Effects of psychoactive drugs on operant responding and non-operant activity of rats with hippocampal system damage

The effects of various psychoactive drugs (methylphenidate, 0.2-8.0 mg/kg; pentobarbital, 0.5-10.0 mg/kg; caffeine, 3.2-32.0 mg/kg; imipramine, 1.0-20.0 mg/kg; d-amphetamine, 0.1-1.0 mg/kg) on the operant and non-operant behavior rates of adult male Sprague-Dawley rats with various lesion types localized in the septal-hippocampal area were tested in an appetative operant paradigm utilizing both a response contingent (VI50 sec) and a response non-contingent (VT50 sec) schedule. In general, both pentobarbital and imipramine reduced the rate of both behavioral measures in a dose-dependent manner while the psychomotor stimulants tended to decrease operant rates and increase non-operant rates to varying degrees in all groups. There were differential drug effects among the various lesion types which would indicate specific drug responsivity patterns. These results are discussed in terms of their usefulness in understanding the therapeutic effects of these drugs in treating possible hippocampal dysfunction.     

大鼠眶下神经干注射秋水仙碱对三叉神经痛觉敏感征发作的影响

目的观察于大鼠眶下神经干注射秋水仙碱是否对三叉神经痛有治疗作用.方法将一个1 mm2的滤纸片(浸有0.2%苦毒素)直接放置于两侧闫脑尾侧1～2 mm颈髓质上表面至少5 min,形成三叉神经痛模型.于右侧眶下神经干注射0.4 g/L秋水仙碱200 μL.于用药后当日和第2,5,6天分别对实验侧与对照侧大鼠胫前肌肌电图(EMG)发放进行记录.测量EMG波的振幅、时限、每次发作持续时间、开始出现发作的时间及至不发作的全程时间,并进行统计学对比分析.结果注射秋水仙碱对EMG各项指标中的振幅影响最大.实验侧术后第2天EMG振幅为(110.00±14.14)μV较手术当日(613.33±180.37)μV明显减小,术后第5,6天EMG振幅分别为(285.71±68.28)μV和(264.62±119.77)μV,虽有所回升,但与对照侧差异有显著性意义(P＜0.001).结论0.4 g/L秋水仙碱对三叉神经痛有一定的治疗作用.     

秋水仙碱对阵发性心房颤动导管消融术后早期复发及炎性因子的影响

[目的]探讨秋水仙碱对阵发性心房颤动(房颠)导管消融术后早期复发及炎性因子的影响.[方法]将80例行导管消融术的阵发性房颤患者,随机分为两组:观察组40例给予秋水仙碱;对照组40例为安慰剂对照.观察术后3个月两组患者复发率,比较消融术前、术后两组间血清高敏-C反应蛋白(hs-CRP)、白细胞介素-6(IL-6)水平的变化.[结果]消融术后,观察组复发率低于对照组(P＜0.05),观察组的hs-CRP及IL-6水平显著低于对照组(P＜0.05),且与术前比较,观察组术后hs-CRP及IL-6水平降低(P＜0.05),对照组术后hs-CRP及IL-6水平较前增高(P＜0.05).将治疗组进一步分为复发组和未复发组,未复发组hs-CRP及IL-6的术后下降幅度大于复发组(P＜0.05).[结论]秋水仙碱有助于预防阵发性房颤导管消融术后早期复发,其早期复发率的减少可能与减轻消融术后炎症反应有关.     

Colchicine in clinical medicine. A guide for internists

Colchicine (COL) has been used in medicine for a long time. It is well recognized as a valid therapy in acute flares of gouty arthritis, familial Mediterranean fever (FMF), Behçet's disease, and recurring pericarditis with effusion. It has also been used to treat many inflammatory disorders prone to fibrosis, mostly with disappointing therapeutic results.The pharmacotherapeutic mechanism of action of COL in diverse diseases is not fully understood, thought it is known that the drug accumulates preferentially in neutrophils, and this effect is useful in FMF.COL shows a large interindividual bioavailability. Furthermore, interactions with drugs interfering with CYP3A4 dependent enzymes and P-glycoprotein occur and are clinically important. The dosage of COL must be reduced in patients with relevant hepatic and/or renal dysfunction. However, when appropriately used and contraindications have been excluded, oral COL is a safe treatment.     

秋水仙碱在心血管疾病中应用的研究进展

秋水仙碱是一种独特、复杂的抗炎剂,几十年来一直用于预防痛风的急性炎症发作。近年来,临床试验已证明其在一系列心血管疾病中的潜力。冠心病是一种慢性血管炎症性疾病,其主要病理特征是内膜下脂蛋白累积引发异常免疫反应,进而导致富含脂质的炎症斑块形成。炎性反应与冠心病的发生发展密切相关,其中中性粒细胞的浸润及活动被认为是冠心病进展的重要机制。秋水仙碱可通过与微管蛋白二聚体结合而影响细胞的有丝分裂过程,抑制微管蛋白引发的白细胞运动、胞吐和吞噬作用,中断核苷酸结合寡聚化结构域样受体蛋白3炎症小体激活与吞噬,中断白三烯与细胞因子生成,减少微管相关炎症细胞趋化,尤其是中性粒细胞趋化、黏附和募集。秋水仙碱对血小板的作用主要表现在抑制血小板活化及血小板与白细胞相互作用2个方面。抗炎、抗血小板聚集是秋水仙碱治疗心血管疾病的重要机制,其中抗炎可能是秋水仙碱发挥治疗效果的核心机制。低剂量、长疗程的秋水仙碱干预方案可能对心血管疾病患者具有实质性好处。本文主要对秋水仙碱作为附加疗法在心包炎、冠心病、急性冠脉综合征、支架内再狭窄、心房颤动、心力衰竭等心血管疾病中的应用作一综述。     

Effect of colchicine on the murine immune response induced by Aggregatibacter actinomycetemcomitans

The aim of the present study was to test the hypothesis that colchicine may alter Aggregatibacter actinomycetemcomitans-induced immune response and abscess formation in mice. BALB/c mice were either sham-immunized or immunized with heat-killed A. actinomycetemcomitans. Spleen cells were stimulated with heat-killed A. actinomycetemcomitans in the presence or absence of colchicine. Specific IgG subclass antibodies, interferon-γ (IFN-γ), interleukin-4 (IL-4) and cell proliferation were determined. The animals were sham-immunized (group I) or immunized with heat-killed A. actinomycetemcomitans (groups II–VII). Colchicine was administered intraperitoneally before (group III), on the same day of (group IV), or after (group V) the primary immunization and on the same day of (group VI) or after (group VII) the secondary immunization. All groups were challenged with viable A. actinomycetemcomitans. The levels of serum-specific IgG subclasses and both IFN-γ and IL-4 before and after bacterial challenge were assessed. The diameter of skin lesions was assessed. The results showed that colchicine augmented splenic-specific IgG1 and IL-4 as well as cell proliferation but suppressed specific IgG2a and IFN-γ levels. Enhancement of serum-specific IgG1 and IL-4 levels, suppression of specific IgG2a and IFN-γ levels as well as DTH response, and delayed healing of the lesions were observed in groups IV and VI, but not in the remaining groups of animals. Therefore, these results suggest that colchicine may induce a T helper 2 (Th2)-like immunity specific to A. actinomycetemcomitans in vitro and that colchicine administered on the same day as the immunization may stimulate a non-protective Th2-like immunity in A. actinomycetemcomitans-induced infections in mice.     

Different effect of hippocampal granule cell destruction on amygdaloid kindling in Sprague-Dawley and Wistar rats

The hippocampal granule cells receive major inputs via the perforant path from other limbic structures such as the amygdala (AM). In this study, we examined Sprague-Dawley (SD) and Wistar rats, the effect of bilateral destructions of the hippocampal granule cells on the process of AM kindling and kindled AM seizures after completion of kindling. The granule cells were selectively and completely destroyed bilaterally by intra-hippocampal injections of colchicine. The left AM was used as the primary kindling site and the right AM as the secondary site. In SD rats, prior destruction of the granule cells caused a marked delay in the seizure development of both the primary AM kindling and subsequent secondary AM kindling. However, once AM kindling was established in SD rats, the destruction of granule cells was totally ineffective in preventing kindled seizures. In Wistar rats, unlike SD rats, prior destruction of the granule cells failed to change the rate of kindling at the primary and secondary sites. However, Wistar rats showed a transient and marked regression of kindled seizures when the granule cells were destroyed after the completion of AM kindling. In both strains, granule cell destruction had no effect on the re-establishment of kindled seizures at the time of primary-site re-test. These findings suggest that hippocampal granule cells of SD and Wistar rats play different roles in AM kindling.     

Colchicine inhibits fracture union and reduces bone strength—in vivo study

Introduction: Recent studies have demonstrated that Colchicine (CO) prevents heterotopic ossification (HO) after total hip replacement in patients suffering from familial Mediterranean fever (FMF). Other investigators have proved that CO is an in vitro inhibitor of proliferation of osteoblasts and osteosarcoma cells, and is a non-selective mitosis inhibitor and selective inhibitor of mineralization.Methods: A double blind prospective study comprised four groups of adult rats. The left posterior tibia in each rat was fractured except in one of the control groups. The study groups were treated with CO 1 mg/kg/day 1 week before, or on the fracture day. The control groups did not receive CO treatment. Six weeks after fracture induction the groups were compared radiographically mechanically and histologically.Results: Prolonged CO treatment had a significant negative influence on fracture healing according to radiological, clinical, mechanical (p < 0.02), and pathological parameters (p < 0.0001).Conclusions: We were able to demonstrate that prolonged CO treatment reduced bone healing.     

Does Colchicine Really Induce Bone Formation in the Rodent Bone Marrow?

Intravenous injection of a single dose of colchicine into inbred strains of BALB/c and CFW/L1 mice and into WAG rats did not effect rapid intramedullar bone formation and resorption, as has been claimed by the research group from Tokyo Medical and Dental University [14–17]. The applied doses of colchicine arrested metaphase during the first 4 hours postadministration and were noxious for hemopoietic tissue (necrosis of bone marrow was evident in 2 and 4 day specimens), but on longitudinal, serial sections of long bones there was no evidence of stimulation of osteogenesis at any point in time (2–26-day specimens). It is postulated that the system of ectopic osteogenesis by colchicine injection is not reproducible in mice and WAG rats, and the apparently osteogenic effect of colchicine, observed by the Ogura group [14–17], was mistakenly described as congenital osteopetrosis. Received: 10 May 1996 / Accepted: 31 December 1996