Long-lasting increase in the set point for cocaine self-administration after escalation in rats

Rationale: When access time to a continuous schedule of drug self-administration is restricted, animals tend to limit intake to a certain level over time and across doses. This observation suggests an endogenous constraint or set point that determines the individual’s preferred level of pharmacological effects. Objectives: To assess whether the transition to increased levels of drug intake is associated with a change in set point. Methods: Two groups of rats were trained on a 1-h continuous schedule of cocaine self-administration (250 μg/injection), after which access to cocaine was increased to 6 h in one group (Long Access or LgA rats) or kept to 1 h in the other group (Short Access or ShA rats). After 22 sessions on this regimen, different doses of cocaine were tested (31.25, 62.5, 125, and 250 μg/injection). For each dose, the post-response time-out period was reduced to 4 s to reduce any temporal limitations on self-injections and subjects were tested several times. Results: In LgA rats, the first hour intake escalated over time and eventually reached a level 200% greater than that of ShA rats. Though all rats maintained relatively constant intake across doses, LgA rats took nearly two times as much cocaine than ShA rats. When access to cocaine for LgA rats was reduced to 1 h, intake returned very slowly toward pre-escalation levels but was still elevated even after 2 months of reduced availability. Conclusions: These data suggest that the transition to escalated levels of intake is associated with a long-lasting change in cocaine set point. Received: 12 February 1999 / Final version: 21 May 1999     

Mucoadhesive Polymers in Peroral Peptide Drug Delivery. VI. Carbomer and Chitosan Improve the Intestinal Absorption of the Peptide Drug Buserelin In Vivo

Purpose. To evaluate the effect of the crosslinked poly(acrylate) carbomer 934P (C934P) and its freeze-dried neutralized sodium salt (FNaC934P) as well as chitosan hydrochloride on the intestinal absorption of the peptide drug buserelin. Methods. Buserelin was applied intraduodenally in control buffer, 0.5% (w/v) C934P, 0.5% (w/v) FNaC934P, 1.5% (w/v) chitosan hydrochloride or FNaC934P/chitosan hydrochloride (1:1 (v/v)) mixture in rats. Results. All polymer preparation showed a statistically significant improvement of buserelin absorption compared to the control solution. The absolute bioavailabilities for the different polymer preparations were: control, 0.1%; 0.5% FNaC934P, 0.6%; 0.5% C934P, 2.0%; chitosan hydrochloride, 5.1% and FNaC934P/chitosan hydrochloride (1:1 (v/v)) mixture, 1.0%. The higher bioavailability with chitosan hydrochloride compared to C934P and FNaC934P indicates that for buserelin the intestinal transmucosal transport enhancing effect of the polymer plays a more dominant role than the protection against proteases such as -chymotrypsin. Conclusions. The mucoadhesive polymers carbomer 934P and chitosan hydrochloride are able to enhance the intestinal absorption of buserelin in vivo in rats, and may therefore be promising excipients in peroral delivery systems for peptide drugs.     

Modell eines computergestützten qualitätssicherungssystems in der verbrennungsintensivtherapie

Zusammenfassung Ausgehend von Überlegungen für ein angemessenes Qualitätssicherungssystem im intensiv-medizinischen Bereich werden die Voraussetzungen für ein ganzheitliches Qualitätsmanagementsystem im Krankenhaus entworfen. Die Grundlage für ein dynamisches Qualitätssicherungssystem ist auf der dokumentatorischen Ebene eine umfassende Datenbasis, die auf einer zeitlich und datentechnisch unbegrenzten Patientenakte basiert. Die notwendige Hard- und Softwarestruktur wird durch die konsequente Anwendung einer Client-Server-Architektur gewährleistet. Die ständige Überprüfung der bestehenden Qualitätsziele in einem ökonomischen Regelkreis benötigt ein System mit flexiblen Abfragemechanismen. Dieser informatorische Datenzugriff auf jeder Hierarchieebene der Krankenhausstruktur wird durch das Konzept des Data-Warehouse ermöglicht, das als Datenbanksystem mit subjektorientierten, integrierten, zeitvariablen und beständigen Informationen konzipiert ist.

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A computer-assisted quality-assurance model for burn intensive care applications

The prerequisites for an integrated quality management system for hospitals were developed as a result of considerations regarding the necessity of an appropriate quality-assurance system for the intensive care sector. The basis for a dynamic quality-assurance system on the documentational level is a comprehensive data base containing patient files unlimited in terms of time and data technology. The necessary hardware and software structure will be provided by consistent application of a client-server architecture. Permanent surveillance of existing quality objectives within the scope of an economic close-loop system requires a system with flexible query mechanisms. Informational data access from all hierarchical level within the hospital organization is facilitated by the data warehouse concept, a data base system with subject-oriented, integrated, time-variable, and persistent data.

     

Progressive-ratio performance maintained by drug infusions: Comparison of cocaine,diethylpropion, chlorphentermine,and fenfluramine

Cocaine, diethylpropion, chlorphentermine, and fenfluramine were compared on a drug-maintained progressive-ratio procedure in baboons. Intravenous infusions of drug were contingent on completion of a fixed-ratio response requirement (fixed number of lever-press responses) with a 3-h time-out period following each infusion. Prior to testing each dose of drug, stable self-infusion performance was first established with 0.4 mg/kg cocaine when the fixed-ratio requirement was 160. Subsequently, a test dose of drug was substituted for the standard dose of cocaine. If the dose of drug maintained a criterion level of self-infusion performance (six or more infusions per day for 2 days), the ratio requirement was systematically increased every day until the breaking point at which the self-infusion performance fell below a criterion level (one or zero infusionsper day). Fenfluramine did not maintain criterion self-infusion performance at any dose tested (0.02–5.0 mg/kg). The dose ranges of the other drugs that maintained maximum breaking points were 1.0–5.6 mg/kg for chlorphentermine, 1.0–3.0 mg/kg for diethylpropion, and 0.1–0.4 mg/kg for cocaine. Within-animal comparison of the maximum breaking points indicated that cocaine maintained the highest breaking points, followed in order by diethylpropion, chlorphentermine, and fenfluramine. The rank ordering of these drugs with the breaking point measure corresponds well with both the results of other animal experiments on measurement of reinforcing efficacy of these drugs and with the clinical information about the human subjective effects and abuse of these drugs.     

The microcomputer revolution

The role of microcomputers in the analytical laboratory is growing rapidly as applications software becomes more generally available. In this survey, the impact of microcomputers on the practice of analysis in pharmaceutical and biomedical areas is examined in the context of available hardware. The advent of 16-bit microcomputers and the implications of computer access to networked data bases are also discussed.     

电针“曲泉”穴对小鼠胆汁分泌的影响

本实验用具备胆瘘的大鼠颈静脉恒速灌注肝胆酸钠10μmol/(100g·h)维持胆汁酸池恒定条件下,观察电针“曲泉”穴对肝胆汁分泌的影响及与受体的炎系。结果表明:电针“曲泉”穴,胆汁流量、胆汁K~+、Na~+、Cl~-、HCO_3~-排出量均显著增加,(P<0.01),但不影响胆酸的排出量。说明电针“曲泉”穴有利胆作用,所刺激肝胆汁本属不依赖胆汁酸部分。在本实验条件下,静脉给予阿托品(0.2mg/kg),酚妥拉明2.5mg/(kg·h))、心得安(5mg/kg)对胆汁分泌无显著影响,但阿托品有加强其利胆效应的倾向(P>0.05),而心得安则完全抑制其效应(P<0.01)。结果表明:“曲泉”穴的利胆效应与β受体有关,与α受体关系不大,并提示M受体或阿托品及体液因素如促胰液素,胰高血糖素等亦可参与“曲泉”穴的利胆机制。     

骨科下肢侧卧位手术牵引架的研制及临床应用

目的研制并临床验证一种简便、实用、灵活、科学的骨科下肢侧卧位手术牵引架.方法1999年1月～2003年1月采用本手术设备共进行了51例均在侧卧位状态下进行的手术;其中股骨粗隆间骨折23例、股骨粗隆下骨折4例,行DHS22例、Gamma钉5例;股骨中下段骨折24例,行股骨交锁钉3例、梅花钉3例、LCDCP18例.结果采用本手术设备的手术情况是DHS、Gamma钉组的平均手术时间为51±19min、出血量为100士57ml,交锁钉组的手术时间为70±19min、出血量为312±94ml;与常规的仰卧位手术比较P＜0.01,同时方便C-臂X光机透视,尤其是侧位透视.此外,还可运用本手术设备进行股骨中下段骨折的其他各种内固定手术,牵引效能好,方便术区皮肤消毒及术中骨折复位.结论本骨科下肢侧卧位手术牵引架结构简单、零部件少、装卸容易、适应症广、操作方便、利于C-臂X光机透视,术中出血量少、损伤小、手术时间短,具有较好的实用型、先进性、科学性,值得临床推广应用.     

三黄软膏皮肤用药毒性实验研究

为观察三黄软膏药物外用的安全性 ,进行了动物完整皮肤及破损皮肤长期接触三黄软膏 ,经皮肤渗透对局部及全身产生的毒性和反应的恢复程度 ,用三黄软膏 2g·kg-1、10g·kg-1剂量 (分别相当于 6 0kg人临床用量的 10、5 0倍 )连续对家用兔外用给药4周及停药恢复性观察 2周。结果表明给药期动物的皮肤状况、全身症状、行为活动、摄食、粪便性状、体重增长、血液学均未见明显的毒性反应 ,而高剂量组动物血液生化指标AST、ALT明显增高 ,病理组织学检查时肝水肿明显 ,可见有一定的毒性反应 ;停药期动物的血液生化指标AST、ALT肝组织病理组织学检查恢复正常 ,其他各项指标均未见明显的毒性反应 ,可见该毒性反应是可逆恢复的。表明三黄软膏在临床用药范围内连续使用是比较安全的。     

磷脂聚合物在医药学中的应用

目的在简介磷脂的基础上 ,概括了磷脂类似物和磷脂聚合物的合成方法及其在医药领域中的应用。方法在参阅国内外相关文献的基础上 ,进行分析、整理和归纳。结果磷脂聚合物的合成方法已经发展的比较成熟 ,但是在医药方面的应用主要限于磷脂聚合物型脂质体、聚乙二醇(PEG)修饰型脂质体和磷脂修饰型聚合物。结论具有两亲性和生物相容性的磷脂及其聚合物在医药领域具有广泛的发展前景     

肺部听诊在开胸术后呼吸道管理中的应用

目的 探讨开胸手术后呼吸道管理中肺部听诊的必要性。方法 分析288例手术术后肺部听诊及时发现患并发症的临床资料和护理方法。结果 362例手术患中出现并发症的288例经积极治疗、认真护理后均好转。结论 开胸术后呼吸道管理中肺部听诊可早观察、早发现术后感染和并发症，有助于预见性、针对性护理和观察护理措施效果，减少术后并发症的发生率，值得推广。