Cocaine tolerance: Interactions among random-ratio and random-interval reinforcement-schedule parameters and repeated exposure to cocaine

Food-deprived pigeons were trained to peck a key under either a three-component multiple random-ratio 5, random-ratio 25, random-ratio 125 schedule or a three-component multiple random-interval 10-sec, random-interval 30-sec, random-interval 125-sec schedule of food presentation. Following determination of acute effects of cocaine (1.0-13.0 mg/kg), are-sponse-rate-reducing dose was given before each daily session. Once performance under conditions of daily administration had become stable, other doses occasionally were substituted for the usual daily dose so that dose effects could be assessed. Tolerance, i.e., a rightward shift in the dose-effect curve was observed in all subjects. For subjects studied under the random-ratio schedules, however, the robustness of the tolerance usually was related to the schedule-parameter value; tolerance was great at lower random values. By contrast, subjects whose responding was maintained by random-interval schedules were less likely to show tolerance that was schedule-parameter dependent. The results also provide suggestive evidence that dose may be an important factor in determining effects of repeated cocaine exposure; repeated administration of larger doses may be less likely to result in tolerance than similar exposure to smaller doses.     

EFFECTS OF ANGIOTENSINS II AND III ON GLOMERULOTUBULAR BALANCE IN RATS

1. The role of angiotensin as a modulator of proximal glomerulotubular (GT) balance was investigated in anaesthetized rats by examining the relationship between glomerular filtration rate (GFR) and absolute proximal reabsorption (APR) during removal of endogenous angiotensin II (AII) and III (AIII) with enalaprilat (CEI) and then during their subsequent replacement by intravenous infusions. 2. Enalaprilat lowered mean arterial blood pressure (MABP) and increased renal blood flow (RBF), GFR, urine flow rate and sodium excretion. Filtration fraction (FF) was not altered. Absolute proximal reabsorption, derived from fractional lithium clearance, increased by only 48% of the change expected for 'perfect' GT balance. 3. Angiotensin II replacement corrected MABP, GFR and plasma renin level, but reduced RBF and increased FF; APR was decreased and GT balance was restored. Urine flow and sodium excretion remained above control values with AII. 4. Replacement with AIII did not correct the hypotension but completely reversed the renal and renin responses to enalaprilat and restored GT balance without affecting FF. 5. It was concluded that the relation between proximal reabsorption and GFR is considerably modified by the intrarenal angiotensin concentration. The findings are best explained by a direct stimulation of proximal tubular sodium transport by angiotensin at the concentrations existing in anaesthetized rats.     

心肌酶测定在窒息新生儿心肌损害32例中的应用价值

目的通过对32例窒息后心肌受累的新生儿治疗前后心肌酶谱测定，了解心肌酶谱在窒息新生儿心肌损害诊治中的意义。方法32例均自入院后12h及治疗后5～7天各静脉采血1次，作GOT、LDH、CK、CK-MB检查。结果窒息后心肌损害治疗前后心肌酶谱各项指标比较差异均有显著统计学意义（P〈0．01），出院时心肌酶多恢复正常。结论对窒息新生儿做心肌酶谱检查，有利于早期发现心肌损害并及时治疗，并可作为判断疗效及预后的指标。     

Analysis of the mechanism of action of bradykinin on human basilar artery in vitro

Summary Bradykinin (BK) initially produced concentration-related relaxations of human basilar artery in vitro. Concentration-effect curves constructed at 2 h intervals to BK over an 8 h period were reproducible. The rank order of potency of three kinins on the human basilar artery was found to be BK > methionyl-lysyl-BK > des-Arg⁹-BK. The B₂-receptor antagonist Thi^5,8 d-Phe⁷-BK but not the B₁-receptor antagonist des-Arg⁹-Leu⁸-BK selectively blocked BK-induced relaxations of the human basilar artery.The relaxant effects of bradykinin and acetylcholine but not papaverine were attenuated after removal of the endothelium or treating the tissues with BW755C. Indomethacin was without effect. Concentration-effect curves to angiotensin I were markedly attenuated by captopril at a concentration which had no effect on BK, angiotensin II or 5-hydroxytryptamine responses. It is concluded that BK induced relaxations of the human basilar artery are mediated via activation of a B₂ receptor and the response is dependent upon the release of a factor present in the endothelium. Angiotensin converting enzyme is present in the human basilar artery and is important for the conversion of angiotensin I to angiotensin II but apparently not for the degradation of BK. It is likely that other kininases are present and active in the tissue. Send offprint requests to E. T. Whalley at the above address     

影响α-淀粉酶分离液澄清度的因素

本文根据凝聚和絮凝原理,研究了无机盐和高分子絮凝剂加入量对枯草杆菌BF 7658α-淀粉酶分离液澄清度的影响。实验结果表明,氯化钙可使α-淀粉酶发酵液的ζ电位降低,分离液的澄清度增加,用氯化钙和磷酸氢二钠来处理发酵液,则其分离液的澄清度较单用氯化钙为大,阴离子型高分子絮凝剂如海藻酸钠加入量对分离液澄清度也有一定影响。实验中还发现,澄清的发酵液在10℃下贮存可保持澄清透明状态。     

Protective genes expressed in endothelial cells of second hamster heart transplants to rats carrying an accommodated first graft

Abstract: Accommodation refers to survival of a xenograft despite the presence of anti-donor organ antibodies and complement. We have recently shown that accommodation of a hamster heart transplanted to a rat receiving short-term cobra venom factor (CVF) and continuing cyclosporine A (CyA) therapy is associated with i) the expression in the endothelial cells (EC) and smooth muscle cells of the graft of a number of "protective" genes, ii) a prominent intragraft Th2 cytokine profile, and iii) the relatively heavy deposition of IgG2c antibodies on the EC of the graft. In contrast, rejecting grafts do not express the protective genes, have a Th1 cytokine profile, and apparently have lesser amounts of IgG2c. These findings are consistent with host factors (Th2 cytokines and IgG2c) contributing to xenograft accommodation. To test whether these host factors may predispose to the development of accommodation, we placed a second hamster heart into each of 12 rats carrying a surviving first heart; recipients were, at the time, receiving only CyA. Whereas first grafts transplanted to rats receiving only CyA survive for 3 to 4 days, 11 out of 12 second transplants survived more than 20 days, and the other survived for 7 days. Nine of the twelve were not rejected: of these, four were removed between day 35 and 132 for study, and the remainder are still beating at 35 to 52 days. The surviving second hearts we studied had accommodated in that the picture on immunopathology was the same as for surviving first hearts. We suggest that the Th2 cytokines and perhaps the IgG2c response are factors in allowing prolonged survival of the second grafts and, further, that these factors contribute to the expression in the EC and smooth muscle cells of the surviving second hearts of the protective genes.     

大肠杆菌表达耐热DNA聚合酶的纯化和鉴定

目的探讨工程菌表达的耐热ＤＮＡ聚合酶的纯化方法。②方法收集ＩＰＴＧ诱导带有耐热ＤＮＡ聚合酶（ＴＤ聚合酶）基因表达质粒的工程菌株ＤＨ－ＴＤ４，用溶菌酶裂解，６０℃处理后，上清液用硫酸铵沉淀，根据溶解度差异进行粗分级，然后进行离子交换层析细分级，并经聚合酶链式反应（ＰＣＲ扩增）鉴定其活性。③结果纯化的ＴＤ聚合酶具有良好的聚合活性。④结论溶解度差异与离子交换层析是工程菌表达的耐热ＤＮＡ聚合酶纯化的主要步骤。基因工程制备的ＤＮＡ聚合酶可用于ＰＣＲ检测     

C-fos expression in the rat nucleus basalis upon excitotoxic lesion with quisqualic acid: a study in adult and aged animals

Summary. A unilateral quisqualic acid lesion was placed in the nucleus basalis magnocellularis of 3- and 24-month-old rats, and the animals were sacrificed at different times post-surgery. The morphology and the number of the cholinergic neurons of the nucleus basalis were analyzed by means of immunohistochemistry for cholineacetyltransferase, in order to evaluate the size and severity of the lesion. Immunohistochemistry for the immediate early gene c-fos was also performed in order to clarify its role in the process of neurodegeneration following the excitotoxin injection. The DNA laddering and TUNEL techniques were used to define the type of cell death involved. At short times (4 hr) the lesion induced alterations in the morphology of cholinergic neurons of the nucleus basalis. Subsequently, a significant decrease in the number of neurons was found in comparison to the contralateral unlesioned side. In the older animals the loss of cholineacetyltransferase immunoreactivity had an earlier onset (4 hr) than in the young (24 hr). C-fos expression was induced by the lesion and not by saline injection in the nucleus basalis and in neighbouring areas of the brain as early as 4 hr after surgery. The c-fos protein was no longer present by 24 hr. Furthermore, the c-fos gene product was consistently absent from the nuclei of cholinergic cells. The aged animals exhibited a slower and smaller increase in c-fos as measured by counting the labelled nuclei in the injected area. Analysis of DNA fragmentation did not provide any evidence for apoptosis as the type of cell death involved in the cholinergic degeneration. These results indicate that the c-fos protein might have a protective role in the response to excitotoxic lesions. Furthermore, we have shown that the aged brain displays a reduced ability to produce a c-fos-mediated plastic response to the lesion. Received December 17, 1997; accepted February 17, 1998     

酵母菌2号培养最佳条件的选择

成人特发性乳糖酶缺乏症的发生率极高，这些人进食牛奶后会出现胃肠胀气、腹痛、腹泄等对牛奶不耐受的消化不良症状。为解决这一问题，自１９８９年起，国内外不少学者是主张有产替代疗法，即将人工培养制备纯化的乳糖酶直接加入牛奶中以水解其中的乳糖来弥补成人乳糖酶的缺乏。