Colchicine-induced Inhibition of Fat Globule Development in Hepatocytes of Rats Injected with Ethionine

To examine the effect of colchicine on ethionine induced fatty liver, adult female rats were starved overnight and then injected i.p. with 1 g kg ethionine at 11th hour of fasting; then a half of the rats were also injected i.p. with 2.5 mg kg colchicine twice at 3 and 6 h after the single administration of ethionine. Similarly, fasted control rats were injected i.p. with vehicle alone at the above times. All of the rats were sacrificed after a 20 h fast, and the hepatocytes in periportal areas were observed ultra-structurally. In addition, total lipids in the liver tissue were extracted and determined biochemically. Although similar significant increases of triglyceride were observed in the liver tissue of all ethionine-injected rats, the hapatocytes in the group treated with both chemicals had fewer cytoplasmic fat globules (CFG) than those in the group treated with ethionine only. On the other hand, the diameters of markedly increased membrane-bound lipid particles (MLP) in the double treated group were distributed mainly in the range 0.2–0.4 μm, compared with those (0.1-0.2 μm) in the other groups. These findings indicate that colchicine inhibits the development of CFG in ethionine injured hapatocytes. Acta Pathol Jpn 39: 281∼288, 1989.     

Hippocampal granule cells are necessary for normal spatial learning but not for spatially-selective pyramidal cell discharge

Summary The effects of massive destruction of granule cells of the fascia dentata on the spatial and temporal firing characteristics of pyramidal cells in the CA1 and CA3 subfields of the hippocampus were examined in freely moving rats. Microinjections of the neurotoxin colchicine were made at a number of levels along the septo-temporal axis of the dentate gyri of both hemispheres, resulting in destruction of over 75% of the granule cells. By contrast there was relatively little damage to the pyramidal cell fields. As assessed by three different behavioral tests, the colchicine treatment resulted in severe spatial learning deficits. Single units were recorded from the CA1 and CA3 subfields using the stereotrode recording method while the animals performed a forced choice behavioral task on the radial 8-arm maze. Considering the extent of damage to the dentate gyrus, which has hitherto been considered to be the main source of afferent information to the CA fields, there was remarkably little effect on the spatial selectivity of place cell discharge on the maze, as compared to recordings from control animals. There was, however, a change in the temporal firing characteristics of these cells, which was manifested primarily as an increase in the likelihood of burst discharge. The main conclusion derived from these findings is that most of the spatial information exhibited by hippocampal pyramidal cells is likely to be transmitted from the cortex by routes other than the traditional trisynaptic circuit. These routes may include the direct projections from entorhinal layers II and III to CA3 and CA1, respectively.     

Studies on intracellular transport of secretory proteins in the rat exocrine pancreas

Summary The possible role of microtubules and microfilaments in the secretory process of the rat exocrine pancreas was analysed in vitro using isolated pancreatic lobules. Colchicine and vinblastine as microtubule inhibitors, hexylene glycol as a microtubule stabilizer, and cytochalasin B as a disruptive agent for microfilaments were used in increasing concentrations to test their effects on protein synthesis, intracellular transport, zymogen discharge, and cellular respiration.Colchicine only at 10^–2 M concentrations inhibits protein synthesis, while vinblastine inhibits at 10^–6 and 10^–5 M by 20% and at 10^–4 M by 55%. A similar inhibition is observed with 1.5% concentrations of hexylene glycol while cytochalasine B at 1,5 and 10 g/ml is without effect on protein synthesis. Colchicine and vinblastine have their major effects on intracellular transport both in secretion studies and cell fractionation experiments. Colchicine in concentrations between 10^–3 to 10^–5 M inhibits discharge of newly synthesized proteins by 50%, while vinblastine shows a dose-response relationship of 40% inhibition at 10^–6 M to 90% at 10^–4 M. Discharge of amylase is uniformly reduced by 30% by both colchicine and vinblastine in the whole dose range. The pronounced effect of colchicine and vinblastine is evident in cell fractionation studies: both drugs inhibit the disappearance of protein radioactivity from microsomes and its appearance in zymogen granules; similarly the peak radioactivity in smooth microsomes (Golgi) appears delayed. No differential effect on the secretory process was observed with 1.5% concentrations of hexylene glycol or cytochalasin B at 1.5 and 10 g/ml concentrations. A fines tructural analysis of microtubules and microfilaments in the exocrine pancreatic cell reveals their distribution in all parts of the cytoplasm and in relation to all cell organelles. Both systems (microtubules, microfilaments) seem to be connected, at least in certain areas of the cytoplasm and at the plasma membrane.The reduction of transport efficiency by microtubule inhibitors results in a deposition of secretory material in the cisternal space of the rough endoplasmatic reticulum, which leads to the formation of paracrystals. Colchicine at 10^–3 M concentrations leads to an enlargement of condensing vacuoles in the Golgi complex.A short communication on the same subject was presented at a Symposion on Stimulus-Secretion-Coupling in the Gastro-intestinal Tract, Titisee (May 27–29, 1975).Supported by Deutsche Forschungsgemeinschaft (Ke 113/8).     

桂枝芍药知母汤联合西药治疗急性痛风性关节炎的疗效和安全性Meta分析

目的：系统评价桂枝芍药知母汤联合西药治疗急性痛风性关节炎的安全性和疗效。方法：计算机检索PubMeb、The Cochrane Library、EMBASE、Web of Science、国家知识基础设施数据库（CNKI）、中国学术期刊数据库（CSPD）、中文科技期刊数据库（CCD）和中国生物医学文献数据库（CBM）,搜索桂枝芍药知母汤联用西药与单用西药治疗急性痛风性关节炎的疗效与安全性临床随机对照试验,并用改良后的Jadad量表对纳入的文献质量进行初步评价,利用Revman5.3软件进行Meta分析。结果：共纳入7篇文献,共498例患者。Meta分析结果显示：中西药联用观察组患者总有效率明显高于西药对照组,差异有统计学意义（RR=1.20,95%CI为1.12～1.28,P<0.000 01）;中西药联用观察组在降低BUA（MD=-61.35,95%CI为-93.17～-29.53）,CRP（MD=-1.83,95%CI为-2.56～-1.11）,ESR（MD=-3.93,95%CI为-6.60～-1.26）,关节肿胀积分（SMD=-2.89,95%CI为-3.36～-2.43）和关节疼痛积分（SMD=-3.11,95%CI为-3.87～-2.35）的效果明显优于西药对照组,差异有统计学意义（P<0.05）;中西药联用干预的观察组不良反应发生率明显低于西药对照组（P<0.05）。结论：桂枝芍药知母汤联合西药治疗急性痛风性关节炎的疗效和安全性明显优于单用西药,但受纳入研究质量和数量的限制,仍需更多高质量的临床随机对照试验来证实上述结论。     

Colchicine-induced myoneuropathy mimicking polyradiculoneuropathy

We report a patient with colchicine-induced myoneuropathy. Myoneuropathy is an under-recognized complication of colchicine. The weakness seen in our patient improved fairly rapidly after discontinuation of colchicine.     

Carotid intima-media thickness,lipid profile,serum amyloid A and vitamin D status in children with familial Mediterranean fever

Aim of the workIt was to estimate the carotid intima-media thickness (CIMT), lipid profile, serum amyloid A and vitamin D in Familial Mediterranean Fever (FMF) patients and to explore the relationship between CIMT and FMF.Patients and methodsThe study comprised forty-five FMF patients diagnosed during the attack free period and 40 healthy children with similar demographic features as control. The diagnosis of the FMF cases was confirmed by clinical, laboratory assessments and confirmed by the molecular diagnosis. The CIMT, lipid profile, complete blood picture, serum amyloid A (SAA) levels, vitamin D and the growth pattern were investigated.ResultsThe study showed no significant difference of CIMT among patients and controls, significant decrease of vitamin D levels, while lipid profile parameters, triglyceride (TG) to HDL-Cholesterol (HDL-C) ratio, serum amyloid A were significantly increased. A significant correlation was present between the CIMT with the serum cholesterol, low density lipoprotein and triglycerides as well as between SAA and the number of attacks. In addition, vitamin D levels showed significant negative correlation with colchicine. M694I mutation was the most prevalent among FMF patients. Growth parameters were normal in FMF cases.ConclusionThis study sheds light that the normal CIMT in the FMF patients makes it difficult to describe the children as having subclinical atherosclerosis although the higher TG/HDL ratio reflects their risk of atherosclerosis. Moreover, significant decrease of vitamin D in FMF patients was observed. The growth parameters of the FMF patients on regular treatment of colchicine were not affected.     

Efficacy of Colchicine in the Treatment of Mesenteric Panniculitis in a Young Patient

Mesenteric panniculitis (MP) is a rare inflammatory and fibrotic disease of the mesentery of unknown etiology. It has various clinical and radiological manifestations, posing a diagnostic challenge for clinicians. Its diagnosis is indicated via radiologic imaging and is usually confirmed via peritoneal biopsies. We describe a case of a patient with histopathologically proven MP, in which steroid dependence was successfully managed with colchicine.     

Development of amyloidosis in Behçet's syndrome with isolated mucocutaneous involvement

Development of secondary amyloidosis is an infrequent complication in patients with Behçet's syndrome (BS). It has been reported that multiple systemic involvement, long disease duration, and male gender are major clinical factors accompanying the development of amyloidosis in BS. We report a case of secondary amyloidosis in a patient diagnosed as having BS with a positive pathergy test 9 years previously and who had isolated mucocutaneous involvement. Regular use of colchicine since the diagnosis and somewhat mild progress of the disease could not prevent the development of secondary amyloidosis in this patient. He is alive and receives hemodialysis regularly.