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PubMed1989

Comparison of colchicine toxicity on different dysmyelinating mutant models.

The administration of colchicine to dysmyelinating mutant mice may serve as an in vivo pharmacological tool for the study of the mechanisms involved in the formation of the myelin sheath. The study of the acute toxicity of colchicine in these mutants demonstrated that male animals were much more sensitive than female animals. All of the mutants and their controls were also more resistant to colchicine than the Swiss strain usually used in toxicity studies.

Animals↗
PubMed1989

[Treatment of Behçet's syndrome with colchicine].

The aim of the present study was to investigate the usefulness of colchicine in the treatment of Behçet's syndrome. Ten patients suffering from Behçet's syndrome were selected for this purpose. The patients were treated with 1 mg/day of colchicine associated with 1 mg of betametasone during the initial florid phase of the disease. After the acute phase, betametasone was withdrawn. The patients were observed for a period ranging from 5 to 23 months. Biochemical and immunological parameters were measured at time 0 and every month in order to monitor the disease and the possible side effects of colchicine. All patients had a satisfactory control of the disease without showing any toxic effect.

Adult↗
PubMed1989

Colchicine treatment of abdominal pains in porphyric patients.

Four hepatic porphyria patients were treated with colchicine for abdominal pains. Colchicine administration during prodromal abdominal symptoms prevented the development of these abdominal crises. When colchicine was given after initiation of the crisis the duration and magnitude of the abdominal pains decreased.

Abdomen↗
PubMed1988

Colchicine causes intrasomatic neurofilament bundles in the mesencephalic trigeminal nucleus and intradendritic bundles in other brain regions.

The effect of a single intracerebroventricular injection of colchicine on the distribution of organelles in neurons of the mesencephalic nucleus of the trigeminal nerve, the inferior colliculus and the deep cerebellar nuclei was studied. In the mesencephalic nucleus of the trigeminal nerve colchicine produced a dramatic accumulation of neurofilament bundles in the soma of these neurons and did not produce a reduction in the number of lysosomes. In other neuronal populations studied, colchicine produced neurofilament bundles in the dendrites and a reduction of lysosomes from the soma of neurons.

Animals↗
PubMed1977

Steps in mitogenic action of concanavalin A. I. Colchicine- and cytochalasin B-sensitive events.

The role of colchicine-sensitive and CB-sensitive events in Con A-inducible activation of spleen cells and thymocytes was investigated by exposing the cells to varying concentrations of the drugs, separately or in combination, in serum-free or serum-supplemented medium and at different stages of the culture. In the initial phase, thymocytes were much more sensitive to colchicine than spleen cells. In adequate doses, either colchicine or CB alone could completely inhibit the activation process; when both drugs were combined, the resulting effect was, as a rule, not additive. It was possible to separate the delayed spontaneous agglutination (which is a concomitant of the mitogenic effect of Con A) from activation by selectively inhibiting the former with CB. It was thus concluded that the delayed agglutination is not a prerequisite for activation to be accomplished. Following a low dose of CB which is known to inhibit cell mobility without blocking activation, agglutinates cannot form spontaneously, but do so when cell collisions are produced by mechanical forces.

Agglutination↗
PubMed1986

Mitochondria in living cells cultured from human chorionic villi: the effects of colchicine on numbers and distribution.

Fluorescence microscopy of living first trimester human placental cells and choriocarcinoma cells in cultures was carried out using the vital fluorescent dye Rhodamine 123. The length and distribution of mitochondria and, in the normal cells, their reaction to colchicine treatment is described. It appears that in the presence of colchicine the distribution of mitochondria in normal placental cells becomes more restricted to the perinuclear cytoplasm and that the mean length of mitochondria is reduced. However, the total length of all the mitochondria in treated cells is not significantly different from that in paired cells which were not exposed to the drug. It is inferred from this result that mitochondrial shortening in the presence of colchicine is not an elastic shortening consequent on the removal of cytoskeletal elements which promote extension of the organelle. Rather it is brought about by fragmentation of the organelle into tandem segments.

Cell Line↗
PubMedDate not supplied

[Isolation of DNA probes for the detection of sequences amplified in colchicine-resistant cells].

Earlier we have found that the development of resistance to colchicine in mammalian cells in vitro is due to gene amplification leading to decreased plasma membrane permeability to the selective agent and some other unrelated drugs. By a stepwise self-renaturation procedure followed by chromatography on hydroxyapatite we isolated the fraction of middle-repeated sequences (DNAc0t = 10-250) enriched in amplified DNA from the DNA of colchicine-resistant Djungarian hamster cell line. Blotting-hybridization with [32P]DNAc0t = 10-250 performed in the presence of the excess of unlabelled DNA from wild type cells reveals amplified sequences in resistant cell lines. The comparison of DNAs from cell lines resistant to colchicine, adriablastin and actinomycin D showed that common but not identical DNA sequences are amplified in these cases. In situ hybridization with [3H]DNAc0t = 10-250 indicates that amplified sequences are located in the long homogeneously staining regions (HSRs) of the marker chromosomes. These results suggest that DNAc0t = 10-250 may be used for screening of recombinant molecules containing amplified sequences.

Animals↗
PubMed1986

The phagocytosis of yeast cells by monocytes: effects of colchicine, beta-lumicolchicine, and gamma-lumicolchicine.

The effect of microtubule antagonist (MA) colchicine and its two non-MA derivatives beta-lumicolchicine and gamma-lumicolchicine on the phagocytosis of yeast cells by glass-adherent monocytes were studied with a fluorescence quenching technique which allowed a distinction between the adherence and engulfment phases of phagocytosis. The engulfment of yeast cells was depressed by colchicine (p = 0.031) but not by the lumicolchicines. The adherence of yeast cells to the monocytes, on the other hand, was depressed by gamma-lumicolchicine (p = 0.028). The colchicine effect suggests that cytoplasmic microtubules play a role in the engulfment process whereas the lumicolchicine effect suggests a role of nucleoside transport over the cell membrane in the adherence process of phagocytosis.

Cell Adhesion↗
PubMedDate not supplied

Reversal effect of isaxonine on modifications of rat polymorphonuclear migration by colchicine.

Using a modified Boyden chamber, random migration and chemotaxis of rat polymorphonuclear leucocytes (PMN) were assessed after incubation in vitro in a solution of colchicine (1.5 X 10(-5) M). The results obtained were compared to random migration or chemotaxis of the same cellular pool treated in vitro or in vivo by N-isopropyl-amino-2-pyrimidine phosphate (isaxonine 4.10(-5) M or 75 and 150 mg/kg respectively). Isaxonine partially inhibited the effect of colchicine on PMN chemotaxis while random migration remained unaffected. Isaxonine might partially inhibit the noxious effect of colchicine on microtubule disruption by a direct effect (polymerization of free tubulin) and/or indirect effect (impairment of disorganizing activity) on PMN microtubules.

Animals↗
PubMed1978

Colchicine induces multiple axis formation and stalk cell differentiation in Dictyostelium discoideum.

Colchicine is shown to have several effects on the development of the pseudoplasmodia of the cellular slime mould Dictyostelium discoideum. At concentrations of 0.01 M and above culmination was prevented, while differentiation of cells into stalk cells occurred at the rear of cell masses. Essentially all cells transformed into stalk cells when slugs were left on colchicine agar for a long time. At concentrations of 0.01 M normal slug architecture was maintained while above 0.025 M pseudoplasmodia reorganized into multiple mounds. Each of these mounds developed an apparently normal discrete tip which was devoid of prespore cells as shown by immunofluorescent staining. The same effects were observed in growing cultures and in regulating slugs treated with colchicine. The data are consistent with the ideas that microtubules are involved in the maintenance of slug architecture and in the differentiation of stalk cells. The modes by which these intracellular structures may operate in these functions are discussed.

Animals↗
PubMed1987

Psoriatic arthritis treated with oral colchicine.

We investigated the use of colchicine in psoriatic arthritis to determine if we could confirm the good results obtained in an earlier, uncontrolled study. Twelve of 15 patients with psoriatic skin lesions and arthritis completed a 16-week placebo controlled double blind crossover study. A significant improvement was noted in grip strength, Ritchie's index, joint size, joint pain and overall therapeutic assessment. Psoriatic skin lesions were not improved by colchicine. The few side effects observed were related to gastrointestinal intolerance, which were usually controlled by temporarily reducing the dose of the drug. Our results indicate that 1.5 mg colchicine daily is an effective treatment for psoriatic arthritis.

Administration, Oral↗
PubMed1987

Effect of colchicine on the activity of cathepsin B and D in human liver cirrhosis.

The activity of cathepsin B and D in human liver biopsy specimens from cirrhotic patients before and after one year of colchicine treatment was studied. The hydroxyproline content as a marker of the amount of collagen in tissue specimens was also determined. The hydroxyproline content in the liver samples was two or threefold that of the control group. After colchicine it remained unchanged or in some patients its values were decreased. Cathepsin B activity was higher in cirrhotic liver samples as compared with the controls, whereas the increased activity of cathepsin D was not significant. The ratio of cathepsin B and D activity to hepatic hydroxyproline content was significantly reduced in cirrhotic livers. Colchicine treatment was followed by an increase in the levels of the enzymes investigated as well as by a significant rise in the ratio of cathepsin B and D activity to hepatic hydroxyproline content.

Cathepsin B↗
PubMedDate not supplied

Colchicine treatment effects on liver cirrhosis assessed by liver blood flow measurements.

Hepatic fibrosis is common in all chronic liver diseases. This fibrosis induces morphological, functional and hemodynamic changes. Among the antifibrotic drugs, colchicine gave the most encouraging results. In a group of 22 patients with liver cirrhosis, the hemodynamic changes were studied before and after 24 months of antifibrotic treatment with colchicine (1 mg daily, 5 days a week). The liver blood flow (LBF) was estimated every year by a noninvasive radioisotopic method. After colchicine therapy the determinations showed, an obvious improvement of the liver blood flow with an increase of K (from 0.159 to 0.1678) (p less than 0.001) and a per cent decrease of delta from 44 to 32 (p less than 0.001), thus showing an improvement of the liver blood supply. The simultaneous and favourable changes of the liver biochemical tests and of the sinusoidal hemodynamic parameters strongly suggest that the perfusion improvement, induced by a loss of liver collagen, might explain the tendency of the biochemical data to resume normal values.

Adult↗
PubMed1986

Multiple drug-resistant human KB carcinoma cells independently selected for high-level resistance to colchicine, adriamycin, or vinblastine show changes in expression of specific proteins.

We have established four cell lines derived from the human KB carcinoma cell line which express high-level multiple drug resistance. One of these lines was selected for resistance to colchicine, one was selected for resistance to colchicine in the presence of the tumor promoter, mezerein, one for resistance to vinblastine, and one for resistance to adriamycin. All of these cell lines are cross-resistant to the other selective agents. The development of multidrug resistance in these cultured human carcinoma cells is associated with a limited number of specific protein alterations revealed by high resolution two-dimensional gel electrophoresis and Western blot analysis. These protein alterations in multidrug-resistant lines include the decreased prevalence of members of a family of proteins of molecular mass 70,000 to 80,000 daltons, pI 4.8-5.0, the increased synthesis of a protein of molecular mass 21,000 daltons, pI 5.0, in the colchicine-resistant cell lines only, and the increased expression of a 170,000-dalton protein in membrane preparations from all of the resistant cells. The loss of the 70,000- to 80,000-dalton proteins in the multidrug-resistant lines, which can also be demonstrated by immunoprecipitation of these proteins with specific antisera, is associated with a loss of translatable mRNA for these proteins. These studies suggest that only a limited number of protein changes occur in multidrug-resistant cell lines.

Animals↗
PubMed1985

The effects of colchicine on the ultrastructure of the dental epithelium and odontoblasts of teleost tooth buds.

Secretory granule ultrastructure of teleost inner dental epithelial (IDE) cells has been reported to be similar to procollagen granules of other cells synthesizing collagen. This study describes the ultrastructure of secretory products in odontogenic cells during enameloid matrix formation in cichlids after inhibition of granule secretion with colchicine. Thirty-six fish were injected with 0.1 mg colchicine, then three were killed first at 2-hr intervals for 12 hr, then daily for 5 days. Tooth buds were processed for transmission electron microscopy, and ultrastructural alterations were assessed for each post-injection interval. Four hours post-injection, IDE cells contained increased numbers of secretory granules, lightly stained granules, dilated cisternae of the granular endoplasmic reticulum, and intercellular amorphous material. After 6 hr, the IDE intercellular amorphous material additionally contained electron dense deposits, and after 8 hr, the intercellular material had fibers similar in appearance to enameloid collagen. No ultrastructural changes were detected in odontoblasts that were in close proximity to the enameloid matrix. Only odontoblasts synthesizing predentin were affected by colchicine, and the observed alterations were similar to those seen in IDE cells. It is concluded that IDE cells synthesize and secrete ectodermal enameloid matrix collagen.

Amelogenesis↗
PubMed1985

The prevention of amyloidosis in familial Mediterranean fever with colchicine.

Colchicine has been used since 1972 to prevent the acute attacks of familial Mediterranean fever. The present study shows that colchicine is also effective in the prevention of amyloidosis. If initiated in patients without evidence of renal disease there is no appearance of proteinuria and no progression to renal insufficiency over long follow-up periods. Moreover, it ameliorates the course of the disease in patients with amyloid nephropathy and normal renal function. It does not alter the course of the disease if initiated after renal function is even mildly impaired. These findings suggest that colchicine prevents the new deposition of amyloid.

Adult↗
PubMed1985

The influence of certain colchicine derivatives on the growth characteristics of L cells.

Colchicine and its derivatives (demecolcine, 2-demethyldemecolcine and acetylated 2-demethyldemecolcine) blocked the mitotic activity of L cells and inhibited proliferation and DNA synthesis. This effect depended on the length of the exposure and the concentration of the substances tested (from 0.05 micrograms/ml up to 2.6 micrograms/ml). The greatest values of plating efficiency, cell proliferation, mitotic index and inhibition of DNA synthesis, respectively, were found after the application of colchiciline (0.2 micrograms/ml). These effects were reversible, since L cells underwent regeneration of the mitotic spindle and renewal of their function after the removal of colchiciline. Reversible effects were much less with other colchicine derivatives tested. The different effects of colchicine and its derivatives were due to their chemical structure, which determines the interactions with respective L cell receptors and thus modifies the mechanism of action on the mitotic apparatus of L cells.

Animals↗
PubMed1985

Extraction of a murine tumor-specific antigen from cells and plasma membranes using 1-butanol: augmentation of antigen yield by colchicine.

The purpose of this investigation was to examine the ability of single-phase aqueous solutions of 1-butanol to release immunoprotective tumor antigen activity from partially purified plasma membranes of the methylcholanthrene-induced fibrosarcoma, MCA-F. Tumor antigen activity was assessed by s.c. immunization of syngeneic C3H/HeJ mice 10 days prior to supralethal challenge. Although brief incubation of intact MCA-F cells in 2.5% butanol releases potent immunoprotective activity, application of this protocol to plasma membranes did not result in antigen extraction. Modification of the extraction protocol using higher concentrations of butanol and longer extraction times did release measurable tumor antigen activity. However, a significant amount of the membrane-associated activity remained with the insoluble membrane fraction, as demonstrated by the immunoprotective capacity of the extracted membranes. The dramatic difference in the extractability of antigen from intact cells and plasma membranes suggested that membrane architecture may influence antigen release. To investigate this possibility, we extracted with butanol MCA-F cells that had been preincubated in colchicine. Treatment of cells with colchicine significantly potentiated the extraction of tumor antigen activity. Augmentation of antigen yield was also observed when plasma membranes were pretreated with colchicine prior to 2.5% butanol extraction. These results suggest that the tumor-specific transplantation antigen may be directly or indirectly associated with the cytoskeleton underlying the plasma membrane.

1-Butanol↗