溴莫尼定对视网膜缺血性损伤神经保护作用的实验研究

目的：探讨溴莫尼定(brimonidine)对视网膜缺血性损伤神经的保护作用。方法：新西兰大耳白兔32只，随机分为正常对照组、生理盐水治疗组、噻吗心安(timolol)治疗组、brimonidine治疗组，每组8只。后3组为损伤治疗组，通过生理盐水前房高压灌注的方法，制成视网膜缺血动物模型，在视网膜缺血前lh其结膜囊内分剐给予生理盐水、0．5％timolol眼液或0．2％brimonidine眼液局部治疗。在灌注后7d，观察图形视网膜电图(P-ERG)b波振幅变化，并进行组织形态学观察和视网膜神经节细胞(RGC)计数分析。结果：灌注后7d，3个损伤治疗组相对b波振幅恢复率为：7％、11％和64％，RGC标准丢失率为：43％、38％和12％，brimori-die治疗组视网膜组织形态结构接近正常对照组，而生理盐水治疗组和timolol治疗组视网膜内层组织结构损伤明显。结论：Brimonidine局部治疗对缺血诱导的视网膜结构和功能的损害有明显的神经保护作用。     

Leukotriene receptor antagonists. 2. The [[(tetrazol-5-ylaryl)oxy]methyl]acetophenone derivatives

A series of [[(tetrazol-5-ylaryl)oxy]methyl]acetophenones was synthesized and evaluated as antagonists of leukotriene D4 induced contractions of guinea pig ileum. Substitutions at the 3-position of the acetophenone with ethyl (66), propyl (68), butyl (83), and isobutyl (84) gave -log IC50 values of 7.9, 8.0, 7.8, and 7.7, respectively. Equally potent compounds were obtained when the tetrazol-5-yl group was connected to the second benzene ring in the para position with a chemical bond (67), methylene (68), or ethylene (71). For retention of high antagonist activity, the acetophenone should be substituted in the 2-position by a hydroxyl group and the tetrazole ring should have an acidic hydrogen atom. 1-[2-Hydroxy-3-propyl-4-[[4-(1H-tetrazol-5-ylmethy) phenoxy]methyl]phenyl]ethanone (68, LY1632443) has undergone extensive pharmacologic evaluation for its potential as an antiasthma agent.     

Diabetes alters μ and κ opioid binding in rat brain regions: comparison with effects of food restriction

Diabetic rats display changes in opioid pharmacology and brain regional levels of opioid peptides and prodynorphin mRNA. Previous investigations of opioid receptor binding, carried out in whole-brain homogenates, have, however, failed to detect changes. In the present study, quantitative autoradiography was used to measure μ and κ opioid receptor binding in discrete brain regions of streptozotocin-treated diabetic rats. Measurement was limited to regions that previously displayed opioid binding changes in chronically food-restricted rats, since our primary aim is to identify brain mechanisms that mediate adaptive responses to persistent metabolic need and adipose depletion. Diabetics displayed strong trends or statistically significant changes which matched seven of the thirteen binding changes observed in food-restricted rats. In no case did diabetics display changes in the opposite direction. The two statistically significant changes common to food-restricted and diabetic rats are increased κ binding in the medial preoptic area and decreased μ binding in the lateral habenula. The possible functional significance of these changes is discussed.     

Herpetic croup: two case reports and a review of the literature

Croup is an acute infectious illness usually occurring in children; it is characterized by brassy cough and stridor. The main pathogens include mainly parainfluenza and influenza viruses. Recently there have been reports of prolonged croup caused by the herpes simplex viruses. We report two cases of prolonged croup due to herpes simplex types 1 and 2. We also review and summarize the reported pediatric cases of herpetic croup.     

Time course of changes in ETB receptor density and function in tracheal airway smooth muscle during respiratory tract viral infection in mice.

1. In the current study, the density and function of ETA and ETB receptors in mouse tracheal airway smooth muscle were determined over the time course of respiratory tract infection with influenza A/PR-8/34 virus. 2. Quantitative autoradiographic studies using [125I]-endothelin-1 revealed that the tracheal airway smooth muscle from control mice contained ETA and ETB sites in the ratio of 49%:51% (+/- 2%, n = 29 mice). Respiratory tract viral infection was associated with increases in the density of ETA sites and decreases in the density of ETB sites at days 1, 2 and 4 post-inoculation which were reversible by day 19. For example, at day 4 post-inoculation, a time when the manifestations of viral infection were at or near their peak, the ratio of ETA:ETB sites was 72%:28% (+/- 4%, n = 6 mice, P < 0.05). In contrast, at day 19 post-inoculation, by which time viral infection had essentially resolved, the ratio of ETA:ETB sites was similar to control (51%:49% (+/- 3%), n = 6 mice). 3. Endothelin-1 was a potent spasmogen in isolated tracheal airway smooth muscle preparations from control mice (ED70 = concentration producing 70% of contraction induced by 10 microM carbachol = 6.3 nM (95% confidence limits, 4.0-10; n = 6 mice)). Neither the ETA receptor-selective antagonist, BQ-123 (3 microM), nor the ETB receptor-selective antagonist, BQ-788 (1 microM) alone had any significant inhibitory effect on endothelin-1-induced contractions of mouse isolated tracheal smooth muscle. However, simultaneous treatment with BQ-123 (3 microM) and BQ-788 (1 microM) resulted in a 10 fold rightward shift in the concentration-effect curve to endothelin-1 (ED70 = 60 nM, (44-90; n = 6 mice, P < 0.05)), indicating that contraction was mediated via both ETA and ETB receptors. 4. Endothelin-1 evoked similar concentration-dependent contractions of tracheal smooth muscle isolated from control and virus-inoculated mice. In the presence of the ETB receptor-selective-antagonist, BQ-788 (1 microM), the potency and maximum response to endothelin-1 were similar in preparations from control and virus-inoculated mice at all time points investigated. However, unlike control responses, endothelin-1-induced contractions in preparations from virus-infected mice were significantly inhibited by the ETA receptor-selective antagonist, BQ-123. For example, at day 4 post-inoculation, the contractile response to 30 nM endothelin-1, in the presence of BQ-123 (3 microM), was only 20 +/- 12% (n = 6 mice, P < 0.05) of that produced in control preparations under similar conditions. However, at day 19 post-inoculation, contraction evoked by 30 nM endothelin-1 in the presence of BQ-123 (3 microM), was similar to that in preparations from control mice. 5. In summary, during the early stages (days 1-8 post-inoculation) of respiratory tract infection with influenza A/PR-8/34 virus, we observed decreases in the density of tracheal airway smooth muscle ETB receptors which were reflected in decreases in ETB receptor-mediated airway smooth muscle contraction. In addition, during the same period of viral infection we observed increases in the density of tracheal airway smooth muscle ETA receptors which were not associated with increased function of the ETA receptor-effector system linked to contraction. Virus-associated modulation of ETA and ETB receptor density and function was reversible with recovery from infection.     

mRNAs encoding ribulose-1,5-bisphosphate carboxylase remain bound to polysomes but are not translated in amaranth seedlings transferred to darkness

When light-grown seedlings of amaranth are transferred to total darkness, synthesis of the large subunit (LS) and small subunit (SS) of ribulose-1,5-bisphosphate carboxylase [RbuP₂Case; 3-phospho-D-glycerate carboxylase (dimerizing), EC 4.1.1.39] is rapidly depressed. This reduction in RbuP₂Case synthesis occurs in the absence of any corresponding changes in levels of functional mRNA for either subunit. Four hours after light-to-dark transition little, if any, changes in the distribution of LS and SS mRNAs on polysomes could be detected. The association of these mRNAs with polysomes was authenticated by treatment with RNase A or puromycin. Furthermore, polysomes were able to synthesize LS and SS precursor in cell-free translation systems supplemented with inhibitors of initiation. Therefore, during a light-to-dark transition LS and SS mRNAs remained bound to polysomes but were not translated in vivo, suggesting that control is exercised, in part, at the translational elongation step.