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PubMed1986

Destruction and reorganization of the receptor membrane in labellar chemosensory cells of the blowfly. Long-lasting latent action of colchicine.

Electron micrographs of sections of the labellar chemosensilla of the blowfly, Phormia regina, showed that treatment with sodium deoxycholate (DOC; 7.2 mM for 2 min) destroyed the distal processes of the receptors from up to 10 microns from the tip of the sensillum, but these processes regenerated almost completely within 0.5 h. However, when DOC treatment was preceded by colchicine treatment (25 mM for 2 min), greater than 10 h was required for complete regeneration. Sugar receptor responses supported these findings and disclosed a more detailed time course of regeneration after DOC treatment: without colchicine pretreatment, the destroyed distal process completely regenerated in 0.3-1.0 h, but with pretreatment, regeneration began at 3 h and reached the chemosensillar tip at 8 h at the earliest. Hardly any depression of the response was observed for 8 h after treatment with colchicine alone, but a transient depression was detected at 12 h. Based on these results, the role of microtubules in the maintenance of the receptor membrane is discussed.

Animals↗
PubMed1998

The effect of colchicine treatment on sperm production and function: a review.

Colchicine is used for the treatment of various diseases including gouty arthritis, familial Mediterranean fever (FMF) and Behcet's disease. As a modulator of the microtubules at the cytoskeleton level, it arrests cell division at metaphase and inhibits microtubular-dependent cell motility. Controversy exists as to the adverse effect of colchicine on sperm production and function in healthy subjects as well as in gout, FMF and Behcet's patients. Sperm analysis shows a spectrum of pathology, from oligo- and azoospermia to normospermia with disturbances in sperm motility. These inconsistent sperm pathologies can be explained in part by the variability of the pathophysiology of the underlying disease. Thus, it seems that colchicine by itself may not have a significant direct adverse effect on sperm production and function.

Behcet Syndrome↗
PubMed1982

Protection against chronic pyelonephritis in rats by suppression of acute suppuration: effect of colchicine and neutropenia.

Previous experiments in rats have suggested that renal scarring after acute, obstructive pyelonephritis due to Escherichia coli results from parenchymal damage due to acute inflammation and suppuration. To assess the role of acute infiltration by polymorphonuclear leukocytes (PMNLs) in the pathogenesis of chronic pyelonephritis (CPN), rats were either treated with colchicine to depress leukocyte motility or rendered neutropenic with a single dose of cyclophosphamide. Colchicine given during acute pyelonephritis reduced kidney inflammation and protected against CPN two months later. Similarly, neutropenia reduced acute inflammation and protected against chronic parenchymal destruction and scarring. Protection against renal scarring in both colchicine-treated and neutropenic rats occurred despite higher renal bacterial counts during acute pyelonephritis. These experiments provide further evidence that CPN (renal scarring) results from kidney damage that occurs during early acute obstructive pyelonephritis. This damage appears to result from infiltration of the kidney by PMNLs rather than direct damage from bacterial infection.

Abscess↗
PubMedDate not supplied

Colchicine poisoning: report of a fatal case with body fluid analysis by GC/MS and histopathologic examination of postmortem tissues.

A suicide caused by oral ingestion of colchicine is reported. Postmortem examination revealed circulating Pelger-Huet polymorphonuclear leukocytes and numerous mitotic and chromatin bodies in tissues with rapid cell turnover. Colchicine was identified by gas chromatography/mass spectrometry (GC/MS) of an organic extract of a urine specimen obtained about 36 h after the patient's original hospitalization. The clinical history and pathology of this rarely encountered intoxication are correlated with previous reports, and the rapid detection of colchicine by GC/MS is discussed.

Adult↗
PubMed2002

The single laser flow cytometric micronucleus test: a time course study using colchicine and urethane in rat and mouse peripheral blood and acetaldehyde in rat peripheral blood.

A single laser flow cytometric procedure to quantify micronucleus frequency in rat and mouse peripheral blood was evaluated. Reticulocytes express the transferrin receptor (also known as the CD71-defined antigen). When combined with a DNA stain, antibodies against this antigen can be used to differentially label and quantify micronucleated reticulocytes. The object of this study was to evaluate the method for rat and mouse peripheral blood using flow cytometry and compare the results obtained between two laboratories (GlaxoWellcome and Litron Laboratories). The compounds selected were the rodent carcinogens colchicine, urethane and acetaldehyde. Colchicine gives a positive response in the rat bone marrow micronucleus assay and an inconclusive result in the rat peripheral blood micronucleus assay. The latter two are both established rat carcinogens readily detected in both the bone marrow and peripheral blood micronucleus assays. In these experiments both rat and mice were treated with either colchicine or urethane and rats alone treated with acetaldehyde. After a single treatment, repeat sampling of peripheral blood was made at 0, 24, 48 and 72 h. Replicate blood samples were obtained and fixed for flow cytometric analysis at both facilities. The micronucleated reticulocyte frequency of each blood sample was determined by analysing 20 000 total reticulocytes per blood sample. The data suggest that the single laser flow cytometric procedure resulted in consistent reticulocyte and micronucleated reticulocyte frequencies between laboratories. Furthermore, these flow cytometric data compare favourably with previously published data.

Acetaldehyde↗
PubMed1994

Treatment of recurrent pericarditis with colchicine.

Corticosteroid therapy, because of its frequent and severe side effects should be avoided if possible, and colchicine may be an effective substitute in steroid-dependent recurrent pericarditis. The aim of our study was to assess the usefulness of colchicine in recurrent pericarditis before initiating corticosteroid treatment. Nineteen consecutive patients (10 males, nine females, age 46 +/- 7 years) with recurrent pericarditis (two episodes or more) were included in this prospective open-label study. Before the study, the patients suffered a total of 57 episodes of pericarditis (mean = 3.0 +/- 0.5 episodes.patient-1) despite the use of non-steroidal anti-inflammatory drugs. The mean interval time between the episodes was 7.3 +/- 5.3 months. Colchicine was given at a loading dose of 3 mg and a maintenance dose of 1 mg daily (for 1 to 27 months (mean = 7.7). During the clinical follow-up, the efficacy was estimated by the occurrence of new episodes of pericarditis and by the need for corticosteroid treatment. No recurrence occurred in 14 out of the 19 patients (74%) during a follow-up of 37.4 +/- 6.5 months. In four out of the 19 patients (21%), five recurrences occurred, which resolved without corticosteroids. Follow-up at 23.8 +/- 12.7 months was free of further recurrence. Only one patient (5%) had several recurrences and required corticosteroids for chronic rheumatism. Tolerance was good except for two cases of diarrhoea, one case of hypothyroidism due to associated long-term antidiarrhoeal therapy (containing iodine), and one case of mild leucopenia.(ABSTRACT TRUNCATED AT 250 WORDS)

Colchicine↗
PubMed1978

Dissociation constant of Tetrahymena tubulin-colchicine complex.

Tetrahymena tubulin has a very low affinity for colchicine. The dissociation rate constant (k-1) and association rate constant(k+1) of Tetrahymena tubulin for colchicine were determined in comparison with those of porcine brain tubulin. The k+1 value of Tetrahymena tubulin was about one-twentieth that of porcine brain tubulin, and k-1 of Tetrahymena tubulin was about 680 times greater than that of brain tubulin. The dissociation constant (k-1/k+1) of Tetrahymena tubulin (2.7 X 10(-3) turned out to be ten thousand times greater than that of brain tubulin. This large Kd value explains well the high colchicine concentration requirement reported to block cell division of cilia regeneration of this protozoan.

Animals↗
PubMed1997

The efficacy of interferon alpha on colchicine-resistant familial Mediterranean fever attacks: a pilot study.

About a quarter of familial Mediterranean fever (FMF) patients have recurrent painful attacks of polyserositis despite regular colchicine treatment. There is no known alternative drug for colchicine-resistant cases. We had previously observed a patient with FMF whose painful attacks disappeared during the 6 month period of interferon alpha (IFN) treatment for his chronic hepatitis B. The objective of the present study was to investigate the possible beneficial effect of IFN on these episodes. Twenty-one consecutive attacks in seven adult patients with FMF were treated at early onset with IFN, the dosage being 3-10 million I U s.c. Eighteen of the 21 attacks could be halted in a mean time of 3.05 h, while the intensity of abdominal pain remained very low. Observed side-effects were generally mild and acceptable. IFN may be a useful adjunct for the treatment of colchicine-resistant attacks in FMF patients.

Adult↗
PubMed1997

Apoptosis in rat hippocampal dentate gyrus after intraventricular colchicine.

The aim of this study was to examine the neurodegenerative effects of intraventricular colchicine on granule cells of the hippocampal dentate gyrus and to characterise the modality of neuronal cell death. Male Sprague-Dawley rats were killed 24 hours after a single injection of colchicine into the third ventricle and nuclear morphology, DNA single strand breaks and high molecular weight DNA fragments were analysed to discriminate necrotic from apoptotic cell death. In situ detection of fragmented DNA was performed also on cerebellar sections. The results show that dentate granule cells and cerebellar neurons in the granule cell layer are vulnerable to colchicine administered intraventricularly and that the affected neurons undergo apoptosis.

Animals↗
PubMed2002

Of liver, whisky and plants: a requiem for colchicine in alcoholic cirrhosis?

Colchicine decreases liver fibrosis in experimental and human disease, but a meta-analysis recently concluded that colchicine should not be used for liver fibrosis or cirrhosis irrespective of the aetiology. In this issue, Cortez-Pinto et al. confirm such negative conclusions in their series of 55 outpatients with biopsy-proven alcoholic cirrhosis followed for a median of 3.5 years. Although well tolerated, colchicine did not affect either the annual incidence rate of complications or liver function tests. Current treatment of alcoholic cirrhosis includes correction of nutritional deficiencies, exogenous administration of antioxidants (notably S-adenosylmethionine and polyenylphosphatidylcholine), and liver transplantation. In the future, preventive/therapeutic strategies will include campaigns to decrease alcohol abuse aimed at subjects genetically prone to develop alcoholic liver injury, prevention of liver fibrosis via inhibition of the Na+/H+ exchange, stimulation of apoptosis of stellate cells, antagonism of cytokines involved in liver injury, degradation of extracellular matrix, and reversal of ethanol-induced inflammatory and fibrotic changes via increased nitric oxide levels. On the grounds that it renders the hepatocyte more vulnerable to necrosis, steatosis has a key role in the pathogenesis of alcoholic and non-alcoholic liver disease. Conditions associated with insulin resistance have been recognized as risk factors for chronic liver disease and hepatocellular carcinoma in the alcoholic. This suggests that, through steatosis, insulin resistance could be a co-factor of alcoholic liver disease. Were such a hypothesis confirmed, it would unify our view of the pathogenesis of alcoholic and non-alcoholic liver disease, with all its inherent therapeutic implications.

Colchicine↗
PubMed2000

Colchicine treatment in a patient with neutrophilic dermatosis associated with rheumatoid arthritis.

Neutrophilic dermatoses (ND) are characterized by epidermal and dermal infiltrates of polymorphonuclear leukocytes (PMN), without any infectious or other detectable agents as a cause. We describe a case of ND, which very rapidly improved upon colchicine treatment. The patient was a 67-year-old female with an 8-month history of dusky-red, tender, swollen plaques and nodules with superimposed vesicles and bullae on the buttocks, hands, and ankles associated with rheumatoid arthritis. The diagnosis of ND was made on the basis of the clinical and histopathological features of the skin lesions. She was treated with 0.6 mg of oral colchicine twice daily. Within one week, the erythematous plaques and arthralgia began to recede and disappeared within four weeks. In our case, colchicine seemed to improve the signs and symptoms of ND and appeared to be more effective than the other drugs we had used.

Aged↗
PubMed1980

Effect of colchicine on polymorphonuclear leucocyte chemotaxis in human volunteers.

1 The effect of colchicine on polymorphonuclear leucocyte chemotaxis was assessed in eight healthy volunteers. Four of them received 1.0 mg colchicine and the other four received placebo daily for 8 successive days. 2 Chemotaxis decreased significantly within 24 h of the ingestion of colchicine; the values remained low throughout the 8 days of treatment and returned to normal within 48 h of cessation of medication. 3 There were no significant changes in the placebo treated subjects.

Adult↗
PubMed1983

The effect of long-term colchicine therapy in patients with recurrent polyserositis on the capacity of blood platelets to synthesize thromboxane A2.

Thromboxane B2 (TXB) production during platelet activation was measured in 13 patients with recurrent polyserositis on long-term colchicine therapy and 10 healthy controls. Plasma colchicine concentration in patients ranged between 0.8-7.8 ng/ml (2.0-19.5 X 10(-9) M). Thromboxane production induced during aggregation by arachidonic acid or collagen and serum TXB2 levels (clotted blood, 37 degrees C, 1 h) did not differ among patients and controls. Previous studies reporting platelet function defects including anomalous TXB2 production, were performed in vitro using colchicine concentrations markedly exceeding the therapeutic range.

Adolescent↗
PubMed1983

Colchicine ultrasensitivity of lymphocytes in chronic lymphocytic leukaemia.

It has been previously reported that, in comparison with normal lymphocytes, the lymphocytes in chronic lymphocytic leukaemia (CLL) are ultrasensitive in culture to the cytocidal action of colchicine. In this report the results of 240 colchicine studies in 87 patients with CLL are presented and analysed in terms of the diagnostic, clinical and haematological significance of colchicine ultrasensitivity (CUS) in CLL. All patients with CLL showed very significantly increased CUS of lymphocytes. The CUS did not vary with clinical and haematological status or time and only very rarely with treatment. There was no correlation between % CUS and subsequent course or survival. The results in CLL and in other forms of lymphocytosis and in non-Hodgkin's lymphoma are compared. It is concluded that the test is of considerable diagnostic value, particularly in identifying low-count and treated CLL and in the exclusion of non-CLL lymphocytosis. It appears to have no prognostic value but may have future application in monitoring treatment which selectively eliminates the abnormal cell population.

Adult↗
PubMed1993

Effects of colchicine on the induction of ornithine decarboxylase and its gene expression by the phorbol ester tumour promoter.

The activity and gene expression of ornithine decarboxylase (ODC, an indicator of tumour promotion) were induced by the phorbol ester tumour promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA), in mouse skin. In the present study, the effect of colchicine, a microtubule-disrupting agent, on ODC activity and its gene expression were investigated. On administration of colchicine (100 micrograms) intraperitoneally 1.5 h before TPA treatment, ODC activity and ODC mRNA levels stimulated by TPA were suppressed to about 52 and 64%, respectively. These results suggest the involvement of a microtubule or colchicine-sensitive substrate in the signal transduction system for gene expression.

Animals↗
PubMed1979

Beneficial effects of colchicine in experimental nephrotoxic serum nephritis in the rat.

Glomerulonephritis was induced in rats by multiple injections of rabbit anti-rat kidney serum. Colchicine was administered daily for 4 months to nephrotoxic serum treated rats and untreated control animals. Nephritic rats receiving colchicine had significantly less proteinuria and less glomerular damage than unprotected nephritis animals. A possible role for colchicine in the early treatment of human glomerulonephritis is suggested.

Animals↗
PubMed1993

Colchicine-induced accumulation of estrogen receptor and progestin receptor immunoreactivity in atypical areas in guinea-pig brain.

Using immunocytochemical techniques, cells containing estrogen and progestin receptors have been observed in many discrete regions of the guinea-pig forebrain, including the mediobasal hypothalamus and preoptic area. While most reaction product is located within cell nuclei, we have reported abundant reaction product in perikaryal cytoplasm and neuronal processes as well. Ultrastructural analysis has revealed the presence of estrogen and progestin receptors in atypical subcellular sites within the hypothalamus, including dendrites and axon terminals. In order to determine if microtubule-dependent intracellular transport is involved in intraneuronal transport of steroid hormone receptors, ovariectomized guinea-pigs were injected intracerebroventricularly with the microtubule inhibitor, colchicine, and brain sections at the level of the hypothalamus were immunostained for estrogen receptors. This treatment resulted in the appearance of estrogen receptor immunoreactivity in the paraventricular and mediodorsal thalamic region, areas typically devoid of estrogen receptor-immunoreactive cells in guinea-pigs. In a second study on progestin receptors, we observed the colchicine-induced accumulation of progestin receptor immunoreactivity in the paraventricular thalamic, mediodorsal thalamic and lateral dorsal thalamic areas as well as in the medial amygdala, all areas typically devoid of progestin receptor immunoreactivity. While estradiol injection induced progestin receptor immunoreactivity in the hypothalamus and preoptic area as described previously, it had no effect on the colchicine-induced accumulation in the thalamus and amygdala. These results provide evidence that in some neurons, progestin receptors and estrogen receptors are transported intracellularly, apparently at a rapid enough rate that they do not ordinarily accumulate within the perikaryon.

Amygdala↗