Secondary sulphonylurea failure: what pathogenesis is responsible?

Sulphonylurea (SU) stimulates insulin secretion by pancreatic beta-cells and is generally used as a first-line treatment for type 2 diabetes. However, after long-term SU treatment (six months or over), some patients begin to show an increase in blood glucose once again (secondary SU failure). Two theories have been put forward to explain this failure--dysfunction of the proinsulin conversion machinery or insulin resistance. However, the primary pathogenesis behind secondary SU failure still needs to be investigated. Using a reliable technique that specifically identifies intact proinsulin (IPI), total proinsulin (TPI) and specific insulin (SI), this study aims to discover if a defect in the proinsulin converting mechanism plays a role in SU failure. Three groups were recruited for this study: healthy controls (n=8), SU responders (n=38) and secondary SU failures (n= 46). Serum concentrations of insulin-related molecules released in response to a standard glucose challenge test were compared between the groups. It was found that total SI was lower in the patient groups (P<0.05 compared to the control group), while TPI and IPI showed no distinct difference between the three groups (P>0.05). TPI:SI ratio and IPI:SI ratio showed marked increases in the patient groups (P<0.05 compared to control group), with no obvious quantitative difference between SU responders and secondary SU failures (P>0.05). Similar results for the Homa Insulin Resistant Index were found between the two patient groups. Interestingly, blood glucose at 180 mins after glucose challenge was significantly higher in the secondary SU failure group (P<0.05), with no correlation to SI, while the SU responder group showed good correlation between the parameters (P<0.05). We conclude that type 2 diabetes is associated with obvious dysfunction in the proinsulin-converting process and shows severe SI deficiency in responding to glucose challenge. Dysfunction of the proinsulin conversion mechanism was not an extra cause responsible for SU failure.     

检测Epstein-Barr病毒特异性细胞毒性T淋巴细胞方法的建立及其初步研究

目的建立一种非放射性、简便易行的可检测特异性细胞毒性Ｔ淋巴细胞的方法，并且初步应用于Ｅｐｓｔｅｉｎ－Ｂａｒ病毒的细胞免疫应答。方法用重组的ＥＢＶ－ＬＭＰ１痘苗病毒、ＴＫ＋痘苗病毒和杆状病毒系统表达的ＥＢＶ－ＬＭＰ１蛋白分别免疫Ｂａｌｂ／Ｃ小鼠，用Ｐ８１５细胞和乳酸脱氢酶法检测ＥＢ病毒特异性细胞毒性Ｔ细胞的杀伤效应。结果重组ＥＢＶ－ＬＭＰＩ痘苗病毒免疫组原发ＣＴＬ水平和体外诱生的二次ＣＴＬ水平均高于ＴＫ＋痘苗病毒免疫组和正常组；杆状病毒系统表达的ＥＢＶ－ＬＭＰ１蛋白免疫组的ＣＴＬ水平也明显高于正常鼠。结论本法可以较好的反映ＥＢ病毒特异性细胞毒性Ｔ细胞的水平，而且再一次说明ＬＭＰ１基因能够诱发特异性的细胞免疫。     

Prediction of apatite lattice constants from their constituent elemental radii and artificial intelligence methods

Lattice constants (LCs) of all possible 96 apatite compounds, A(5)(BO(4))(3)C, constituted by A[double bond]Ba(2+), Ca(2+), Cd(2+), Pb(2+), Sr(2+), Mn(2+); B[double bond]As(5+), Cr(5+), P(5+), V(5+); and C[double bond]F(1-), Cl(1-), Br(1-), OH(1-), are predicted from their elemental ionic radii, using pattern recognition (PR) and artificial neural networks (ANN) techniques. In particular, by a PR study it is demonstrated that ionic radii predominantly govern the LCs of apatites. Furthermore, by using ANN techniques, prediction models of LCs a and c are developed, which reproduce well the measured LCs (R(2)=0.98). All the literature reported on 30 pure and 22 mixed apatite compounds are collected and used in the present work. LCs of all possible 66 new apatites (assuming they exist) are estimated by the developed ANN models. These proposed new apatites may be of interest to biomedical research especially in the design of new apatite biomaterials for bone remodeling. Similarly these techniques may also be applied in the study of interface growth behaviors involving other biomaterials.     

Progressive decrease of proinsulin secretion in sulphonylurea-treated type 2 diabetes

Progressive deterioration of beta-cell function is proposed as a disease-related factor of sulphonylurea (SU) failure in type 2 diabetes. If it gradually worsens over time then disease duration may mirror the progressive beta-cell deterioration. The aim of the present study is to assess whether or not disease duration is influential in remodelling the secretion pattern of insulin-like molecules and in glucose control of SU-treated type 2 diabetes. A research model is used to investigate proinsulin secreting capacity over time, using two groups of patients: i) disease duration <5 years (n=62), comprising SU responders (SUr; n=48) and SU failures (SUf; n=14); and ii) disease duration > or = 5 years (n= 37), comprising an SUr group (n=17) and an SUf group (n=20). Blood samples are taken at 0 h, 0.5 h 1 h, 2 h and 3 h during a standard oral glucose tolerance test and measured for glucose, total proinsulin (TPI), intact proinsulin (IPI) and specific insulin (SI) concentrations. Pairwise comparison of estimated marginal means of blood glucose, SI, IPI and TPI levels at each time point are carried out between groups and subgroups. (SUr vs. SUf). Homa insulin resistance index (IR index) is applied to analyse IR between the groups. It was found that patients with shorter disease duration had higher proinsulin (TPI and IPI) levels at all time points (P<0.05), together with a lower glucose level at 2 h and 3 h (P<0.05). Homa insulin index analysis showed no difference between the two groups (P=0.26). Results also showed that the SUr group had a significantly lower glucose level at Oh and 3h (P<0.05), although no significant difference in insulin and proinsulin levels was found between the SUr and SUf groups. In conclusion, proinsulin may play an important role in glucose control in SU-treated type 2 diabetes, but the effect is reduced in SUf patients.     

Pharmacological basis for use of madecassoside in gouty arthritis: anti-inflammatory,anti-hyperuricemic,and NLRP3 inhibition

Objectives: Gouty arthritis is caused by the deposition of monosodium urate (MSU) crystals in joints, which is associated with the rise of serum urate content. This study aims to investigate the therapeutic effect of Madecassoside on gouty arthritis and hyperuricemia.

Methods: DBA/1 mice were intradermally injected with MSU to stimulate joint inflammation or intraperitoneally injected with MSU to trigger peritonitis. Moreover, ICR mice were exposed to potassium oxonate to stimulate hyperuricemia.

Results: Madecassoside repressed MSU-triggered pad swelling, joint 99mTc uptake, and joint inflammation in DBA/1 mice with gouty arthritis. Neutrophil infiltration and IL-1β & IL-6 & MCP-1 secretion was also alleviated in lavage fluids from DBA/1 mice with peritonitis due to Madecassoside treatment. Furthermore, Madecassoside decreased MSU-induced neutrophil cytosolic factor 1, caspase-1 and NLRP3 expression in mice with peritoneal inflammation. In hyperuricemic mice, Madecassoside improved renal dysfunction. Serum uric acid, BUN, and creatinine were down-regulated by Madecassoside.

Conclusion: These findings indicate that Madecassoside has potential to ameliorate inflammation in both acute gouty arthritis model and peritonitis model, probably via regulating IL-1β and NLRP3 expression.

Practical point: Madecassoside also exhibited a urate-lowering effect and a renal protective effect in hyperuricemic mice.     

术前孤立性CRP升高与体外循环术后并发症的相关性

目的探讨无感染的、术前孤立性C-反应蛋白(CRP)增加,对于体外循环心脏术后的结果,是否有预测性价值。方法分术前孤立性CRP升高(10.5～70.2mg／L)50例(A组)与CRP正常(＜10mg／L)50例对照(B组),B组匹配A组在年龄、性别和疾病种类,两组均进行体外循环心脏手术。结果A组脓毒性并发症(20％)比对照组(2％)多(P＜0.01)。这些病人微生物学阳性仅10％。A组中需要儿茶酚胺支持的占28％,而B组仅12％(P＜0.05)。A组较B组术后需呼吸机支持的时间明显延长(25.2±6.2h比6.6±0.5h)(P＜0.01)、ICU滞留时间也较B组长(4.6±0.8d比2.6±0.3d)(P＜0.05)。结论术前孤立性CRP升高的病人,体外循环术后,发生脓毒性并发症的可能性明显增加。且大多数病例微生物学实验阴性,推测大多数脓毒性并发症是由于全身炎症反应综合征的原因。     

急性上尿路梗阻无尿80例诊治分析

目的：分析急性上尿路梗阻性无尿80例的诊断和治疗方法,以尽早诊断,及时治疗。方法：报告1989-1999年收治的急性上尿路梗阻性无尿患者80例,诊断依据为少尿以致无尿、水肿、血尿素氮和肌酐进行性增高,初步诊断首选腹部平片（KUB）和B超及肾图检查。结果：10例患者术前行血液透析,手术治疗53例,包括输尿管切开取石术18例,肾造瘘术20例,狭窄段输尿管切除膀胱再植8例,输尿管腹壁皮肤造口术7例,双“J”管内引流术27例,结论：本病病因,病情复杂多变,应采取不同的治疗措施。     

鼻咽癌放疗患者T细胞亚群测定的临床分析

目的探讨鼻咽癌(NPC)分期及放疗对免疫与肿瘤复发、转移及肿瘤退缩的相关性.方法每位病人放疗前及放疗后各测定T细胞亚群指标一次.结果早、晚期鼻咽癌放疗前后T细胞亚群相比,除早期鼻咽癌CD3下降无统计学意义外,余CD3、CD4、CD4/CD8下降;CD8升高均有统计学意义,晚期鼻咽癌的改变尤为突出,有极显著统计学意义(P＜0.001).放疗后肿瘤退缩与否的T细胞亚群测定无统计学意义.放疗后肿瘤有复发或转移者CD4、CD4/CD8下降有极显著统计学意义(P＜0.001).CD8升高有统计学意义.结论T细胞亚群指标的测定,对鼻咽癌患者的免疫功能状况,放疗对免疫功能的影响,对鼻咽癌放疗后复发及转移的可能性判断均有一定的临床意义.     

Analysis of the factors influencing the therapeutic effects of onychomycosis

From July 1 994to June 1 999,5 4 5 onychomyco-sis patients were treated with Itraconazole and com-pleted their treatment courses with complete follow-up in out- patientdepartment.The recovery rate was83.1 4% and 79.2 3% in fingernail and toenail dis-eases respectively.But following phenomena werefound:( 1 ) Some new nails stopped growing in cer-tain length,even if the treatment continued;( 2 )Some damaged nails reappeared soon after the treat-ment ceased;( 3) Some damaged nails with deep- co…     

用组织多普勒技术评价扩张型心肌病室壁运动

OBJECTIVE: To evaluate the characteristics of wall motion in cases of dilated cardiomyopathy (DCM) by the use of Doppler tissue imaging (DTI). METHODS: We observed 30 DCM patients and 30 normal volunteers. For the assessment of short axis motion, the myocardial velocities (MV) and transmural myocardial velocity gradients (MVG) of the middle segments of anterior interventricular septum and left ventricular posterior wall were recorded through parasternal long axis view. We detected the MV of the middle segments of left ventricular walls to evaluate the long axis motion through apical windows(4-chamber, 2-chamber and long axis). RESULTS: Four kinds of abnormal presentations of the waves were seen in DCM cases. The patients' MV of were obviously lower as compared with the controls', especially in long axis; the patients' MVG also decreased significantly (P < 0.05). In the patient group, the heterogeneity of wall motion disappeared too. CONCLUSION: PW-DTI can quantitatively assess the above abnormalities of DCM and provide supplementary information for clinical use.