氟对人体T细胞数目的影响及硼砂拮抗作用的观察

将３８例地氟病人分为硼砂治疗组和治疗对照组，通过对病人外周血Ｔ淋巴细胞亚群含量的检测，观察了氟对人体Ｔ３、Ｔ４、Ｔ８淋巴细胞含量的影响以及硼砂的拮抗作用。结果表明，在本研究条件下，地氟病人外周血Ｔ３、Ｔ４淋巴细胞数目明显减少，硼砂对此变化无明显的拮抗作用。     

氟对大鼠免疫器官的影响及“抗氟灵”对氟拮抗作用的研究

本文研究了对大鼠免疫器官的影响及“抗氟灵”对氟的拮抗作用。２４只大鼠被随机分成３组,Ａ组为阴性对照组,Ｂ组对染氟组,Ｃ组为氟加“抗氟灵”组,观察与检测了所有动物的胸腺及脾脏的蛋白质含量,脏器重量,脏器系数及形态学变化。结果显示;Ｂ组动物胸腺与脾脏的蛋白含量,脏器重量,脏器系数均明显下降,胸腺皮质明显变薄,淋巴细胞稀疏;Ｃ组动物的这些指标变化不明显。     

Characteristics of pentobarbital discrimination in the gerbil: Transfer and antagonism

Experiment 1. Gerbils were trained in a T-shaped maze to discriminate the effects produced by pentobarbital (P-barb. 15 mg/kg, i.p.) and the effects of saline. The response, a left or right turn in the maze, was thus contingent upon the prevailing training condition (P-barb. or saline). The criterion of performing 8 correct first trial choices in 10 consecutive sessions was reached within 20 training sessions. Tests with descending doses of P-barb. yielded an ED₅₀ of 9 mg/kg. Tests with phenobarbital (40 mg/kg) or diazepam (2 and 4 mg/kg) solely maintained the drug response. P-barb. discrimination was reversed by megimide (ED₅₀: 8.5–9.6 mg/kg) and metrazol (ED₅₀: 24.9–27.9 mg/kg). Thus megimide was approximately 3 times more effective than metrazol. Metrazol (40 and 80 mg/kg) also counteracted the phenobarbital and diazepam response. Picrotoxin (2.5 and 5 mg/kg) was less effective whereas caffeine (100 mg/kg) and piracetam (100–1000 mg/kg) did not upset P-barb. discrimination. Experiment 2. Naive gerbils had to discriminate mixtures of P-barb. (15 mg/kg) plus either 40 or 80 mg/kg of metrazol from saline already at the start of the discriminative training. The drug combinations produced discriminable effects since most gerbils reached the acquisition criterion (8/10), although more slowly than gerbils trained with P-barb. solely. Gerbils trained without a drug stimulus (saline vs. saline) never attained the criterion during 60 consecutive sessions. In conclusion, reversal of established discrimination (Expt. 1) does not necessarily mean that the same drug combination lacks discriminable effects as demonstrated in Experiment 2.     

Antagonist activity of the antipsychotic drug lithium chloride and the antileukemic drug imatinib mesylate during glioblastoma treatment in vitro

Objectives: Glioblastoma (GBM), the most common primary tumour of the central nervous system, is characterised by a high malignancy and poor prognosis. The aims of this study were to investigate whether the combination of imatinib mesylate (IM) and lithium chloride (LiCl) exhibited a synergistic effect in treatment and to determine whether midkine (MK) affected the fate of this treatment in vitro.

Methods: Monolayer and spheroid cultures of the T98G human GBM cell line were treated with an IM and LiCl combination for 72 h. The cell proliferation index, apoptotic index, cell cycle distribution, apoptotic and anti-apoptotic protein levels, and cAMP level as well as the cellular morphology and ultrastructure were evaluated.

Results: All applications inhibited cell proliferation and induced apoptosis. The most substantial decreases in cell proliferation and the caspase-3, epidermal growth factor receptor (EGFR), platelet derived growth factor receptor-alpha (PDGFR-α), multidrug resistance protein-1 (MRP-1), aquaporin-4 (AQP-4) and cAMP levels were induced by the LiCl treatment, which exhibited more pronounced effects compared with the combination treatment. LiCl was less effective in decreasing the MK and B cell lymphoma-2 (Bcl-2) levels compared with the combination treatment. The most substantial decrease in the p170 levels was identified following the combination treatment, whereas IM induced the second greatest decrease. LiCl alone had no effect on the p170 levels. IM induced the most substantial decrease in the phospho-glycogen synthase kinase 3-beta (p-GSK-3β)/glycogen synthase kinase 3-beta (GSK-3β) ratio, and LiCl induced the second most substantial decrease. Both LiCl and the combination treatment induced G2 + M arrest, whereas IM induced G0 + G1 arrest after 72 h of exposure. An apoptotic appearance and autophagic vacuoles were commonly identified in the LiCl, combination and IM groups, respectively.

Conclusions: The combination of IM and LiCl exhibited an antagonist effect, and MK had a role at this antagonism.     

Effects of the synalbumin insulin antagonist in vivo; its examination with a new method

Summary A new method was elaborated for examinationin vivo of the synalbumin insulin antagonist. It was shown that the glucose concentration of incubated liver homogenates prepared from untreated rats increased with time. Previous intravenous insulin administration prevented this increase. If insulin was injected together with albumin prepared from the serum of diabetic patients, this effect of insulin was antagonized.

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In vivo Effekte des Synalbumin Insulin Antagonisten; Untersuchungen mit einer neuen Methode

Zusammenfassung Zur Untersuchung desin vivo Effektes des Synalbumin Insulin Antagonisten wurde eine neue Methode ausgearbeitet. Es wurde nachgewiesen, daß die Glucose-Konzentration des Rattenleberhomogenisates während einer Inkubation zunimmt. Eine der Ratte im voraus gegebene Insulininjektion hemmte diese Zunahme. Wenn aber das Insulin zusammen mit aus dem Serum von Diabetikern gewonnenem Albumin gegeben wurde, war dieser Effekt des Insulins nicht nachweisbar.

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Effets in vivo de l'antagnoniste de l'insuline, la synalbumine; Etude par une méthode nouvelle

Résumé Un nouvelle méthode à été mise au point pour l'examenin vivo de l'effet antagoniste de la synalbumine, vis-à-vis de l'insuline. On a démontré l'augmentation dans le temps de la teneur en glucose des homogénéisats de foie d'une population de rats temoins, tandis que cette augmentation ne se manifeste pas dans les homogénéisats de rats préalablement traités par injection intraveineuse d'insuline. Par contre si l'insuline injectée était mélangée avec de l'albumine extraite du sérum de personnes diabétiques, cet effet de l'insuline était annulé.

     

Antiproliferative effects of interferonγ in combination withα-difluoromethylornithine on human carcinoma cell cultures

The antiproliferative effects of human recombinant interferon (IFN) in combination with -difluoromethylornithine (DFMO) or as single agents were assessed on human cell cultures derived from carcinomas of the breast (MCF-7), the ovary (EFO-27) or the kidneys (EGI-4). Results were obtained in proliferation assays by direct cell counting. The cell lines differed considerably in their sensitivities to the antiproliferative effect of IFN as compared by the 50% inhibition doses of the growth (ID₅₀). In contrast to the findings with IFN, similar antiproliferative effects resulted from the application of comparable doses of DFMO. While IFN induced cytotoxic effects in EGI-4 cells, DFMO produced only cytostatic actions in the cell lines analyzed. Synergistic growth inhibition resulted from the combined application of IFN and DFMO in EFO-27 cell cultures. This finding was most pronounced after treatment with IFN or DFMO doses below the respective ID₅₀ values. However, antagonistic effects occurred in cells of the line EGI-4 after DFMO had been combined with IFN at concentrations below the cytotoxic dose range. Within the sensitivity of our proliferation assay, no synergistic interactions were found in MCF-7 cell cultures. In the cell lines tested, no relation between the sensitivity for the single agents and the effectivity of the drug combination was identified. Despite promising synergistic effects in the moderately IFN-sensitive ovarian carcinoma cell line EFO-27, the efficacy of the IFN/DFMO combination was restrained by possible antagonistic effects as demonstrated in the highly IFN-sensitive EGI-4 renal carcinoma cell cultures. We conclude that the differential interaction patterns in the cell cultures analyzed preclude general suggestions for clinical studies using IFN and DFMO.Abbreviations IFN interferon - DFMO difluoromethylornithine This work was part of the doctoral thesis of Mariam Klouche     

The effects of scopolamine and physostigmine on fixed-interval behaviour in the rat

The purpose of this research was to determine if 2 drugs, scopolamine and physostigmine which have opposite effects on cholinergic transmission also produce opposite effects on fixed-interval (FI) performance. Scopolamine and a wide range of doses of physostigmine were administered singly and concurrently to a number of rats responding on a FI 2 min schedule. Scopolamine produced a disruption in FI curvature which could be antagonized by physostigmine, but physostigmine by itself produced no consistent change.This research was carried out to fulfill the requirements for the degree of Doctor of Philosophy at the University of Western Ontario, London, Ontario, Canada. The author wishes to acknowledge the assistance of Dr. F. M. Van Fleet. The research was also supported by grant APA 268 of the National Research Council of Canada.     

The role of the cholinergic system in the development of increased naloxone potency in mice

Pretreatment of mice with the anticholinesterase (anti ChE) drugs tacrine or physostigmine augmented the antinociceptive potency of morphine given 3 h later, but had no effect on the antagonist potency of naloxone. Pretreatment with either of these anti ChE drugs together with morphine not only augmented the potency of a subsequent dose of morphine, but also enhanced the antagonist potency of naloxone to a greater extent than after pretreating with morphine only. Neostigmine did not affect the potency of either morphine or naloxone, suggesting that this phenomenon involved central cholinergic mechanisms. Atropine prevented the increase in naloxone potency caused by morphine pretreatment, and greatly reduced the effect of morphine plus the anti ChE drugs. The effects of these various pretreatments on the development of “acute dependence” to morphine was also studied. None of the three anti ChE drugs caused any change in this phenomenon, as tested by naloxone-precipitated jumping, although this was significantly increased by pretreatment with either atropine sulphate or atropine methyl nitrate. It is concluded that the increase in naloxone potency following morphine pretreatment involves both a cholinergic mechanism plus narcotic analgesic action. This phenomenon does not seem to be related to the development of either acute tolerance or acute dependence.     

(R)-methanandamide and Delta 9-THC as discriminative stimuli in rats: tests with the cannabinoid antagonist SR-141716 and the endogenous ligand anandamide

RATIONALE AND OBJECTIVES: (R)-methanandamide (AM-356), a metabolically more stable chiral analog of the endocannabinoid ligand anandamide, was used as a representative of fatty acid ethanolamide CB1 receptor ligands to characterize the discriminative stimulus functions of anandamides. METHODS: Rats discriminated between 10 mg/kg (R)-methanandamide and vehicle administered IP 15 min prior to session onset. Another group of rats was initially trained to discriminate between 3 mg/kg Delta9-THC and vehicle given IP 30 min prior to session onset; for anandamide testing, the animals were retrained with 1.8 and 5.6 mg/kg Delta9-THC. A two lever operant methodology (FR10) was used. RESULTS: Delta9-THC was more potent than (R)-methanandamide at both 15 and 30 min post-injection, irrespective of the training drug used. Additional tests with 10 and 18 mg/kg (R)-methanandamide suggested that the effects were declining by 1 h. The cannabinoid antagonist SR 141716 (0.3 and 1 mg/kg) produced rightward shifts in the Delta9-THC dose-response curve for Delta9-THC-appropriate responding and for (R)-methanandamide-appropriate responding (surmountable antagonism). SR-141716 (0.3 and 1 mg/kg) antagonized the ability of (R)-methanandamide to occasion either Delta9-THC-appropriate responding or (R)-methanandamide-appropriate responding. This antagonism was surmountable only at a dose of 0.3 mg/kg SR-1421716 in the (R)-methanandamide-trained rats. SR-141716 did not antagonize the rate-decreasing effects of (R)-methanandamide in either the Delta9-THC or the (R)-methanandamide trained rats. Response suppression precluded testing doses higher than 30 mg/kg (R)-methanandamide. Tests with SR-141716 (1 and 10 mg/kg) alone resulted in <3% Delta9-THC-appropriate responding. With 10 mg/kg SR-141716, response rate was significantly lower as compared to the rate observed during a vehicle test. Tests with anandamide (10 and 18 mg/kg) resulted in 41% and 85% (R)-methanandamide-appropriate responding at a 3-min pre-treatment time, but in a maximum of 15% (R)-methanandamide-appropriate responding at a longer (15 min) pre-treatment time. In the Delta9-THC (1.8 and 5.6 mg/kg) trained rats, anandamide never produced more than about 20% Delta9-THC-appropriate responding. CONCLUSION: The results add to a growing body of evidence indicating that there are both similarities and dissimilarities between classical cannabinoids such as THC and endogenous fatty acid ethanolamides.