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Colchicine neurotoxicity demonstrates the cholinergic projection from the supracommissural septum to the habenula and the nucleus interpeduncularis in the rat.

Colchicine injections in the supracommissural septum of the rat caused degeneration of several neurons in the nucleus triangularis septi and the nucleus septofimbrialis. The lesions resulted in significant decreases of choline acetyltransferase in the habenula (-34%) and in the nucleus interpeduncularis (-36%), thus demonstrating the existence of a major cholinergic projection to these nuclei from the supracommissural septum. A large fall in choline acetyltransferase was also noticed in the dorsal hippocampus as a consequence of colchicine damage to the fimbria-fornix fibers crossing the injected area.

Animals↗

The microtubule depolymerizing drugs nocodazole and colchicine inhibit the uptake of Listeria monocytogenes by P388D1 macrophages.

Uptake of Listeria monocytogenes by different mammalian cells like macrophages and epithelial cells is dependent on functional actin filaments and hence susceptible to inhibition by cytochalasin. Here we show that phagocytic uptake of L. monocytogenes by P388D1 macrophages is also highly sensitive to treatment with the microtubule depolymerizing drugs nocodazole and colchicine. This sensitivity is cell type specific and much less pronounced in bone marrow-derived macrophages and Caco-2 epithelial cells. In contrast to nocodazole and colchicine, the microtubule stabilizing drug taxol has no significant effect on the uptake of L. monocytogenes by all three cell types tested.

Actins↗

Colchicine blocks the effects of secretin on bile duct cell tubulovesicles and plasma membrane geometry and impairs ductular HCO3- secretion in the pig.

Secretin causes the bile duct cells to secrete HCO3-. To examine whether the transformation of duct cell ultrastructure that follows secretin stimulation depends on microtubules and is important for ductular HCO3- secretion, we examined the effect of colchicine on ductular HCO3- secretion and on the morphology of cells lining bile ductules of anaesthetized pigs. Colchicine blocked secretin-dependent cytoplasmic clearance of tubulovesicles and prevented expansion of the basolateral plasma membrane in duct cells and reduced the ductular HCO3- secretory response from 132 +/- 25 mumol min-1 to 97 +/- 14 mumol min-1. In contrast, lumicolchicine did not affect secretin-dependent tubulovesicle clearance or plasma membrane geometry or ductular HCO3- secretion. Accordingly, secretin-dependent cytoplasmic clearance of tubulovesicles in bile duct cells appears to depend on microtubules and to be important for ductular HCO3- secretion.

Animals↗

Colchicine-induced tubular, vesicular and cisternal organelle aggregates in absorptive cells of the small intestine of the rat. I. Morphology and phosphatase cytochemistry.

Treatment of rats with colchicine administered intraperitoneally at a dosage of 0.5 mg per 100 g of body weight for 6 hr induces extensive accumulations of tubular-vesicular and cisternal organelles in the absorptive cells of the small intestine. The formation of these organelle aggregates coincides with a reduction of microtubules and massive changes in the cellular organization including alterations of the Golgi apparatus and the plasma membrane. In most cases the accumulated tubules and vesicles contain a homogeneous electron-dense matrix, the cisternae often having the character of rigid lamellae. The organelle aggregates mainly occupy apical cell portions subjacent to the terminal web as well as basal cellular regions close to the basolateral plasma membrane. Tubular-vesicular as well as cisternal organelles react strongly for thiamine pyrophosphatase (TPPase), inosine diphosphatase (IDPase), acid phosphatase (AcPase) and trimetaphosphatase (TMPase). The staining pattern of TMPase differs from that of the other phosphatases in that the reaction is restricted to the colchicine-induced tubular-vesicular and cisternal aggregates, whereas TPPase, IDPase, and AcPase, respectively, also appear over Golgi stacks, multivesiculated bodies and plasma membrane. This phosphatase reactivity indicates the lysosomal character of the organelle aggregates.

Acid Anhydride Hydrolases↗

Relationships between cytoplasmic microtubular complex, DNA synthesis and cell morphology in mouse embryonic fibroblasts (effects of age, serum deprivation, aphidicolin, cytochalasin B and colchicine).

Aging, aphidicolin, serum deprivation and cytochalasin B induce a decrease in the rate of DNA synthesis, an increase in cell flattening (cell surface increase) and an extension of the cytoplasmic microtubular complex (CMTC). Age and experimental conditions affect the protein content of the cell, but there is no relationship between cell morphology and cell protein content. Serum deprivation, aphidicolin and cytochalasin B are more effective on DNA synthesis and cytoplasmic actin complex (CAC) of late than of early fibroblasts. Despite these facts, the cell morphology of late cells is fairly stable and is not affected by experimental conditions, which exert an "aging effect" upon the cell morphology in earlier cultures. Colchicine acts upon the CMTC, cell morphology and DNA synthesis at all ages of the cultures. It also induces disruption of the CAC, the intensity of the disruption depending on both the length of the treatment and the age of the culture: the sensitivity of the actin-microfilaments to colchicine increases with the mitotic age of the cells. We suggest that the microtubular integrity is needed, but not sufficient, to preserve the organization of the CAC into microfilaments. We propose a logical model comprising feedback loops between the number of the mitotic cycles, the rate of DNA synthesis, the extention rate of the plasma membranes and CMTC in normal fibroblasts. CMTC is associated, in this model, with the expression of negative or positive controls, depending on the grade of its extension (Fig. 9).

Animals↗

The ionic dependence of action potentials induced by colchicine in an insect motoneurone cell body.

1. The ionic requirements of the action potential recorded in the cell of an identified cockroach (Periplaneta americana) motoneurone following pre-treatment of the animal with colchicine have been studied. 2. Small cubes of gelatin containing 1% colchicine were implanted into one metathoracic leg near to the nerve trunk containing the axon of the identified motoneurone. 3. Electrophysiological experiments were performed 4--10 days after this treatment, when action potentials which frequently overshoot zero potential can be recorded from the cell body. Such action potentials are not normally seen in untreated animals. 4. Sodium-free solution reversibly abolished the action potential within 5 min. 5. Tetrodotoxin (10(-8)M) reversibly depressed the action potential. It was totally abolished by 10(-7)M tetrodotoxin, but this effect was not reversible. 6. Saline solution containing 40 mM manganous chloride either had no effect on the action potential amplitude, or caused a slight increase. It also caused prolongation of the falling phase and loss of the after-hyperpolarization. These effects were all reversible. 7. It is concluded that sodium carries a major proportion of the inward current of the action potential in this neurone. Some calcium probably enters also, and may, at least in part, be responsible for triggering the delayed rise in potassium conductance during the action potential.

Action Potentials↗

Nature of colchicine resistance in golden hamster.

The unresponsiveness of the golden hamster to colchicine has been shown to be the result of a resistance of individual cells to the drug. This resistance makes it possible to use hamsters with heterotransplanted tumors for testing the in vivo effects of colchicine on the tumors, with no toxic host reactions.

Animals↗

Chromosome pairing: effect of colchicine on an isochromosome.

Two separable stages in the process of chromosome pairing have been demonstrated. The first results in a close spatial relationship of homologs, and the second results in synapsis and formation of chiasmata. Colchicine reduces chiasma formation in conventional bivalents but not in an isochromosome. Thus, colchicine affects only the first stage of pairing.

Chromosome Aberrations↗

Synaptic transmission depressed by colchicine blockade of axoplasmic flow.

Colchicine, which inhibits axoplasmic transport and induces organelle alterations in nerve terminals, was injected intraocularly in pigeons. Electrical stimulation of the optic nerve yielded normal evoked potentials in retinotectal fibers, whereas postsynaptic responses recorded in the tectum were reduced. Postsynaptic depression suggests a deficit of synaptic transmission, presumably dependent on colchicine interference with migrating material.

Animals↗

Lens epithelial cell elongation in the absence of microtubules: evidence for a new effect of colchicine.

Embryonic chick lens epithelial cells cultured in serum-supplemented medium elongated in the absence of microtubules after treatment with the antimicrotubule drug nocodazole. Colchicine, at concentrations lower than those that dissociate microtubules, blocks cell elongation and the associated increase in cell volume. These results indicate that an increase in cell volume, not microtubules, is responsible for lens cell elongation and suggest a previously undescribed effect of colchicine on cell volume regulation.

Animals↗

Prolonged reduction in polymorphonuclear adhesion following oral colchicine.

Polymorphonuclear leucocyte (PMN) function was studied in 7 healthy subjects before and after 5 mg of colchicine taken in divided doses over 24 hours. Mean adherence to nylon fibre colums fell from a pretreatment level of 51% to 33.6% by day 1, remained low (31.8%) at day 5, and returned to pretreatment levels only by about day 9. Random motility (agarose plate method) fell from 932 micrometers to 688 micrometers by day 1, but had returned to normal by day 5. Directed migration and the phagocytic index (opsonised Candida albicans method) were not affected by colchicine treatment. In this marked and prolonged reduction in PMN adhesion implies an influence on maturing PMN precursors in bone marrow. Adherence to nylon fibres may reflect in-vivo properties of PMN which are important in the pathogenesis of acute gouty arthritis.

Administration, Oral↗

Colchicine suppression of corneal healing after strabismus surgery.

Two patients who had previously undergone uneventful operations for strabismus showed healing of corneal dellen and erosion after withdrawal of colchicine therapy. It is suggested that the exhibition of colchicine therapy for familial Mediterranean fever in these two cases was responsible for initial persistence of these two postoperative complications.

Adolescent↗

Mouse red cell rosette formation and the colchicine sensitivity test: relative usefulness in the differential diagnosis of chronic lymphocytic leukaemia and B lymphocytic lymphoma.

Mouse erythrocyte (M) rosette formation and colchicine sensitivity were compared for their ability to differentiate chronic lymphocytic leukaemia (CLL) from B cell non-Hodgkin's lymphoma (NHL) with overspill. Twenty-two cases of CLL and eight of NHL were studied along with 31 normal adults. Results from the patients in both tests differed significantly from the controls but colchicine sensitivity failed to differentiate them further. M Rosettes, on the other hand, while increased in some patients with NHL were, without overlap, much more numerous in those with CLL, and clearly distinguished the two conditions. A significant autolymphocytotoxic effect of plasma from both study groups was also noted which was not found in the controls.

Adult↗

Reversal of nephrotic syndrome due to AA amyloidosis in psoriatic patients on long-term colchicine treatment. Case report and review of the literature.

A case of nephrotic syndrome due to AA amyloidosis in a young woman suffering from erythrodermic psoriasis and psoriatic arthropathy is reported. The nephrotic syndrome regressed completely during long-term (57 months) colchicine treatment. There are 39 case reports in the literature of psoriasis associated with amyloidosis. More than 85% of these patients had concomitant arthropathy. This suggests that arthritis may be an important factor in the appearance of amyloidosis. 59% of psoriatics with amyloidosis had renal failure and 56% of them died shortly after diagnosis of amyloidosis. These observations support the view that amyloidosis associated with psoriasis is an aggressive disease that may be fatal. However, the clinical course of our patient suggests that renal amyloidosis associated with psoriasis may be successfully treated by colchicine.

Adult↗

The positioning of rye homologous chromosomes added to wheat through the cell cycle in somatic cells untreated and treated with colchicine.

The arrangement of chromosome pairs 5RL and 7R added to the wild type and the ph1b mutant line of hexaploid wheat are analyzed in 2N somatic root tip cells during the cell cycle relative to the arrangement that chromosomes 5RL show in 4N tapetal cells produced after colchicine treatment. Both homologous chromosome pairs are identified at interphase and mitosis by fluorescence in situ hybridization. In nuclei at interphase, chromosomes appear as discrete domains that show the Rabl orientation. Homologous chromosomes are predominantly non-associated and their positioning seems not to be influenced by the Ph1 gene that suppresses homoeologous meiotic pairing. This pattern of arrangement contrasts with the high level of somatic pairing that sister chromosomes show in the interphase that follows chromosome duplication induced by colchicine. Disruption of pairing observed in some 4N nuclei is produced at c-anaphase which suggests no topological redistribution of homologues during conformation of the new nucleus. Homologous chromosomes show no predominant arrangement in ellipsoidal metaphase plates, which contrasts with the preferential opposite location of homologues in human prometaphase rosettes. Differences between chromosomes in the variation of the length through the cell cycle and in the chromatin morphology when the Ph1 is absent suggest different patterns of chromatin condensation in both chromosomes.

Cell Cycle↗

The binding of colchicine and its derivatives to bovine and human serum albumin and human plasma.

The protein binding of colchicine and its derivatives demecolcine and desacetylcolchiceine was studied by equilibrium dialysis at 22 degrees C and pH 7.38 in bovine and human serum albumin and human plasma. Colchicine and demecolcine (2 X 10(-4) -5 X 10(-4) mol/l) is not bound to proteins. The binding of desacetylcholchiceine was 60--80% in the range 10(-4)-5 X 10(-4) mol/l. The association constant for a single binding site was 8.03 X 10(3) 1/mol for human serum albumin and 13.20 X 10(3) 1/mol for human plasma. The binding profiles for desacetylcholchiceine were quite similar in human serum albumin (4% conc.) and human plasma (3.8% conc. of albumin fraction). We suggest that desacetylcolchiceine was likely to be bound predominantly to albumin. Salicylic acid in vitro, at clinical concentrations (1.8--14.5 X 10(-4) mol/l), significantly decreases the binding of desacetylcolchiceine to human serum albumin.

Animals↗

Effect of colchicine on the electrophysiological properties of the toad sciatic-gastrocnemius preparations in vivo.

The effects of a single subepineural injection of colchicine on the toad sciatic-gastrocnemius preparation were studied in vivo. The resting membrane potential of the gastrocnemius muscle fibres declined by 15% at day 5. This was followed 2 days later by dispersion and reduction in the amplitude of the compound muscle action potential, decrease in the slope of the accommodation index curve (AI), and a decreased electromyographic interference pattern. These changes were progressive and led to blockage of electrical activity and appearance of pseudodenervation after 2 weeks. Pseudodenervation was confirmed on finding similar alterations in the AI profile in neurotomized toads. In contrast, the hind limbs of toads paralysed by d-tubocurarine had normal muscle AI. The decrease in the AI on the colchicine-treated side was dependent on the length of the severed nerve left attached to the muscle, indicating a centrifugal effect of the drug.

Action Potentials↗