽酶4(DPP-4)抑制剂。这项研究的目的是确定利格列汀在2型糖尿病小鼠中的潜在抗中风功效。为了了解功效是否由血糖调节介导,与磺酰脲格列美脲进行了比较。为了确定利格列汀介导的功效是否取决于糖尿病背景,在非糖尿病小鼠中进行了实验。通过给小鼠喂高脂饮食32周来诱发2型糖尿病。用利格列汀/格列美脲治疗小鼠7周。在治疗的第4周,通过短暂性中脑动脉闭塞诱发中风。在整个实验过程中,评估了血液DPP-4活性,胰高血糖素样肽1(GLP-1)水平,葡萄糖,体重和食物摄入量。通过确定中风量和纹状体/皮层中存活的神经元的立体定量来测量缺血性脑损伤。我们在2型糖尿病和正常小鼠中显示了利格列汀的显着抗中风功效,而格列美脲仅在正常小鼠中被证明对中风有效。这些结果表明,由利格列汀介导的神经保护作用与葡萄糖无关,并且可能涉及GLP-1。这些发现可能为DPP-4抑制剂的开发提供动力,以预防和治疗糖尿病患者的中风。
  • 【与儿童和青少年使用第二代抗精神病药有关的代谢并发症的管理建议。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Ho J,Panagiotopoulos C,McCrindle B,Grisaru S,Pringsheim T,Canadian Alliance for Monitoring Effectiveness and Safety of Antipsychotics in Children (CAMESA) guideline group.
    BACKGROUND & AIMS: BACKGROUND:Second-generation antipsychotics are commonly associated with metabolic complications. These medications are being used more frequently for the treatment of mental health disorders in children, which has stimulated the need for creating formal guidelines on monitoring their safety and effectiveness. Previous guidelines have been developed for monitoring metabolic and neurological complications. To assist practitioners who perform these monitoring procedures, a complementary set of treatment recommendations have been created for situations in which abnormal measurements or results are encountered. OBJECTIVE:To create evidence-based recommendations to assist in managing metabolic complications in children being treated with second-generation antipsychotics. METHODS:A systematic review of the literature on metabolic complications of second-generation antipsychotic medications in children was conducted. Members of the consensus group evaluated the information gathered from the systematic review of the literature and used a nominal group process to reach a consensus on treatment recommendations. Wherever possible, references were made to existing guidelines on the evaluation and treatment of metabolic abnormalities in children. RESULTS:Evidence-based recommendations are presented to assist in managing metabolic complications including weight gain; increased waist circumference; elevation in prolactin, cholesterol, triglyceride and glucose levels; abnormal liver function tests and abnormal thyroid studies. CONCLUSION:The use of second-generation antipsychotics requires proper monitoring procedures. The present treatment guideline provides guidance to clinicians on the clinical management of metabolic complications if they occur.
    背景与目标: 背景:第二代抗精神病药通常与代谢并发症相关。这些药物被更频繁地用于治疗儿童的精神疾病,这刺激了建立监测其安全性和有效性的正式指南的需求。已经开发了用于监测代谢和神经系统并发症的先前指南。为了帮助执行这些监视程序的从业人员,针对遇到异常测量或结果的情况创建了一套补充的治疗建议。
    目的:建立基于证据的建议,以帮助管理接受第二代抗精神病药治疗的儿童的代谢并发症。
    方法:对儿童第二代抗精神病药物的代谢并发症的文献进行了系统的综述。共识小组成员评估了从文献系统回顾中收集的信息,并使用名义上的小组程序就治疗建议达成共识。尽可能参考有关儿童代谢异常评估和治疗的现有指南。
    结果:提出了循证医学建议,以帮助控制包括体重增加在内的代谢并发症。腰围增加;催乳激素,胆固醇,甘油三酸酯和葡萄糖水平升高;肝功能检查异常和甲状腺检查异常。
    结论:使用第二代抗精神病药需要适当的监测程序。本治疗指南为临床医生就代谢并发症(如果发生)的临床管理提供了指导。
  • 【可以使用囊肿体积来分层with c骨移植重建囊肿缺损后发生并发症的风险吗?】 复制标题 收藏 收藏
    DOI:10.1016/j.jcms.2017.05.010 复制DOI
    作者列表:Safi AF,Grandoch A,Dreiseidler T,Nickenig HJ,Zöller J,Kreppel M
    BACKGROUND & AIMS: INTRODUCTION:The role of the volume of radicular and dentigerous cysts on clinical symptoms is unclear and potentially may predict development of pre- and postoperative complications, especially after cystectomies with large bony defects. Therefore the aim of this study was to assess pre- and postoperative symptoms associated to the volume of jaw cysts. MATERIAL AND METHODS:Retrospective chart review of 111 patients with follicular or dentigerous cysts from 2008-2012. Anterior iliac crest grafts were used to fill defects after cystectomy. χ2-test was performed to analyze associations between two qualitative variables. Binary logistic regression analysis was used as multivariate analysis. P-values p < 0.05 were considered as significant. Volume measurement was performed in a semiautomatic segmentation method with the software "ITK-Snap". RESULTS:Postoperative hypaesthesia correlated significantly with histology (p = 0.025) and localization (p = 0.006). Volume was associated significantly with preoperative hypaesthesia (p = 0.052), postoperative hypaesthesia (p < 0.001), wound healing complications (p < 0.001) and length of wound healing complications (p = 0.001). Multivariate analysis identified volume as independent risk factor for postoperative hypaesthesia (p = 0.015). CONCLUSIONS:Volume analysis appears to be a method that allows risk stratification after surgery of jaw cysts. Therefore we recommend a precise treatment planning with the means of volume analysis to improve therapy outcome of patients with jaw cysts.
    背景与目标: 引言:根管性和牙状囊肿的体积在临床症状上的作用尚不清楚,可能潜在地预测术前和术后并发症的发生,特别是在具有大骨缺损的膀胱切除术之后。因此,本研究的目的是评估与颌骨囊肿体积相关的术前和术后症状。
    材料与方法:回顾性分析2008年至2012年间111例滤泡性或齿状囊肿患者的病历。膀胱切除术后,使用前terior骨移植物填补缺损。进行χ2检验以分析两个定性变量之间的关联。二元逻辑回归分析用作多元分析。 P值p <0.05被认为是显着的。使用软件“ ITK-Snap”以半自动分割方法进行体积测量。
    结果:术后感觉低下与组织学(p = 0.025)和局限性(p = 0.006)显着相关。容量与术前感觉不足(p = 0.052),术后感觉不足(p <0.001),伤口愈合并发症(p <0.001)和伤口愈合并发症的时间(p = 0.001)显着相关。多变量分析确定了体积为术后感觉不足的独立危险因素(p = 0.015)。
    结论:体积分析似乎是一种允许对颌骨囊肿进行手术后进行危险分层的方法。因此,我们建议采用体积分析的方法制定精确的治疗计划,以改善颌骨囊肿患者的治疗效果。
  • 【运动心电图和th体层成像在糖尿病患者无症状冠状动脉疾病检测中的评估。】 复制标题 收藏 收藏
    DOI:10.1136/hrt.63.1.7 复制DOI
    作者列表:Koistinen MJ,Huikuri HV,Pirttiaho H,Linnaluoto MK,Takkunen JT
    BACKGROUND & AIMS: :Thallium tomographic imaging and exercise electrocardiography were performed on 136 diabetic patients without symptoms of heart disease. Thirty three patients had post-exercise thallium defects and 19 had ST 1 mm greater than or equal to segment depression during exercise electrocardiography. Both tests were positive in 13 patients. Coronary angiography was subsequently performed on 33 patients with either scintigraphic and/or electrocardiographic evidence of myocardial ischaemia. Angiographically significant coronary artery disease (greater than or equal to 50% narrowing of the coronary artery lumen) was detected in 13 patients. Six patients had minimal coronary artery stenosis (less than 50%), and 14 had normal coronary arteries. Six patients refused cardiac catheterisation. In 14 out of 27 patients with post-exercise thallium defects coronary angiography did not show any coronary artery stenoses (positive predictive accuracy 48%). Exercise electrocardiography showed only one false positive result (positive predictive accuracy 94%) but failed to detect coronary artery disease in three patients with a positive scintigraphic result. The accuracy of a positive exercise electrocardiographic test seems to be better than that of a positive thallium tomographic scan for detecting asymptomatic coronary artery disease in diabetic patients. The high number of false positive thallium defects may be the result of technical features inherent in thallium tomography and/or the possible disease of the small intramyocardial arteries in diabetic patients.
    背景与目标: :对136例无心脏病症状的糖尿病患者进行了to体层断层显像和运动心电图检查。在运动心电图检查中,有33例运动后al缺陷患者,其中19例ST大于或等于节段压低1 mm。两项测试均阳性13例。随后对33例有心肌缺血的闪烁显像和/或心电图证据的患者进行了冠状动脉造影。在13例患者中发现了具有血管造影意义的冠状动脉疾病(大于或等于50%的冠状动脉腔狭窄)。 6例患者的冠状动脉狭窄程度最小(少于50%),而14例具有正常的冠状动脉。六名患者拒绝心脏导管插入术。在运动后th缺陷的27例患者中,有14例冠状动脉造影未显示任何冠状动脉狭窄(阳性预测准确性为48%)。运动心电图检查仅显示一个假阳性结果(阳性预测准确率94%),但在3个闪烁显像结果阳性的患者中未能检测到冠心病。积极的运动心电图检查的准确性似乎比阳性的X线体层摄影检查的准确性要好,以检测糖尿病患者的无症状冠状动脉疾病。大量假阳性positive缺陷可能是may断层扫描固有的技术特征和/或糖尿病患者心肌小动脉可能的疾病的结果。
  • 【在一项1型糖尿病患者的随机试验中测试的分散注射策略的结果是,门冬胰岛素的吸收得到增强。】 复制标题 收藏 收藏
    DOI:10.2337/dc12-1319 复制DOI
    作者列表:Mader JK,Birngruber T,Korsatko S,Deller S,Köhler G,Boysen S,Augustin T,Mautner SI,Sinner F,Pieber TR,AP@home Consortium.
    BACKGROUND & AIMS: OBJECTIVE:We investigated the impact of two different injection strategies on the pharmacokinetics and pharmacodynamics of insulin aspart in vivo in an open-label, two-period crossover study and verified changes in the surface-to-volume ratio ex vivo. RESEARCH DESIGN AND METHODS:Before the clinical trial, insulin aspart was injected ex vivo into explanted human abdominal skin flaps. The surface-to-volume ratio of the subcutaneous insulin depot was assessed by microfocus computed tomography that compared 1 bolus of 18 IU with 9 dispersed boluses of 2 IU. These two injection strategies were then tested in vivo, in 12 C-peptide-negative type 1 diabetic patients in a euglycemic glucose clamp (glucose target 5.5 ± 1.1 mmol/L) for 8 h after the first insulin administration. RESULTS:The ex vivo experiment showed a 1.8-fold higher mean surface-to-volume ratio for the dispersed injection strategy. The maximum glucose infusion rates (GIR) were similar for the two strategies (10 ± 4 vs. 9 ± 4; P = 0.5); however, times to reach maximum GIR and 50% and 10% of the maximum GIR were significantly reduced by using the 9 × 2 IU strategy (68 ± 33 vs. 127 ± 93 min; P = 0.01; 38 ± 9 vs. 49 ± 16 min; P < 0.01; 23 ± 6 vs. 30 ± 10 min; P < 0.05). For 9 × 2 IU, the area under the GIR curve was greater during the first 60 min (219 ± 89 vs. 137 ± 75; P < 0.01) and halved until maximum GIR (242 ± 183 vs. 501 ± 396; P < 0.01); however, it was similar across the whole study period (1,361 ± 469 vs. 1,565 ± 527; P = 0.08). CONCLUSIONS:A dispersed insulin injection strategy enhanced the effect of a fast-acting insulin analog. The increased surface-to-volume ratio of the subcutaneous insulin depot can facilitate insulin absorption into the vascular system.
    背景与目标: 目的:我们在开放标签,两期交叉研究中研究了两种不同的注射策略对体内门冬胰岛素的药代动力学和药效学的影响,并验证了离体表面积与体积比的变化。
    研究设计和方法:在临床试验之前,将门冬胰岛素离体注射到植入的人腹部皮肤皮瓣中。皮下胰岛素贮存库的表面体积比是通过微焦点计算机断层扫描技术评估的,该技术比较了1个大剂量的18 IU与9个分散的大剂量的2 IU。然后在首次胰岛素给药后的正常血糖葡萄糖钳位(葡萄糖靶标5.5±1.1 mmol / L)中,在12名C肽阴性1型糖尿病患者体内测试了这两种注射策略。
    结果:离体实验显示,分散注射策略的平均表面体积比高1.8倍。两种策略的最大葡萄糖输注速率(GIR)相似(10±4 vs. 9±4; P = 0.5);但是,通过使用9×2 IU策略,达到最大GIR以及达到最大GIR的时间分别减少了50%和10%(68±33 vs. 127±93 min; P = 0.01; 38±9 vs. 49± 16分钟; P <0.01; 23±6 vs. 30±10分钟; P <0.05)。对于9×2 IU,在最初的60分钟内GIR曲线下的面积更大(219±89对137±75; P <0.01),并且减半直到最大GIR(242±183对501±396对; P < 0.01);但是,在整个研究期间,情况相似(1,361±469对1,565±527; P = 0.08)。
    结论:分散胰岛素注射策略增强了速效胰岛素类似物的作用。皮下胰岛素贮存库增加的表面积与体积之比可以促进胰岛素吸收进入血管系统。
  • 【CD11c在慢性淋巴细胞性白血病中的表达被重新审视,与并发症和生存有关。】 复制标题 收藏 收藏
    DOI:10.1111/ijlh.12695 复制DOI
    作者列表:Umit EG,Baysal M,Durmus Y,Demir AM
    BACKGROUND & AIMS: INTRODUCTION:Chronic lymphocytic leukemia (CLL) is a disorder of mature but dysfunctional monoclonal B cells. Microenvironment, antigenic stimulation and genetical mutations are demonstrated in etiopathogenesis. We aimed to evaluate the expression of CD11c in patients with CLL and its possible clinical significance. METHODS:Data of 259 patients with CLL between 2010 and 2016 in Trakya University Faculty of Medicine, including age at diagnosis, sex, whole blood count, stage, percentage of CLL cells in bone marrow, line of treatments, development of Richter's transformation and secondary tumors, autoimmune complications, IgG level, prognostic cytogenetic analysis, and length of survival were recorded from files. RESULTS:151 patients were male (58.3%) and 108 were male (41.7%). Mean age was 70 (21-92) years. CD11c was observed to be positive (>%20) in 103 patients (39.8%). Development of Richter's transformation, secondary tumors and ITP was significantly frequent in patients with CD11c positivity (P values .000, .003, .000 respectively). Also, IgG levels were significantly lower in this group (P = .000). Hemoglobin level, RAI stage and bone marrow CLL infiltration percentage were statistically related with CD11c (P values .036, .037, .000 respectively). Finally, CD11c was statistically related (in positive group 70 months, negative group 79 months, P = .001). CONCLUSION:CD11c, expressed not only in Hairy cell leukemia but also in dendritic cells, macrophages and monocytes is a differentiation marker for inflammation. Prolonged inflammation in the microenvironment of CLL cells may cause a susceptibility to autoimmune disorders and secondary tumors in CLL, in this way, an increase in mortality.
    背景与目标: 简介:慢性淋巴细胞性白血病(CLL)是一种成熟但功能失调的单克隆B细胞疾病。微环境,抗原刺激和遗传突变已在病因学中得到证实。我们旨在评估CD11c在CLL患者中的表达及其可能的临床意义。
    方法:特拉基亚大学医学院2010年至2016年间259例CLL患者的数据,包括诊断年龄,性别,全血细胞计数,分期,骨髓CLL细胞百分比,治疗方法,里氏转化的发展和继发性从文件中记录肿瘤,自身免疫并发症,IgG水平,预后细胞遗传学分析和生存期。
    结果:男性151例,占58.3%;男性108例,占41.7%。平均年龄为70(21-92)岁。在103例患者中(39.8%)观察到CD11c阳性(>)。 CD11c阳性患者中Richter转化,继发性肿瘤和ITP的发生非常频繁(分别为P值.000,.003,.000)。此外,该组的IgG水平显着降低(P = .000)。血红蛋白水平,RAI分期和骨髓CLL浸润百分比与CD11c具有统计学相关性(P值分别为.036,.037和.000)。最后,CD11c具有统计学相关性(阳性组70个月,阴性组79个月,P = .001)。
    结论:CD11c不仅在毛细胞白血病中表达,而且在树突状细胞,巨噬细胞和单核细胞中表达,是炎症的分化标志。 CLL细胞微环境中的长时间炎症可能会导致自身免疫性疾病和CLL中继发性肿瘤的易感性,从而增加死亡率。
  • 【过氧化物酶体增殖物激活受体γ及其配体对链脲佐菌素诱导的糖尿病模型中血-视网膜屏障的影响。】 复制标题 收藏 收藏
    DOI:10.1167/iovs.05-1432 复制DOI
    作者列表:Muranaka K,Yanagi Y,Tamaki Y,Usui T,Kubota N,Iriyama A,Terauchi Y,Kadowaki T,Araie M
    BACKGROUND & AIMS: PURPOSE:To clarify whether endogenous peroxisome proliferator-activated receptor gamma (PPARgamma) and its ligand, rosiglitazone, affect retinal leukostasis and the associated vascular leakage using an experimental diabetic model. METHODS:Diabetes was induced in heterozygous PPARgamma+/- mice and Brown Norway rats with an intraperitoneal streptozotocin (STZ) injection. Retinal leukostasis and leakage, quantified by concanavalin A (Con A) lectin perfusion labeling combined with a fluorophotometric dextran leakage assay, were investigated at 120 days in diabetic PPARgamma+/- and wild-type mice and at 21 days in diabetic rats receiving rosiglitazone or the vehicle. The retinal protein expression levels of vascular endothelial growth factor (VEGF), tumor necrosis factor (TNF)-alpha, and the intercellular adhesion molecule (ICAM)-1 were investigated by means of the ELISA assay. RESULTS:In the diabetic PPARgamma+/- mice, retinal leukostasis and leakage were greater than in the diabetic wild-type mice. In addition retinal leukostasis and leakage were suppressed by treatment with rosiglitazone in experimental diabetic rats. ELISA analysis revealed that the upregulated ICAM-1 expression in the diabetic rat retina was reduced by rosiglitazone treatment. CONCLUSIONS:An endogenous pathway involving PPARgamma provides protection against retinal leukostasis and retinal leakage in diabetes and treatment with PPARgamma specific ligands inhibits retinal leukostasis and retinal leakage in diabetic rats.
    背景与目标: 目的:使用实验性糖尿病模型来阐明内源性过氧化物酶体增殖物激活受体γ(PPARgamma)及其配体罗格列酮是否会影响视网膜白细胞形成和相关的血管渗漏。
    方法:通过腹腔注射链脲佐菌素(STZ)在杂合性PPARγ/-小鼠和褐挪威大鼠中诱导糖尿病。通过伴刀豆球蛋白A(Con A)凝集素灌注标记结合荧光光度右旋糖酐泄漏测定定量研究视网膜白细胞的形成和渗漏,在糖尿病PPARγ/和野生型小鼠中在120天时以及在接受罗格列酮或糖尿病的糖尿病大鼠中在21天时进行了研究。车辆。 ELISA法检测了血管内皮生长因子(VEGF),肿瘤坏死因子(TNF)-α和细胞间黏附分子(ICAM)-1的视网膜蛋白表达水平。
    结果:糖尿病PPARγ/-小鼠的视网膜白细胞增多和渗漏大于糖尿病野生型小鼠。此外,在实验性糖尿病大鼠中,通过罗格列酮治疗可抑制视网膜白细胞形成和渗漏。 ELISA分析显示,罗格列酮治疗可降低糖尿病大鼠视网膜中ICAM-1的表达。
    结论:涉及PPARγ的内源性途径为糖尿病患者的视网膜白细胞增多和视网膜渗漏提供了保护,而PPARγ特定配体的治疗抑制了糖尿病大鼠的视网膜白细胞减少和视网膜渗漏。
  • 【姜黄素是姜黄(姜黄)的活性成分,可改善大鼠糖尿病性肾病。】 复制标题 收藏 收藏
    DOI:10.1111/j.1440-1681.2006.04468.x 复制DOI
    作者列表:Sharma S,Kulkarni SK,Chopra K
    BACKGROUND & AIMS: :Chronic hyperglycaemia in diabetes leads to the overproduction of free radicals and evidence is increasing that these contribute to the development of diabetic nephropathy. Among the spices, turmeric (Curcuma longa) is used as a flavouring and colouring agent in the indian diet every day and is known to possess anti-oxidant properties. The present study was designed to examine the effect of curcumin, a yellow pigment of turmeric, on renal function and oxidative stress in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced by a single intraperitoneal injection of STZ (65 mg/kg) in rats. Four weeks after STZ injection, rats were divided into four groups, namely control rats, diabetic rats and diabetic rats treated with curcumin (15 and 30 mg/kg, p.o.) for 2 weeks. Renal function was assessed by creatinine, blood urea nitrogen, creatinine and urea clearance and urine albumin excretion. Oxidative stress was measured by renal malonaldehyde, reduced glutathione and the anti-oxidant enzymes superoxide dismutase and catalase. Streptozotocin-injected rats showed significant increases in blood glucose, polyuria and a decrease in bodyweight compared with age-matched control rats. After 6 weeks, diabetic rats also exhibited renal dysfunction, as evidenced by reduced creatinine and urea clearance and proteinuria, along with a marked increase in oxidative stress, as determined by lipid peroxidation and activities of key anti-oxidant enzymes. Chronic treatment with curcumin significantly attenuated both renal dysfunction and oxidative stress in diabetic rats. These results provide confirmatory evidence of oxidative stress in diabetic nephropathy and point towards the possible anti-oxidative mechanism being responsible for the nephroprotective action of curcumin.
    背景与目标: :糖尿病中的慢性高血糖症导致自由基的过度产生,并且越来越多的证据表明这些自由基有助于糖尿病性肾病的发展。在香料中,姜黄(姜黄)每天在印度饮食中用作调味剂和着色剂,并且已知具有抗氧化特性。本研究旨在检查姜黄素(一种姜黄黄色素)对链脲佐菌素(STZ)诱导的糖尿病大鼠肾功能和氧化应激的影响。在大鼠中通过腹膜内单次注射STZ(65 mg / kg)诱发糖尿病。注射STZ后四周,将大鼠分为四组,即对照大鼠,糖尿病大鼠和经姜黄素(15和30 mg / kg,口服)治疗2周的糖尿病大鼠。通过肌酐,血液尿素氮,肌酐和尿素清除率以及尿白蛋白排泄评估肾功能。通过肾脏丙二醛,还原型谷胱甘肽和抗氧化酶超氧化物歧化酶和过氧化氢酶来测定氧化应激。与年龄相称的对照大鼠相比,注射链脲佐菌素的大鼠显示血糖,多尿明显增加,体重下降。 6周后,糖尿病大鼠还表现出肾功能不全,这由肌酐和尿素清除率降低和蛋白尿以及氧化应激显着增加所证实,氧化应激由脂质过氧化作用和关键抗氧化酶的活性决定。姜黄素的慢性治疗可显着减轻糖尿病大鼠的肾功能不全和氧化应激。这些结果提供了糖尿病性肾病中氧化应激的确证证据,并指出可能的抗氧化机制负责姜黄素的肾保护作用。
  • 【加拿大多胎妊娠的发生率和并发症:专家会议的程序。】 复制标题 收藏 收藏
    DOI:10.1016/s1472-6483(10)60681-5 复制DOI
    作者列表:
    BACKGROUND & AIMS: :This paper reports the proceedings of a consensus meeting on the incidence and complications of multiple gestation in Canada. In addition to background presentations about current and possible future practice in Canada, the expert panel also developed a set of consensus points. The need for infertility to be understood, and funded, as a healthcare problem was emphasized, along with recognition of the emotional impact of infertility. It was agreed that the goal of assisted reproduction treatment is the delivery of a single healthy infant and that even though many positive outcomes have resulted from twin or even triplet pregnancies, the potential risks associated with multiple pregnancy require that every effort be made to achieve this goal. The evidence shows that treatments other than IVF (such as superovulation and clomiphene citrate) contribute significantly to the incidence of multiple pregnancy. There is an urgent need for studies to understand better the usage and application of these other fertility technologies within Canada, as well as the non-financial barriers to treatment. The final consensus of the expert panel was that with adequate funding and good access to treatment, it will be possible to achieve the goal of reducing IVF-related multiple pregnancy rates in Canada by 50%.
    背景与目标: :本文报道了关于加拿大多胎妊娠的发生率和并发症的共识会议的会议记录。除了关于加拿大目前和将来可能的做法的背景介绍之外,专家小组还制定了一系列共识点。作为医疗保健问题,人们需要理解和资助不育症,并认识到不育症的情感影响。一致认为,辅助生殖治疗的目标是分娩一个健康的婴儿,即使双胞胎或什至三胞胎妊娠产生了许多积极的结果,但与多次妊娠相关的潜在风险仍需要尽一切努力来实现。目标。证据表明,除IVF以外的其他治疗方法(如超排卵和柠檬酸克罗米芬)对多胎妊娠的发生率有显着影响。迫切需要进行研究以更好地了解加拿大其他这些生育技术的使用和应用,以及治疗的非财务障碍。专家小组的最终共识是,只要有足够的资金和良好的治疗机会,就有可能实现将加拿大IVF相关的多胎妊娠率降低50%的目标。
  • 【髋臼周围骨盆切开术后的并发症和患者满意度。】 复制标题 收藏 收藏
    DOI:10.1007/s00264-007-0372-3 复制DOI
    作者列表:Biedermann R,Donnan L,Gabriel A,Wachter R,Krismer M,Behensky H
    BACKGROUND & AIMS: :Periacetabular osteotomy (PAO) is a well established method to treat hip dysplasia in the adult. There is, however, a lack of information on the subjective outcome of patients with complications after PAO. The purpose of this study was therefore to assess the influence of complications on the patients' post-operative wellbeing and function: 60 PAOs on 50 patients were investigated retrospectively after a mean follow-up of 7.4 years. The patients' self-reported assessment of health and function was evaluated by the Medical Outcomes Short Form-36 (SF-36) and the Western Ontario and McMaster Universities (WOMAC) questionnaires at last follow-up. Forty healthy persons served as a control group. Of the 60 interventions 13 had no complications. Minor complications occurred in 25 (41%) and in 22 (37%) at least one major complication occurred. SF-36 summary measure was 76.4 for PAO patients and 90.3 for the control group. Mean WOMAC score was 25.1. Patients with major complications had a similar subjective outcome as patients with minor or without complications, but persistent dysaesthesia due to lateral femoral cutaneous nerve dysfunction led to a worse subjective function. Lesions of the lateral femoral cutaneous nerve have much greater influence on patients' self-assessed functional outcome after PAO than previously reported and greater attention has to be given to this supposedly minor complication.
    背景与目标: 小前截骨术(PAO)是一种成熟的治疗成人髋关节发育不良的方法。但是,缺乏有关PAO术后并发症患者的主观结果的信息。因此,本研究的目的是评估并发症对患者术后健康和功能的影响:在平均随访7.4年后,对50例患者的60个PAO进行了回顾性研究。在最后一次随访中,通过医学成果简表36(SF-36)以及西安大略和麦克马斯特大学(WOMAC)的问卷对患者的健康和功能自我评估进行了评估。 40名健康人作为对照组。在60项干预措施中,有13项没有并发症。轻微并发症发生在25(41%)和22(37%)中,至少发生了一次重大并发症。 SF-36总结指标为PAO患者为76.4,对照组为90.3。 WOMAC平均得分为25.1。具有严重并发症的患者的主观结局与具有轻微并发症或无并发症的患者相似,但由于股外侧皮神经功能障碍导致的持续感觉迟钝导致较差的主观功能。股外侧皮神经病变对PAO后患者自我评估的功能结局的影响要比以前报道的要大得多,因此必须对这种所谓的轻微并发症给予更大的关注。
  • 【在糖尿病apoE缺乏症小鼠中,富含1,3-二酰基甘油的油可引起较少的动脉粥样硬化并降低血浆胆固醇。】 复制标题 收藏 收藏
    DOI:10.1016/j.atherosclerosis.2006.08.024 复制DOI
    作者列表:Fujii A,Allen TJ,Nestel PJ
    BACKGROUND & AIMS: OBJECTIVE:Recent studies have demonstrated that 1,3-diacylglycerol (1,3-DAG) has several metabolic advantages over triacylglycerol (TAG) in humans and in animal models despite both oils having a similar fatty acid composition. In our current study, we have examined the effects of long-term feeding of a 1,3-DAG-rich oil on the dyslipidemia and atherosclerosis in the experimental model of the diabetic apolipoprotein E (apoE)-deficient mouse that develops accelerated atherosclerosis. METHODS AND RESULTS:Diets containing 1,3-DAG-rich oil or TAG oil were administered to control non-diabetic apoE-dificient and diabetic apoE-deficient mice for 20 weeks. In diabetic apoE-deficient mice, 1,3-DAG reduced the extent of atherosclerotic lesions in the aortic arch and thoracic aorta by 37 and 44%, respectively, compared to TAG. Further, in diabetic apoE-deficient mice, plasma total cholesterol and triglyceride levels were significantly lower in the 1,3-DAG-fed group than in the TAG-fed group. This occurred partially through an apparent reduction in the size of triglyceride-rich lipoproteins but not apparently by reducing the number of lipoprotein particles. By contrast the control non-diabetic apoE-deficient mice showed no differential responses to the type of oil at least over 20 weeks. CONCLUSIONS:We have demonstrated that dietary 1,3-DAG-rich oil reduced atherosclerosis in diabetic apoE-deficient mice, and was associated with reduction in plasma cholesterol especially within larger triglyceride-rich lipoproteins.
    背景与目标: 目的:最近的研究表明,尽管两种油具有相似的脂肪酸组成,但在人和动物模型中,1,3-二酰基甘油(1,3-DAG)比三酰基甘油(TAG)具有若干代谢优势。在我们当前的研究中,我们在糖尿病性载脂蛋白E(apoE)缺陷型小鼠模型中,长期食用富含1,3-DAG的油对血脂异常和动脉粥样硬化的影响,这种小鼠会加速动脉粥样硬化。
    方法和结果:给予含1,3-DAG丰富的油脂或TAG油脂的饮食,以控制非糖尿病apoE缺乏和糖尿病apoE缺乏的小鼠20周。在糖尿病apoE缺陷型小鼠中,与TAG相比,1,3-DAG分别将主动脉弓和胸主动脉的动脉粥样硬化病变程度降低了37%和44%。此外,在糖尿病apoE缺陷型小鼠中,1,3-DAG喂养组的血浆总胆固醇和甘油三酯水平显着低于TAG喂养组。这部分是由于富含甘油三酸酯的脂蛋白大小的明显减少而发生的,而不是由于减少脂蛋白颗粒的数量而明显发生的。相比之下,对照非糖尿病apoE缺陷型小鼠至少在20周内未显示出对油脂类型的差异反应。
    结论:我们已经证明,富含饮食的1,3-DAG的油可以减少糖尿病apoE缺乏症小鼠的动脉粥样硬化,并且与血浆胆固醇的降低有关,尤其是在较大的富含甘油三酸酯的脂蛋白中。
  • 【肺移植后早期和晚期气道并发症:发生率和处理。】 复制标题 收藏 收藏
    DOI:10.1016/s0003-4975(97)83852-0 复制DOI
    作者列表:Kshettry VR,Kroshus TJ,Hertz MI,Hunter DW,Shumway SJ,Bolman RM 3rd
    BACKGROUND & AIMS: BACKGROUND:Airway anastomosis complications continue to be a source of morbidity for lung transplant recipients. METHODS:This study analyzes incidence, treatment, and follow-up of airway anastomotic complications occurring in 127 consecutive lung transplant airway anastomoses (77 single lung and 25 bilateral sequential lung). Complications were categorized as stenosis (11), granulation tissue (8), infection (7), bronchomalacia (5), or dehiscence (3). Follow-up after treatment ranged from 6 months to 4 years. RESULTS:Nineteen airway anastomosis complications (15.0%) occurred in 18 patients. Telescoping the airway anastomosis reduced the complication rate to 12 of 97 (12.4%), compared with 7 of 30 (23.3%) for omental wrapping, (p = 0.15). Complications developed in 13 of 77 single-lung airway anastomoses (16.9%) versus 6 of 50 bilateral sequential lung recipients (12.0%). Treatment consisted of stenting (9 airway anastomoses), bronchodilation (8), laser debridement (4), rigid bronchoscopic debridement (2), operative revision (2), and growth factor application (2). There was no difference in actuarial survival between patients with or without airway anastomosis complications (p = 1.0). CONCLUSIONS:Airway anastomosis complications can be successfully managed in the immediate or late postoperative period with good outcome up to 4 years after intervention.
    背景与目标: 背景:气管吻合并发症仍然是肺移植接受者发病的来源。
    方法:本研究分析了127例连续的肺移植气道吻合术(77例单肺和25例双侧序贯肺)发生的气道吻合并发症的发生率,治疗和随访情况。并发症分为狭窄(11),肉芽组织(8),感染(7),支气管软化(5)或裂开(3)。治疗后的随访时间为6个月至4年。
    结果:18例患者发生了19例气道吻合并发症(15.0%)。伸缩气道吻合术使并发症发生率降低至97例中的12例(12.4%),而网膜包裹术的并发症发生率为30例中的7例(23.3%)(p = 0.15)。 77例单肺气道吻合中有13例发生了并发症(占16.9%),而50例双侧连续肺接受者中有6例发生了并发症(占12.0%)。治疗包括支架置入术(9例气道吻合术),支气管扩张术(8),激光清创术(4),硬支气管镜清创术(2),手术翻修(2)和生长因子应用(2)。有或没有气道吻合并发症的患者之间的精算生存率无差异(p = 1.0)。
    结论:气道吻合并发症可在术后即刻或晚期成功治疗,干预后长达4年的效果良好。
  • 【微创冠状动脉旁路移植术中的吻合并发症。】 复制标题 收藏 收藏
    DOI:10.1016/s0003-4975(97)00416-5 复制DOI
    作者列表:Pagni S,Qaqish NK,Senior DG,Spence PA
    BACKGROUND & AIMS: BACKGROUND:Anterior wall myocardial revascularization through a left anterior minithoracotomy is an increasingly accepted procedure. Technical failure at the anastomotic site, promoting persistent or recurrent angina, is known to occur and may be underrecognized. This report summarizes the incidence of technical failure in an initial clinical experience and describes potential causes of early postoperative complications. METHODS:Between December 1995 and May 1996, 15 patients underwent left internal mammary artery-to-left anterior descending artery revascularization without extracorporeal circulation. The surgical indication was single-vessel coronary disease in all patients. We exposed the left anterior descending artery target site through a 10-cm left anterior fourth space thoracotomy. The fourth costal cartilage was resected and the left internal mammary artery was harvested under direct visualization. Two 4-0 polypropylene sutures snared in tourniquets proximal and distal to the anastomotic site were used to obtain a bloodless field and stabilization of the left anterior descending artery. RESULTS:All patients had procedures initially deemed successful based on disappearance of angina or postoperative transthoracic Doppler examination of the internal mammary artery 3 to 5 days postoperatively. However, 3 patients presented with recurrent angina at 2, 6, and 8 weeks. Angiography or direct visualization at operation demonstrated the technical complication (stenosis at the anastomotic site in 2 and snare injury in the native vessel in 1). Two patients required reoperation. CONCLUSIONS:Initial results with minimally invasive coronary bypass grafting have generated great enthusiasm worldwide, but there is no consensus on how the procedure should be performed. These results suggest that a nonstabilized anastomosis results in an unacceptable failure rate. Furthermore, sutures encircling the left anterior descending artery should not be used for vessel stabilization as injury of the artery may occur.
    背景与目标: 背景:通过左前小切口开胸术进行前壁心肌血运重建已成为越来越多的接受方法。众所周知,发生在吻合部位的技术衰竭会导致持续性或复发性心绞痛,并且这种认识可能未得到充分认识。该报告总结了最初的临床经验中技术失败的发生率,并描述了术后早期并发症的潜在原因。
    方法:1995年12月至1996年5月,有15例患者进行了左乳内动脉至左前降支血运重建,无体外循环。所有患者的手术适应症均为单支冠状动脉疾病。我们通过一个10厘米的左前第四间隙开胸术暴露了左前降支目标部位。切除第四肋软骨,并在直接观察下收集左乳内动脉。在吻合部位近端和远端的止血带中缠结的两条4-0聚丙烯缝合线用于获得无血流区域并稳定左前降支动脉。
    结果:所有患者均根据术后心绞痛的消失或术后3至5天经胸腔内多普勒检查确定最初的手术成功。但是,有3例患者在第2、6和8周出现了复发性心绞痛。术中的血管造影或直接可视化显示出技术并发症(在吻合口处狭窄2个,在天然血管中圈套器损伤1个)。两名患者需要再次手术。
    结论:微创冠状动脉旁路移植术的初步结果在全世界引起了极大的热情,但对于该手术的执行方法尚无共识。这些结果表明,不稳定的吻合术会导致不可接受的失败率。此外,环绕左前降支动脉的缝合线不应用于稳定血管,因为可能会发生动脉损伤。
  • 【在肥胖和II型糖尿病患者的骨骼肌中,PPAR-γ基因表达升高。】 复制标题 收藏 收藏
    DOI:10.2337/diab.46.7.1230 复制DOI
    作者列表:Park KS,Ciaraldi TP,Abrams-Carter L,Mudaliar S,Nikoulina SE,Henry RR
    BACKGROUND & AIMS: The peroxisome proliferator activated receptor PPAR-gamma has been identified as a nuclear receptor for thiazolidenediones, which are compounds with insulin-sensitizing properties in several tissues, including skeletal muscle. To determine whether this receptor is expressed and possibly involved in insulin action/resistance in skeletal muscle, PPAR-gamma mRNA abundance and its regulation by insulin were quantified in muscle tissue and cultures from lean and obese nondiabetic and type II diabetic subjects using competitive reverse transcription-polymerase chain reaction (RT-PCR). In muscle biopsy specimens, PPAR-gamma mRNA was elevated in obese nondiabetic and type II diabetic subjects (23.4 +/- 4.2 and 28.0 +/- 5.69 x 10(3) copies/microg total RNA, respectively; both P < 0.05) compared with lean nondiabetic control subjects (9.4 +/- 2.3 x 10(3) copies/microg total RNA). Significant positive correlations were present among skeletal muscle PPAR-gamma mRNA levels, BMI (r = 0.67, P < 0.01), and fasting insulin concentration (r = 0.76, P < 0.001). PPAR-gamma mRNA levels were also elevated in muscle cultures from type II diabetic subjects compared with lean nondiabetic control subjects (330.1 +/- 52.9 vs. 192.1 +/- 27.0 x 10(3) copies/microg total RNA, P < 0.05). Insulin stimulation of muscle tissue (by hyperinsulinemic-euglycemic clamp for 3-4 h) or muscle cultures (30 nmol/l for 120 min) stimulated PPAR-gamma mRNA expression up to fourfold (10.0 +/- 2.7 to 41.3 +/- 7.4 x 10(3) copies/microg total RNA, P < 0.05, and 174.9 +/- 56.9 to 268.2 +/- 78.6 x 10(3) copies/microg total RNA, P < 0.05, respectively). In summary, PPAR-gamma mRNA expression in human skeletal muscle is acutely regulated by insulin and is increased in both obese nondiabetic and type II diabetic subjects in direct relation to BMI and fasting insulinemia. We conclude that abnormalities of PPAR-gamma may be involved in skeletal muscle insulin resistance of obesity and type II diabetes.

    背景与目标: 过氧化物酶体增殖物激活受体PPAR-γ已被确定为噻唑烷二酮的核受体,噻唑烷二酮是在包括骨骼肌在内的多个组织中具有胰岛素敏感特性的化合物。为了确定该受体是否在骨骼肌中表达并且可能参与了胰岛素的作用/抗性,使用竞争性逆转录技术从瘦和肥胖的非糖尿病和II型糖尿病患者的肌肉组织和培养物中定量了PPAR-γmRNA的丰度及其受胰岛素的调节。 -聚合酶链反应(RT-PCR)。在肌肉活检标本中,肥胖的非糖尿病和II型糖尿病受试者的PPAR-γmRNA升高(分别为23.4 /-4.2和28.0 /-5.69 x 10(3)拷贝/微克总RNA;两者均P <0.05),与瘦肉相比非糖尿病对照受试者(9.4 /-2.3 x 10(3)拷贝/微克总RNA)。骨骼肌PPAR-γmRNA水平,BMI(r = 0.67,P <0.01)和空腹胰岛素浓度(r = 0.76,P <0.001)之间存在显着正相关。与瘦型非糖尿病对照受试者相比,II型糖尿病受试者的肌肉培养物中的PPAR-γmRNA水平也有所升高(330.1 /-52.9与192.1 /-27.0 x 10(3)拷贝/微克总RNA,P <0.05)。胰岛素刺激肌肉组织(通过高胰岛素-正常血糖钳夹3-4小时)或肌肉培养物(30 nmol / l持续120分钟)刺激的PPAR-γmRNA表达增加至四倍(10.0 /-2.7至41.3 /-7.4 x 10 (3)拷贝/微克总RNA,P <0.05和174.9 /-56.9至268.2 /-78.6 x 10(3)拷贝/微克总RNA,P <0.05)。总而言之,人骨骼肌中的PPAR-γmRNA表达受到胰岛素的急性调节,在肥胖的非糖尿病和II型糖尿病患者中,PPAR-γmRNA的表达均与BMI和空腹胰岛素血症直接相关。我们得出结论,肥胖和II型糖尿病的骨骼肌胰岛素抵抗可能与PPAR-γ异常有关。

  • 【术前使用糖皮质激素减少食管癌食管切除术后并发症的风险:荟萃分析】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Raimondi AM
    BACKGROUND & AIMS: OBJECTIVE:Preoperative glucocorticoid administration has been proposed to reduce postoperative morbidity. This is not frequently done before esophageal resection because of insufficient knowledge on its effectiveness. The purpose was to assess the effects of preoperative glucocorticoid administration in adults undergoing esophageal resection for esophageal carcinoma. METHODS:Studies were identified by searching the Cochrane Controlled Trials Register, Medline, Embase, Scielo and Cochrane Library, and by a manual search for relevant articles. In this systematic review, the last search for clinical trials was performed in December 2005. This review included randomized studies of patients with potentially resectable carcinomas of the esophagus that compared preoperative glucocorticoid administration with placebo. Data were collected by the reviewer, and quality of the trial was assessed using Jadad scoring. Odds ratio with 95% confidence intervals was used to assess the significance of the difference between treatment arms. RESULTS:Four randomized trials involving 169 patients were found. There were no differences in postoperative mortality, anastomotic leakage, hepatic and renal failure between the glucocorticoid and placebo groups. There were fewer postoperative respiratory complications (95% CI= 0.09-0.46), sepsis (95% CI= 0.10-0.81), and total postoperative complications (95% CI=0.06-0.23) with preoperative glucocorticoid administration. CONCLUSION:Prophylactic administration of glucocorticoids is associated with decreased postoperative complications.
    背景与目标: 目的:建议术前给予糖皮质激素可降低术后发病率。由于对食管切除术的有效性了解不足,因此在食管切除术前并不经常这样做。目的是评估术前糖皮质激素对食管癌行食管切除术的成年人的治疗效果。
    方法:通过检索Cochrane对照试验注册簿,Medline,Embase,Scielo和Cochrane图书馆,并通过手动搜索相关文章来鉴定研究。在这项系统评价中,对临床试验的最后一次搜索是在2005年12月进行的。该评价包括对可能切除的食道癌患者进行的随机研究,该研究比较了术前使用糖皮质激素与安慰剂的情况。审阅者收集数据,并使用雅达(Jadad)评分对试验质量进行评估。具有95%置信区间的赔率用于评估治疗组之间差异的显着性。
    结果:共找到四项涉及169例患者的随机试验。糖皮质激素组和安慰剂组之间在术后死亡率,吻合口漏,肝和肾衰竭方面无差异。术前给予糖皮质激素治疗的患者术后呼吸系统并发症(95%CI = 0.09-0.46),败血症(95%CI = 0.10-0.81)和术后并发症总数(95%CI = 0.06-0.23)较少。
    结论:糖皮质激素的预防性给药可减少术后并发症。

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