Transplantation of discordant pig islet xenografts in diabetic rats.

Xenotransplantation of pig islets under the kidney capsule (KC) of diabetic rats was performed. Natural preformed ACI rat anti-pig leukocytotoxicity, leukoagglutination and hemagglutination antibody titers ranged from Neat-1: 16, 1:8-1:32 and 1:128-1:256, respectively (n = 14). Normal ACI sera were non-toxic to pig islets during short term incubation. Pig islet xenograft survival times in the nonimmunosuppressed ACI rats, ACI rats immunosuppressed with antithymocyte serum (ATS) or cyclosporin A were 3.8 +/- 0.4 (mean +/- SE; n = 5), 10.4 +/- 0.7 (n = 13) and 6.0 +/- 1.0 (n = 5) days, respectively. Pig islets implanted in the abdominal testis of ACI recipients immunosuppressed with 5 doses ATS survived for a mean of 6.4 +/- 1.0 days (n = 7). The mean K rate following an intravenous glucose tolerance test (IVGTT) in ACI rats 1 week after transplantation with pig islet under the KC was 2.2 +/- 0.4 (n = 10) compared to that of 2.91 +/- 0.30 found in normal control rats (n = 8). Peak insulin at 1 min was 60.1 +/- 3.9 microU/ml (n = 4). Histological and immunohistochemical examination showed that the xenograft from recipients treated with 5 doses of ATS still contained well-preserved islet tissue with many insulin- and glucagon-containing cells on the day of graft removal when blood glucose had returned to hyperglycemic level. Both CD4 and CD8 positive cells were in the vicinity of the graft tissue.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of a high protein diet on the evolution of diabetes in streptozotocin-induced and spontaneously diabetic “BB” wistar rats

Summary Recently, we demonstrated a reduction in the diabetogenic action of streptozotocin (STZ) in rats previously adapted to a high protein (HP) diet. These data suggested that amelioration of diabetes resulted from the combination of two effects of the HP diet: initial protection against the diabetogenic action of the drug at the time of exposure and subsequent improvement of the induced diabetic condition. The present study evaluated the effects of a HP diet on the evolution of the metabolic condition in rats with STZ-induced or spontaneous diabetes (BB Wistar rats). Two days after STZ injection, the animals were given isocaloric HP (70% protein, 8% fat) or control (66% carbohydrate, 16% protein, 8% fat) diets for 15 days. After 13 days, the STZ-treated rats fed HP diet showed an impressive decrease in severity of diabetes, as judged by rate of body weight change, plasma glucose, urine volume and glycosuria, serum and pancreatic insulin. The BB Wistar rats, already diabetic for 5 weeks before being transferred to the HP or control diet, were treated with daily injections of insulin. After 31 days on the HP diet, the BB rats showed reduced insulin requirement, reduced blood and urinary glucose levels, but no difference in body weight gain or pancreatic insulin content. The data show that short-term use of HP diets can greatly improve the diabetic condition in STZ-treated animals, but that the beneficial effects of the diet are much less marked in rats with chronic spontaneous diabetes. These data suggest that the ameliorating effect of HP diet is fully manifested only when the diabetic rats have a sufficient number of residual functioning B-cells.     

Low-dose ibuprofen in self-medication of mild to moderate headache: a comparison with acetylsalicylic acid and placebo

A double-blind, threefold crossover, double-dummy trial was performed, investigating the efficacy of 200 mg ibuprofen compared with 500 mg acetylsalicylic acid and placebo in patients who usually treated their headaches with over-the-counter drugs. Ninety-five patients suffering from mild to moderate migraine or episodic tension-type headache were included. Seventy-seven patients entered the intention-to-treat analysis and 65 completed all three treatments. For the main response criterion, a minimum 50% decrease of headache intensity on a visual analogue scale at I h after treatment, ibuprofen was significantly superior to acetylsalicylic acid and placebo. This was true for migraine attacks and tension-type headache episodes. Towards the end of the observation period (150 min), the differences between ibuprofen and acetylsalicylic acid were no longer significant. In conclusion, ibuprofen was at least equivalent to acetylsalicylic acid and superior to placebo.     

SecA suppresses the temperature-sensitive SecY24 defect in protein translocation in Escherichia coli membrane vesicles.

Genetic analysis of protein secretion in Escherichia coli has identified secY/prlA and secA as components of the secretory apparatus. We have examined the roles of the secY(prlA) gene product (an integral membrane protein) and the soluble secA gene product in translocation of OmpA and alkaline phosphatase precursors in an in vitro system. The protein translocation defect of the secY24 mutation was recently demonstrated in vitro as was its suppression by an S300 extract. We show here that the extract was essentially inactive in SecY24 suppression when SecA protein was removed from it by immunoaffinity chromatography. Furthermore, purified SecA protein suppressed the SecY24 defect. Preincubation of the inactivated SecY24 membrane vesicles either with S300 containing SecA or with purified SecA protein reconstituted the membranes and restored the translocation activity when assayed in the absence of additional soluble proteins. These results suggest that the SecY24 translocation defect is suppressed by SecA interacting, directly or indirectly, with SecY24 on the cytoplasmic membrane.     

The protective activity of ICRF-187 against doxorubicin-induced cardiotoxicity in the rat

Summary The protective activity of the bisdioxopiperazine ICRF-187 against the cardiotoxicity of doxorubicin was evaluated in the rat using both functional and histological assays. Animals that had received a single i. v. dose of doxorubicin (4 mg/kg) alone were compared with those that had been pretreated with a single i. v. injection of saline or ICRF-187 (40 or 60 mg/kg). All rats showed a transient reduction in body weight during the first 3 weeks after drug administration. The greatest reduction (16%) was observed in animals that had received a combination of ICRF-187 (40 or 60 mg/kg) and doxorubicin. Deaths related to cardiotoxicity were observed only in rats that had received doxorubicin alone and in those treated with saline; most of the deaths occurred at between 8 and 13 weeks after drug administration. Sequential assessments of heart function showed a persistent depression of cardiac output in animals that had received doxorubicin, with or without pretreatment with ICRF-187. The reduction in cardiac output observed in rats that had been pretreated with ICRF-187 (40 or 60 mg/kg) amounted to 15% and 30% after 12 and 20 weeks, respectively, indicating that cardioprotection was only partial. Nevertheless, this represented a marked improvement as compared with the 35% reduction in cardiac output measured at 12 weeks in animals that had received doxorubicin but without pretreatment with ICRF-187. Histological examination of animals that had died during the course of the study and had received doxorubicin after pretreatment with saline revealed severe myocardial lesions typical of doxorubicin-induced damage. In contrast, animals that had been pretreated with ICRF-187 and survived for up to 20 weeks after treatment showed a marked amelioration of these lesions. The present findings may be interpreted as a true cardioprotection or a delay in the onset of the cardiotoxicity of doxorubicin resulting from pretreatment with the bisdioxopiperazine ICRF-187. Although prior and ongoing clinical trials clearly indicate that ICRF-187 protects patients well against doxorubicin-induced heart damage, further investigations are required beforehigh doses of ICRF-187 can be used as a means of increasing the protective activity of this drug against doxorubicin-induced cardiotoxicity.This work was supported by the Cancer Research Campaign     

麝香保心丸对内皮素-1诱导原代培养的人脐动脉血管平滑肌细胞增殖的影响

目的:观察麝香保心丸(SXBXW)对内皮素-1(ET-1)诱导原代培养的人脐动脉血管平滑肌细胞(VSMCs)增殖作用的影响。方法:建立ET-1刺激原代培养人脐动脉VSMCs增殖的细胞模型,设对照组、ET-1组、ET-1+SXBXW0.25g/L组、ET-1+SXBXW0.5g/L组、ET-1+SXBXW1.0g/L组和ET-1+SXBXW2.0g/L组,采用MTT法测定ET-1和SXBXW对细胞增殖的影响;用台盼蓝拒染和乳酸脱氢酶检测方法观察不同浓度的SXBXW对VSMCs的毒性作用;用流式细胞术观察ET-1和SXBXW对VSMCs增殖周期的影响。结果:与对照组相比,ET-1可显著促进VSMCs的增殖,一定剂量的SXBXW能够有效地抑制ET-1诱导的VSMCs细胞增殖,呈剂量依赖性;SXBXW抑制细胞增殖,但对活细胞数目和乳酸脱氢酶释放量均没有影响,提示对VSMCs无毒性作用。ET-1能够刺激VSMCs从G1期进入S期,从而促进细胞增殖,而SXBXW能抑制这一作用。结论:SXBXW能够有效抑制ET-1诱导的VSMCs增殖作用,其作用机制可能与其抑制细胞周期从G1期进入S期有关。     

海南百岁老人12项肥胖相关指标与全因死亡的关联研究

目的描述和分析BMI、腰围、腰臀比、腰高比、小腿围、腰围小腿围比值(WCR)、脂质蓄积指数(LAP)、内脏脂肪指数(VAI)、中国内脏脂肪指数(CVAI)、身体形态指数、中国身体形态指数(CABSI)和身体圆度指数与海南百岁老人全因死亡间的关联。方法整群抽样方法抽取的海南百岁老人共1 002人。随访时间的M(Q1, Q3)为4.16(1.31, 5.04)年, 结局为全因死亡, 使用Cox比例风险回归分析各肥胖相关身体测量指标与全因死亡的关联, 并使用受试者工作特征曲线曲线下面积(AUC)进行比较。结果总人群中小腿围对全因死亡的判定能力最强, AUC为0.61(95%CI:0.57～0.64), 分性别结果与总人群一致(P<0.05)。WCR次之(AUC为0.58), 再次是BMI、LAP和腰围, AUC分别为0.55、0.55和0.54, 而CABSI、腰臀比和VAI的判定能力较弱, AUC分别为0.51、0.50和0.50。结论本研究比较了12项肥胖相关指标与海南百岁老人全因死亡间的关联, 发现小腿围的预测判定能力最好, 且呈剂量反应关系, 提示可作为长寿老人死亡风险预测的参...     

短程应用rhG-CSF佐治小儿急性白血病疗效观察

目的　探讨短程应用重组人粒细胞集落刺激因子（ｒｈＧ－ ＣＳＦ） 佐治急性白血病强化疗所致骨髓抑制期的疗效。方法　将４５ 例急性白血病随机分为两组。对照组予常规治疗,治疗组在常规治疗同时加用ｒｈＧ－ ＣＳＦ,短程应用,共计３ ｄ。结果　治疗组骨髓抑制期恢复时间（７．７ ±１ ．２２ ｄ） ,较对照组（１０ ．７ ±４ ．５６ ｄ） 显著缩短（ Ｐ＜ ０．０５）,继发感染发生率（６０ ．８ ％）与对照组（６６ ．７ ％） 相比差异无显著意义（Ｐ＞０ ．０５）,但感染控制时间治疗组（４．３７ ±５ ．６１ ｄ） 较对照组（７ ．０８ ±３．６１ ｄ） 明显缩短（Ｐ＜０ ．０５）,成分输血量（ 均值３４０ ｍｌ） 较对照组（均值５４０ ｍｌ）显著减少（ Ｐ＜０ ．０１）,缓解率及缓解后无病生存期无明显差异（Ｐ＞ ０．０５）。结论　ｒｈＧ－ ＣＳＦ短程应用佐治急性白血病对强化疗后缓解骨髓抑制,顺利完成强化疗方案,疗效肯定,费用亦降低,值得临床推广应用。     

Validation of a self-administered questionnaire in Chinese in the assessment of eczema severity

The purpose of this study was to validate the Chinese version of the Nottingham Eczema Severity Score (NESS) in determining the severity of atopic dermatitis (AD). Each parent or patient filled out a questionnaire in Chinese based on the NESS. A physician then repeated the NESS independently. Finally, the severity of AD was evaluated according to the Scoring Atopic Dermatitis (SCORAD) scale. The NESSs, severity grades, and SCORAD were analyzed for agreement and correlation. The severity grading agreed with the physician's grading in 38 of 52 parents (73%) and in 16 of 18 children (89%) who self-evaluated the severity of their AD. The weighted kappa (95% confidence interval [CI]) for parents with children less than 10 years old, parents with children > or =10 years old, and patients who self-evaluated their AD were 0.79 (0.66-0.91), 0.85 (0.69-1.00), and 0.74 (0.36-1.00), respectively. The R2 for the NESS by parents, the NESS by patients, and the SCORAD scores was 42.1%, 47.5%, and 49.8%, respectively. When compared with the parents, the older children who self-evaluated their AD showed a better correlation of the NESS with the SCORAD index. The self-administered questionnaire appears to be useful in assessing AD severity in Chinese children.     

Radioimmunoassay of motilin

A radioimmunoassay method of motilin was developed in our laboratory and was validated in dogs with a platinum monopolar electrode in the duodenum. We confirmed that a bolus infusion of 0.3 M tris-buffer solution or 0.1 N HCl solution in the duodenum produces a significant rise in plasma immunoreactive motilin (IRM) concentrations. This coincided with a marked increase in the percentage of spike potentials on slow waves of the duodenum, similar to phase III of interdigestive myoelectric-activity (MA). A possible relationship between plasma IRM and interdigestive MA of canine duodenum was studied. It was found that cyclic changes occurred in the fasting plasma IRM concentrations in dogs. While the peak motilin concentration was always observed in phase III, the lowest concentration of motilin was found in phase I of interdigestive MA in the duodenum. In dogs with the electrodes in the duodenum and jejunum, the peak IRM concentration did not correlate with phase III of interdigestive MA in the jejunum. A dose of synthetic porcine motilin, 0.06 g/kg/hr, which produced the plasma IRM concentration comparable to the peak fasting motilin concentration, could induce an identical phase III in the duodenum. These observations indicate that there is a relationship between cyclic changes in plasma IRM concentrations and interdigestive MA of the duodenum. It is suggested further that motilin is a hormone which may play an important role in inducing phase III of interdigestive MA in the duodenum.This work was supported by the Gastrointestinal Research Fund at The Genesee Hospital.