Discriminative stimulus properties of the serotonin agonist MK 212

In an attempt to clarify the role of 5-hydroxytryptamine (5-HT) in the discriminative stimulus properties of MK 212 (6-chloro-2[1-piperazinyl]pyrazine), male Sprague-Dawley rats were trained to discriminate 0.5 mg/kg of this compound from saline. While the putative 5-HT agonists fenfluramine and m-chlorophenylpiperazine (MCPP) mimicked MK 212 in a dose-related manner, d-lysergic acid diethylamide (LSD), 8-hydroxy-2(di-n-propylamino)tetralin (8-OHDPAT), 5-methoxy-N,N-dimethyltryptamine (5-MeODMT), quipazine, Ru 24969, and 1-(m-trifluoromethylphenyl)piperazine (TFMPP) failed to substitute completely. The 5-HT₁/5-HT₂ antagonists BC 105, metergoline, and methysergide completely blocked the MK 212 cue, while the selective 5-HT₂ antagonists ketanserin and pirenperone, the dopamine antagonists haloperidol and spiperone, and the beta-noradrenergic antagonist propranolol were without effect. The substitutions of fenfluramine and MCPP for MK 212 support a role for 5-HT in the MK 212 cue; however, the lack of substitution of many other 5-HT agonists is difficult to explain. The complete antagonism by 5-HT₁/5-HT₂ but not by selective 5-HT₂, antagonists suggests the possibility that 5-HT₁ receptors mediate the stimulus properties of MK 212. Further research is needed to support this hypothesis and to investigate the relative role of 5-HT and other neurotransmitters in the stimulus effects of MK 212.Portions of this research were presented at the Meeting of the Committee on Problems of Drug Dependence Satellite Session (International Study Group Interested in Drugs as Reinforcers and the Society for the Stimulus Properties of Drugs) in Baltimore, MD (1985)     

ITP患者骨髓及血液检测指标与疗效关系的探讨

目的：为观察血小板表面相关抗体Ｇ（ＰａＩｇＧ）、外周血血小板计数（ＢＰＣ）、平均血小板容积（ＭＰＶ）、骨髓巨核细胞计数（ＭＫ）与产板型巨核细胞比例（ＰＰＭＫ）对特发性血小板减少性紫癜（ｉｄｉｏｐａｔｈｉｃ ｔｈｒｏｍｂｏｃｙｔｏｐｅｎｉｃｐｕｒｐｕｒａ,ＩＴＰ）患者疗效的预计价值。方法：采用Ｃｏｕｌｔｅｒ全自动血球分析仪及双抗体夹心ＥＬＩＳＡ法等,对７３例ＩＴＰ患者治疗前和治疗后的ＢＰＣ、ＭＰＶ、     

新生大鼠脑白质损害模型神经胶质细胞的凋亡及 MK2、Nogo-B的表达研究

目的观察2日龄(P2)新生大鼠脑白质损害(WMD)后神经胶质细胞凋亡及丝裂原活化蛋白激酶活化蛋白激酶2(MK2)、Nogo-B的变化;探讨神经胶质细胞凋亡与MK2、Nogo-B变化的时相关系。方法制备新生鼠WMD模型,分别于WMD后30 min、1 h、4 h、12 h、1 d、3 d、7 d、14 d及21 d处死大鼠,TUNEL法检测脑白质神经细胞凋亡,免疫组化(SP)法检测Nogo-B蛋白的表达,原位杂交(POD法)检测MK2 mRNA表达。结果WMD组大鼠凋亡指数在缺氧缺血4 h、12 h、1 d、3 d、7 d组与对照组相比,差异有统计学意义(P<0.05);WMD后1 h MK2mRNA在脑室周围白质及胼胝体区表达上调,并于损伤后3 d达到高峰。Nogo-B在WMD后12 h表达增加,3 d达高峰,在12 h、1 d、3 d、7 d的表达与对照组相比,差异有统计学意义(P<0.05)。结论MK2、Nogo-B在新生大鼠脑白质损害时表达增高,提示其参与了脑白质损害。     

Effects of the NMDA-antagonist,MK-801, on stress-induced alterations of dopamine dependent behavior

The effects of pretreatment with the non-competitive NMDA antagonist (+)MK-801 on the behavioral alterations induced by repeated restraint stress were investigated. Repeatedly stressed (restraint stress 2 h a day × 10 days) mice showed enhanced sensitivity to the inhibitory effects of a low dose of direct dopamine agonist, apomorphine (0.25 mg/kg), on climbing behavior. On the other hand, no changes were observed for the stimulatory effect of the high dose of apomorphine (3 mg/kg) on this behavioral response. Mice pretreated with MK-801 (0.15 mg/kg) before the stressful experience did not show altered response to the low dose of apomorphine (0.25 mg/kg). Finally, ten daily injections with 0.15 mg/kg MK-801 did not affect the behavioral response to the low dose of apomorphine, but enhanced the stimulatory effect of the high dose of the dopaminergic agonist on climbing behavior. Therefore, it is possible that the protective action of MK-801 against stress-induced behavioral alteration is due to changes in sensitivity of postsynaptic receptors.     

中期因子及MVD在胃癌中的表达及临床意义

目的探讨中期因子（midkine,MK）在胃癌组织中表达及其与微血管密度（MVD）和临床病理特征的关系,探讨影响胃癌患者长期生存的预后因素。方法应用免疫组化两步法检测107例胃癌组织中中期因子和CD34的表达,并以31例正常胃黏膜标本作对照。对CD34阳性血管进行MVD计数,并结合临床资料进行统计学分析。结合随访资料,应用Cox比例风险模型对可能影响胃癌预后结果的参数进行分析。结果胃癌组织中的中期因子阳性表达率分别为69．2％,MVD为32．74±6．46;正常胃黏膜组织中期因子0．00％,MVD为14．55±4．07,胃癌组织中中期因子表达率及MVD均明显高于正常胃黏膜组织（均P〈0．01）。中期因子表达与胃癌的大小、有无淋巴结转移、浸润深度、TNM分期有关（均P〈0．01）,而与患者年龄、性别无关。在胃癌组织中中期因子的表达与MVD呈正相关（r=0．592,P〈0．01）。MVD与胃癌的大小、浸润深度、有无淋巴结转移、TNM分期有关（均P〈0．01）。Cox单因素回归分析表明胃癌的大小、浸润深度、有无淋巴结转移、病理分期、中期因子表达与胃癌的预后有关（P〈0．05）,而性别、年龄等与预后无关（P〉0．05）。但经Cox多因素回归分析,只有肿瘤的病理分期、MK表达具有独立的预后意义（P〈0．05）。结论在胃癌组织中,中期因子的过度表达可能在肿瘤的血管生成和进展过程中起着重要作用。MK过表达可作为评估胃癌患者预后的独立指标,从而指导胃癌的治疗。     

MK801慢性处理引起皮层神经元3H-GABA释放的改变

Excitatory amino acids are involved in acute and chronic neurodegenerativediseases.Little is known about the potential consequences of chronic blockade of NMDA receptors (onesubtype of excitatory amino acid receptors).Receptor function measured as ³H-GABA release inculture media after pretreatment with MK801 was studied in rat cortical neurons in primary cultures.Cultured neurons were exposed to 1μmol·L^-1 MK801 for 4 days since the 14th day.Glutamate( 1 mmol·L^-1 )evoked ³H-GABA release was shown to be significantly increased(control0.2174‰±1.40‰; MK801 treatment 0.763%±0.192%).KCl 40 mmol·L^-1 stimulation showedno such effect.This result suggests that the NMDA receptor function of releasing neurotransmitterschanged after chronic treatment with noncompetitive antagonists.     

Translation and validation of Taiwan Chinese version of the self-regulation questionnaire for gynecologic cancer survivors

ObjectiveTo culturally adapt the self-regulation questionnaire to the Taiwan Chinese version (TC-SRQ) and to evaluate its psychometric properties for gynecologic cancer survivors.Materials and methodsA cross-sectional study was employed with a purposive sample of 287 gynecologic cancer survivors. The TC-SRQ was adapted from a Germany version through back-translation to ensure its quality. For construct validity, confirmatory factor analysis (CFA) was used to assess the TC-SRQ measurement model with fit indexes including the χ² test, the root mean square error of approximation (RMSEA), and the normed fit index (NFI), the comparative fit index (CFI), and non-normed fit indices (NNFI). For concurrent validity, the Taiwanese version of the European Organization for Research and Treatment of Cancer's 30-item core quality of life (EORTC QLQ-C30) questionnaire was used as a criterion measure for quality of life (QOL). Reliability was evaluated by internal consistency and test-retest reliability.ResultsFor a modified measurement model of TC-SRQ, the model fit (χ² = 311.23, P = .0; RMSEA = .088; NFI = .97, CFI = .98, NNFI = .97) was acceptable. The evidence of construct validity of TC-SRQ scale was confirmed by the model estimates. TC-SRQ correlated positively with the global QOL, physical, cognitive, emotional, and social functioning domains, and negatively with fatigue and pain domains of EORTC QLQ-C30. For known groups validity, TC-SRQ was correlated with groups attributed by age, family support, health status, and sleep quality. A Cronbach's α of .91 indicated good internal consistency; the test-retest reliability was .82.ConclusionsTC-SRQ is a valid and reliable instrument for assessing self-regulation in gynecologic cancer survivors.     

Paclitaxel-related dermatological problems: Not only alopecia occurs

ObjectiveDermatological problems after chemotherapy are often neglected with gynecological oncologists. Since paclitaxel is one of most popular agents for gynecology organ-related cancers, dermatologic change after paclitaxel treatment is seldom reported before.Case reportTwo patients with gynecological organ malignancy who underwent the postoperative dose-dense weekly schedule of paclitaxel 80 mg/m² plus carboplatin (area of curve 5) every three weeks had repeat dermatological problems (skull, facial and upper trunk areas) during the treatment. They included dermatitis, eczema, and folliculitis. Topical use of anti-fungal cream and oral anti-histamine agents stopped the disease progression and all had completed their chemotherapy without interruption.ConclusionClinicians should be aware of paclitaxel-induced skin toxicities, especially on the skull, face and upper trunk areas to minimize the occurrence of severe morbidity and to provide the better quality of life when cure is our primary priority in the management of gynecological organs-related malignancies.     

Continuous recording of intrapulmonary “Compressed air” as a sensitive noninvasive method of measuring bronchial obstruction in guinea pigs

The method presented is based on whole-body plethysmography. The apparatus consisted of two chambers (a=respiratory, b-body chamber) separated by a tight water-filled rubber cuff which was fixed around the head of the animal. Experiments were performed under constant gas conditions: temperature 30°C, 100% relative humidity, the volumes of the two chamber being identical. Volume changes in the chamber (V _a, V _b) were recorded continuously by means of pressure transducers. Respiratory flow was calculated by differentiation of V _a with respect to time. The three parameters V _a, V _b and respiratory flow allowed the calculation of breathing frequency, inspiration/expiration ratio, (peak) expiratory flow and specific airway conductance. In addition we describe a new parameter indicating bronchial obstruction: a graphical plot of V _b against V _a produces a closed loop, the area of which reflects the degree of airway obstruction, and we read off the parameter we term compressed air from this graph. In our hands this parameter was more than ten times as sensitive as other measures of bronchial obstruction. Using this new technique we have carried out pharmacological studies with eicosatetraynoic acid (ETYA), 2-aminomethyl 4-t-butyl-6-iodophenol (MK 447=radical scavenger), the histamine₁ antagonist elemastine and the histamine₂ antagonist cimetidine. In allergen-tested animals we observed mild protective effects of ETYA when given as an aerosol (3 mg) and pronounced effects of MK 447 (4 mg i.p.). Combined H₁H₂-antagonism was much more effective in preventing allergen-induced bronchial obstruction than H₁-antagonism alone.Supported by Deutsche Forschungsgemeinschaft (Do 240/1)