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The endolymphatic sac and inner ear homeostasis. I: Effect of glycerol on the endolymphatic sac with or without colchicine pretreatment.

The combined effects of glycerol and colchicine on the endolymphatic sac were investigated in mice. Glycerol induced signs of secretion from the epithelium with formation of secretory granules in the light epithelial cells. Other characteristics of the epithelial lining were also changed resulting in an increased widening of the lateral intercellular spaces, a partial collapse of the lumen and with a deposition of a stainable substance within the lumen. This reaction lasted from 30 min to 24 h following the injection. Pretreatment with colchicine was found to decrease or inhibit the glycerol-induced secretion of macromolecules into the sac. The lumen collapsed but frequently there was no presence of stainable substance. Animals treated with both glycerol and colchicine showed marked signs of inner ear malfunction which could indicate that the secretory activity in the sac might be closely related to the regulation of inner ear fluid homeostasis and that functional disturbances in this system may lead to disorders of inner ear function.

Animals↗

Characteristics of the binding of colchicine to porcine brain, cerebellum, pancreas, kidney, liver and spleen soluble protein: a comparative study.

Quantitative determination of tubulin levels present in the cytosol of different porcine organs was performed by a sensitive radioimmunoassay. The relationship between the amount of protein from liver or spleen and the colchicine bound was curvilinear, possibly due to the presence of an inhibitor of colchicine-tubulin binding in those organs. The rate of decay of colchicine binding increases when protein concentration decreases in brain, cerebellum, kidney and pancreas but it increases when protein concentration increases in liver and spleen.

Animals↗

Effects of vinblastine and colchicine on the rat adrenal cortex: morphometric and cytochemical studies.

The effects of administration of anti-microtubular drugs--vinblastine and colchicine--on the ultrastructure of the zona fasciculata cells of young rat adrenal were studied. Young male rats were injected with vinblastine and sacrificed 2 hr later or with colchicine and sacrificed 3 hr after drug administration. Animals injected with isotonic saline in same experimental conditions served as controls. Ultrastructural alterations provoked by both drugs, vinblastine or colchicine, were identical and were most prominent in the Golgi areas. They appeared enlarged and crowded with round, or slightly elongated light vesicles, acid phosphatase, and osmium negatives. The Golgi dictyosomes, although keeping their normal morphology, were less numerous and presented cisternae which were narrower and shorter than controls. Electron-dense vesicles, round or elongated, and acid phosphatase positive--lysosomes--were observed in great number in the Golgi areas, intermingled with light vesicles. The relative volume of light vesicles and lysosomes of the treated animals was significantly increased when compared with controls, but the relative volume of dictyosomes was significantly decreased. Also the numerical density of light vesicles and lysosomes of the injected rats was significantly increased when compared with controls. These alterations are highly suggestive of the Golgi involvement in the adrenal secretory process.

Acid Phosphatase↗

Arachidonic acid metabolites and colchicine in Behçet's disease (BD).

Vasculitis is accepted to be the basis of Behçet's disease (BD) which is a multisystem disease, and the arachidonic acid(AA) metabolites acting as balancing mediators in the organism are accepted to be responsible for the vasculitis. In this study, we examined the prostaglandin E2 (PGE2) and leukotriene C4 (LTC4) levels of the patients with BD before and after colchicine therapy. We found a statistical decrease in the PGE2 and LTC4 levels after colchicine therapy compared to the previous levels, concluding that colchicine inhibits the inflammation and the polymorphonuclear leukocyte (PML) chemotaxis by inhibiting the cyclooxygenase and lipoxygenase pathways.

Adolescent↗

Chromosomal abnormalities and birth defects among couples with colchicine treated familial Mediterranean fever.

OBJECTIVE: To determine whether colchicine prescribed for familial Mediterranean fever is teratogenic. STUDY DESIGN: Reproductive histories were analyzed from 326 couples referred for prenatal diagnosis because 1 partner was affected. Numbers of chromosomal abnormalities and birth defects were compared with numbers expected from published rates. RESULTS: There were 901 pregnancies, and amniocentesis had been performed in 566, all but 3 conceived while taking colchicine. Seven numerical chromosomal abnormalities were found, not statistically significantly greater than the 4.99 expected from maternal age and gestation of diagnosis (P = .24): unbalanced structural abnormalities were 6, compared with 3.22 expected (P = .11). There were 7 birth defects, a considerably lower rate than reported in local malformation registers. CONCLUSION: The current policy of routine amniocentesis in pregnancies of couples taking colchicine should not be changed until sufficient data accumulates to establish whether the higher number of chromosomal anomalies in this group is significant.

Abnormalities, Drug-Induced↗

Giardia lamblia: evaluation of the in vitro effects of nocodazole and colchicine on trophozoites.

Giardia lamblia is the most commonly detected parasite in the intestinal tract of humans and other mammals causing giardiasis. Giardia presents several cytoskeletal structures with microtubules as major components such as the ventral adhesive disk, eight flagella axonemes, the median body and funis. Many drugs have already been tested as antigiardial agents, such as albendazole and mebendazole, which act by specifically inhibiting tubulin polymerization and hence microtubule assembly. In the present work, we used the microtubule inhibitors nocodazole and colchicine in order to investigate their direct and indirect effects on Giardia ultrastructure and attachment to the glass surface, respectively. Axenically grown G. lamblia trophozoites were treated with nocodazole or colchicine for different time intervals and analyzed by light and electron microscopy. It was observed that trophozoites became completely misshapen, detached from the glass surface and failed to complete cell division. The main alterations observed included disc fragmentation, presence of large vacuoles, and appearance of electrondense deposits made of tubulin. The cytokinesis was blocked, but not the karyokinesis, and membrane blebs were observed. These findings show that Giardia behavior and cytoskeleton are clearly affected by the commonly used microtubule targetting agents colchicine and nozodazole.

Animals↗

Colchicine for the prevention of the postpericardiotomy syndrome: the COPPS trial.

Preliminary data have shown that colchicine may be considered for the prevention of the postpericardiotomy syndrome (PPS). The COlchicine for the Prevention of Post-pericardiotomy Syndrome (COPPS) study is a multicenter, double blind, placebo-controlled, randomized trial that will enroll 360 patients after cardiac surgery. The primary end point will be the PSS rate at 12 months. The study will be the first large randomized placebo-controlled trial in this area, and will provide important evidence regarding the possible benefit of colchicine for the primary prevention of the PPS.

Colchicine↗

Inter- and intra-nuclear differences in galanin expression between the hypothalamic paraventricular and supraoptic nuclei in colchicine-untreated rats.

Not much is known of the topography of galanin expression in the hypothalamic supraoptic (SON) and paraventricular (PVN) nuclei neurons in colchicine (an axoplasmic inhibitor)-untreated animals. Insight into the biological implication(s) of galanin expression in the PVN and SON will depend, at least in part, on the nature of its distribution in colchicine-untreated animals. In this study therefore, the topographical distribution of galaninergic profiles was examined in the PVN and SON of colchicine-untreated rats. Staining in the parvocellular PVN (PVN(p)) was predominantly as varicose thin galanin fiber processes while the magnocellular PVN (PVN(m)) contained large cell soma and fiber processes. The relative fiber density was higher in the anterior, periventricular and medial PVN(p) than in the dorsal, lateral and posterior subdivisions. Large-sized cells and thick fibers were limited to the posterior PVN(m) while the anterior and medial PVN(m) contained varicose profiles. Light- and intensely-stained galanin-positive cells as well as large- and small-diameter (varicose or non-varicose) fibers were observed in the SON. The large and thin fibers exhibit preferential ventral and dorsal distribution, respectively. Together with the complexity of specific afferent and efferent connections within the PVN and SON, these observations underscore heterogeneous galanin expression and raise potential implications for understanding the biological role of galanin by physiologically challenging stimuli.

Animals↗

Time course of changes in cholinergic and neurotrophin-related markers after infusion of colchicine into the basal forebrain.

After bilateral infusions of colchicine or vehicle in the rat nucleus basalis magnocellularis, the time course of changes in several cholinergic and neurotrophin-related markers were assessed. Animals were sacrificed at 3, 7, 14, 28, 35 and 84 days post-lesion, and both the NBM and cortical areas were assessed. Sections were stained immunohistochemically for choline acetyltransferase (ChAT) or p140trk (trk) or histochemically for acetylcholinesterase (AChE). ChAT activity and neurotrophin protein levels were assessed regionally. The number of ChAT immunoreactive NBM neuronal profiles decreased beginning 3 days post-lesion and reach maximal loss by 28 days post-lesion, with no recovery. Examination of trk-IR around the NBM revealed a time-dependent decrease in trk-IR of magnocellular neuron and an increase in trk-IR of astrocytes at 14 and 28 days post-lesion. The density of AChE-stained cortical fibers was maximally decreased 3 days post-lesion followed by an increase in fiber staining across the remaining time points. Cortical ChAT activity showed the largest decrease at 7 days followed by recovery 84 days after colchicine infusion. There was an increase in NGF in the parietal cortex after colchicine infusion but no change in BDNF level. These patterns of changes in the cholinergic and neurotrophin-related markers suggest an association between NGF and lesion-induced compensatory responses in the basal forebrain cholinergic system.

Acetylcholinesterase↗

Alteration of GABA transporter expression in the rat cerebral cortex following needle puncture and colchicine injection.

In the adult cerebral cortex, GABA transporters (GATs) are expressed by both neurons and astrocytes. GAT-1 immunoreactivity is found in axon terminals of GABAergic neurons and astrocytes, while GAT-3 immunolabeling occurs only in the latter. The present study was designed to determine whether the expression of GAT-1 and GAT-3 in the adult rat cerebrum changes after needle lesion and colchicine infusion. Following a needle puncture or a saline injection, immunolabeling for GAT-1 and GAT-3 was slightly increased in an area around the needle track. Not only was the neuropil labeling for both GATs increased, but also a few neuronal somata were found to be immunoreactive for GAT-1. Colchicine injections induced a striking increase in immunolabeling for both GATs in the neuropil in an area adjacent to the needle path and surrounding it. A homologous region of the contralateral hemisphere also showed a moderate increase of immunoreactivity in the neuropil for both GATs. Furthermore, this contralateral site showed many neuronal somata immunolabeled for GAT-1. These changes were mainly detected during the first 5 days following intracortical lesions. These results indicate that (1) the upregulation of GAT-1 and GAT-3 in cortical interneurons and astrocytes is caused by both mechanical and chemical factors associated with the injections; (2) increased GAT-1 and GAT-3 expression contralateral to the site of colchicine injection is mediated by transcellular signaling across the corpus callosum; and (3) the lesion-induced GAT expression may play a protective role by helping to balance excitatory and inhibitory neuronal activities.

Animals↗

Tubulovesicular transcytotic pathway in isolated rat hepatocyte couplets in culture. Effect of colchicine and taurocholate.

Isolated rat hepatocyte couplets in short-term culture (6 h) were labeled for 3 min with horseradish peroxidase (HRP) to characterize the transcytotic vesicle transport pathway in this cell culture system that retained an "apical" canalicular membrane polarity. Microtubules were identified with monoclonal antibodies to beta-tubulin and fluorescein iso-thiocyanate-labeled goat-antimouse antibody and were concentrated in the apical domain, a structural polarity that was eliminated by pretreatment with colchicine. In control cells, HRP immediately labeled vesicles and tubules in the submembrane regions of the periphery of the cell. Within 10 min tubules and vesicles were prominently labeled in pericanalicular regions, a process blocked by colchicine but not by lumicolchine or taurocholate administration. A quantitative morphometric analysis utilizing a Zeiss Videoplan-2 image analyzer established that (a) HRP-containing structures increased in density, area, length, and diameter in the pericanalicular region by 10 min; (b) colchicine, but not lumicolchicine, pretreatment diminished their density, area, and length; and (c) taurocholate (50 microM), a choleretic and biliary lipid-stimulating bile acid, had no effect on HRP density or percentage of area in the pericanalicular region, but decreased the diameter of the pericanalicular HRP-containing structures and increased the percentage of tubules containing HRP from 29% to 40%. Tubules were particularly prominent in thick sections (400 nm) in both peripheral and pericanalicular regions and were viewed as continuous anastomosing linear arrays in stereo-paired micrographs. These studies established that isolated rat hepatocyte couplets maintain a highly polarized tubulovesicular transcytotic pathway in short-term culture that is micro-tubule-dependent. Taurocholate stimulates the transformation of tubules from vesicles in this isolated rat hepatocyte couplet system.

Animals↗

Is colchicine effective in Peyronie's disease? A pilot study.

OBJECTIVES: The treatment of Peyronie's disease with oral or topical agents has not been entirely satisfactory. In this pilot study, we hypothesized that colchicine, known to induce collagenase activity and decrease collagen synthesis, might be an ideal agent in the treatment of Peyronie's disease. METHODS: Colchicine was administered orally for 3 to 5 months to a group of 24 previously untreated patients with Peyronie's disease. RESULTS: Peyronie's plaque decreased or disappeared in 12 of the 24 patients, 7 of 9 patients with painful erections reported significant relief, and penile curvature was improved in 7 of 19 cases. Erectile status, narrowing of the penis, and accompanying Dupuytren's contracture did not change in any of the cases. CONCLUSIONS: Although this pilot study shows some promising results of the use of colchicine in the treatment of Peyronie's disease, the ultimate usefulness of this agent will be determined only by a prospective double-blind clinical study.

Aged↗

Microtubule cytoskeleton perturbation induced by taxol and colchicine affects chaperonin containing TCP-1 (CCT) subunit gene expression in Tetrahymena cells.

We report the existence of a CCT epsilon subunit gene that encodes subunit epsilon of the chaperonin CCT (chaperonin containing TCP-1) in Tetrahymena pyriformis. This work focuses on the study of the effects of the microtubule polymerizing agent taxol and the depolymerizing agent colchicine on microtubule dynamics and their role in the regulation of tubulin and CCT subunit genes. Under taxol treatment some TpCCT and tubulin genes are distinctly expressed until 30 min of treatment. Cytoplasmic TpCCT mRNA levels slightly decrease while tubulin transcripts are increasing. In colchicine treated cells TpCCT and tubulin transcripts decrease in the initial 30 min of treatment and then start to increase. However, both antimitotic agents induce TpCCT and tubulin gene transcription. This induction does not correlate with increased steady-state levels of TpCCT proteins and seems to be necessary to replete cytoplasmic TpCCT mRNAs. Moreover, we found that TpCCT epsilon and TpCCT alpha but not TpCCT eta are present in the insoluble fraction after a postmitochondrial fractionation that contains components of the ciliate cortex structure, basal bodies and cilia. This suggests that some TpCCT subunits may be associated with these structures. The association of TpCCT epsilon subunit is stimulated either by taxol or colchicine treatment. These observations support the idea that CCT subunits could have additional roles in vivo.

Actins↗

Colchicine in dermatology.

Colchicine is a medication most often used to treat symptoms of gout. This drug has also been shown to have beneficial effects on cutaneous conditions, including leukocytoclastic vasculitis, psoriasis, and Sweet's syndrome. Colchicine inhibits the function of polymorphonuclear leukocytes, and dermatoses with a strong presence of these cells may benefit the most from the administration of this medication. A review of the pharmacology, mechanism of action, and adverse reactions of colchicine is also presented.

Colchicine↗

Colchicine overdose: report of two cases and review of the literature.

Colchicine overdose is an uncommon but serious problem that may be missed or ignored unless the physician is aware of the significant potential for, and the various stages of, toxicity. We report two fatal cases in which the potential for lethal complications was not initially realized. Both patients developed multiple organ damage characteristic of severe colchicine toxicity. Awareness and appropriate initial therapy are important if death is to be prevented in colchicine overdose.

Adolescent↗

Selective action of colchicine on protein synthesis and release in a clonal line of rat glial cells.

The effect of colchicine on protein synthesis and secretion in stationary cultures of clonal rat glial cells C6 was examined. Colchicine inhibited the synthesis of the brain specific S100 protein in intact cells but not in a cell-free protein synthesizing system derived from these cells. There was no demonstrable effect of the drug on the synthesis of any of the several hundred proteins resolved by a two-dimensional electrophoretic analysis. However, colchicine specifically enhanced the secretion of several proteins of molecular weighs of 30,000 and of 200-300,000 into the medium. Two of the high molecular weight proteins were apparently membrane proteins whose release into the medium was stimulated by the drug.

Animals↗

Regionally selective neurotoxicity of NMDA and colchicine is independent of hippocampal neural circuitry.

The mechanisms by which cerebral ischemia and several neurotoxins cause regionally selective damages to the hippocampal formation are largely unknown. The CA1-selective toxicity of N-methyl--aspartate (NMDA), the CA3-selective toxicity of kainate, and the dentate gyrus (DG)-selective toxicity of colchicine were observed in organotypic entorhino-hippocampal cultures. The selective neurotoxicity of NMDA and colchicine but not kainate was present in isolated tissue cultures of each hippocampal subregion, suggesting that the regional vulnerability is irrespective of the hippocampal trisynaptic pathway. Dispersed cultures of neurons prepared from Ammon's horn and the DG still exhibited a preference for susceptibility to NMDA and colchicine, respectively. Thus, the neurons per se appear to be inherently susceptible to specific toxins independently of their original loci, intrinsic neural circuits, vascular system, or other systemic factors.

Animals↗

Fatal colchicine overdose: report of a case and review of the literature.

Colchicine poisoning is an uncommon, but potentially life-threatening, toxicologic emergency. A case is reported of a 21-year-old woman who presented to the emergency department approximately 1 hour after ingesting 30 mg of colchicine in a suicide attempt. Her clinical course included gastrointestinal distress, metabolic acidosis, pancytopenia, hypotension, adult respiratory distress syndrome, rhabdomyolysis, and hypocalcemia. Despite aggressive medical management, the patient suffered a cardiac arrest and died 8 days after the ingestion. The clinical features of colchicine poisoning are highlighted and current therapeutic options are discussed.

Adult↗