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PubMed1993

Colchicine in diabetes mellitus.

As anti-inflammatory drugs such as acetylsalicylic acid are known to partially restore insulin response to glucose, the possible beneficial effect of colchicine, an anti-gout and anti-inflammatory drug, in non-insulin dependent diabetes mellitus (NIDDM) was studied. Colchicine could significantly reduce blood glucose levels, both fasting and post-prandial when given at a dose of 0.5 mg thrice a day in NIDDM patients. There were no side-effects due to the therapy. This study suggests that colchicine has anti-diabetic properties.

Blood Glucose↗
PubMed1995

[Recurrent pericarditis: our experience with colchicine].

To prove the efficacy of colchicine in the prevention of recurrences of acute pericarditis, 5 patients, age 24 to 64 years (mean 36), were treated during 18 months with 1 milligram daily. Previous treatment with steroids and/or non steroid antiinflammatory agents did not prevent 2-3 recurrences per patient, and was discontinued after entry into the study. There where no further recurrences of acute pericardial episodes during the 24 months of follow-up, and no side effects related to the treatment with colchicine were reported. We conclude that colchicine is effective in preventing the recurrences of acute idiopathic pericarditis.

Adult↗
PubMedDate not supplied

Colchicine in the treatment of mixed cryoglobulinemia.

OBJECTIVE: The best treatment for cryoglobulinemic syndrome (CS) is still an unsolved problem. Recently colchicine has been successfully used to treat vasculitides and other immune-mediated diseases. Therefore, we undertook to treat 17 CS patients with colchicine (1 mg/day for 6-48 months), 8 of them with essential mixed cryoglobulinemia (EMC) and 9 with CS secondary to liver disease. METHODS: In all patients the clinical and laboratory features were evaluated at the beginning of the study and during the first 6-12 months; 10 cases were followed for a longer period (18-48 months). RESULTS: During the first period symptoms improved as follows: purpura in 15 of 17 patients, weakness in 9 of 14 and leg ulcers in 3 of 5. Hepatic and renal function tests, hypocomplementemia, rheumatoid factor (RF) titres and the cryocrit also improved. Prolonged follow-up showed a relapse in the different variables, although they remained at better levels than at the beginning. Only the cryocrit showed a further reduction. CONCLUSION: Though this was a preliminary open study it shows that colchicine is an efficient treatment in CS and suggests that a controlled clinical study should be performed to assess its real value.

Adult↗
PubMedDate not supplied

[Ca2+ ion transport in the sarcoplasmic reticulum of the gastrocnemius muscles of white rats under treatment of the sciatic nerve with a colchicine solution].

In different time after application of 12.5 microM colchicine-inhibitor of exoplasmic current to the ischiadicus the quantity of amino acid residues of methionine and cysteine in the sarcoplasmic reticulum decreases, its protein content changes. The Ca(2+)-ATPase activity increases on the 3d day after colchicine application and decreases on the 14th day. Analogical changes are observed in the capacity of the sarcoplasmic reticulum to transport calcium ions, the Michaelis constant in this case being stable. Passive outflow of Ca2+ from the sarcoplasmic reticulum vesicules changes in such a way: the Michaelis constant decreases with a simultaneous increase in the maximal velocity after 14 and 28 days of colchicine application.

Amino Acids↗
PubMed1997

Increased plasma serotonin following treatment with flavone-8-acetic acid, 5,6-dimethylxanthenone-4-acetic acid, vinblastine, and colchicine: relation to vascular effects.

A number of antitumor agents are known to cause selective reduction in tumor blood flow, leading in some cases to tumor necrosis and growth delay. These agents include flavone acetic acid (FAA), an antitumor agent with high experimental but no clinical antitumor activity, 5,6-dimethylxanthenone-4-acetic acid (DMXAA), a highly active analogue of FAA, endotoxin, vinblastine, and colchicine. We find here that plasma concentrations of serotonin (5-hydroxytryptamine) and its metabolite 5-hydroxyindole acetic acid (5-HIAA) are increased following administration of these agents. Mice were injected with each at the maximum tolerated dose and, at various times later, blood samples were taken, cells and platelets removed by centrifugation, and serotonin and 5-HIAA concentrations were measured by high performance liquid chromatography. FAA and DMXAA induced six- and sevenfold increases in serotonin and 5-HIAA, respectively, with maximal levels 4 h after drug administration. 8-Methylxanthenone-4-acetic acid, an inactive analogue of DMXAA, failed to increase serotonin and caused only a small increase in 5-HIAA. Endotoxin, vinblastine, and colchicine each caused increases in serotonin and 5-HIAA between 2 and 6 h after drug administration. The mitotic poison paclitaxel, despite inducing growth delays of Colon 38 tumors, did not induce tumor necrosis and caused no increase in serotonin or 5-HIAA up to 6 h. The effect of the presence of subcutaneous Colon 38 tumors was tested and found not to affect the induction of increases in serotonin and 5-HIAA by DMXAA and colchicine. We suggest that the increases in plasma serotonin and its metabolite are a result of drug-induced vascular effects in host tissues, and that measurement of these compounds provides a potential means of monitoring drugs exerting vascular effects.

Animals↗
PubMed1996

Colchicine reduces hepatic fibrosis in mice infected with Schistosoma japonicum.

OBJECTIVE: Colchicine has been used clinically to treat hepatic cirrhosis caused by multiple etiologies. MATERIALS AND METHODS: The effect of colchicine on the liver fibrosis of mice infected with Schistosoma japonicum were studied. The morphological observation and morphometric analysis of the infected and untreated, and infected and treated groups were proceeded under the light microscopy, and morphological observation was made under electron microscopy. RESULTS: The results of morphometriic analysis in histological sections showed that the collagen fibers area per schistosome's egg was decreased in the infected and treated groups 10 to 13 weeks after infection. The decrease in the group of 13 weeks was significant statistically. The egg numerical density on area increased continuously from 10 to 13 weeks in both untreated and treated groups in similar degree. The ultrastructural study showed the accumulation of collagen fibrils around the hepatocytes and in the space of Disse decrease and ultrastructural lesion of hepatocytes get recovery in the treated group. CONCLUSIONS: These findings suggest that colchicine has therapeutic effect on schistosomal liver fibrosis, through not only killing off the schistosome but interfering the metabolism of collagen.

Animals↗
PubMed1996

Opisthorchis viverrini: the effects of colchicine and cytochalasin B on the adult tegument.

The roles of the tegumental cytoskeleton were tested by treating adult flukes with colchicine and cytochalasin B. Following a short incubation period (10-20 minutes), colchicine disrupted microtubules in the tegumental cells' processes which, in turn, affected the transport of dense granules from the cells' soma to the tegument; as a result some of these granules were fused together to form membrane-bound vacuoles. In addition, at many spots microtrabeculae were also depolymerized, which resulted in the formation of non-membrane-bound vacuoles and the distension of microvilli to form blebs, some of which were disrupted. After prolonged incubation (120 minutes), general breakdown of the tegumental cytoskeleton occurred, and parts of it were sloughed off. In cytochalasin B treatment, the responses were similar to those of colchicine but with less severity. After a short incubation period (10-20 minutes), the microtrabeculae were depolymerized which led to the formation of non-membrane-bound vacuoles in the apical and middle zones of the tegument. Later, the tegumental microvilli were distended to form blebs but no evidence of tegumental sloughing occurred even in prolonged incubation. From these observations, it was concluded that microtubules played a role in the translocation of granules from the tegumental cells to the tegument which modulated the synthesis of membrane and glycocalyx, while microtrabeculae were involved in the maintenance of the structure and integrity of the tegument.

Animals↗
PubMed1997

Colchicine induced rhabdomyolysis.

A 59-year-old man with chronic obstructive pulmonary disease (COPD), atrial fibrillation, and gout developed acute dyspnea, cough, and diffuse muscle aches and pains. He had commenced colchicine (0.6 mg b.i.d. p.o.), for the first time, one month earlier for recurrent gout attacks. Clinical examination revealed atrial fibrillation, an exacerbation of his pulmonary disease, tender muscles, especially calves, and diffuse muscle weakness. Laboratory results included creatinine phosphokinase 6961 U/l (1% MB), microscopic hematuria, myoglobinuria, elevated creatinine 1.6 mg/dl, and blood urea nitrogen 17 mg/dl. COPD and atrial fibrillation were treated and colchicine was discontinued. The patient made a full recovery. This 2nd reported case of colchicine induced rhabdomyolysis is the first reported in the treatment of gout.

Adrenal Cortex Hormones↗
PubMed1998

Antiproliferative activity of colchicine analogues on MDR-positive and MDR-negative human cancer cell lines.

In this study the in vitro antitumor activity of a series of 20 colchicine analogues was tested and compared with colchicine and thiocolchicine on three different human cancer cell lines, two of which express the multidrug-resistance (MDR) phenotype. At concentrations from 1 nM to 100 microM, all compounds tested inhibited cancer cell proliferation. The IC50 values indicate that the three fluorinated analogues were the most active compounds, with a similar decreasing order of potency (IDN 5005 > IDN 5079 > IDN 5080) on the two MDR-expressing cell lines, whereas thiocolchicine was the most effective compound on the MDR-negative MDA-MB 231 cells. A strong correlation (r = 0.94; P = 0.004) was found between IC50 values obtained using the two MDR-positive cell lines. Conversely, IC50 values obtained in MDA-MB 231 cells did not show a significant correlation with MDR-positive cell lines, thereby suggesting some difference in the antiproliferative mechanism(s) of colchicine analogues. Cell cycle analysis of the most active analogues in breast cancer cells showed a relationship between cell cycle blocking activity and growth inhibition. The most active agents on the MDR-positive MCF7 ADRr cell line, after 24 h of culture, in terms of cell cycle blocking activity were the three fluorinated analogues. Interestingly, after 72 h, when the cell cycle block subsided, a consistent amount of DNA fragmentation was evident. The extent of cell cycle block, measured as the G2/G1 ratio, was significantly correlated with the apoptosis rate expressed as a percentage of DNA fragmentation on both cell lines, thereby suggesting that a large number of blocked cells underwent the apoptotic pathway.

Antineoplastic Agents↗
PubMed1984

Tubulins from different higher plant species are immunologically nonidentical and bind colchicine differentially.

We have initiated immunological and drug-binding studies on the tubulins from different higher plant species. Antibodies were raised against electrophoretically separated rose (Rosa sp.) tubulin alpha- and beta-subunits and characterized by immunoblot autoradiographic assays. Each IgG preparation bound to its antigen and cross-reacted differentially with the respective tubulin subunits from an alga, sea urchin, rabbit, and cow. Antigenic determinants were shared more among the beta-subunits than among the alpha-subunits from these organisms. Tubulins were isolated from cultured cells of carrot (Daucus carota) and hibiscus (Hibiscus rosa-senensis). Immunoautoradiography and quantitation of cross-reactivity on blots showed nonidentity among homologous subunits from rose, carrot, hibiscus, and alga tubulins, with more antigenic differences among alpha-subunits than among beta-subunits. Comparative colchicine-binding assays showed that rose and hibiscus tubulins bound 33% and 65%, respectively, of the colchicine bound by carrot tubulin and that higher plant tubulins bound much less colchicine than bovine brain tubulin under identical conditions.

Journal Article↗
PubMed1999

Colchicine-induced myopathy and neuropathy.

Myopathy and neuropathy that have been induced by colchicine have been described only occasionally, although colchicine is a widely used drug. We describe a case of colchicine-induced myopathy and neuropathy in an 84-year-old woman who had renal impairment. Results from a muscle biopsy showed characteristic vacuolar myopathy and autophagic vacuoles. The cessation of medication resulted in a marked improvement of myopathy.

Journal Article↗
PubMed1995

Interaction of a fluorescent analog of N-deacetyl-N-methyl-colchicine (colcemid) with liver alcohol dehydrogenase.

The evidence for specific binding of N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)--colcemid (NBD-colcemid), a fluorescent analog of colcemid (N-deacetyl-N-methyl-colchicine), to liver alcohol dehydrogenase is presented. Alcohol dehydrogenase bound NBD-colcemid in a time-dependent manner, enhanced the fluorescence intensity, and caused a large blue shift of the emission maximum of the free drug. The specificity of binding was determined for both the colchicine nucleus and the NBD moiety. The binding was not affected by the presence of alcohol or NAD in the reaction mixture. Preincubation of horse liver alcohol dehydrogenase with colcemid inhibited the binding to a considerable extent. NBD-colcemid inhibited the enzymic activity of alcohol dehydrogenase in a mixed-type noncompetitive mode with a Ki value of 32 microM, whereas colcemid showed noncompetitive inhibition with a Ki of 100 microM. The association rate constant of NBD-colcemid binding with liver alcohol dehydrogenase was 587 M-1 s-1 at 25 degrees C. The stoichiometry and dissociation constant of the binding reaction were 0.62/dimer and 12 microM, respectively. Donor quenching experiments showed that both tryptophans of alcohol dehydrogenase transferred energy to the bound NBD-colcemid. Thus, this study reports the binding of a colchicine analog to a protein other than tubulin with high affinity. It is concluded that NBD-colcemid binding to dehydrogenases is a general phenomenon, but the common structural element(s) that is responsible for the binding activity, and which exists among tubulin and dehydrogenases, has yet to be determined.

Alcohol Dehydrogenase↗
PubMed1986

Chronic human colchicine neuropathy and myopathy.

A 43-year-old woman who indiscriminately took colchicine for five years developed a progressive multisystem syndrome that included severe axonal neuropathy and a pathologically striking myopathy. The neuropathy and myopathy were similar to experimental animal colchicine-induced neuromuscular toxicity.

Adult↗
PubMed1999

Dentate gyrus-selective colchicine lesion and disruption of performance in spatial tasks: difficulties in "place strategy" because of a lack of flexibility in the use of environmental cues?

The effects of intradentate colchicine injections on the performance of tasks requiring spatial working and reference memory are controversial. Multiple-site colchicine injections (7 microg/microl; via a drawn micropipette) throughout the dentate gyrus (DG) of rats (nine sites in each hemisphere, 0.06 microl at each site) selectively destroy about 90% of the DG granule cells, as revealed by quantitative stereological estimates; stereology also revealed minor neuronal losses in the CA4 (33%) and CA1 (23%) subfields, but lack of damage to the CA3 hippocampal subfield. Spatial reference and working memory were assessed in Morris' water maze; in the reference memory task, the rats were required to learn a single, fixed location for the platform over several days of training; in the working memory task, animals were required to learn a new platform location every day, in a matching-to-place procedure. Compared to sham-operated controls, lesioned rats showed significant disruption in acquisition of the reference memory water maze task; however, the data reveal that these rats did acquire relevant information about the task, probably based on guidance and orientation strategies. In a subsequent probe test, with the platform removed, lesioned rats showed disruption in precise indexes of spatial memory (e.g., driving search towards the surroundings of the former platform location), but not in less precise indexes of spatial location. Finally, the lesioned rats showed no improvement in the match-to-place procedure, suggesting that their working memory for places was disrupted. Thus, although capable of acquiring relevant information about the task, possibly through guidance and/or orientation strategies, DG-lesioned rats exhibit a marked difficulty in place strategies. This is particularly evident when these rats are required to deal with one-trial place learning in a familiar environment, such as in the working memory version of the water maze task, which requires flexibility in the use of previously acquired information.

Animals↗
PubMed1992

Clinical and cellular effects of colchicine in fibromatosis.

The proliferating cells in fibromatoses are myofibroblasts that produce abundant stromal collagen and contain intracellular native and widely spaced collagen fibers. To assess the clinical and cellular effects of colchicine in such tumors, this drug was administered to three patients, one with musculoaponeurotic desmoid fibromatosis, one with Dupuytren's palmar fibromatosis, and one with Peyronie's disease. All three patients had an excellent clinical response, with reduction of tumor size and improvement of contracture. Two cases were studied ultrastructurally; the main cellular changes detected were collapse of the rough endoplasmic reticulum cisternae, reduction of myofilaments, and disappearance of intracellular widely spaced collagen. The findings from this study indicate another probable application for colchicine and support the concept that collagen fibers can be formed intracellularly.

Adult↗
PubMed1987

Ultrastructure of the choroid plexus epithelium of pigeons treated with drugs: II. Effect of cytochalasin D and colchicine.

A remarkable projection of bleblike protrusions, the expulsion of organelles into the protrusions formed on the apical surface, and the separation into the ventricular lumen of these protrusions was the general cellular response of choroidal epithelial cells to intravenous injection of cytochalasin D (CD). The compact microfilament mass and agglomeration of microtubules at the base of the cluster of protrusions reflect the results of cell contraction and displacement of microfilaments induced by CD. In earlier stages after intravenous injections of colchicine, an obvious increase in the number of various-sized vesicles, vacuoles, and lysosomes in the Golgi region was detected. In the later stages, these organelles were seen to accumulate in the basal portion of the epithelial cells. These changes were accompanied by an increase in vacuoles and the disorganization and displacement of the Golgi complex, and they coincided with a decrease in the number of microtubules in apical and basal cytoplasm. These findings suggest that the action of colchicine results in destruction of the three-dimensional architecture between cytoskeletal network and cell organelles. The present results suggest that the cytoskeletal network plays a role in the spatial coordination of the three-dimensional architecture of cell organelles. The study also indicates that the structural differences in the ventricles of the choroid plexus in drug-treated pigeons are manifestations of regional functional specialization in different parts of the ventricular system.

Animals↗
PubMed1993

Familial Mediterranean fever in the colchicine era: the fate of one family.

In order to demonstrate the effect of prophylactic colchicine treatment on the natural history of familial Mediterranean fever (FMF), a family is presented with 6 out of 9 siblings affected by FMF. Each patient represents a different stage of the amyloidotic kidney disease of FMF and the effect of continuous colchicine treatment on its course. Considered together, the members of this family present an almost complete clinical, genetic, and behavioral picture of the disease.

Adult↗
PubMed1979

Mitoses in peripheral pulmonary epithelium: the effect of colchicine.

Injury in the periphery of the lung was studied in rats given intratracheal trypsin. Mitotic figures were noted in the alveolar epithelium, and colchicine enhanced the yield. Of 65 mitotic figures examined in detail, 46 were present in the alveolar epithelium. Epithelial mitoses were confined to type II cells, many of which contained lamellar inclusions, abundant rough endoplasmic reticulum, and luminal microvilli. Mitoses were not seen in type I cells or in less well differentiated epithelial cells, but they were noted in occasional endothelial and interstitial cells. Colchicine-arrested type II cells were distinguished by radially disposed chromosomes surrounding pairs of centrioles and randomly oriented microtubules. In addition, many of these cells showed a pronounced cortical zone, devoid of microvilli, and others showed cytotoxic degenerative changes. These observations indicate that the alveolar epithelium is renewed exclusively by division of differentiated type II cells.

Animals↗