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PubMed1983

A quantitative study of the position of the Golgi apparatus in the developing chick myocardium. Effects of colchicine administration.

This paper presents a quantitative study of the position of the Golgi apparatus in the developing chick myocardium between stages 8+ and 13+. In addition we have studied the effects of colchicine on the position and structure of the Golgi apparatus. During the formation of the heart tube and loop the position of the Golgi apparatus in the myocytes situated in the vicinity of the dorsal mesocardium is related to that found in the cells of the precardiac mesoderm, but it is completely different from that found in the bulk of myocytes of the heart tube and loop. The position of the Golgi apparatus in both pre- and myocardial cells shows clear significative patterns of polarity. The possible significance of the Golgi apparatus polarity is discussed. After colchicine treatment microtubules disappear, the Golgi apparatus loses its polarization and vacuoles filled with amorphous material and/or collagen fibrils are observed. A possible role of the microtubular system in the maintenance of the structure and polarity of the Golgi apparatus and in the intracytoplasmic transport of the cardiac jelly materials is proposed.

Animals↗
PubMed1979

Inhibition of spindle assembly by colchicine and of cell cycle by cycloheximide. Comparison and combination of their cytological action on cleavage mitoses.

In cleavage mitoses colchicine (2 x 10(-3) M) does not interrupt the cycle of chromatin and its action is exerted on all the mitotic phases. Cycloheximide (10(-3) M) prevent normal condensation of the chromosomes and breakdown of the nuclear envelope; it brings on various nuclear abnormalities, particularly irregularities in chromosome condensation. At 10(-4) M, cycloheximide allows some mitoses, often abnormal ones, but anaphase is inhibited. The action of colchicine, more efficient upon the spindle, obscures the action of cycloheximide when both substances are associated. In return, cycloheximide imposes its action upon chromosome condensation, so that the structure of the nuclei treated by both substances is determined by cycloheximide.

Animals↗
PubMed1983

Inhibition of bone resorption and increased incorporation of 3H-glucosamine into hyaluronate in bone organ cultures treated with dibutyryl cyclic AMP and colchicine.

Addition of dibutyryl adenosine 3':5'-monophosphate (DBCAMP), colchicine or dbcAMP/colchicine to bone organ cultures markedly inhibited bone resorption. Calvaria of newborn mice labeled with 45Ca 3 days before sacrifice were removed and cultured in medium containing 3H-glucosamine. Both agents alone and in combination inhibited 45Ca release. DEAE-cellulose chromatography of the papain-digested medium and bone resolved the 3H-glucosamine-labeled macromolecular material into four peaks. A marked increase in radioactivity was observed in the hyaluronate fraction (peak III) of the chromatographed bone samples. The results indicate that dbcAMP does not mimic the effect of parathyroid hormone on bone resorption, but that it is similar to colchicine in both the inhibition of bone resorption and the increased incorporation of 3H-glucosamine into hyaluronate. Although the role of hyaluronate, if any, in this experimental system remain elusive, the increased radioactivity associated with the hyaluronate fraction may be due to decreased degradation resulting from decreased hyaluronidase synthesis.

Animals↗
PubMed1986

Colchicine treatment of urticarial vasculitis.

A patient with clinically and histologically typical urticarial vasculitis has been treated with 0.5 mg of colchicine three times per day. This treatment resulted in both disappearance of urticarial skin lesions and amelioration of severe systemic symptoms such as abdominal pain, fever and arthralgia. Colchicine is proposed as an effective therapeutic agent for urticarial vasculitis if other drugs are ineffective, poorly tolerated or contraindicated.

Administration, Oral↗
PubMed1981

Abnormal mobility of neonatal polymorphonuclear leukocytes. Relationship to impaired redistribution of surface adhesion sites by chemotactic factor or colchicine.

To determine the mechanism(s) of diminished, stimulated, and directed migration of neonatal (N) polymorphonuclear leukocytes (PMN), chemotactic factor (CF) sensory and PMN effector functions were studied in healthy N and adult or maternal controls (C). N PMN demonstrated high affinity binding for N-formyl-methionyl-leucyl-[3H]phenylalanine (fMLP), which was saturable between 40 and 100 nM as observed with C PMN. The kinetics of binding and the characteristics of dissociation of binding by N PMN were equivalent to control PMN. Both "threshold" and "peak" concentrations (1 and 10 nM, respectively) of fMLP effected comparable PMN chemiluminescence among neonates and controls. An equivalent threshold concentration (0.05 nM) of fMLP effected N and C PMN shape change in suspension, and a maximally effective concentration (5 nM) induced comparable bipolar configuration, although uropod formation was only 38 +/- 8% of N PMN, compared with 73 +/- 11% of C PMN (P less than 0.01). Striking abnormalities of N PMN adherence were identified: mean +/- SD base-line (unstimulated) N adherence values (39 +/- 8%) were equal to C (38 +/- 9%), but diminished increments in response to single CF stimuli were noted among N (fMLP: 42 +/- 7% (N), 70 +/- 11% (C); C5a: 41 +/- 6% (N), 68 +/- 6% (C); BCF: 41 +/- 6% (N), 63 +/- 9% (C), P less than 0.01 for each CF). On sequential exposure to increasing concentrations of CF N PMN failed to demonstrate expected decreased adherence values; sequential stimuli with fMLP (0.1 nM, 10 nM) or C5a (8 microgram protein/ml, 32 microgram protein/ml) effected mean +/- 1 SD values of 51 +/- 9% (N), 30 +/- 9% (C), and 34 +/- 10 (N), 48 +/- 14% (C), respectively. As demonstrated with a latex bead-binding technique, N PMN failed to redistribute adhesion sites to the cell's tail under the same experimental conditions; in 21 N samples studied, restricted unipolar binding occurred in 33 +/- 8% (fMLP) or 37 +/- 7% (C5a) of PMN in contrast to C values of 70% (fMLP), or 71% (C5a), P less than 0.001. Similar findings were observed when PMN were preincubated with colchicine (25 microgram/ml); expected diminished adherence scores (compared with base-line values) were demonstrated with C PMN but not with N cells, P less than 0.01. Additionally colchicine-induced redistribution of adhesion sites as was observed with C samples (72 +/- 14% unipolar binding) was significantly (P less than 0.001) less among N PMN (31 +/- 11% unipolar binding). These investigations indicate that CF sensory mechanisms of N PMN are normal, compared with healthy adult or maternal controls. Diminished stimulated locomotion of the N PMN may be functionally related to reduced modulation of cell adhesiveness by chemotactic stimulation.

Cell Adhesion↗
PubMed1983

Haemodynamic studies in eight cases of acute colchicine poisoning.

1 The authors performed haemodynamic studies in 8 cases of colchicine poisoning. The doses absorbed ranged between 9 and 160 mg (mean dose 39 mg). THe haemodynamic study was performed between the 6th and 72nd h after intoxication, before and after plasma infusion (370 ml over a period of 20 minutes). 2 Four patients had severe shock with decreased cardiac index (CI) and increased sytsemic vascular resistance (SVR). Four patients had a hyperkinetic state with increased CI and decreased SVR. The four patients with cardiac failure died, the others recovered. 3 Haemodynamic study of acute colchicine poisoning is of therapeutic and prognostic interest. Hypovolaemia is always present. An initial decrease of cardiac performance is an index of severity with a lethal outcome.

Adolescent↗
PubMed2006

Long-term clinical effects of interferon gamma-1b and colchicine in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF)/usual interstitial pneumonia is a deadly disease with no effective treatment. The purpose of this randomised prospective multicentric study was to characterise the clinical effects of interferon gamma (IFN-gamma) 1b administered subcutaneously thrice weekly versus colchicine for 2 yrs. This study had no pre-specified end-points. Fifty consecutive IPF patients were randomised. Patients with mild-to-moderate IPF were eligible for the study if they had histologically proven IPF, or, in the absence of surgical biopsy, fulfilled the European Respiratory Society/American Thoracic Society criteria. In the intent-to-treat population, five out of 32 (15.6%) IFN-gamma-1b patients and seven out of 18 (38.8%) colchicine patients died after a median follow-up period of 25 months Patients treated with IFN-gamma 1b showed a better outcome after 2 yrs of therapy, and fewer symptoms, as assessed using the St George's Respiratory Questionnaire, after 12 months of therapy. Also, the IFN-gamma-1b group exhibited a higher forced vital capacity (percentage of the predicted value) after 24 months of treatment. No significant differences were detected in resting arterial oxygen tension, total lung capacity (% pred), transfer factor of the lung for carbon monoxide (% pred) and high-resolution computed tomographic scoring between the two treatment groups. These data suggest that long-term treatment with interferon gamma 1b may improve survival and outcome in patients with mild-to-moderate idiopathic pulmonary fibrosis. Further studies are needed to verify these results.

Adult↗
PubMed1988

Cytochalasins and colchicine increase the lateral mobility of human chorionic gonadotropin-occupied luteinizing hormone receptors on ovine luteal cells.

To determine whether cytoskeletal proteins restrict the mobility of LH-receptor complexes occupied by hCG, we measured the rate of lateral diffusion and the fraction of mobile receptor-hormone complexes by fluorescence photobleaching recovery on luteal cells treated with microtubule and microfilament disruptors and on portions of the plasma membrane separated from the underlying cytoskeleton (blebs). Enzymatically dispersed ovine luteal cells obtained on day 11 from superovulated ewes were pretreated for 1 h at 37 C with cytochalasin B (20 micrograms/ml), cytochalasin D (20 micrograms/ml), or colchicine (40 micrograms/ml). These drugs had no effect on the lateral diffusion of cell membrane glycoproteins labeled with tetramethylrhodamine isothiocyanate-derivatized succinyl Concanavalin-A. However, drug treatment caused a significant increase in the diffusion coefficient and mobile fraction of hCG-occupied LH receptors compared to values obtained on untreated cells. hCG-occupied LH receptors on untreated cells exhibited a mobile fraction of 10.3%, and these mobile complexes had a diffusion coefficient of 3.3 X 10(-11) cm2 sec-1.hCG-occupied LH receptors on cytochalasin B-treated cells had a diffusion coefficient of 9.0 X 10(-11) cm2 sec-1, with 26% fluorescence recovery. Cytochalasin D and colchicine caused significantly greater increases in hCG mobility to 22.0 and 22.5 X 10(-11) cm2 sec-1, respectively, although the mobile fraction remained at about 25-30%. That binding of hCG to the LH receptor restricts lateral mobility through interactions of the hormone-occupied receptor complex with the cytoskeleton is further indicated by results obtained on membrane blebs. The fraction of mobile hCG-occupied LH receptors on blebs was 52.3%, and complexes had a diffusion coefficient of 1.7 X 10(-10) cm2 sec-1. The hormone-induced restriction of LH receptor lateral diffusion had no effect on the lateral mobility of tetramethylrhodamine isothiocyanate-epidermal growth factor-labeled receptors.

Animals↗
PubMed1993

Patterns of adrenocorticotropin secretagog release with hypoglycemia, novelty, and restraint after colchicine blockade of axonal transport.

Colchicine blockade of axonal transport from the paraventricular nucleus to the median eminence was used to indirectly infer hypothalamic ACTH secretagog release in awake rats. Median eminence contents of CRF, arginine vasopressin (AVP) and oxytocin (OT) were determined by RIA after insulin-induced hypoglycemia, restraint, and novelty. Insulin decreased circulating glucose concentrations and increased ACTH and corticosterone values. Median eminence CRF and AVP content declined but OT content did not. Both novelty and restraint stressors increased circulating ACTH and corticosterone concentrations. Secretagog measurements indicated decreases in OT content without concomitant decreases in either CRF or AVP with both stressors. These results indicate that: 1) colchicine blockade of axonal transport is useful in studying patterns of secretagog release in animals undergoing psychological stressors; 2) in contrast to physical stressors, OT appears to be a major component of the hypothalamic-pituitary-adrenal response to psychological stress; 3) the patterns of secretagog release differ with regards to physical and psychological stressors.

Adrenocorticotropic Hormone↗
PubMed1976

Elimination by Hydra interstitial and nerve cells by means of colchicine.

Hydra treated with colchicine or Colcemid become depleted of 95-99% of their interstitial cells and derivatives of this stem cell: nematoblasts, nematocytes and nerve cells. A second treatment removes most or all remaining interstitial cells. The most effective treatment is an 8-h immersion of whole Hydra attenuata in 0.04% Colcemid or 0.4% colchicine. Interstitial cells are eliminated through phagocytosis by both ectodermal and endodermal epithelial cells. The endodermal digestive cells send processes through the mesoglea which engulf interstitial cells and retract them into the endoderm. The resultant hydra, though devoid of nematocysts, can be artificially fed: these animals grow and bud and can be used to study the behaviour and development of tissue lacking nerve and interstitial cells.

Animals↗
PubMed1977

Effects of colchicine and vinblastine on the phytohaemagglutinin-induced transformation of lymphocytes.

The effects of 2 microtubular-disruptive drugs, colchicine and vinblastine, on the phytohaemagglutinin (PHA)-induced blast transformation and mitogenic stimulation of human lymphocytes were studied. Both drugs markedly inhibited cell growth and DNA synthesis and lowered the mitotic index. No microtubules were seen with the electron microscope in cells treated with PHA plus colchicine or vinblastine. Moreover, the PHA-induced development of all organelles was partially inhibited by these drugs, especially that of the Golgi complex. As compared to cells treated with PHA alone, the dictyosomes were fewer, not so clearly localized in one area of the cytoplasm, and contained a decreased number of cisternae and an increased number of vacuoles. These results indicate that cytoplasmic microtubules play an important role in the PHA-induced blast transformation and mitogenic stimulation of lymphocytes. It is suggested that the microtubules function in the structural organization of the cell and particularly the Golgi complex. In the drug-induced absence of microtubules this and other organelle systems do not respond as usual to PHA stimulation, which could largely explain the decreased cell growth. This in turn suggests that lowered mitotic activity is a result of inhibition of cell growth, as a critical amount of G1-associated cell growth is believed to be required for the initiation of DNA synthesis and thus mitosis.

Colchicine↗
PubMed1978

Modulation of the effect of colchicine and cytochalasin B on fibroblast aggregates by the substratum.

In previous investigations, we have shown that aggregates of normal human fibroblasts displayed a remarkable number of morphogenetic properties in suspension and on a substratum. The present investigation has attempted to illustrate more clearly the role of colchicine- and cytochalasin-sensitive structures in the observed ultrastructural properties of the fibroblasts in this system. Cytochalasin B and colchicine alter the surface ultrastructure of the cells as well as the behaviour of the cells during aggregate outgrowth. In addition, the effects of both drugs on the cells in the aggregates are modulated by the attachment of the aggregates to a substratum.

Cell Aggregation↗
PubMed1980

Effects of colchicine on endocytosis of horseradish peroxidase by rat peritoneal macrophages.

Horseradish peroxidase (HRP) was used as an exogenous marker to study the effects of microtubule-disruptive drugs on endocytosis in cultures of thioglycollate-elicited rat peritoneal macrophages. Colchicine and vinblastine, but not lumicolchicine or cytochalasin B, reduced HRP uptake by about 30-40%. However, as determined by stereological measurements, the size of the HRP-containing compartment within the cells remained unaltered. In both control cells and cells treated with colchicine or vinblastine the HRP-reactive vesicles were preferentially located close to the dictyosomes (stacks of cisternae) despite the fact that the Golgi complex was disorganized in the treated cells. These results suggest that intact cytoplasmic complex was disorganized in the treated cells. These results suggest that intact cytoplasmic microtubules are required to maintain a normal rate of fluid phase endocytosis in macrophages. On the other hand, it seems as if microtubules are not necessary for the translocation of newly formed endocytic vesicles/lysosomes to the dictyosomes, from which they probably are supplied with digestive enzymes.

Animals↗
PubMed1998

Effects of wheat germ agglutinin and colchicine on microtubules of the mitochondria-rich cells and Ca2+ uptake in tilapia (Oreochromis mossambicus) larvae.

The organization of the microtubules and actin filaments in the gills of tilapia (Oreochromis mossambicus) larvae was revealed by confocal microscopy. The fluorescence intensity of the microtubules in the gills was increased by adding wheat germ agglutinin (WGA, 40 ng ml-1) to the ambient water for 30 min, but the staining pattern of the actin filaments was not changed. The fluorescence intensity of the microtubules in the gills was decreased by treatment with the microtubule-disrupting reagent colchicine at 0.2 mmol l-1 for 4 h. WGA treatment concurrently raised Ca2+ influx rates, and the increase was particularly large when the larvae were kept in water with extremely low Ca2+ levels ([Ca2+]=0.002 mmol l-1). Colchicine treatment, in contrast, reduced the Ca2+ influx rate. These results indicate that the microtubule network in tilapia gills, particularly in mitochondria-rich cells, could play a critical role in the uptake of Ca2+ in tilapia larvae.

Actins↗
PubMed1996

Inhibition of mitogen-induced changes in intracellular fluorescein fluorescence polarization of human peripheral blood lymphocytes by colchicine, vinblastine and cytochalasin B.

We have previously reported that the exposure of human peripheral blood lymphocytes (PBL) to a variety of stimulants caused rapid changes in intracellular fluorescein fluorescence polarization (IFFP) in the activated cells. In the present study we further analyzed possible mechanisms responsible for the changes in IFFP in PBL exposed to phytohaemagglutinin (PHA) and anti-CD3 antibody. By employing several agents which are known to affect the polymerization of the cytoskeleton we showed that both cytochalasin B, which regulates the microfilaments structure, and vinblastine and colchicine, which affect the microtubules, completely abolished the changes induced in IFFP of human PBL by both PHA and anti-CD3. This effect was dose dependent and was noted at concentrations ranging from 10 to 100 microM of cytochalasin B and 10 microM of vinblastine and colchicine. The effect of these cytoskeleton modulators occurred within 20 minutes after the initiation of activation with PHA. Our results indicate that activation with PHA and anti-CD3 causes early changes in the microtubules and microfilaments components of the cytoskeleton. The possible application of IFFP measurement in analyzing early changes in the cytoskeleton following cell activation is discussed.

Colchicine↗
PubMed2000

[Natural organic compounds that affect to microtubule functions: syntheses and structure-activity relationships of combretastatins, curacin A and their analogs as the colchicine-site ligands on tubulin].

Microtubules (MT) are cylindrical polymers of the protein tubulin (TN) alpha, beta-heterodimer, and are known to be the main component of spindles in mitotic apparatus of eucaryotic cells. MT are also involved in many other basic and essential cell functions. There are a number of natural and synthetic compounds that interfere with MT function to cause the mitotic arrest of eucaryotic cells. Such antimitotic agents show a broad biological activity, and can be used for medicinal and agrochemical purposes. On the other hand, they are important also as the biochemical tools for understanding the dynamics of MT network. Most of such antimitotic agents, with a few exceptions, bind to beta-TN. Among them, colchicine (CLC), vinblastine and taxol have played major roles in practical uses as well as in biochemical studies of MT functions. They all bind to beta-TN but their binding sites are different. We have worked on a variety of antimitotic agents that bind to either of colchicine-site, vinblastine-site and taxol-site, in discovery, structures, biological actions and/or interactions with TN. In this paper, the results of our studies on CLC-site ligands were summarized; (1) synthetic analogs of combretastatin A-4 (CBS A-4), isolated as a cytotoxic compound produced by a species of South African tree Combretum caffrum, (2) curacin A (CU-A), a cytotoxic metabolite of a marine cyanobacteria Lyngbya majuscula, and its related compounds. Interactions of these compounds with TN were studied and structure-activity relationships of these two classes of compounds were discussed.

Bibenzyls↗
PubMed2003

Case report. Hepatic portal venous gas: transient radiographic finding associated with colchicine toxicity.

Hepatic portal venous gas has traditionally been associated with a grave prognosis and high mortality. However, with the advent of ultrasound and CT, numerous less serious causes have been associated with this dramatic radiological finding. We present a previously unreported association with colchicine toxicity. The patient ingested a large dose of colchicine and was subsequently found to have portal venous gas on CT. The source of gas was felt to be intestinal gas penetrating through the demonstrated bowel injury. No surgical intervention was deemed necessary and the finding resolved spontaneously.

Colchicine↗
PubMed1989

The inhibitory effects of colchicine, vinblastine and cytochalasin D on lymphocyte blastogenic responses.

The inhibitory effects of colchicine, vinblastine and cytochalasin D on blastogenic responses of equine, bovine and canine peripheral blood lymphocytes (PBL) were investigated. These drugs inhibited blastogenic responses of each PBL. The concentrations for 50% recovery in PBL blastogenic response of colchicine and vinblastine were lower in equine and canine PBL than in bovine PBL. This suggested that microtubules may be more concerned in blastogenic response of equine and canine PBL than of bovine PBL. On the other hand, the concentration for 50% recovery in PBL blastogenic response of cytochalasin D was almost the same in the PBL of each animal. This meant that microfilaments made only a small contribution to the lymphocyte blastogenic response.

Animals↗