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.     

骨形态发生蛋白4转基因治疗大鼠的胫骨缺损

目的:观察基因工程技术构建人骨形态发生蛋白4复制缺陷腺病毒的成骨效果。方法:实验于2006-03/08在安徽医科大学第一附属医院实验动物中心完成。实验分组:选取普通级雄性SD大鼠30只,体质量(200±10)g,全部动物胫骨上端部分分别造成8mm×5mm长方形缺损。采用自身对照法,右侧骨缺损为实验组,左侧骨缺损为对照组。实验组植入人骨形态发生蛋白4复制缺陷腺病毒复合明胶海绵,对照组植入单纯明胶海绵。实验评估:术后分别于4,6,8周麻醉后处死10只动物,取材行X线、组织病理、免疫组织化学、透视电镜检查,观察成骨情况。结果:纳入30只大鼠,全部进入结果分析。①大鼠胫骨缺损X线、组织病理学检查结果:术后8周实验组和对照组骨缺损均得到修复,但实验组无论从成骨时间、成骨效果、新生骨量等方面都要优于对照组。其中各时间点实验组骨密度明显高于对照组,差异有显著性意义[4周:(95.91±16.33),(87.93±11.52);6周:(128.34±10.64),(102.41±9.81);8周:(138.36±10.49),(121.56±9.63);P<0.01]。各时间点实验组新生骨占骨缺损面积比明显高于对照组,差异有显著性意义[4周:(41.39±5.65)%,(26.58±5.62)%;6周:(80.35±7.25)%,(65.41±6.52)%;8周:(96.45±2.76)%,(82.22±7.30)%;P<0.01]②术后4周免疫组织化学染色结果:实验组软骨及骨痂内呈强阳性反应,而对照组骨痂内骨形态发生蛋白4表达微弱。结论:人骨形态发生蛋白4重组腺病毒具有良好的成骨活性,骨形态发生蛋白4直接转基因治疗能够加快骨缺损的修复。     

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.