Taxol counteracts colchicine blockade of axonal transport in neurites of cultured dorsal root ganglion cells

Taxol does not affect axonal transport in cultured neurites. Preincubation of this drug inhibits the effects of colchicine on axonal transport and morphology in cultured neurites. A reduction of the free tubulin density by preincubated taxol might prevent the disruption of microtubules by colchicine.     

Colchicine sensitizes human hepatocellular carcinoma cells to damages caused by radiation

AIM: We studied the effect of colchicine combined with radiation on the survival of human hepatocellular carcinoma (HCC) HA22T/VGH cells. METHODS: Twenty-four hours after treatment with 0-8 ng/mL colchicine, HA22T/VGH cells were irradiated at various doses (0,1, 2, 4, and 8 Gy). Colony assay was performed to assess the surviving cell fraction. Survival curves were fitted by using a linear-quadratic model to estimate the sensitizer enhancement ratio (SER). Flow cytometry was used for cell cycle analysis. RESULTS: Colchicine at lower concentrations (1 and 2 ng/mL) had obvious synergy with radiation to inhibit HCC cell growth, whereas higher concentrations (4 and 8 ng/mL) had only additive effect to radiation. Pretreatment with 1 and 2 ng/mL colchicine for 24-h enhanced cell killing by radiation with SERs of 1.21 and 1.53, respectively. G2/M arrest was only observed with higher colchicine doses (8 and 16 ng/mL) after 24-h treatment; this effect was neither seen with lower doses (1, 2, and 4 ng/mL) nor with any dose after only 1 h of treatment. CONCLUSION: Our results suggest that colchicine has potential as an adjunct to radiotherapy for HCC treatment. Lower doses of colchicine possess radiosensitizing effects via some mechanism other than G2/M arrest. Further study is necessary to elucidate the mechanism.     

Effectiveness of colchicine in a case of recurrent compressive rheumatoid pericarditis

Survival is impaired in rheumatoid pericarditis complicated by cardiac compression by either tamponade or constriction. Conventional therapy with non-steroidal anti-inflammatory agents and glucocorticoids is frequently ineffective in reversing severe cardiac impairment and/or in preventing recurrences. Colchicine, an effective and safe treatment of idiopathic and post-viral pericarditis, has not been studied in rheumatoid pericarditis. We describe the case of a 44-year-old woman with a 1-year history of rheumatoid arthritis who developed rheumatoid pericarditis complicated with tamponade. Pericardiocentesis relieved the symptoms, but pericarditis recurred at a high dose of prednisone of 70 mg/day. Colchicine at a dose of 1 mg/day prevented recurrences and had a significant sparing effect on steroids, which were reduced to 6 mg/day. This is the second case report describing the effectiveness of colchicine therapy in rheumatoid pericarditis complicated with tamponade. These cases suggest that colchicine should be considered in the treatment of rheumatoid pericarditis.     

Persistence of colchicine resistance in Ehrlich-Lettré ascites tumors and cell strains

Summary The effect of colchicine on mitoses of mutant HD33 Ehrlich-Lettré ascites cells growing in vivo and in vitro was studied.HD33 mouse ascites tumors are colchicine-resistant. The LD₅₀ of colchicine in mice bearing HD33 ascites tumors was 1.4 mg/kg body weight (b.w.), but a single dose of 3.33 mg colchicine/kg b.w. failed to suppress the anaphase of HD33 tumor mitoses for 24h. No change in the level of colchicine resistance was observed after 269 weekly transplantations of HD33 ascites tumors without colchicine.In suspension culture, growth of HD33 ascites cells ceased at 1.5×10^-6 M colchicine. 10^-5 M colchicine suppressed the anaphase of HD33 mitoses and produced typical C-mitoses within one hour. The same effects on mitoses of colchicine sensitive Ehrilich ascites cells in vitro were achieved with 10^-6 M colchicine.In HD33 ascites cell cultures grown without colchicine, only a slight increase in colchicine sensitivity was registered after 5 years. Parallel cultures were propagated for the same period in the presence of 10^-7 M colchicine (HD33C ascites cells) without detectable growth alterations; the resistance level increased slightly. The limit of 10^-6 M colchicine was tolerated by the ascites cells in permanent culture without growth reduction (HD33CS ascites cells). ³H-colchicine binding studies suggest a permeability barrier of the plasma membrane as a mechanism of genetically fixed resistance.Some of the results have been reported at the International Symposium on Microtubules and Microtubular Inhibitors, Beerse, Belgium, Sept. 2–5, 1975     

Predictive factors of recurrence after pediatric acute pericarditis

ObjectiveThe predisposing factors for pericarditis recurrence in the pediatric population have not yet been established. This study aimed to define the risk factors for the unfavorable prognosis of pediatric acute pericarditis.MethodsThis was a retrospective study that included all patients with acute pericarditis treated from 2011 to 2019 at a tertiary referent pediatric center.ResultsThe study included 72 children. Recurrence was observed in 22.2% patients. Independent risk factors for recurrence were: erythrocyte sedimentation rate ≥ 50 mm/h (p = 0.003, OR 186.3), absence of myocarditis (p = 0.05, OR 15.2), C-reactive protein ≥ 125 mg/L (p = 0.04, OR 1.5), and non-idiopathic etiology pericarditis (p = 0.003, OR 1.3). Corticosteroid treatment in acute pericarditis was associated with a higher recurrence rate than treatment with non-steroid anti-inflammatory therapy (p = 0.04). Furthermore, patients treated with colchicine in the primary recurrence had lower recurrence rate and median number of repeated infections than those treated without colchicine (p = 0.04; p = 0.007, respectively).ConclusionIndependent risk factors for recurrence are absence of myocarditis, non-idiopathic etiology pericarditis, C-reactive protein ≥ 125 mg/L, and erythrocyte sedimentation rate ≥ 50 mm/h. Acute pericarditis should be treated with non-steroid anti-inflammatory therapy. A combination of colchicine and non-steroid anti-inflammatory drugs could be recommended as the treatment of choice in recurrent pericarditis.     

微管干预剂对大鼠缺氧心肌细胞能量生成的影响

目的 了解缺氧条件下微管干预剂对大鼠心肌细胞能量生成的影响。方法 常规分离、培养大鼠心肌细胞，分为单纯缺氧组、缺氧＋秋水仙碱（微管解聚剂）组及缺氧＋5、10、15 mmol／L紫杉醇（微管稳定剂）组。每组细胞加入刺激剂后，缺氧培养0．5、1．0、3．0、6．0、12．0、24．0h。采用锥虫蓝染色检测细胞死亡率，常规比色法检测细胞肌酸激酶（CK）活性，高效液相色谱法检测细胞腺苷三磷酸（ATP）及腺苷二磷酸（ADP）含量。结果 （1）缺氧＋秋水仙碱组及缺氧＋15mmol／L紫杉醇组细胞培养1．0～24．0h死亡率均高于单纯缺氧组（P〈0．01）；缺氧＋5、10mmoL／L紫杉醇组6．0～24．0h时均低于单纯缺氧组（P〈0．05）。（2）缺氧＋秋水仙碱组培养1．0～12．0h时CK活性均高于单纯缺氧组（P〈0．01）。0．5～12．0h时，缺氧＋15mmoL／L紫杉醇组CK活性均高于单纯缺氧组（P〈0．01）；缺氧＋5、10mmol／L紫杉醇组低于单纯缺氧组（P〈0．05或P〈0．01）。（3）缺氧＋5mmol／L紫杉醇组培养0．5～6．0h ATP含量[（49．9±2．8）、（40．7±2．0）、（25．8±1．9）、（19．1±1．2）μg／10^6个细胞]高于单纯缺氧组[（42．9±5．8）、（29．5±1．8）、（18．2±0．9）、（14．1±0．7）μg／10^6个细胞，P〈0．05或P〈0．01]。0．5～12．0 h时，缺氧＋秋水仙碱组低于单纯缺氧组（P〈0．01）；缺氧＋15mmol／L紫杉醇组低于单纯缺氧组及缺氧＋10mmol／L紫杉醇组（P〈0．01）。各组ADP含量变化趋势与ATP相反。结论 微管解聚剂和高浓度微管稳定剂可使缺氧心肌细胞ATP含量锐减。适宜浓度的微管稳定剂在缺氧早期可促进心肌细胞能量生成，对心肌具有保护作用。     

Colchicine and capsular contracture around breast prostheses

Capsular contracture around the prosthetically reconstructed, breast is a very common problem which often leads to an unacceptable result. Colchicine, a drug known to inhibit contracture activity, was studied in an animal model of capsular contracture. Twenty-four 130 cc silicone gel breast prostheses were implanted subcutaneously into twelve rabbits. Colchicine was given daily in oral doses to half of the animals; the other half were used as controls. The prostheses were maintained insitu for two months. The degree of capsular contracture, as measured by applanation tonometry, was significantly less in the colchicine treated groups. The difference was often visually apparent. This study appears to be the first to demonstrate a significant inhibition of capsular contracture in an animal model by colchicine, an oral medication commonly used in the treatment of gout.Hospital where the work was done: Providence Hospital Southfield, Michigan, USA Correspondence to: C.B. Kelly     

Radial-arm maze deficits produced by colchicine administered into the area of the nucleus basalis are ameliorated by cholinergic agents

Rats were given bilateral injections of colchicine into the area of the nucleus basalis. Colchicine produced dose-dependent alterations in the acquisition of a food-reinforced working-memory task. Colchicine-induced deficits in maze performance were attenuated by cholinergic agents, including physostigmine, RS-86 (2-ethyl-8-methyl-2,8-diazospiro-(4,5)-decan-1,3-dione-hydro bromide) and nicotine. Naloxone and vasopressin did not affect radial-arm maze performance of colchicine-treated rats. Subsequent neurochemical analysis showed that colchicine decreased choline acetyltransferase (ChAT) activity and levels of norepinephrine, dopamine, 3,4-dihydroxyphenylacetic acid, serotonin and 5-hydroxyindoleacetic acid in the neocortex. However, ChAT activity and other neurochemical measures were not altered in the hippocampus or corpus striatum. Histological assessment indicated damage limited to the injection in the area of the nucleus basalis and enlarged cerebrolateral ventricles. These data suggest the possible utility of the colchicine model in the study of cognitive deficits associated with neurodegenerative diseases.     

Behavioral effects of hippocampal system lesions on rats in an operant paradigm

The effects on both operant and non-operant behavior during an operant task of various types of neural damage involving the hippocampal system were studied in adult male Sprague-Dawley rats. Various lesion types localized in the septal-hippocampal area all produced higher than control levels of operant responding under both a contingent variable interval and a non-contingent variable time schedule, an effect opposite to that seen in rats with ventral mesencephalic tegmental lesions. A different lesion effect was seen for the non-operant activity measure in that an activity hierarchy was noted, with colchicine-induced granule cell lesions producing the greatest activity increase and kainic acid-induced pyramidal cell lesions producing virtually no increase. Operant response rate was very sensitive to a switch in response contingency in that all groups significantly reduced operant responding while on the non-contingent schedule. This effect was not seen for the non-operant activity measure which appeared to be far less sensitive to contingency changes. The significance of these results to an understanding of the behavioral functioning of this system is discussed with some emphasis placed on their applicability to clinical cases of hyperactivity.     

Possible effect of subclinical inflammation on daily life in familial Mediterranean fever

This study was performed to investigate the attack-free complaints of patients with familial Mediterranean fever (FMF) and the impact of colchicine on these symptoms and on subclinical inflammation. A questionnaire that includes information about the disease course and symptoms during the attack-free period was administered to the parents of 50 FMF patients. For evaluation of the attack-free period, questions were asked about four items concerning daily activities of the children—weakness, lack of appetite, sleep problems, and decreased activity. The respondents rated the items and the total score was taken as the sum of all of the specific items. The laboratory values were noted from the patients files. During the attack-free period, patients with mild disease had higher total scores, higher weakness, and decreased activity scores than patients with moderate disease. When we compared the daily activity scores before and after colchicine therapy, a statistically significant increase was observed in the total scores and in all of the specific item scores. Also a significant decrease was seen in the erythrocyte sedimentation rate and white blood cell counts, and a significant increase was seen in the hemoglobin levels during the attack-free period after colchicine usage. Regression of inflammation together with improvement in daily activities were observed. FMF patients seem to have complaints during the attack-free period that may be related to subclinical inflammation. Moreover, colchicine besides preventing the FMF attacks and the dangerous complication of amyloidosis also seems to hinder the symptoms of the attack-free period in children with FMF.