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PubMed1996

Demonstration of efficacy of combining corticosteroids and colchicine in two patients with idiopathic sclerosing mesenteritis.

Sclerosing mesenteritis is an uncommon condition of unknown etiology. It is likely to be the fibrous evolution of mesenteric panniculitis. It often has an indolent course but may be complicated by progressive bowel obstruction. The treatment of the symptomatic forms is not well established. The observations of two women (20 and 65 years old) with a relentless downhill course of biopsy-proved sclerosing mesenteritis are described. A treatment regimen with corticosteroid therapy (initially 1 mg/kg/day) and colchicine (1 mg/day) led, in both cases, to a rapid improvement. Abdominal computer tomography showed reduction in the tumor size. The combination of corticosteroids and colchicine is helpful in the management of symptomatic sclerosing mesenteritis. Follow-up with abdominal computed tomography is useful in evaluating the therapeutic impact.

Adult↗
PubMed2004

Influence of irrigation solutions combined with colchicine and diclofenac sodium on articular cartilage in a rat model.

A two stage, controlled animal trial was designed to observe the effects on normal and manually damaged articular cartilage of the rat knee joint of colchicine (COL) and diclofenac sodium (DIC) added into washout solutions. In the first stage, 21 rats were randomized into three groups, and right knees of all groups were washed-out by either COL, DIC or physiologic saline (PS) solutions. The left side was kept as a paired control. After 18 months, all knees were evaluated macroscopically and microscopically for cartilage changes. In the second stage, 25 rats were randomized into four groups, and a 2 x 2 mm defect was created surgically on the medial condyle. The joints were washed out by either COL, DIC or PS solutions. At the end of the six months, macroscopic, microscopic and transmission electron microscopy (TEM) evaluations were performed to observe the changes to the defective area. The results showed that washout procedures with certain arthroscopic fluid modifications revealed macroscopically less fibrillation and surface changes for the COL and DIC groups in the first stage. Colchicine and diclofenac sodium solutions conducted a better effect on the thickness of the cartilage and gave better results according to Mankin's criteria for degeneration. In the second stage, COL and DIC groups showed better effects on the cartilage regeneration. The pharmacological agents added into the arthroscopic washout fluid may have an effect on the ultrastructure and biologic properties of the joint cartilage, and may improve the results of arthroscopic treatment in chondral pathologies, especially in secondary arthritis.

Administration, Topical↗
PubMedDate not supplied

Prevention of recurrences of corticosteroid-dependent idiopathic pericarditis by colchicine in an adolescent patient.

A case of an adolescent patient with idiopathic recurrent pericarditis is reported. On several occasions during a period of 3. 5 years he was shown to be dependent on corticosteroid therapy, and he became cushingoid. After corticosteroids were substituted with colchicine, no further relapses occurred during a period of 29 months. In accordance with the first published pediatric results, colchicine represents an effective and well-tolerated alternative therapy for recurrent idiopathic pericarditis and might replace prolonged administration of corticosteroids.

Adolescent↗
PubMed1998

General features of the recognition by tubulin of colchicine and related compounds.

The kinetic mechanisms of the binding to tubulin of colchicine and eight different analogues have been studied to elucidate details of the recognition mechanism. All of the analogues follow a two step binding mechanism i.e. binding occurs via an initial step with low affinity, followed by an isomerisation of the initial complex leading to the final high affinity state. For several analogues the kinetic and thermodynamic data of both processes are compared here. For all the analogues the delta G1 degree of initial binding at 25 degrees C varies between -13.3 and -28.8 kJ. mol-1. For the second step delta G2 degrees varies between -2.4 and -27 kJ. mol-1. These limited ranges of free energy change are, however, obtained by a great variety of enthalpy changes and compensatory entropy changes. Comparison of the data for the first and second steps indicates that structural alterations of the drugs always change the thermodynamic parameters of the two steps, and the changes in the first and the second steps are in opposite directions. The fact that this range of experimental behaviour can be incorporated into a general mechanism encourages the extension of these investigations to other colchicine analogues and related compounds with potential pharmaceutical applications.

Animals↗
PubMed1998

TrkA immunoreactivity in reactive astrocytes in human neurodegenerative diseases and colchicine-treated rats.

It has been shown that nerve growth factor (NGF) administration is capable of curbing tissue damage in several neurodegenerative disorders. As a first step to learning about the possible functional role of NGF in the astroglial response during neurodegeneration, we have analyzed the expression of the functional receptor for NGF, TrkA, in human neurodegenerative diseases which are accompanied by reactive astrocytosis, as well as in human astrocytomas. We have compared these results with those observed in reactive astrocytes following colchicine-induced cellular damage to adult rats. In the human brain, strong TrkA immunoreactivity is observed in reactive astrocytes in a number of unrelated diseases, including Alzheimer's disease, Huntington's disease, progressive supranuclear palsy, multiple sclerosis, Creutzfeldt-Jakob disease, multifocal leukoencephalopathy and residual hypoxic encephalopathy. Neoplastic astrocytes in grade II and III astrocytomas display strong TrkA immunoreactivity. In the rat brain, reactive astrocytes following mechanical needle injury and colchicine administration show strong TrkA immunoreactivity. The presence of TrkA receptors in reactive astrocytes from different human neurodegenerative diseases and experimentally induced models in rats, and in neoplastic astrocytes suggests that NGF may participate in the astroglial response to different types of injury and neoplastic proliferation. Since astroglial cells are capable of producing NGF, it is plausible that this neurotrophin may function as an autocrine or paracrine factor in TrkA-expressing reactive and neoplastic glial cells.

Animals↗
PubMed2006

Expression and transcriptional activities of nuclear receptors involved in regulation of drug-metabolizing enzymes are not altered by colchicine: focus on PXR, CAR, and GR in primary human hepatocytes.

Recent findings show that colchicine (COL) in submicromolar concentrations downregulates the expression of major drug-metabolizing P450 enzymes in human hepatocytes. Concomitantly, the expression of pregnane X receptor (PXR) and constitutive androstane receptor (CAR) was diminished by COL, whereas expression of glucocorticoid receptor (GR) remained unaltered. A tentative mechanism is perturbation of the GR-PXR/CAR-CYP2/3 signaling cascade, resulting in restricted transcriptional activity of GR receptor by colchicine. In this work we focused on 10-demethylcolchicine (colchiceine; EIN), a structural analogue and a putative metabolite of COL that lacks tubulin-binding activity. We investigated the effects of EIN on the expression of PXR, CAR, and GR receptors in primary cultures of human hepatocytes. In contrast with the effects of COL, EIN does not alter the expression of PXR, CAR, and/or GR receptors mRNAs. In addition, EIN had no effects on transcriptional activities of PXR, CAR, and GR receptors in reporter gene assays using transfected cell lines. Considering that COL and EIN are structurally very close and differ only in their tubulin-binding activity, the data presented imply that the deleterious effects of COL on the GR-PXR/CAR-CYP2/3 cascade are primarily due to perturbation of the microtubule network. Our data support the idea of replacing COL by EIN, which is less toxic and does not interact with xenoreceptors.

Cells, Cultured↗
PubMed2002

Update on colchicine and its mechanism of action.

Colchicine is a unique anti-inflammatory drug with respect to its limited clinical usefulness and its mode of action. Colchicine is mainly indicated for the treatment and prophylaxis of gout and familial Mediterranean fever. Its mode of action includes modulation of chemokine and prostanoid production and inhibition of neutrophil and endothelial cell adhesion molecules by which it interferes with the initiation and amplification of the joint inflammation. This paper discusses its adverse effects and indications.

Colchicine↗
PubMed1983

Analysis of the neurohypophyseal components accumulating in the supraoptic nucleus of the rat after injection of colchicine.

[35S]Cysteine has been injected into the supraoptic nuclei of normal rats and of animals given 7 micrograms colchicine into the cerebrospinal fluid to inhibit transport of neurosecretory granules. Analysis of extracts of the supraoptic nuclei 20 min or 6 h after isotope injections showed that (i) colchicine does not affect biosynthesis, i.e., incorporation of tracer into the common precursors of neurohypophyseal hormones and their associated neurophysins, and (ii) processing of precursors inside the arrested granules proceeds normally.

Animals↗
PubMed1984

Guanosine triphosphate and colchicine affect the activity and the polymeric state of acetyl-CoA carboxylase.

Acetyl-CoA carboxylase was purified 300-fold from rat liver, in the absence of added citrate, by precipitation from an 18,000g supernatant in the presence of Triton X-100 at 105,000g and 20 degrees C, followed by chromatography on phosphocellulose. Acetyl-CoA carboxylase activity in this preparation was activated by preincubation with GTP (0.1-2.0 mM) and with citrate (20 mM). Colchicine (10(-6)-10(-3) M) inhibited enzyme activity and counteracted the effects of GTP and citrate. Sucrose density gradient centrifugation demonstrated that GTP and citrate preincubation promoted the formation of the polymeric, active enzyme, while colchicine engendered disassembly. Preincubation of the purified acetyl-CoA carboxylase at 4 degrees C caused inactivation and disassembly, which was countered by preincubation at 37 degrees C in the presence of GTP or citrate. These results suggest that GTP, like citrate, activates acetyl-CoA carboxylase by enhancing the conversion of the protomeric form of the enzyme to its more active, polymeric state.

Acetyl-CoA Carboxylase↗
PubMed1988

Autoradiographic, ultrastructural and biosynthetic study of the effect of colchicine on enamel matrix secretion and enamel mineralization in hamster tooth germs in vitro.

First upper molar tooth germs of two to three days old hamsters were exposed in vitro to colchicine in concentrations ranging between 10(-7) and 10(-4) M in the presence of 45Ca and/or [3H]-proline for various times up to 18 h. Enamel mineralization was determined by chemical extraction of in vitro incorporated 45Ca and verified ultrastructurally. Quantitative autoradiography compared with water extracts from total explants radiolabelled with [3H]-proline showed a dose-dependent decrease of grain counts over the extracellular enamel to the similar extent as the decrease in radiolabelled amelogenins in water-extracts. It was concluded that water-extracts from total explants represent amelogenins from the extracellular compartment. Enamel matrix secreted in vitro during exposure to high doses of colchicine failed to mineralize and the complete loss was provoked of the distal parts of the secretory ameloblasts including the distal junctional complexes. Nevertheless, the mineralizing pre-exposure enamel neither hypermineralized nor increased uptake of 45Ca. These data do not support the hypothesis that secretory ameloblasts restrict transepithelial calcium transport by directing most of the calcium ions away from the mineralization front. The biosynthetic data furthermore suggest that enamel matrix proteins, only extractable with guanidine-HCl-EDTA, change their physico-chemical nature during secretory amelogenesis in vitro either during secretion or upon their extracellular mineralization.

Amelogenesis↗
PubMed1977

Effects of cytochalasin B and colchicine on attachment of a major surface protein of fibroblasts.

We have investigated the effects of the drugs cytochalasin B and colchicine on the surface levels of the large, external, transformation-sensitive (LETS) glycoprotein. Colchicine neither removed LETS protein from the surface, nor inhibited its regeneration after removal by mild trypsinization. Cells treated with cytochalasin B, however, showed both a 2-3-fold increase in the turnover rate of their surface LETS protein and a marked inhibition in its regeneration. Inhibition of regeneration was not due to inhibition of synthesis or transport to the surface. In fact, in the presence of cytochalasin B, increased quantities of LETS protein were released into the medium. The results are consistent with the idea of an association of LETS protein with the actin-containing microfilaments. However, other possible explanations, such as effects on cellular morphology or on transport of sugar precursors cannot yet be excluded.

Carrier Proteins↗
PubMed1981

Concanavalin A-induced modification of the electrophoretic mobility of lymphocytes. Effect of colchicine and cytochalasin B.

Concanavalin A induces redistribution, i.e. "capping" and endocytosis of its receptors, on the surface of lymphocytes. This phenomenon has been shown to alter the cellular surface charge density. Colchicine, which depolymerises cytoplasmic microtubules, and cytochalasin B, which inactivates microfilaments, were used to determine the transmembrane control of the changes in the electrophoretic mobility of mouse lymphocytes. Colchicine neither inhibited nor modified the lectin-induced changes, irrespective of whether the cells were exposed to this agent before or after the interaction with concanavalin A. Pre-incubation with cytochalasin B, on the other hand, inhibited the alterations induced by concanavalin A. Cytochalasin B also reversed the altered electrophoretic mobilities of concanavalin A-treated lymphocytes. These data provide further confirmation of the relationship between lectin-induced redistribution and the electrokinetic behaviour of lymphocytes and establish that "capping" but not endocytosis of the glycoprotein receptors is responsible for the electrophoretic changes.

Animals↗
PubMed1987

Colchicine blocks the action of parathyroid hormone but not nicotinamide on renal phosphate transport.

Nicotinamide, like parathyroid hormone, is a rapidly acting specific inhibitor of Na+-dependent transport of phosphate (Pi) across the brush-border membrane of the proximal tubule of the mammalian kidney. Pretreatment of rats with colchicine (0.7 mg/kg body weight) for 1 h led to a significantly diminished phosphaturic response to parathyroid hormone (synthetic 1-34 fragment, 4 micrograms/kg). In contrast, the same dose of colchicine had no effect on the renal response to nicotinamide (1.0 g/kg), measured both as the change in urinary Pi excretion and as Na+-dependent Pi uptake by isolated brush-border membrane vesicles. These data suggest indirectly that the intracellular mechanism that mediates the inhibitory effects of nicotinamide on renal Pi transport does not require intact microtubules.

Animals↗
PubMed1975

Effects of colchicine and cycloheximide on the functional and non-functional lipoprotein lipase fractions of rat heart.

In response to food deprivation, total myocardial lipoprotein lipase activity increased gradually over a period of 9 h. Although lipoprotein lipase exists in a functional and non-functional form in the myocardium, most of the increas in activity occurred in the functional (heparin-releasable) lipoprotein lipase fraction. The administration of colchicine, while having no effect on the increase seen in total lipoprotein lipase activity, did inhibit the increase in the functional fraction, while at the same time, caused a marked rise in the activity of the non-functional (non-releasable) fraction. In rats injected with colchicine after a 24-h fast, total lipoprotein lipase activity was not affected, but activity levels in the functional fraction declined while that in the non-functional fraction increased. These results suggest that the functional lipoprotein lipase is constantly being formed in sites not readily accessible to heparin (presumably the myocardial cells) and transported to its site of action, the surface of the endothelial cells of the capillaries. Cycloheximide administration to rats starved for 24 h caused a decline in activity in both the functional (half-life of about 2 h) and the non-functional (half-life of about 4 h) lipoprotein lipase fractions. These results suggest that the functional and non-functional lipoprotein lipase fractions may correspond to two distinct enzyme species.

Animals↗
PubMed1975

Effect of colchicine on collagen, albumin and transferrin synthesis by cirrhotic rat liver slices.

Collagen synthesis was found to be increased in liver slices of rats made cirrhotic by chronic administration of CCl4. The liver function was impaired, as determined by an increased retention of conjugated bilirubin and low serum albumin values. However, when animals received colchicine simultaneously with CCl4, collagen synthesis and deposition were inhibited, and the liver function appeared normal. When a group of rats was made cirrhotic by chronic administration of CCl4, and then kept for 30 days without further treatment, fibrosis persisted and collagen synthesis was very low. However, the liver function was severely impaired. When similar rats received L-azetidine-2-carboxylic acid during the 30-days period following CCl4 administration, there was a slight but not significant improvement in liver function. The collagen synthesis and the extent of fibrosis were similar to the controls. However, if similar rats received colchicine during the 30 days period, collagen synthesis was almost negligible, there was a slight decrease in fibrosis and there was a great improvement in liver function. In all the cirrhotic animals studied, transferrin biosynthesis remained constant.

Animals↗
PubMed1986

Induction of the action potential in innervated slow muscle fibers of the frog. Effects of tetrodotoxin, vincristine and colchicine.

Experiments were made to induce action potentials in innervated slow muscle fibers of Rana temporaria. Drugs were applied to the sciatic nerve or its spinal roots by one of the following methods: implantation of a silastic cuff containing tetrodotoxin (TTX); subepineural injection of TTX combined with subcutaneous injections of vincristine; and epineural application of colchicine or vincristine. Twelve to 50 days later slow fibers responded to direct or indirect stimulation with an action potential. A substantial number of these fibers were innervated by 2 or 3 slow motor axons. It is concluded that these effects of TTX and colchicine (vincristine) are due to inhibition of the axoplasmic transport of an unidentified substance. The results support the hypothesis that the inexcitability of normal slow fibers is due to a 'trophic' effect of their motor axons.

Action Potentials↗
PubMed1990

Whole-cell voltage-clamp study of sodium current in neuroblastoma cells: effects of inhibition of neurite outgrowth by colchicine.

A method is described for the production of large numbers of neurite-free neuroblastoma cells that are especially suitable for studies involving whole-cell voltage clamp. Differentiation in the presence of colchicine yielded cells having abundant sodium channels, highly reproducible peak currents and no space-clamp problems. Treatment with this drug did not alter the electrophysiological properties of the cells. Colchicine might be similarly advantageous in voltage-clamp studies of different ion channels and other types of cultured neurons.

Axons↗