Cytochemical and biochemical localization of lipase and sphingomyelinase activity in mammalian epidermis

Despite a wealth of new information on epidermal lipids and their role in permeability barrier function and desquamation, little is known about the location of the enzymes that regulate their catabolism. In this study we have localized lipase (triacylglycerol hydrolase) and sphingomyelinase in the outer epidermis simultaneously by cytochemical and cell fractionation techniques. Aldehyde-fixed tissues (100-microns slices) incubated in either Tween 85 or triolein plus taurocholate/calcium chloride-containing buffer, pH 7.2 or 4.5, were then exposed to lead to form insoluble soaps, and processed for electron microscopy. Simultaneously, cell homogenates and isolated lamellar body fractions were incubated with methylumbelliferyl oleate under similar conditions, with released, free methylumbelliferone serving as an index of lipase activity. On electron microscopy and cell fractionation, both lipase and sphingomyelinase were localized primarily to intercellular domains in the stratum corneum. In the stratum granulosum lipases were found, both ultrastructurally and biochemically, in lamellar bodies and ultrastructurally in both the perinuclear cistern and mitochondria. In summary, these studies: by demonstrating lipid-catabolic enzymes in the intercellular domains of the stratum corneum, lend further support to the 2-compartment model of the stratum corneum; provide new information about the location of lipid-catabolic enzymes in differentiating epidermis; and provide insights about how lipids are processed during permeability barrier formation and desquamation.     

The partial opioid agonist, buprenorphine, protects against lethal effects of cocaine.

Buprenorphine (0.3-3.0 mg/kg) produced dose-dependent protection against the lethal effects of cocaine in mice. The (+)-enantiomer of buprenorphine did not protect up to doses over 100 times greater than the lowest effective dose of its (-)-enantiomer. The protective effects were also produced by the opioid agonists morphine and methadone, but not by the opioid antagonist, naltrexone. Low doses of naltrexone (0.3-1.0 mg/kg) blocked the protective effects of buprenorphine. Protection conferred by buprenorphine was not observed in CXBK mice, a recombinant inbred strain relatively devoid of mu-opioid receptors. Thus, buprenorphine appears to protect against the lethal effects of cocaine by a process mediated by mu-opioid receptors. The present results should provide some additional safety assurance in future clinical trials with buprenorphine, especially in outpatient trials where cocaine abuse may continue along with treatment.     

The effects of anterior temporal lobectomy (ATL) on the middle-latency auditory evoked potential (MLAEP).

The anatomical and physiological origins of the middle-latency auditory evoked potential (MLAEP) are not well understood. The present investigation was conducted to determine whether the MLAEP derives its origins in part from the anterior temporal lobe. Twelve subjects with intractable seizures were evaluated with the MLAEP pre and post excision of the anterior-mesial temporal lobe (ATL) unilaterally. In our study, component Pa latency was unaffected by the ATL. The Na latency and the Na/Pa amplitude showed significant increases after ATL. The results we interpreted as being consistent with currently held beliefs regarding the origins of Pa. The changes in Na latency and Na/Pa amplitude are hypothesized to reflect a loss of the modulating influence of the cortex on the subcortical generators of Na.     

Treatment failure due to methicillin-resistant Staphylococcus aureus (MRSA) with reduced susceptibility to vancomycin.

We report the first instance in Australia of treatment failure due to a strain of methicillin-resistant Staphylococcus aureus (MRSA) with reduced susceptibility to vancomycin--heteroresistant vancomycin-intermediate S. aureus (hVISA). The infection occurred in a 41-year-old man with multiple risk factors. No transmission of the organism to other patients or the environment was detected. This case may herald the beginning of a new phase of staphylococcal resistance in Australia.     

Endovascular repair of the thoracic aorta in octogenarians.

Background: To evaluate the feasibility and safety of thoracic endografting in the octogenarian population. Methods: Between February 2000 and August 2005, 249 patients with a mean age of 69+/-12.3 years (range 23-91) underwent thoracic endografting. Forty-four patients (27 males and 17 females) were octogenarians with a mean age of 84+/-2.7 years. Indications for intervention included: atherosclerotic aneurysms (26/44, 59%), acute and chronic dissections (9/44, 20.5%), penetrating aortic ulcers (6/44, 14%) and contained rupture (3/44, 7%). Results: Endovascular repair was achieved in all octogenarian patients (44/44, 100%). Mean length of stay was 4.7+/-3.6 days. Two cardiac-related deaths and 1 retrograde dissection death occurred (3/44, 7%). Complications included hemiparesis (n=2) with full recovery at discharge, groin hematoma (n=1), pneumonia (n=2) and stroke (n=1) [6/44, 11%]. Endoleaks were diagnosed in 3 patients [3/44, 7%] (2 type I, 1 type II) at 30-day follow-up. Two patients developed an endoleak beyond 30 days [2/44, 5%] (1 type I, 1 type II). Two re-interventions were necessary at 30 days (1 type I, 1 type II). Mean follow-up was 22 months and there were no device migrations or aortic ruptures. No statistical differences in overall mortality were noted between octogenarians and non-octogenarians at 30 days (7% vs 6%, p=NS), 12 months (18% vs 13%, p=NS) and 24 months (27% vs 15%, p=NS). However, at 5 years post-procedure, octogenarians had a significantly higher overall mortality than non-octogenarians (32% vs 17%, p=0.038). Conclusions: Advanced age is not a contraindication to thoracic endografting with favorable short and mid-term outcomes compared to non-octogenarians.     

脑功能磁共振成像在针刺合谷、足三里与内关、三阴交穴位后的影像学特征变化比较

目的:利用功能磁共振技术观察针刺不同经脉的两组穴位后,人脑运动功能区的活动情况。方法:试验于2004-10/2006-06在中山大学附属第二医院进行。选取健康右利手志愿者11名,均为医学院学生。试验采用多组块设计,包括静息期和针刺期。每个受试者接受4次针刺,针刺穴位依次取右侧合谷、内关、三阴交、足三里穴,针刺同时采用荷兰飞利浦公司生产的Philips Intera1.5T超导型MR扫描仪进行功能磁共振扫描,两穴位刺激成像的间隔时间为15min。采用统计参数图进行数据统计学分析,用t检验分析,P<0.01的象素构成针刺激活的特异性脑区图。结果:11名受试者均进入结果分析。①针刺合谷穴引起平均信号强度升高脑区主要为双侧额中回,中央前后回、颞中上回,同侧楔前叶、岛盖以及对侧舌回、脑岛、顶下小叶。②针刺内关穴引起平均信号强度升高脑区主要为双侧额中回、尾状核、中央前后回、扣带回、颞中上回及对侧岛盖、缘上回、下丘脑、顶下小叶。③针刺足三里穴引起平均信号强度升高脑区主要为双侧颞中回、额中上回,同侧岛叶、枕上回以及对侧中央前后回、岛盖、角回。④针刺三阴交穴引起平均信号强度升高脑区主要为双侧颞中回、额下回、中央后回,同侧顶上小叶、岛叶及对侧中央前后回、顶下小叶。结论:在同一受试者,针刺不同穴位可引起相同部位脑功能区激活,不同人针刺相同穴位激活的脑功能区有一定差异,针刺效果可能并非通过单一脑功能区,而是通过有功能联系的多个脑功能区所形成的一个复杂的流动性网络的相互作用而实现的。     

Early postoperative hyperglycaemia is not a risk factor for infectious complications and prolonged in-hospital stay in patients undergoing oesophagectomy: a retrospective analysis of a prospective trial

Introduction  

Treating hyperglycaemia in hospitalized patients has proven to be beneficial, particularly in those with obstructive vascular disease. In a cohort of patients undergoing resection for oesophageal carcinoma (a group of patients with severe surgical stress but a low prevalence of vascular disease), we investigated whether early postoperative hyperglycaemia is associated with increased incidence of infectious complications and prolonged in-hospital stay.     

Drug-induced lupus: Traditional and new concepts

Drug-induced lupus (DIL) includes a spectrum of drug-induced reactions often characterised by a clinical phenotype similar to that of idiopathic systemic lupus eruthematosus (SLE) but usually lacking major SLE complications. Different drugs may be associated with distinct clinical and serological profiles, and early recognition is crucial. Drugs traditionally associated with DIL include procainamide, hydralazine, quinidine and others, but strong associations with newer agents, such as TNF α (TNFα) inhibitors, are increasingly recognised. The pathogenic mechanisms explaining how drugs that have heterogeneous chemical structure and function lead to autoimmunity are only partially understood. However, it is likely that traditional DIL-associated agents can boost innate immune responses, particularly neutrophil responses, with neutrophil extracellular trap (NET) formation and exposure of autoantigens. Research in the field of DIL is evolving and may provide interesting models for the study of autoimmunity.     

糖尿病大鼠骨代谢变化与立普妥、胰岛素的干预效应

目的:近年细胞培养实验发现他汀类药物可以促进骨形成,采用动物实验观察胰岛素和他汀类药物立普妥对糖尿病大鼠骨代谢的影响,为糖尿病伴骨质疏松的治疗提供实验依据。方法:实验于2005-08/2006-01在大连医科大学病理教研室完成。①实验分组:SD雄性大鼠55只,随机选择10只为空白对照组,余45只经鼠尾静脉注射链尿佐菌素造成糖尿病大鼠模型。其中40只符合造模标准,随机分为糖尿病未治疗组、胰岛素治疗组、立普妥治疗组及胰岛素 立普妥治疗组,每组10只。②实验方法:所有大鼠皆给予相同普通饮食。胰岛素治疗组及胰岛素 立普妥治疗组于实验第4天接受中效胰岛素治疗,6～8U/d分两次颈背部皮下注射。胰岛素剂量按每只鼠每周血糖进行调整。立普妥治疗组及胰岛素 立普妥治疗组于实验第4天给予立普妥1.25mg/kg灌胃。糖尿病未治疗组和空白对照组给予等量生理盐水灌胃。③实验评估:9周末用乙醚麻醉,每组取4只大鼠去眼球取血之后处死。14周末应用同样方法处死剩余大鼠。均取腰椎骨,常规脱钙石蜡包埋,行苏木精-伊红染色。骨组织形态计量学测量平均骨小梁厚度和平均骨小梁间距或弥散度。血中Ⅰ型胶原氨基端肽测定采用竞争性放射免疫检测方法(碘标记)。结果:实验期间大鼠死亡5只,其中糖尿病未治疗组1只于第3周死亡,胰岛素组2只于第6周死亡,胰岛素 立普妥治疗组2只于第7周死亡。①骨组织病理形态学变化:9周末立普妥治疗组、胰岛素 立普妥治疗组及糖尿病未治疗组光镜下见骨质疏松表现。14周末立普妥治疗组及胰岛素治疗组骨组织微观结构恢复至空白对照组水平。②平均骨小梁厚度:9周末:糖尿病未治疗组、胰岛素治疗组、立普妥治疗组及胰岛素 立普妥治疗组均明显低于空白对照组(P<0.01)。14周末:糖尿病未治疗组及胰岛素 立普妥治疗组均明显低于空白对照组(P<0.05)。③平均骨小梁间距或弥散度:9周末:糖尿病未治疗组及胰岛素 立普妥治疗组均明显高于空白对照组(P<0.05)。14周末:糖尿病未治疗组及胰岛素 立普妥治疗组均明显高于空白对照组(P<0.05)。④Ⅰ型胶原氨基端肽水平:9周末:立普妥治疗组和胰岛素 立普妥治疗组均明显高于空白对照组(P<0.01)。14周末:胰岛素治疗组、立普妥治疗组和胰岛素 立普妥治疗组均明显高于空白对照组(P<0.01)。结论:①糖尿病大鼠造模9周出现明显的骨质疏松。②糖尿病大鼠骨质变化表现为骨吸收超过骨形成作用,主要以骨吸收增强为主。③立普妥及胰岛素可以促进糖尿病大鼠骨质的形成,抑制糖尿病大鼠骨质疏松的发生发展。