Effects of antipsychotic drugs on latent inhibition: sensitivity and specificity of an animal behavioral model of clinical drug action

Latent inhibition (LI) of a conditioned emotional response (CER) has been proposed as a quantitative measure of selective attention. We have assessed the parallels of the pharmacology of LI in rats with the clinical pharmacology of schizophrenia. Drug and vehicle treated rats were divided into groups and preexposed 20 times to cage illumination as a CS, or not preexposed. All groups were conditioned with 2 CS-footshock pairings. The following day CER, as measured by interruption of drinking in response to CS presentation, was recorded. LI was observed as a decreased CER in preexposed relative to non-preexposed animals. LI was enhanced by haloperidol 0.3 mg/kg after 7 or 14 daily treatments, but not after a single acute dose. Haloperidol doses of 0.3 and 0.03 mg/kg enhanced LI, while doses of 0.003 and 3.0 mg/kg had no effect. Haloperidol enhancement of LI was unaffected by the coadministration of the anticholinergic agent trihexyphenidyl. Enhancement of LI is exhibited by the antipsychotic drugs fluphenazine, chlorpromazine, thiothixene, thioridazine, mesoridazine, and metoclopramide but not clozapine. The non-antipsychotic drugs pentobarbital, imipramine, chlordiazepoxide, trihexyphenidyl, and promethazine failed to enhance LI. LI exhibits striking parallels to the clinical pharmacology of schizophrenia.Preliminary data were presented in part at the Society for Neuroscience Annual Meeting, Phoenix, AZ, 1989     

Effect of recombinant human granulocyte-macrophage colony-stimulating factor on hematopoietic reconstitution after high-dose chemotherapy and autologous bone marrow transplantation

Recombinant human granulocyte-macrophage colony-stimulating factor (rHuGM-CSF) has been reported to increase the leukocyte count in subhuman primates subjected to total-body irradiation and in patients with the acquired immunodeficiency syndrome. We administered this substance to 19 patients with breast cancer or melanoma treated with high-dose combination chemotherapy and autologous bone marrow support. Groups of three or four patients were treated with 2.0, 4.0, 8.0, 16.0, or 32.0 micrograms per kilogram of body weight per day of glycosylated rHuGM-CSF by continuous intravenous infusion for 14 days, beginning three hours after bone marrow infusion. Total leukocyte and granulocyte recovery was accelerated in these patients as compared with 24 historical controls matched for age, diagnosis, and treatment. Leukocyte counts (mean +/- SD) obtained 14 days after transplantation were 1511 +/- 1003 per microliter in patients given 2 to 8 micrograms per kilogram per day, 2575 +/- 2304 in those given 16 micrograms, and 3120 +/- 1744 in those given 32 micrograms, as compared with 863 +/- 645 per microliter in the controls. No consistent effect on platelet counts was noted. Toxic effects were generally mild and not clearly dose-related in patients given 2 to 16 micrograms per kilogram per day. Edema, weight gain, or myalgias occurred in all patients given 32 micrograms per kilogram; marked weight gain, generalized edema, pleural effusions, and hypotension developed in two patients, one of whom also had acute renal failure. Our results indicate that rHuGM-CSF can accelerate myeloid recovery after high-dose chemotherapy and autologous bone marrow transplantation, over a range of doses that can be tolerated. In this setting the ability to increase the dose is limited by the development of myalgias and fluid retention.     

参麦注射液对内皮细胞增殖和迁移的影响

目的：探讨参麦注射液对血管生成的影响。方法：采用MTT法检测参麦注射液对牛血清和肿瘤细胞条件培养液促进的牛主动脉内皮细胞增殖的影响，采用琼脂糖刮除法检测参麦对牛血清和肿瘤条件培养液促进的牛内皮细胞迁移的影响。结果：在含10％新生小牛血清培养液中和在肿瘤细胞条件培养液中，参麦都能明显抑制牛主动脉内皮细胞增殖，且呈量效关系，对肿瘤细胞条件培养液诱导的内皮细胞迁移抑制作用显著。方法：参麦能抑制牛内细胞增殖和迁移，具有抑制血管生成的作用。     

血清白细胞介素2检测在恶性腹水白细胞介素2治疗中的应用

目的 对恶性腹水患者血清白细胞介素2(IL-2)水平进行测定,了解血清IL-2水平与腹腔灌注IL-2治疗疗效之间的关系,以期获得判定恶性腹水IL-2治疗疗效的指标。方法 54例恶性非肝癌性腹水患者均接受IL-2腹腔灌注治疗,治疗前应用ELISA法检测血清IL-2水平,将IL-2测定值较高的27例患者分为A组,IL-2测定值较低的27例患者分为B组。比较两组患者的治疗效果。结果 血清IL-2测定值较低组IL-2腹腔灌注治疗的有效率为77.8％(21/27),明显高于IL-2测定值较高组的51.9％(14/27,P<0.05)。结论 恶性腹水患者IL-2腹腔灌注治疗前血清IL-2水平高低与IL-2治疗的疗效明显相关,原有IL-2水平较低的患者IL-2腹腔灌注治疗的疗效较好。血清IL-2水平可作为判定IL-2腹腔灌注治疗疗效的指标。     

人膀胱癌细胞nm23蛋白表达量与丝裂霉素抗药指数之间的相关性研究

目的探讨膀胱癌细胞nm23蛋白表达量与丝裂霉素药物敏感性之间的相关性.为临床膀胱移行细胞癌治疗方案选择提供理论依据.方法对32例临床病理诊断为膀胱移行细胞癌标本采用S-P免疫组化和图像分析技术检测细胞的nm23蛋白表达量;同时采用MTT法测定膀胱癌细胞对丝裂霉素的药物敏感性.结果膀胱癌nm23表达量与MMC抗药指数相关,相关指数为0.890(P＜0.001).结论膀胱癌nm23蛋白表达量与MMC抗药指数呈正相关.