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PubMed1977

[Effects of colchicine treatment on rat intestinal disaccharidase activities].

UNLABELLED: The changes in morphology and proliferation kinetics produced by colchicine in the intestinal mucosa are known. Contrarily, the functional changes have yet not been investigated systematically. The aim of this study is to investigate the effects of colchicine treatment on rat intestinal disaccharidase activities. MATERIAL AND METHODS: For the experiments male SPF-Wistar rats, body weight 180--200 g (supplied by Mus-Rattus AG, 8011 Brunnthal, FRG) were used. The animals were kept under constant conditions (6 rats per cage) and fed Altromin (Altromin Gmb H,Lage/Lippe), tap water ad libitum. Per day 6 animals of each test group were scarificed by cervical dislocation at defined time. About 3 cm of the intestine were removed 8--10 cm distally of the pylorus and cut longitudinally. After cautious cleaning the mucosa was detached using a scalpel. The thus obtained specimens of the mucosa were frozen at -- 20 degrees C in an air-tight humidity chamber and preserved there until further handling. For histological examination the correspondent parts of the intestine were fixed in 10% formol. From each specimen 4 different stainings were made (haematoxylin-eosin, Giemsa, PAS and Feulgen stain). Per test series 60--66 rats were used. The following doses of colchicine were applied: 1 X 1.0 mg/kg body weight, 1 X 0.5 mg/kg body weight, 5 X 0.1 mg/kg body weight within 24 hours. The single doses were dissolved in about 0.5 physiological saline and applied intraperitoneally. In each 6 rats per group the activities of the following diasccharidases were measured at 24 hours intervals from the 1st to 10th or 14th day: sucrase, maltase, lactase, and cellobiase. The enzyme activities were determined after the two-step method developed by DAHLQVIST (5,6) which can be used as micromethod. The ascertained enzyme activities were always related to the protein content. Protein determination was done after the method of Folin-Ciocalteu as modified by LOWRY et al. (14). The enzyme activities were expressed in international units per g protein (U/g protein). the results obtained were statistically ascertained by the non-parametric test after Kruskal-Wallis, variance analysis with linear contrasts after Scheffe as well as by double variance analyses (26).

Analysis of Variance↗
PubMed1979

Effects of colchicine on spermiogenesis in the mouse.

The effects of colchicine on spermiogenesis in the mouse were examined. Mice were injected intratesticularly with colchicine in concentrations of 10(-4) M to 10(-6) M for various periods of time. The ultrastructure of the testes was examined and abnormal sperm in the epididymis were scored. Colchicine degraded microtubules in the testis and the treatment caused abnormalities of the head and acrosome of testicular spermatids and also resulted in an increase on the number of epididymal sperm showing abnormal head structure by 5 days after treatment of the testes. These results suggest that structurally intact microtubules are essential for the normal morphogenetic processes of spermiogenesis.

Animals↗
PubMed1972

Colchicine inhibits adrenal medullary secretion evoked by acetylcholine without affecting that evoked by potassium.

In perfused rabbit adrenal glands, colchicine (500 muM) inhibited the catecholamine secretion evoked by acetylcholine (20 mug/ml) but not that evoked by excess potassium (60 mM). Since both stimuli are believed to release catecholamines ultimately by the same secretory process, exocytosis, it is concluded that these inhibitory effects of colchicine exerted against acetylcholine result from an action early in the process of stimulus-secretion coupling, possibly at the level of the acetylcholine receptor, and that it is inappropriate to use such inhibitory effects to support the view that secretion proper (exocytosis) in chromaffin cells involves colchicine-sensitive elements such as microtubules.

Acetylcholine↗
PubMed1979

Studies on the effects of vinblastine and colchicine on Trypanosoma gambiense.

Vinblastine and colchicine induce the anucleate form of Trypanosoma gambiense. Light microscopic studies indicated that the anucleate form was not always produced as a result of inhibition of nuclear duplication, but was formed as a result of delay or inhibition of separation of the two nuclei after completion of nuclear division. Studies showed that vinblastine and colchicine caused disorder in arrangement of axonemal microtubules of the extracellular flagella and increased formation of both protofilaments and the axoneme composed of protofilaments in trypanosomes. Moreover, treatment with colchicine resulted in disintegration of previously existing pellicular microtubules and formation of cytoplasmic projections that appeared as protrusions from a small part of the surface membrane.

Animals↗
PubMed1982

[Effect of protein synthesis inhibitors on the development of denervation-like changes in the frog muscle fiber membrane after colchicine-induced blockade of axoplasmic transport].

Experiments on frogs were made to study denervation-like changes in the properties of muscle fiber membrane produced by axoplasmic transport blockade with colchicine. Injection into the animals of the protein synthesis inhibitors, actinomycin D or puromycin, in conjunction with colchicine application to the nerve prevented the appearance of extrajunctional sensitivity to acetylcholine, but did not affect the denervation-like decrease of resting membrane potential, increase in input resistance, and time constant of the muscle fiber membrane. The evidence obtained supports the ideas on the participation of the substances supplied to the muscle with axonal transport in the neurotrophic control of the skeletal muscles. Besides, it attest to the existence of an independent control over chemosensitivity and electrogenesis on the muscle membrane. The results of applying the protein synthesis inhibitors indicate a possibility of neuronal regulation of the synthesis of cholinoreceptors at the transcriptional level. In this case the appearance of extrajunctional sensitivity to acetylcholine after axotransport blockade with colchicine and after denervation is most likely due to the synthesis of new cholinoreceptors rather than by their lateral diffusion from the junctional zone.

Acetylcholine↗
PubMed1984

Effect of colchicine on T cell subsets of healthy volunteers.

We examined the effect of oral colchicine (1-2 mg/day) on four healthy volunteers' T cell subsets. Colchicine significantly (P less than 0.01) decreased the mean (+/- SD) percent of OKT3+ total T cells (from 70 +/- 16 to 47 +/- 13), OKT4+ helper/inducer T cells (from 44 +/- 9 to 24 +/- 6), and OKT8+ suppressor/cytotoxic T cells (from 27 +/- 7 to 17 +/- 7), but did not significantly affect the OKT4:OKT8 ratio (from 1.64 +/- 0.21 to 1.48 +/- 0.45) or concanavalin A-induced suppressor cell function (from 44 +/- 9% to 47 +/- 13%). Thus, colchicine non-selectively decreased the circulating helper/inducer and suppressor/cytotoxic T cells.

Adult↗
PubMedDate not supplied

Increased autophagocytosis induced by colchicine in rat sympathetic neurons.

The effect of colchicine was followed up in the superior cervical ganglion of rats. An increase was observed in the number of autophagocytosis vacuoles in the neurons, especially three and four hours after the intraperitoneal injection of colchicine (0.05 mg/100 g.b.w.). These vacuoles presented very various ultrastructural characters due to their different content and stage of degradation. Their high number is explained by the action of colchicine upon cytoplasmic microtubules, the secondary inhibition of the intracellular movement, and the blockage or reduction of the fusion of primary lysosomes with the autophagic vacuoles, which are continuously formed in the neuron cytoplasms, as well as in other cells.

Animals↗
PubMed1981

Effects of colchicine and cytochalasin B on vasopressin- and cyclic adenosine monophosphate-induced changes in toad urinary bladder.

Coincident with an increase in water permeability, the ridge-like surface structures of toad bladder granular cells transform to individual microvilli after stimulation with vasopressin (VP) or cyclic adenosine monophosphate (cAMP) by a mechanism that is yet to be defined. To explore the possible role of microtubules and microfilaments in this cell response, colchicine and cytochalasin B were employed to determine whether interference with the function of these components of the cytoskeletal system would prevent the VP- and cAMP-induced conversion of ridges to microvilli. Incubation of toad urinary bladders in 10(-4) M colchicine for 4 hours or 10(-5) M cytochalasin B for 90 minutes before stimulation with 20 mU. per ml. of VP markedly inhibited osmotic water flow. However, neither agent prevented the striking conversion of ridges to surface microvilli induced by VP and cAMP as seen with scanning electron microscopy. In addition, the ridges characteristic of granular cells were maintained in control bladders incubated with colchicine or cytochalasin B, but left unstimulated. Under the conditions of these experiments, these findings suggest that microtubules and microfilaments are not essential for maintenance of normal surface configuration in granular cells of toad urinary bladder, and that they are not involved in the mechanism responsible for VP- and cAMP-induced surface changes that occur in association with increased water permeability of this epithelium.

Animals↗
PubMed1984

The effect of colchicine on the pigmentation of the enamel surface in rat incisors.

The effect of colchicine and lumicolchicine on the secretion of an iron-containing pigment vesicle onto the enamel surface in the rat maxillary incisors has been studied histologically and by line scan analysis of the iron with an X-ray microanalyzer. Rats were killed at intervals of 12 and 24 hours and 3, 6 and 10 days after the subcutaneous injection of colchicine or lumicolchicine at a dose of 1.3 mg/kg. At 10 days after the colchicine injection, two pigmentation-free bands were observed on the enamel surface in each pair of incisors. By the line scan analysis of the iron with an X-ray microanalyzer, the pigmentation-free bands corresponded to the decrease of the iron concentration profile. By the histological observation at 12 and 24 hours after the injection, no remarkable changes were observed from the late pigmentation stage to the regression stage. However, at 3 and 6 days after the injection, the pigmentation-free bands appeared on the enamel surface. A large number of pigment vesicles was observed in the ameloblasts and in the papillary cells facing the pigmentation-free bands. These phenomena were not observed in the rats injected with lumicolchicine. The present study suggests that the secretion of an iron-containing pigment vesicle in the ameloblasts onto the enamel surface is mediated by the microtubules.

Animals↗
PubMed1983

Alterations in microvilli of uterine epithelial cells after colchicine treatment.

Colchicine has been injected intra-peritoneally to pregnant rats to determine the effect of this drug on the microvilli of uterine luminal epithelial cells. Microvilli in control animals (saline injected) were 0.51 +/- 0.07 micron tall, whereas in colchicine treated they were only 0.24 +/- 0.02 micron tall. We conclude that colchicine reduces microvillar height in these cells via interaction with microtubules, and suggest that modulations of microtubules probably contribute to the alterations in the microvilli of these cells seen during normal pregnancy.

Animals↗
PubMed1984

[Treatment of aphthosis with thalidomide and with colchicine].

Thalidomide alone (200-300 mg daily) or associated with colchicine (2-3 mg daily) was given orally to 25 patients with aphthosis: 8 patients with recurrent oral aphthae; 4 patients with recurrent mucocutaneous aphthosis, without visceral involvement, and 13 patients with Behçet's disease (Touraine's aphthosis). A major improvement was noted in all groups, with a rapid healing of mucous lesions and a rapid reduction of pain and burning as compared to prior spontaneous regressions. No new outbreaks were noted at a dose of 50-100 mg thalidomide and 1 mg colchicine daily. Under oral administration of the drugs, thrombophlebitis was noted in 1 case (third group) only. In the other patients with Behçet's disease, skin aphthae, ocular symptoms, arthritis, superficial nodular phlebitis quickly disappeared with treatment. The efficiency of the drugs is only temporary, since new lesions usually appeared a few weeks after the end of treatment. Due to the relatively small number of cases studied in each group, no conclusions can be drawn concerning the efficiency of thalidomide alone compared to the association of the two drugs. However, this open trial does support the usefulness of thalidomide, or thalidomide and colchicine, in recurrent mucocutaneous aphthae, aphthosis and Behçet's disease.

Adult↗
PubMed1984

1-Acetyl-3-acetoxy-5'5-diphenylhydantoin has colchicine-like activity.

1-Acetyl-3-acetoxy-5'5-diphenylhydantoin (Ac-DPH) is a synthetic derivative of diphenylhydantoin with unusual properties: 1) it inhibits microtubular polymerization and depolymerizes established microtubules; 2) it blocks colchicine binding and displaces colchicine from microtubular protein, although it bears no resemblance to colchicine; and 3) it does not arrest human lymphocytes in metaphase, in contrast to diphenylhydantoin or its metabolite, 5-(4-hydroxyphenyl)-5-phenylhydantoin (HPPH).

Animals↗
PubMed1981

Humoral immunodeficiency in chickens induced by chemical bursectomy with colchicine applied on the anal lips.

Colchicine was applied on the anal lips of chickens on 4 consecutive days after hatching. At the ages of 4 and 10 weeks the agglutinin responses to Brucella abortus and to sheep red blood cells (SRBC) after intraperitoneal and per anum immunization were decreased in these animals. IgG and IgM antibodies to Brucella, measured by enzyme-linked immunosorbent assay (ELISA), were also diminished in 12-week-old chickens. The total concentration of plasma IgG, measured by the ELISA-inhibition method, was diminished whereas the IgM level was not influenced by the colchicine treatment. These results broadly resemble the findings after surgical bursectomy or cyclophosphamide treatment. It can be concluded that colchicine applied on the anal lips of chickens causes a long-lasting deficiency of humoral immunity and thus seems to be a useful new tool in the exploration of the humoral-immune functions of the chickens.

Anal Canal↗
PubMed1982

Interactions of the tau-tubulin-vinblastine complex with colchicine, podophyllotoxin, and N,N'-ethylenebis(iodoacetamide).

Microtubule assembly is inhibited by anti-mitotic drugs such as colchicine or podophyllotoxin and also by sulfhydryl-oxidizing reagents, but it is not known which tubulin-tubulin interactions are disrupted by these agents. We have studied the interactions of a complex of tubulin, vinblastine, and tau protein with these agents. This complex has the form of a spiral filament and may consist of tubulin dimers joined end to end as in a protofilament; presumably, therefore, the lateral interaction sites should be accessible in this structure but not in the intact microtubule. Unlike the microtubule, the complex binds to colchicine and podophyllotoxin with high affinity. Again, unlike intact microtubules, the complex reacts with N,N'-ethylene-bis(iodoacetamide) to generate an intra-chain cross-link in beta-tubulin. Tubulin molecules containing this cross-link are unable to polymerize, suggesting that formation of this cross-link involves sulfhydryl groups that are critical for assembly. These results are consistent with a model whereby colchicine-, podophyllotoxin-, and sulfhydryl-oxidizing agents inhibit microtubule assembly by preventing lateral interactions between tubulin molecules in adjacent protofilaments.

Animals↗
PubMed1983

Colchicine use for familial Mediterranean fever. Observations associated with long-term treatment.

Of 85 patients with familial Mediterranean fever receiving continuous prophylactic colchicine therapy, 62 (73 percent) have had a significant reduction in the severity and frequency of their attacks. All 62 have been observed for three years or more, for a total of 4,680 patient-months and a mean duration of 75.5 months. Of the 85 patients, 23 (27 percent) did not complete three years of treatment for a variety of reasons. Diarrhea was the most common side effect, necessitating reduction of colchicine dosage in 12 patients, but discontinuation of treatment in only one. No other significant side effects were observed. Continuous, prophylactic colchicine therapy is effective in preventing the recurrent febrile paroxysms of familial Mediterranean fever and is indicated in those patients who are incapacitated by frequent attacks or who are at risk for amyloidosis developing.

Adolescent↗
PubMed1981

Ultrastructural aspects of colchicine ultrasensitivity in CLL lymphocytes.

Circulating lymphocytes from patients with chronic lymphatic leukaemia show extreme sensitivity to colchicine, with 80%-90% cell death after exposure to 10(-7) M colchicine for 20 h in vitro. This is 100,000-times greater than the dose required (10(-2) M) for a similarly toxic effect on normal lymphocytes. A time course series of fixations during the 20-h exposure of chronic lymphoid leukaemia (CLL) lymphocytes to 10(-7) colchicine revealed an entire spectrum of ultrastructural alterations well in advance of any sign of cell death, previously only ascertained by nuclear pycnosis in the light microscope. The changes included the appearance of large numbers of intermediate filaments, loss of surface microvilli, mitochondrial alterations and the formation of annulate lamellae. Mitochondrial changes included disruption of the cristae, swelling and tight clumping of the entire mitochondrial population into a single region of the cytoplasm.

Adolescent↗
PubMed1982

The effect of colchicine and vinblastine on the secretory activity of ameloblasts in the mouse lower incisor as revealed by autoradiography after injection of 35S-sodium sulphate.

The effect of colchicine (0.1 mg/100 g of body weight) and vinblastine (0.2 mg/100 g of body weight) on the secretory activity of ameloblasts in the mouse lower incisor was investigated using autoradiography, 10, 30, 120 min after a single injection of 25S-sodium sulphate. colchicine did not inhibit the synthesis of glycosaminoglycans but delayed the exocytosis of the labeled products into the enamel. Vinblastine inhibited both the biosynthetic activity of ameloblasts and the exocytosis, the latter in an higher degree than colchicine.

Ameloblasts↗
PubMed1982

Treatment of pustulosis palmaris et plantaris with oral doses of colchicine.

The effect of oral doses of colchicine on pustule formation was studied in 32 patients with pustulosis palmaris et plantaris without associated psoriasis. Oral administration of colchicine, 1 to 2 mg daily, was started during periods of disease exacerbation, and the dosage was gradually decreased to 0.5 to 1 mg daily in responsive patients. Thirteen patients showed complete clearing of pustulation, and 14 patients showed a remarkable reduction in pustule formation after two to eight weeks of treatment. One patient did not respond and four discontinued treatment because of nausea or diarrhea. During a three-month follow-up evaluation after treatment was stopped, relapse occurred in eight cases. Colchicine appears to be effective in the suppression of acute exacerbations of pustulosis palmaris et plantaris.

Administration, Oral↗