Consequence of long-term exposure to corticosterone or dexamethasone on ethanol consumption in the adrenalectomized rat,and the effect of type I and type II corticosteroid receptor antagonists

The daily fluid intake of male Wistar rats with simultaneous access to 6% ethanol and water was determined during a baseline period (1 week), following adrenalectomy (1 week) and for 3 weeks following SC implantation of hormone pellets containing corticosterone (CORT) or dexamethasone (DEX). Ethanol consumption dropped during the first week of adrenalectomy (ADX) but increased again in the absence of hormone replacement to reach preoperative levels during the ensuing weeks. The CORT treatment, which produced plasma hormone levels similar to the 24-h mean concentration of adrenally intact rats, not only reversed the effect of ADX on alcohol consumption but also enhanced it to levels above those observed in intact rats. Water intake was not affected by the CORT treatment. DEX implants stimulated water intake, but did not enhance the drinking of ethanol. SC injections of RU 28318 (type I corticosterone receptor antagonist; 10 mg/kg) or mifepristone (RU 38486; type II receptor antagonist; 25 mg/kg) at the beginning and halfway through three daily, 6-h tests failed to affect ethanol drinking in adrenally intact rats or in ADX rats bearing CORT implants. Similarly, there was no effect of giving the two antagonists in combination. These results suggest that exogenous CORT can induce excessive alcohol intake in genetically unselected rats and that this facilitatory effect may be mediated by non-genomic cellular mechanisms.     

青山抗癌注射液抑制小鼠肿瘤生长的实验研究

目的：研究青山抗癌注射液对动物移植性肿瘤生长的影响．方法：以小鼠移植性肉瘤S180和肝癌H22为模型，以顺铂(DDP)为阳性对照，生理盐水(阳)为阴性对照，观察青山抗癌注射液对肿瘤生长的影响。结果：青山抗癌注射液不同剂量组对小鼠移植性肉瘤S180和肝癌H22的生长均显示了明显的抑制作用，与NS对照组相比，P＜0.01，且呈现出量效关系．结论：青山抗癌注射液具有抑制肿瘤生长的作用.     

Interactions between growth hormone and dexamethasone in skeletal growth and bone structure of the young mouse

Summary The present study investigated the interactions of growth hormone (GH) and glucocorticoid on skeletal growth and bone structure in young mice. The purpose of this study was to examine the possible prevention by GH of the damage inflicted by dexamethasone (Dex) at sites of skeletal growth and ossification. Dex (1 mg/kg) with or without rat GH (rGH) or bovine GH (bGH), 1 mg/kg, was given for 4 weeks, from age 3–7 weeks, to female ICR mice. Tibiae, humerus, and vertebrae were analyzed morphometrically and biochemically. Growth, as determined by the mouse weight, tibial length, and humerus protein content was found to be compromised by dexamethasone. This was prevented by rGH or bGH. The epiphyseal growth plate width, trabecular bone volume, cortical bone width, mineral bone content, and alkaline and acid phosphatase activity were decreased by dexamethasone. These were prevented by rGH or by bGH. The findings of the present study suggest that in the mouse, GH can decrease or even avoid some of the pathological features in growing bones inflicted by high-dose glucocorticoid treatment.     

Cerebral sodium sensors in the sodium-deplete sheep

The sodium intake of sodium deplete sheep was studied during local, push-pull perfusion of different solutions within the third cerebral ventricle. Sheep were made sodium deplete by continuous loss of parotid saliva, and were allowed access to 0.6 M NaHCO₃ solution for 2 h daily. Local perfusion within the third cerebral ventricle was performed before and during the access to sodium solution. Four perfusion sites were used: anterior dorsal and ventral, and posterior dorsal and ventral. Perfusion of 200 mM Na-csf caused a decrease in sodium intake at each perfusion site. Perfusion of ouabain, 10⁻⁶M, caused a reduction in sodium intake only during perfusions within the anterior portion of the third ventricle. The results may indicate that specific neuronal elements sensitive to changes in intracellular sodium concentrations are located around the anterior portion of the third cerebral ventricle. These neurones, however, are not exclusive sites from where sodium intake of sodium deplete sheep can be influenced.     

Modeling the pharmacokinetics and pharmacodynamics of dexamethasone in depressed patients

Summary Changes in time course effected by cortisol suppression and the relationship of these changes to the plasma dexamethasone concentration of suppressor and non-suppressor patients are described in this report on a combined pharmacokinetic-pharmacodynamic model.Thirteen depressed patients (8 suppressors and 5 non-suppressors) received an intravenous dose (1.5 mg) of dexamethasone. The drug-induced effect changes are found to lag behind, in time, the plasma drug level changes. To accurately relate the temporal relationship of effect changes to plasma dexamethasone levels, a pharmacodynamic model (sigmoid-Emax) was combined with a pharmacokinetic model that incorporated an effect compartment. The magnitude of the time-lag was quantified by the half-time of equilibration between concentrations in the hypothetical effect compartment and the plasma dexamethasone levels (t_&frac;k_eo).The t_&frac;k_eo of the nonsuppressing group was about 50 of that of the suppressing group, indicating that for a given plasma level the onset and termination of effect for the nonsuppressing group is about two times more rapid than for the suppressing group. Moreover, the model can estimate the effect-site concentration that causes one-half of the maximal predicted effect (EC₅₀), a measure of an individual's sensitivity to dexamethasone. The receptor sensitivity (as determined from the EC₅₀ ratio) of the suppressing group was about twice that of the nonsuppressing group.     

Phosphate end dialysis value : a misleading parameter of hemodialysis efficiency

Despite low end dialysis serum phosphate levels (P_e) the control of phosphate retention remains often unsatisfactory in dialyzed patients. In order to assess the value of P_e in dialyzed children as an indicator of dialytic phosphate removal, we studied serum phosphate kinetics over the period of dialysis and post dialysis and compared these with urea kinetics. A multicenter study was conducted in the 21 French pediatric hemodialysis units and included 144 children under 15 years of age. Blood urea and phosphate concentrations were measured at the beginning, at 45 min later, at the end of dialysis, and 30 min post dialysis. At 60 min and at 360 min post dialysis measurements were made only for a subgroup of 12 children. From the serum levels, reduction ratios for urea (URR) and phosphate (PRR) and post dialysis rebound for urea (PDUR) and phosphate (PDPR) were calculated. URR (over the dialysis session, 72%±9%) was higher than PRR (47%±12%). Moreover, urea removal continued throughout the dialysis period, while most of the reduction in phosphate occurred in the initial dialysis period. Post dialysis urea rebound was limited to the 60th min post dialysis, whereas post dialysis phosphate rebound occurred until the 360th min post dialysis; by this time the serum phosphate levels had almost reached the predialysis levels. In summary, serum phosphate kinetics over dialysis and post dialysis periods in children appear to be misleading for the quantification of phosphate removal, i. e., phosphate clearance is a poor indicator of dialytic phosphate removal. Received September 21, 1995; received in revised form and accepted June 11, 1996     

地塞米松对冷藏离体肺表面活性物质和顺应性的影响

目的:观察地塞米松对冷藏离体肺表面活性物质和顺应性的影响.方法:32只家兔肺随机均分为对照组、地塞米松冷藏(4℃)保存24h、72h、120h3个组.对照组:测定室温条件下的肺表面活性物质及顺应性.冷藏组:肺离体后立即置于含有地塞米松台式液中冷藏,在相应时间取出肺,室温条件下复温后,置入生理盐水中,测定肺表面活性物质,并测定注气(生理盐水)和抽气(生理盐水)过程中,肺容积在10ml、20ml、30ml时的肺顺应性.结果:冷藏24h组注水、抽水;72h组肺容积在10ml、20ml抽气、冷藏120h组在肺容积为10ml、20ml抽气的肺顺应性同对照组比较,差异无显著性(P>0.05).其余各组、项与对照组比较差异具有显著性(P<0.05),伴有表面活性物质的减少.结论:地塞米松冷藏离体肺顺应性增大,其影响程度随冷藏时间的延长而增加,同时伴有肺表面活性物质的减少.     

川芎嗪和参麦注射液对老龄大鼠脑缺血再灌注胃肠损伤的作用

目的 :研究川芎嗪和参麦注射液及其配伍对老龄大鼠脑缺血再灌注胃肠损伤作用。方法 :选SD 2 0～ 2 2月龄大鼠分为对照组、模型组、尼莫通组、川芎嗪组、参麦组、川芎参麦组 ,测各组脑电图幅度的变化 ,胃肠组织、血清、血液和下丘脑中的生化指标及胃肠生理变化。结果 :川芎嗪和参麦注射液对老龄大鼠脑缺血再灌注胃肠组织损伤有明显保护作用。结论 :其保护作用机制与拮抗自由基损伤、调节ATP酶活性和降低肿瘤坏死因子及调节单胺类神经递质的变化有关。川芎嗪和参麦注射液及其配伍的作用机制有所不同     

婴幼儿良性颅内压增高症78例诊治分析

目的 :探讨婴幼儿良性颅内压增高症的促发因素及治疗。方法 :对 78例婴幼儿良性颅内压增高症患儿的临床资料进行分析。结果 :在促发因素中 ,发热性疾病或呼吸道感染占 41 .0 % ,药物因素占 34.6% ,中耳炎占 5 .1 %。反映感染性疾病和药物是诱发婴幼儿良性颅内压增高的重要因素 ,中耳炎所占比例下降 ;全部病例经积极治疗基础疾病 ,用甘露醇及地塞米松降颅压均全部痊愈。结论 :婴幼儿良性颅内压增高症呈良性预后 ,临床医生在小儿用药上要重视药物的剂量及不良反应。     

白莪星注射液对Hep-2细胞VEGF表达影响的实验研究

目的　探讨白莪星注射液对Hep - 2细胞VEGF表达的影响。 方法　根据抗癌药物敏感性实验的方法 ,计算出体外药物敏感性实验所用药物的一般浓度 ,分 4组 :阴性对照组、治疗组 1 (1 0 0倍稀释 )、治疗组 2 (1 0 0 0倍稀释 )、阳性对照 (顺铂 4 0 μmol/l) ,流式细胞仪检测VEGF的表达。 结果　 4组VEGF表达阳性率分别为 :5 72± 0 2 8%、3 34± 0 76 %、3 6 4± 0 2 1 %、4 6 0± 0 6 1 % ;1 0 0倍稀释组和 1 0 0 0倍稀释组VEGF表达阳性率显著低于阴性对照 (P <0 0 5 )。结论　白莪星注射液对VEGF蛋白的表达有抑制作用 ,白莪星注射液抗癌的分子机制与肿瘤血管形成有关