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.     

Deletion of stem-loop 3 is compensated by second-site mutations within the Gag protein of human immunodeficiency virus type 1

Encapsidation of human immunodeficiency virus type 1 (HIV-1) RNA involves specific interactions between viral Gag proteins and viral RNA elements located at the 5' untranslated region (UTR). These RNA elements are termed packaging (psi) or encapsidation (E) signals and mainly comprise the stem-loop 1 (SL1) and SL3 RNA structures. We have previously shown that deletion of the SL1 sequences is compensated by second-site mutations within Gag. Similar studies are now extended to SL3 and the results demonstrate that deletion of this RNA structure is rescued by two point mutations, i.e., A11V in p2 and I12V in nucleocapsid (NC). These two compensatory mutations are different from those associated with the rescue of SL1 deletion, suggesting that SL1 and SL3 may bind to different residues of Gag during viral RNA packaging. Analysis of virion-derived RNA in native agarose gels shows that deletion of SL3 leads to decreases in both viral RNA packaging and dimerization. These defects are corrected by the compensatory mutations A11V and I12V. Yet, defects in viral RNA dimerization at an early stage that were caused by the SL3 deletion in the context of a viral protease-negative mutation cannot be overcome by these two suppressor mutations. Therefore, the positive effects of A11V and I12V on dimerization of the SL3-deleted RNA must have taken place at the maturation stage.     

Criteria for the administration of KI for thyroid blocking of radioiodine

Scientific data are reviewed to evaluate the risks of radioiodine uptake and to compare those risks with the benefits and risks of low milligram doses of stable potassium iodide (KI). The limit of 25 rad to the thyroid due to radioiodine uptake is adopted as the "break-even" point above which 130-mg KI doses should be administered. The biological and radiological kinetics of radioiodine for protracted uptakes were derived from the Medical Internal Radiation Dose Committee (MIRD) model (MIRD75). Resulting calculations yielded estimates of dose commitment rates to the thyroid as a function of thyroidal uptake. The extrapolated value of the 1-hr inhalation curve for 131I with 30% uptake compares well with the established MPCa value and intercepts the origin. The calculated KI-blocking efficiency as a function of time after radioiodine uptake agrees well with previously reported experimental data. The prevention or "blocking" of 25 rad to the thyroid was the criterion used to define critical values of radioiodine in the thyroid. Critical values are functions of isotope, the duration of uptake and the elapsed time between inhalation and assay of thyroid content. The presence of radioiodine in the thyroid in amounts greater than the critical value indicates that more than 25 rad to the thyroid can be averted, and KI should be administered in the absence of contraindications. Critical average concentrations are implicitly defined by the method of calculation used in the derivation. Critical average concentrations are presented as criteria for KI administration when assays of the radioiodine content of the thyroid are unavailable. Illustrative applications of critical values and critical average concentrations are presented in the Appendix.     

Histiocytoid hemangioma of the heart with peripheral eosinophilia

A histiocytoid hemangioma of the heart is reported, which was found incidentally in a man with unusually high eosinophilia. The eosinophilia subsided dramatically following removal of the tumor. The "histiocytoid" or the "epithelioid" appearance of the tumor cells and the presence of vacuolated cells were the characteristic microscopic features. The endothelial origin of this tumor was verified by positive immunostaining for factor VIII-related antigen and ultrastructural demonstration of intracytoplasmic lumen formation, abundant cytoplasmic filaments, pinocytotic vesicles, and prominent basal lamina. The presence of mitotic activity, cellular pleomorphism, and tumor necrosis raised the possibility of its malignant potential. The occurrence of this tumor in the heart may be mistaken for a myxoma clinically and a metastatic carcinoma pathologically.     

用SpA协凝法快速检测脑脊液中脑膜炎球菌抗原

用CoA法检测37份临床诊断为"流脑"患者脑脊液中脑膜炎球菌抗原,并与细菌培养法和CIE法比较,其阳性率分别为43.24%、32.43%和27.03%,以CoA法阳性率最高。发病1天者CoA法的阳性数可达11/20,其测得的抗原滴度相等或高于CIE法,是一种具有实用价值的诊断方法,值得推广。     

Reversal of ethanol and indomethacin-induced suppression of hepatic DNA synthesis by 16,16-dimethyl prostaglandin E2

Investigations were undertaken to determine effectiveness of 16,16-dimethyl prostaglandin E2 (dmPGE2) in overcoming the suppressive effects of ethanol and/or indomethacin on hepatic DNA synthesis. Adult litter mate Sprague-Dawley rats were subjected to sham operation or partial hepatectomy. Immediately after partial hepatectomy, and at 8-hr intervals for 24 hr, the rats were given: (a) ethanol with and without dmPGE2 or (b) indomethacin with and without ethanol and/or dmPGE2. DmPGE2 produced a significant increase in DNA synthesis in sham-operated (p less than 0.001) and untreated partially hepatectomized animals (p less than 0.025). Ethanol and indomethacin caused a 6- and 18-fold reduction, respectively, in hepatic DNA synthesis following partial hepatectomy. DmPGE2 overcame the inhibitory effect of ethanol (p less than 0.005) and indomethacin (p less than 0.0005) in partially hepatectomized animals. Mitoses were decreased concomitantly with ethanol and/or indomethacin-induced reduction in DNA synthesis and increased with administration of dmPGE2. It is concluded that dmPGE2 increases hepatic DNA synthesis and regeneration in normal rat liver and overcomes their inhibition when ethanol and/or indomethacin is given after partial hepatectomy. Timing of dmPGE2 administration is crucial. When given 30 min before ethanol, it completely inhibits suppression of regenerative activity; omission of this "priming" dmPGE2 dose results in only 44% of DNA synthesis obtained in control animals.     

新洁尔灭对小白鼠抗早孕的病理组织学观察

本文报告用不同剂量的新洁尔灭和同体积生理盐水注入怀孕5天小白鼠的宫腔内,3天后杀死,观察其蜕膜、胚泡、宫内膜腺体和卵巢黄体病理学改变。实验表明:对照组无改变。实验组小白鼠的蜕膜细胞全部退变坏死。病变随着给药量的递增而渐趋严重;同时胚泡亦有退变和坏死。提示:新洁尔灭对早期妊娠小白鼠是有抗早孕效果的。根据实验结果,我们认为新洁尔灭对小白鼠抗早孕的机制,很可能是一个综合因素,有直接的,也有间接的。作者强调在抗早孕机制诸因素中,蜕膜退变坏死是一个重要的因素。