再发性低血糖对幼鼠脑内GLUT1及GLUT3表达的影响

目的观察再发性低血糖后脑内葡萄糖转运蛋白1(glucose transporter 1,GLUT1)及葡萄糖转运蛋白3(GLUT3)表达的变化,从而探讨无症状低血糖的发生机制。方法将80只15日龄野生型小鼠随机分为正常对照组及低血糖组,每组40只。低血糖组给予正规胰岛素腹腔注射3次,每次剂量为5U/kg,对照组注射等体积生理盐水。两组分别在最后1次注射后12、24、48及72 h处死小鼠取脑组织(每组每时间点10只),应用免疫组化方法观察小鼠脑内GLUT1及GLUT3表达的变化。结果低血糖后脑内微血管上GLUT1表达有增加趋势,皮质增加高于海马,72 h皮质GLUT1表达显著高于对照组;低血糖后48、72 h皮质及海马GLUT3表达均显著高于相应对照组。结论再发性低血糖后脑内GLUT1及GLUT3适应性增高,这种适应既能节省神经元的能量代谢,但也能削减神经元对低血糖的反应。     

急性有机磷杀虫药中毒中间综合征的临床分析

目的探讨急性有机磷杀虫药中毒中间综合征（intermediate syndrome,IMS）的诊断治疗。方法回顾性分析10例IMS患者临床表现和治疗方法。结果有机磷中毒中间综合征的10例患者均出现不同程度呼吸肌麻痹症,及时建立人工气道及机械通气和乙酰胆碱酯酶（AchE）复能剂应用,治愈8例,死亡2例。结论 IMS应早期识别,建立人工气道与机械通气是抢救成功的重要方法。     

Ectopic expression of rhombotin-2 causes selective expansion of CD4-CD8- lymphocytes in the thymus and T-cell tumors in transgenic mice

Although the proto-oncogene rhombotin-2 (RBTN-2) is widely expressed in most tissues, it is not expressed in T cells. We investigated the potential for overexpression of RBTN-2 to cause tumors in T cells and other tissues by constructing transgenic mice that expressed RBTN-2 under control of the metallothionein-1 promoter. Despite overexpression of RBTN-2 in all tissues, transgenic mice developed T-cell tumors only, thus indicating that tumorigenesis caused by RBTN-2 is T-cell-specific. Thymic tumors were found between 37 and 71 weeks and were invariably associated with metastasis to nonlymphoid organs. Thymuses from apparently healthy transgenic mice were also examined. In some mice there was an 10-fold increase in the CD4-CD8- thymocyte subset, yet the total number of thymocytes was the same as that in wild-type mice. Thymic homeostasis was maintained by a compensatory reduction in the CD4+CD8+ subset. The expansion of CD4-CD8- thymocytes was associated with increased expression of RBTN-2 and with increased cell proliferation. No differences were found in the proportion of thymocytes undergoing apoptosis in transgenic mice. Furthermore, RBTN-2- induced expansion of CD4-CD8- cells did not block differentiation of these cells. Thymuses with 30% CD4-CD8- cells were essentially monoclonal, indicating that all thymic immunophenotypes were derived from a single clone. Overall, our data are consistent with the following scenario: (1) RBTN-2 expression in T cells causes selective and polyclonal proliferation of CD4-CD8- thymocytes accompanied by a compensatory decrease in other thymocyte subsets; (2) a clone with growth advantage and differentiation potential is selected and populates the thymus; and (3) this clone eventually breaches homeostasis of the thymus, accompanied or followed by metastasis to other organs.     

Macrolides: A Canadian Infectious Disease Society position paper

Since the introduction of erythromycin in 1965, no new compounds from the macrolide antimicrobial class were licensed in Canada until the 1990s. Clarithromycin and azithromycin, since their introduction, have become important agents for treating a number of common and uncommon infectious diseases. They have become prime agents in the treatment of respiratory tract infections, and have revolutionized the management of both genital chlamydial infections, by the use of single-dose therapy with azithromycin, and nontuberculous mycobacterial infections, by the use of clarithromycin. The improvement of clarithromycin and azithromycin over the gastrointestinal intolerability of erythromycin has led to supplanting the use of the latter for many primary care physicians. Unfortunately, the use of these agents has also increased the likelihood for misuse and has raised concerns about a resultant increase in the rates of macrolide resistance in many important pathogens, such as Streptococcus pneumoniae. This paper reviews the pharmacology and evidence for the current indications for use of these newer agents, and provides recommendations for appropriate use.Key Words: Azithromycin, Clarithromycin, Erythromycin, Macrolides, Review, Therapeutic useErythromycin A is a naturally occurring, microbiologically active compound of the macrolide class of antibiotics. Chemical modification of erythromycin A''s 14-membered lactone ring has led to the formation of semisynthetic derivatives with not only improved bioavailability and tolerability, but also expanded spectrums of microbiological activity and improved pharmacokinetic profiles. Such modifications produced clarithromycin, classified as a macrolide because it retains the central 14-membered lactone ring (1,2), and azithromycin, classified as an azalide due to its 15-membered aglycone ring (1). The latter two compounds are the newest agents in the macrolide class licensed for use in Canada. Roxithromycin and dirithromycin are available in other countries.These compounds are clinically active against Gram-positive and Gram-negative cocci, and Gram-negative bacilli (primarily Haemophilus influenzae, Legionella species, Moraxella catarrhalis, Campylobacter jejuni, Bordatella pertussis and Helicobacter pylori). Azalides such as azithromycin have exhibited superior activity against Gram-negative pathogens and are generally less active against Gram-positive pathogens. Intracellular pathogens such as Chlamydia species, Mycoplasma species, Ureaplasma species, Borrelia species and nontuberculous mycobacteria species show varying susceptibilities. On the basis of their microbial activity, both the macrolides and azalides have been shown to be clinically useful in the treatment of uncomplicated skin and soft tissue infections, upper and lower respiratory tract infections, sexually transmitted Chlamydia trachomatis infection and peptic ulcer disease. Additionally, the improved pharmacokinetic profiles and acid stability exhibited by the newer agents may lead to enhanced patient adherence through less frequent dosing and improved bioavailability in the presence of food.     

Pituitary growth hormone response in rats during a 24-hour infusion of growth hormone-releasing factor

The pituitary GH response during a 24-h iv infusion of GH-releasing factor (hpGRF-44; 15 micrograms/h) and to a subsequent bolus injection of hpGRF-44 (2 micrograms) was studied in conscious, freely moving male rats pretreated with antiserum against somatostatin. Within 2 h of the initiation of the hpGRF-44 infusion, plasma GH concentrations rose from 169 +/- 16 to 2465 +/- 307 (+/- SE) ng/ml. By 6 h, plasma GH concentrations began to fall. They decreased slowly and reached a nadir of 490 +/- 107 ng/ml by 12 h. Rats infused for 24 h with hpGRF-44 failed to respond to a 2-micrograms bolus injection (iv) of hpGRF-44, whereas rats infused for 24 h with saline responded with a normal increase in plasma GH. The pituitary GH content of rats treated with saline was significantly greater than that of rats treated with hpGRF-44. These results demonstrate that the capacity of the pituitary to respond to GRF can be exhausted after the chronic administration of hpGRF-44 and that this lack of response appears to be due, in part, to a depletion of pituitary stores of GH.