Stretched attend posture,a non-social form of ambivalence,is sensitive to a conflict-reducing drug action

Based upon the ethological element stretched attend to a conspecific, which reflects ambivalence between approach and avoidance in a social context, a simple, non-social behavioral method for studying conflict behavior in mice was investigated. Thus, stretched attend posture (SAP) and other behavioral acts were measured in untreated or drug-treated mice which were individually placed on a perforated platform previously rubbed with foreign male urine and boluses. In naive, untreated mice, the occurrence of SAP was partly housing- and lighting-dependent. After repeated exposure to the test situation, untreated mice showed less SAP, whereas static behavior (immobility and activity at rest) was increased. After single oral treatment with diazepam, clobazam or phenobarbital, SAP was reduced, whereas static behavior or going forwards in SAP was increased. Chlorpromazine and imipramine did not influence SAP. In naive mice, single IP injection of pentylenetetrazol did not significantly increase SAP. The similarity in the behavioral response between experienced, untreated mice and naive animals treated with diazepam, clobazam, or phenobarbital suggests that drug-treated mice behaved as if they were already familiar with the test situation. The latter drug-induced changes are consistent with data obtained in animal models which are based upon the measurement of behavioral inhibition. Under the present test conditions, pentylenetetrazol did not show anxiogenic properties. Nevertheless, the SAP test, based primarily on the measurement of the ambivalence element, offers a simple procedure for examining the conflict-reducing properties of drugs, dispensing with the need of noxious stimuli or prior training.Some of these results were presented at the 15th Annual USGEB/USSBE Meeting in Fribourg, Switzerland (17–18 March 1983) and, published in abstract form in Experientia (1983) 39(6):681–682     

Implications of the 2018 Canadian Cannabis Act: Should regulation differ for medicinal and non-medicinal cannabis use?⋆

The regulatory framework for access to medical cannabis has been established in Canada since 2001, with the number of patients seeking access growing substantially over the years. With the novel enactment of the Cannabis Act in October 2018, Canada now maintains two distinct mechanisms for accessing cannabis - one for medical cannabis and the other for non-medical cannabis. With two regulatory access mechanisms in place, questions have arisen in the country as to the necessity of maintaining regulatory separation and the integrity of the medical access framework. A single framework would remove the gate-keeping function that the medical profession currently holds, streamlining processes and simplifying the current regulatory landscape. This approach has been advocated for by the Canadian Medical Association, despite objections from multiple stakeholders. Critical questions arise should the medical access framework be dissolved into a single, non medical-based regulatory framework. Insurance coverage, control mechanisms, market incentives, and patient obligations represent some examples of these issues. This paper will expand upon these considerations and highlight why maintaining two separate access mechanismss best serves the Canadian public. As medicinal cannabis continues to be liberated in international jurisdictions, this paper can help to illuminate the current status of medical cannabis in Canada, and provide insights to those from other countries on our current approach and domestic challenges.     

支气管动脉灌注化疗治疗晚期原发性肺癌近期疗效影响因素分析

目的探讨经支气管动脉灌注化疗(BAI)治疗晚期肺癌近期疗效的影响因素。方法回顾性分析1990年3月至2006年6月间胸部X线片复查资料相对完整的82例经BAI治疗的原发性晚期肺癌的近期疗效。结果完全有效(CR)10例(12.2%)、部分有效(PR)32例(39.0%)、轻微有效(MR)23例(28.0%)、稳定(SD)15例(18.3%)、进展(PD)2例(2.4%)。单因素方差分析结果显示,半月时肿瘤缩小率(TDR1/2month)(χ2=25.92,P<0.01)、BAI次数(TBAI)(χ2=17.70,P<0.01)、肿瘤大小(Tsize)(χ2=14.21,P<0.01)和肿瘤血供丰富程度(χ2=6.59,P<0.01)对近期疗效的影响具有统计学意义。对年龄、病理类型等12项协变量进行二项分类Logistic回归分析,采用向后删除法经10步二次迭代,得到Logistic回归方程:P(1)=1/[1 e-(-8.953 2.656TDR1/2month 1.382TBAI 1.230Tsize)],方程对BAI近期疗效有效与无效的预测正确率分别为85.7%和70.0%。结论第1次BAI后半月时的肿瘤缩小率、BAI治疗次数和肿瘤的大小是影响BAI近期疗效的因素。     

A Theoretical Model for the Margination of Particles within Blood Vessels

The margination of a particle circulating in the blood stream has been analyzed. The contribution of buoyancy, hemodynamic forces, van der Waals, electrostatic and steric interactions between the circulating particle and the endothelium lining the vasculature has been considered. For practical applications, the contribution of buoyancy, hemodynamic forces and van der Waals interactions should be only taken into account, whilst the effect of electrostatic and steric repulsion becomes important only at very short distances from the endothelium (1–10 nm). The margination speed and the time for margination t_s have been estimated as a function of the density of the particle relative to blood , the Hamaker constant A and radius R of the particle. A critical radius R_c exists for which the margination time t_s has a maximum, which is influenced by both and A: the critical radius decreases as the relative density increases and the Hamaker constant decreases. Therefore, particles used for drug delivery should have a radius smaller than the critical value (in the range of 100 nm) to facilitate margination and interaction with the endothelium. While particles used as nanoharvesting agents in proteomics or genomics analysis should have a radius close to the critical value to minimize margination and increase their circulation time.     

Behandlung mit Mexiletin

Summary Pharmacokinetics of the antiarrhythmic agent mexiletine were found to be highly variable. Ineffective or toxic doses can be avoided by monitoring mexiletine concentrations in patients plasma. However, the success of antiarrhythmic therapy is mainly determined by the severety of the underlying disease. Therefore, the efficacy of treatment with mexiletine should be controlled by Holter monitoring.

Herrn Prof. Dr. G. Schütterle zum 60. Geburtstag gewidmet     

Free choice ethanol intake of laboratory rats under different social conditions

To study the effects of different kinds of social deprivation on voluntary ethanol (ETOH) intake male Wistar rats were housed by (a) individual caging, (b) contact caging (partial social deprivation), and (c) group caging (four individuals per cage). In the latter condition the individuals were separated once a week from each other for 24 h. The rats simultaneously received water 5%, 10% and 20% ETOH for a period of 14 weeks. Additional control animals received water. Isolated individuals drank significantly more alcohol than group-housed or contact-caged rats. After a few days they preferred the 20% solution. Circadian measures revealed a discontinuous intake of high doses (> 0.5 g/kg/h) during short time periods. Contact-caged rats consumed much less ETOH, but both the preference for 20% ETOH and the circadian course of intake were similar to those occurring after isolation. ETOH intake of group-housed individuals was low. These individuals preferred the 5% solution and continuously consumed small ETOH doses. During the period of short-term isolation they drank even more ETOH than long-term isolated individuals. In contrast to the latter, the enhancement of intake decreased after some weeks. It is suggested that the differences between the housing groups not only reflect different degrees of isolation stress, but may also be explained by a contribution of different reinforcing or aversive psychotropic effects of ETOH. Reduction of isolation stress is probably most important in the situation of short term separation, whereas dose-dependent reinforcement via social stimulation or sedation may affect the drug taking behavior under the other social conditions.