Hyperglycaemia compensates for the defects in insulin-mediated glucose metabolism and in the activation of glycogen synthase in the skeletal muscle of patients with Type 2 (non-insulin-dependent) diabetes mellitus

Summary Insulin resistance and a defective insulin activation of the enzyme glycogen synthase in skeletal muscle during euglycaemia may have important pathophysiological implications in Type 2 (non-insulin-dependent) diabetes mellitus. Hyperglycaemia may serve to compensate for these defects in Type 2 diabetes by increasing glucose disposal through a mass action effect. In the present study, rates of whole-body glucose oxidation and glucose storage were measured during fasting hyperglycaemia and isoglycaemic insulin infusion (40 mU·m^–2min^–1, 3 h) in 12 patients with Type 2 diabetes. Eleven control subjects were studied during euglycaemia. Biopsies were taken from the vastus lateralis muscle. Fasting and insulin-stimulated glucose oxidation, glucose storage and muscle glycogen synthase activation were all fully compensated (normalized) during hyperglycaemia in the diabetic patients. The insulin-stimulated increase in muscle glycogen content was the same in the diabetic patients and in the control subjects. Besides hyperglycaemia, the diabetic patients had elevated muscle free glucose and glucose 6-phosphate concentrations. A positive correlation was demonstrated between intracellular free glucose concentration and muscle glycogen synthase fractional velocity insulin activation (0.1 mmol/l glucose 6-phosphate: r=0.65, p<0.02 and 0.0 mmol/l glucose 6-phosphate: r= 0.91, p<0.0001). In conclusion, this study indicates an important role for hyperglycaemia and elevated muscle free glucose and glucose 6-phosphate concentrations in compensating (normalizing) intracellular glucose metabolism and skeletal muscle glycogen synthase activation in Type 2 diabetes.     

Possible protective immunity in human opisthorchiasis

Chronic infections with the liver flukes Opisthorchis viverrini and Clonorchis sinensis affect over 30 million people in southeastern Asia. With ongoing exposure, reinfection readily occurs following curative treatment and cumulative infections result in significant morbidity and a predisposition to cholangiocarcinoma. Though protective immunity has never been described in human opisthorchiasis, heterogeneity in worm burden occurs and a small number of exposed residents of endemic areas remain apparently uninfected. To explore the nature of this heterogeneity, we compared levels of serum antibody (Ab) to O. viverrini measured by an enzyme-linked immunosor-bent assay in 83 stool egg-positive and 49 stool egg-negative residents of an O. viverrini-endemic area in Thailand. Compared to the egg-positive residents, the egg-negative group had significantly higher levels of immunoglobulin (Ig)G, IgA and IgM to adult worm homogenate (AWH) and total Ab to metacercaria homogenate (MH). Furthermore, immunoblot analyses revealed that a significantly higher proportion of sera from the egg-negative residents had IgA reactivity against a 38-k Da AWH antigen and IgM reactivity against carbohydrate epitopes of a 42-k Da AWH glycoprotein antigen. These findings support a hypothesis that the egg-negative group includes individuals who may be immunologically resistant to this usually chronic infection.     

甲氟哌酸体外抗菌活性及对耐药感染者的治疗

对天津市新近临床分离的414株细菌进行了甲氟哌酸(Pflx)和氟哌酸(Nflx)体外抗菌活性研究。结果显示Pflx对绝大多数肠杆菌和细菌、不动杆菌有良好抗菌活性,抑菌率>90％。对绿脓杆菌、MSSA及凝固酶阴性葡萄球菌有中度抗菌作用,抑菌率分别为85％、87.5％、87.5％。对MRSA和链球菌抗菌活性稍差,抑菌率在40％～68.42％之间。Nflx体外抗菌活性和Pflx相似。此外,18例药敏试验耐Pflx和Nflx细菌感染患者,经Pflx治疗,肺化脓症1例显效,余17例难治性尿路感染者1例痊愈、9例显效、5例进步、2例无效。     

Effects of zymosan-activated plasma and phorbol myristate acetate on isolated, perfused rabbit lungs

The effects of complement activation on pulmonary vascular permeability are disputed. In rabbit lungs perfused with autologous blood, zymosan activated plasma (ZAP) induced a moderate increase in pulmonary vascular resistance (PVR), but did not detectably change the vascular permeability within 2 h. The stronger neutrophil granulocyte (PMN) activator, phorbol myristate acetate (PMA), usually gave larger PVR increases and also increased pulmonary vascular permeability. Lungs from neutropenic animals, similarly perfused and given PMA, showed unchanged PVR reactions but had no apparent increase in vascular permeability. Lungs perfused with cell-free medium and given PMA displayed modest PVR increases, and no measurable permeability change. The lung preparatory procedure itself markedly influenced leukocyte circulation. Exsanguination of lung donors decreased the concentration of circulating PMN significantly, and they virtually disappeared from the perfusate within minutes after start of lung perfusion. PMN-mediated effects must therefore have been caused by cells already sequestered in the lungs. We conclude that ZAP does not induce an increased pulmonary vascular permeability in isolated, perfused rabbit lungs, in contrast to PMA. The permeability effects of PMA appear to be PMN dependent.     

血管内皮功能障碍对肥胖伴高血糖患者胰岛分泌功能的影响

目的　探讨血管内皮功能障碍对胰岛 β细胞分泌功能的影响。 　方法　正常体重(NW )组 81例 ,单纯肥胖 (Ob)组 14 0例 ,肥胖伴高血糖 (Ob HG)组 97例。测定体质指数 (BMI)、腰臀围比 (WHR)、血压、血脂、空腹血糖和胰岛素 (FBG和FIns)及餐后血糖和胰岛素 (2hBG和 2hIns)。采用稳态模式法评价胰岛素抵抗 (HOMA IR)和 β细胞功能 (HOMA β)。用高分辨率血管外超声测定肱动脉对血流介导的内皮依赖性血管扩张 (EDD)及硝酸甘油的扩张反应。　结果　与Ob组比较 ,Ob HG组WHR、血压、甘油三酯 (TG)、FIns、2hIns和HOMA IR等显著升高 ,HOMA β明显降低 ,并伴有EDD所标志的血管内皮功能显著下降。相关分析显示 ,β细胞功能与EDD在Ob HG组呈显著正相关 (r=0 2 5 9,P <0 0 5 ) ,在Ob组和NW组无显著相关。在对Ob HG组影响EDD的因素进行控制后 ,EDD仍与 β细胞功能显著相关 (r =0 4 5 8,P <0 0 1)。多元逐步回归分析表明影响 β细胞功能的主要因素在Ob HG组为FBG、FIns和EDD ,在Ob组为FBG和HOMA IR。　结论　内皮依赖性舒张功能障碍可能是导致肥胖者 β细胞功能衰退 ,引发 2型糖尿病 (T2DM )的重要危险因素。     

AmpC酶在主要肠杆菌科和非发酵菌中的携带率及耐药性

目的：调查主要肠杆菌科细菌和非发酵菌产AmpC酶和ESBLs的状况及对常用抗菌药物的耐药性，指导临床合理用药。方法：常规培养分离细菌，应用VTTEK微生物自动分析仪和API鉴定系统鉴定病原菌；药敏试验采用K-B纸片扩散法；AmpC酶检测采用三维试验法；ESBLs检测采用双纸片确认试验。结果：主要肠杆菌科细菌产AmpC酶和ESBLs的阳性率分别为18．9％，52．8％，其中以大肠杆菌、肺炎克雷伯、产酸克雷伯、阴沟肠杆菌为主，同时产2种酶的菌株占15．4％；绿脓杆菌产AmpC酶和ESBLs酶的阳性率分别为18．2%，，42．0％，同时产2种酶的菌株占13．6％；不动杆菌的产酶率均在8．0％以下,产酶菌的耐药率高于非产酶菌，除绿脓杆菌外，产AmpC酶菌株的耐药率高于产ESBLs菌株．主要肠杆菌科细菌对泰能(IMP)的敏感性为99．5%，而对舒普深(CPZ)的耐药率平均为13．8％；非发酵菌对IMP，马斯平(FEP)、CPZ的耐药率平均分别为20．4％，44．3％，18．6％.结论：主要肠杆菌科细菌的产酶率高于非发酵菌，产AmpC酶的菌株已近20．0%，应引起临床的高度重视；绿脓杆菌产ES-BLs的菌株也较高，也应该加强监控．对产酶菌引起感染的治疗应根据细菌药敏试验结果，合理选择有效的抗菌药物联合治疗；对重症感染患的治疗应根据药敏试验结果重点应用泰能或舒普深治疗。     

血清瘦素水平的影响因素及相关性分析

目的探讨血清瘦素水平的影响因素及相关性分析.方法从2003年3～8月门诊体验人群中随机抽取标本150人,并排除糖尿病及高血压,测定FBS、血脂水平、血清瘦素水平(LEP)、胰岛素水平(INS),瘦素、胰岛素测定均采用放射免疫方法.胰岛素敏感性以敏感指数(IAI)评价.结果血清瘦素水平女性明显高于男性;相关分析显示血清瘦素水平与性别(SEX)、年龄(AGE)、体重指数(BMI)、INS显著正相关(r分别为0.429,0.329,0.249,0.322,P＜0.05);与LOGIAI显著负相关(r=0.322,P＜0.05),与TC,TG无明显相关;在调整年龄、BMI后,多远逐步回归分析显示血清瘦素水平仍与INS,LOGIAI显著相关.结论血清瘦素水平与TC,TG均无相关,提示高脂血症患者血清瘦素水平与正常人群比较无明显改变;血清瘦素水平与LOGIAI负相关,高瘦素水平人群胰岛素敏感性降低、存在胰岛素抵抗,提示瘦素-胰岛素轴的存在,瘦素是胰岛素抵抗的一个独立危险因素.肥胖患者存在高瘦素血症、瘦素抵抗.如果能弄清瘦素、胰岛素抵抗、肥胖之间的相互作用关系及因果关系,可能对瘦素抵抗、胰岛素抵抗相关痰病的防治有一定的意义.     

Potential risk factors for infection with Candida spp. in critically ill patients

The incidence, risk factors and prognostic factors for candidal infection were determined in a prospective study of 280 infected patients. Thirty-one (11%) patients were infected with Candida spp., sub-divided into 18 (58%) with C. albicans, and 13 (42%) with non-albicans spp. (six C. glabrata, three C. parapsilosis, and one each of C. krusei, C. tropicalis, C. guilliermondii and C. lusitaniae). Infection with Candida spp. was always associated with concurrent bacterial infection. By univariate logistic regression analysis, the degree of morbidity and the duration of mechanical ventilation were independent predictive factors for death, but infection with Candida spp., was not. Factors associated with Candida spp. infection were the degree of morbidity, intensive care unit length of stay, alterations of immune response, and the number of medical devices involved. By multivariate logistic regression analysis, the only independent risk factor for candidal infection was intensive care unit length of stay.