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PubMed1992

Use of granulocyte colony-stimulating factor in the treatment of pancytopenia secondary to colchicine overdose.

OBJECTIVE: To report a case of pancytopenia following colchicine overdose and to discuss the use of granulocyte colony-stimulating factor (G-CSF) for treating this severe complication. CASE SUMMARY: A 19-year-old man developed pancytopenia four days after ingestion of approximately 50-60 0.6-mg colchicine tablets in a suicide attempt. His pancytopenia resolved after subcutaneous administration of one 300-micrograms dose of G-CSF. The patient recovered from his other multiorgan disturbances during his hospitalization and was discharged from the hospital with elevated liver enzyme concentrations. CONCLUSIONS: Colchicine overdose is rare, but can be fatal. The use of G-CSF appears to be beneficial in alleviating bone marrow depression in colchicine overdose situations.

Adult↗
PubMed1989

Effect of colchicine on the intracellular transport of secretory proteins in rat liver parenchymal cells. Immunocytochemical observations.

We studied the effects of colchicine on the intracellular transport of secretory proteins in rat liver parenchymal cells using the direct immunoenzyme technique. Livers were perfusion-fixed 0.5, 1, and 2 h after injection of colchicine. Vibratome sections of the fixed liver were stained using peroxidase-conjugated Fab' of anti-albumin or anti-fibrinogen. By light microscopy, reaction deposits showing albumin and fibrinogen were observed in the cytoplasmic granules of hepatocytes. Such stained granules decreased 30 min after injection, but later increased gradually and crowded in the cytoplasm. The Golgi complex stained for the proteins decreased after 30 min but increased in the juxtanuclear region after 60 min. The analysis of serial sections showed that colchicine severely disturbed the spatial relationship between the Golgi apparatus and the bile canaliculus. We obtained similar results by electron microscopy; a positive reaction for albumin and fibrinogen was observed in a small number of the cytoplasmic granules after 30 min. After 1 h of treatment, most of the Golgi complexes were fragmented and lost their stacked cisternae. However, they reappeared accompanied with vacuolated cisternae and secretory granules, which were partially stained for albumin and fibrinogen. After 2 h, the secretory granules positive for both proteins accumulated further. Some of them lined a long the plasma membrane, and others made a cluster in the cytoplasm. The profiles showing exocytosis were very rarely seen. These results showed that in the first 30 min, colchicine primarily disturbs partially the Golgi assembly but does not affect the post Golgi secretory pathway much. Later, the drug affects both the post Golgi pathway and the Golgi assembly, and it causes a marked accumulation of secretory granules.

Albumins↗
PubMed1998

Colchicine, D-penicillamine, and prednisone in the treatment of idiopathic pulmonary fibrosis: a controlled clinical trial.

STUDY OBJECTIVE: We compared the long-term efficacy of the combination of colchicine and/or D-penicillamine with prednisone, in comparison to prednisone alone in patients with idiopathic pulmonary fibrosis (IPF). DESIGN: Nonrandomized prospective study in patients with IPF confirmed by biopsy specimen. SETTING: National Institute of Respiratory Diseases, Mexico. PATIENTS: Fifty-six IPF patients were included in this study. Patients received either colchicine/ prednisone (n=19), D-penicillamine/prednisone (n=11), D-penicillamine/colchicine/prednisone (n=11), or prednisone alone (n=15). Prednisone therapy was started at 1.0 mg/kg/d for 1 month followed by a biweekly taper to a maintenance dose of 15 mg/d. Colchicine was administered at a daily dose of 1.0 mg, and D-penicillamine was given at a daily dose of 600 mg. MEASUREMENTS AND RESULTS: Response to therapy was assessed by changes in lung function test results as measured by total and vital lung capacities, arterial blood gas analysis at rest breathing room air, and survival. No significant differences either in lung mechanics or in arterial gases were found in any group relative to the baseline measurement. Thirteen of the 56 patients died during the first 2 years, and 29 were dead at 5 years follow-up. Comparison of survival curves by Cox regression model showed no statistically significant difference among the four groups. Known side effects attributable to prednisone were more common and severe than those attributable to the other drugs. CONCLUSIONS: Our results suggest that neither colchicine nor D-penicillamine modified the progressive course of prednisone-treated IPF, and that the search for new drugs is imperative.

Adult↗
PubMed1977

Interaction of colchicine with DNA molecules.

Colchicine (7.5 X 10-6M or 3.3 X 10-5M) was incubated at pH 7.0, 10.0, or 12.0 with high-molecular DNA from salmon sperm (7 X 10-5M or 3.5 X 10-5M DNA-P) at 40 degrees C. Interaction was monitored by UV spectrophotometry; Amax/Amin ratios, difference and additive spectra, and the quantity of colchicine bound to DNA were presented as functions of time, ionic strength and DNA concentration. Using NMR techniques, delta deltav 1/2/deltac values, chemical shifts and half-line widths of colchicine protons were analyzed as a function of the DNA/colchicine ratio, thus proving the interaction between alkaloid and DNA. An intercalation of the tropolone moiety of colchicine between the nitrogenous bases of DNA is suggested.

Animals↗
PubMed1993

Effect of colchicine and taxol on stimulation of G protein GTPase activity in anterior pituitary lobe of rats by gonadotrophin- and thyrotrophin-releasing hormones.

Colchicine and taxol, which are known to influence tubulin function, were used to delineate the possible role of tubulin in signal transduction in the anterior pituitary lobe. Anterior pituitary lobes, obtained from adult male rats, were processed by discontinuous sucrose gradient centrifugation to obtain plasma membranes. The low Km GTPase activity (EC 3.6.1.) was assayed in 5 micrograms membrane protein using [gamma-32P]GTP at 37 degrees C in an ATP-regenerating buffer containing 1 mumol unlabelled GTP l-1. Ten nmol l-1 each of colchicine, lumicolchicine and taxol maximally stimulated the GTPase activity by about 40% (P < 0.05). A time-course study revealed that 100 nmol colchicine l-1 stimulated the enzyme activity by 55, 74, 89 and 53% at 5, 10, 20 and 30 min, respectively (P < 0.05); lumicolchicine (100 nmol l-1) stimulated the GTPase activity by 44, 36, 11 and 55% at 5, 10, 20 and 30 min, respectively (P < 0.05). Taxol (100 nmol l-1) stimulated the enzyme activity by 39 and 25% at 20 and 30 min, respectively (P < 0.05). Gonadotrophin-releasing hormone (GnRH) and thyrotrophin-releasing hormone (TRH) stimulated the low Km GTPase activity in a concentration-dependent manner, by up to 40-60% (P < 0.05). In the presence of 100 nmol colchicine l-1, the ability of GnRH or TRH to stimulate the GTPase activity was inhibited.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Action of colchicine on hepatic schistosomal granuloma.

Amorphous material and altered collagen fragments within dilated secretory vesicles and cisternae of fibroblast cytoplasm were the main ultrastructural changes seen in hepatic periovular granulomas formed in mice infected with Schistosoma mansoni and treated with colchicine. Despite promoting ultrastructural changes in the fibroblasts found in hepatic periovular granulomas, colchicine administration to infected mice did not significantly change the light microscopic appearance of the hepatic schistosomal lesions, did not diminish the amount of total hepatic collagen, and did not change the collagen isotypes in the granulomas, as observed after a comparative study with non-colchicine treated infected control mice. When administered to mice two weeks after curative treatment of schistosomiasis with praziquantel, colchicine did not seem to increase extracellular collagen degradation or to induce a more rapid resorption of hepatic periovular granulomas, although still promoting ultrastructural alterations in fibroblasts.

Animals↗
PubMed1995

Enzyme cytochemical study of alkaline phosphatase in rat hepatocytes--change of location after colchicine administration or bile duct ligation.

Changes in location of alkaline phosphatase (ALP) in rat hepatocytes after two different treatments were examined by the enzyme cytochemical technique. Although reaction deposits which indicate ALP activity were observed mainly in the bile canalicular membranes until 6 hr after colchicine administration, they were present not only in the bile canalicular membranes but also in the sinusoidal and lateral membranes 12 hr after drug administration. Eighteen and 24 hr after colchicine administration, a large number of reaction deposits were seen in the sinusoidal membranes and in the mutual membranes between adjacent hepatocytes, where the bile canaliculi were completely deformed and complex interdigitations appeared. On the other hand, after bile duct ligation, reaction deposits appeared in every domain of the plasma membranes. Twenty-four hr after colchicine administration to bile-duct-ligated rats, an increase in the number of the reaction deposits was observed, but the location of ALP remained unchanged. The present study suggests that intracellular transport and location of ALP in hepatocytes may be controlled by a common mechanism in colchicine-treated and bile-duct-ligated rats.

Alkaline Phosphatase↗
PubMed1983

Induction of hepatic alkaline phosphatase by colchicine: role of cholestasis and bile acids.

We studied the induction of hepatic alkaline phosphatase by colchicine, a drug which impairs bile flow. By analogy to bile duct obstruction, where retained bile acids induce alkaline phosphatase, we hypothesized that the mechanism of induction involves the drug's cholestatic property and subsequent intrahepatic retention of bile acids. After administering colchicine to bile-fistula rats, we monitored bile flow. In colchicine-treated rats which did not develop cholestasis, we varied the transhepatic flux of taurocholate 15-fold over the physiologic range in order to study the role of intrahepatic bile acids. Induction of alkaline phosphatase was observed when cholestasis was absent and the bile acid flux was 5% of normal. The magnitude of enzyme induction was not augmented by increasing the transhepatic flux of taurocholate. The results demonstrate that colchicine induces hepatic alkaline phosphatase by a mechanism which operates independently of cholestasis and is not modified by the level of bile acid in the liver.

Alkaline Phosphatase↗
PubMed1998

[Treatment of idiopathic pulmonary fibrosis with colchicine].

BACKGROUND: Experimental and clinical evidences suggest that colchicine can be effective in the treatment of patients with idiopathic pulmonary fibrosis. AIM: To assess the effect of colchicine in the treatment of idiopathic pulmonary fibrosis. PATIENTS AND METHODS: Patients with clinically diagnosed idiopathic pulmonary fibrosis were treated with colchicine in doses of 0.5 to 1 mg/day, according to tolerance and followed for periods ranging from 7 to 40 months. The clinical and radiological score reported by Watters et al was used for the longitudinal assessment of patients. Maintenance or improvement in forced vital capacity and maintenance or decrease in alveolar arterial O2 gradient during follow up, were considered as positive therapeutic responses. RESULTS: Seventeen patients (10 male, aged 61 to 81 years old) were studied. Their basal score for dyspnea was 5.8 (over 20), for the chest X ray examination was 2.4 (over 3) and for CT scan was 2.8 (over 3). Basal FVC was 77% of predicted value (range 51-108%), basal FEV, was 82% (range 59-117%) and FEV1/FVC was 0.82 (range 0.68-0.95). PaO2 at rest was 78 mm Hg (ranges 63-97). Alveolar-arterial PO2 gradient was 16 mm Hg (range 5-31.6) at rest and 31 mm Hg (range 5.7-51.4) after exercise. Six patients (35%) had a positive response to therapy. CONCLUSIONS: The response rates of these patients to colchicine are at least similar to those obtained with steroids, but with less side effects.

Aged↗
PubMed2000

In colchicine-treated rats, cellular distribution of AQP-1 in convoluted and straight proximal tubule segments is differently affected.

In cells along the nephron, the recycling of various components between the plasma membrane and intracellular organelles by vesicle trafficking depends on intact microtubules (MT). Previous studies of rats treated with the MT-disrupting drug colchicine showed that some brush-border membrane (BBM) transporters in renal proximal convoluted tubule cells (PCTC) become internalized in numerous vesicles randomly scattered in the cytoplasm. In this study, we compare the intracellular distribution of MT and several BBM proteins [megalin, vacuolar (V)-ATPase, water channel aquaporin-1 (AQP-1)] as well as endocytosis of the in-vivo-injected fluorescent marker FITC-dextran in PCTC and proximal straight tubule cells (PSTC) in control and colchicine-treated rats. Immunoblotting and immunocytochemical data show that in the PCTC and PSTC colchicine treatment causes: (1) disappearance of MT, (2) strongly diminished endocytosis of FITC-dextran, and (3) marked loss of megalin and V-ATPase from the BBM and their redistribution into intracellular vesicles. Similar pattern was observed for the distribution of AQP-1 in the PCTC. However, in the PSTC, the staining intensity of AQP-1 in the BBM, as well as its intracellular distribution remained unaffected by colchicine treatment. We conclude that in the PSTC, either MT play a minor role in the recycling of AQP-1 between the BBM and intracellular vesicles or BBM AQP-1 turns over much more slowly than in the PCTC.

Animals↗
PubMed2001

Current aspects of colchicine therapy -- classical indications and new therapeutic uses.

Colchicine has been traditionally used for the treatment of gout. At present there is no generally accepted alternative to colchicine for the treatment of acute attacks or for the prevention of further attacks. The complex actions of this substance, which are mainly attributable to its stabilising action on the cytoskeleton and cell membranes, and its special pattern of distribution form the basis for the results presented here regarding the prophylactic or therapeutic actions of colchicine in a whole range of other diseases. This is all the more significant in that in several instances it concerns diseases that have so far been unsatisfactorily controlled by other treatments. Because of its astonishing absence of side effects, some authors consider that low dose colchicine may be considered as an alternative to previous therapies or even a means of first choice. It is therefore incorrect to think that medical research has shown little interest in this long-known potential and has not sought to confirm promising options by means of controlled studies. Fibrotic and inflammatory systemic diseases and those in which leucocytic chemotaxis play a role seem to be particularly predestined for this.

Adult↗
PubMedDate not supplied

Growth and IGF-1 levels of children with familial Mediterranean fever on colchicine treatment.

OBJECTIVE: To evaluate growth process and insulin like growth factor-1 (IGF-1) levels in children with familial Mediterranean fever (FMF). METHODS: This prospective study group consisted of 51 children with FMF under colchicine therapy (20 boys, 31 girls) and 42 healthy children (22 boys, 20 girls). All children were prepubertal. Bone ages and IGF-1 levels were determined in all cases. Height velocity (HV), height standard deviation score (SDS), target height and target height SDS were calculated. RESULTS: There was no statistical difference in age, HSDS, target height SDS and bone ages between healthy and diseased subjects. HV of children with FMF did not differ significantly from the control group. There was no statistical difference in age, HSDS, target height SDS and bone ages between healthy and FMF subjects. HV of children with FMF did not differ significantly from the control group. There was no significant correlation between disease duration, number of attacks, erythrocyte sedimentation rate and HV, HSDS and IGF-1 levels of FMF patients. There was positive correlation between cumulative colchicine dose and HV (r = 0.29). CONCLUSION: Growth and IGF-1 levels of children with FMF do not differ from their healthy peers. However, there was positive correlation between HV and cumulative colchicine dose. This study suggests that colchicine not only has no adverse influence on growth, but more by suppressing disease activity and inflammation it has an enhancing role.

Age Determination by Skeleton↗
PubMed1998

Effects of colchicine on parotid gland: structural and biochemical studies.

The present study involves the analysis of structural, ultrastructural and biochemical modifications induced by colchicine (Col) in Guinea Pig parotid gland. The biochemical studies showed that the highest concentration of soluble proteins occurred 4 hs after colchicine injection. The curve of a-amylase activity in the gland showed an increase in enzyme activity over control at approximately 4 hs post-injection. At 8 hours the rise was even greater. The structural and ultrastructural analyses of the gland revealed that 4 hs post-injection colchicine exerts its maximum inhibitory effect on secretion. At this treatment time, the cytoplasm contained granules of various sizes and sharp outlines. Large areas of the cytoplasm exhibited material which resembled the granular content and seemed to result from the fusion of granules. No secretion was found in the lumen of the ducts. The inhibitory effect on secretion would be due to the disassembly of microtubules which would in turn impair transport of the granules to the apical surface of the membrane and eventual exocytosis. We herein propose that the effects of colchicine in the experimental conditions of this study would be largely reversible at 24 hours. At this time, structural, ultrastructural and biochemical features were similar to those of controls.

Animals↗
PubMedDate not supplied

Colchicine neuromyopathy: a report of six cases.

Colchicine has been in use for therapeutic purposes for many years. It can, however, cause subacute onset muscle and peripheral nerve toxicity in patients with chronic renal failure. In this report we describe 6 patients who developed neuromyopathy after the administration of colchicine. All patients presented with proximal muscle weakness, elevated serum creatine kinase (CK) levels, and neuropathy and/or myopathy on electromyography (EMG). The diagnosis of colchicine toxicity was confirmed in all cases by the normalization of CK levels and EMG after discontinuation of the drug. Toxicity developed in 4 renal failure patients on therapeutic doses of the drug, while one patient took a massive dose for suicidal reasons, and the other was on high-dose therapy. Patients using colchicine--especially those with renal failure--should be warned about the side effects of the drug and physicians should be careful in the administration of the drug.

Adult↗
PubMed1976

Termination of pseudopregnancy by administration of prostaglandin F2alpha and termination of early pregnancy by administration of prostaglandin F2alpha or colchicine or by removal of embryo in mares.

At day 24 of gestation, pregnant mares were allotted to 1 of 5 treatment groups (3 to 5 mares/group): group A--nontreated controls; group B--intraembryonic injection of 4 mg of colchicine on day 24; group C--removal of embryo on day 24; group D--subcutaneous injection of 1.25 mg of prostaglandin F2alpha (PGF2alpha) on day 32; and group E--removal of embryo on day 24 and subcutaneous injection of PGF2alpha on day 32. In all mares treated with colchicine (group B), the fetal bulge was absent within 2 days. The interval from injection of colchicine to onset of estrus was very short (mean, 4 days). These results indicated that treatment with colchicine was lethal to the 24-day embryo, and pseudopregnancy did not occur. Surgical removal of the embryo (group C) resulted in pseudopregnancy characterized by a prolonged interval from treatment to return to estrus (mean, greater than 31 days), prolonged production of progesterone, and prolonged maintenance of tense uterine and cervical tone. The interval from treatment to ovulatory estrus was longer (P less than 0.05) for group C mares than for group B mares. The mean interval from treatment to complete loss of tense tubular uterine tone was not significantly different between group A pregnant controls (28.3 days) and group C pseudopregnant mares (30 days). Treatment of pregnant mares (group D) with a single injection of PGF2alpha on day 32 resulted in loss of pregnancy in 4 of 4 mares within 2 to 5 days, and in all group D mares a large decrease in progesterone concentration occurred on day 33, 34, or 35. Although subsequent reproductive activity was variable, all group D mares rapidly lost the tense uterine and cervical tone characteristic of early pregnancy. These results indicated that a single subcutaneous injection of 1.25 mg of PGF2alpha caused loss of pregnancy, and pseudopregnancy did not occur. Treatment of group E mares, which had been made pseudopregnant by removal of embryo, with 1.25 mg of PGF2alpha resulted in termination of pseudopregnancy in 5 of 5 mares. All group E mares returned to estrus within 2 to 5 days after treatment, and progesterone concentration decreased (P less than 0.05) within 2 days after treatment. There was no significant difference in loss of tense tubular uterine or cervical tone between pregnant (group D) and pseudopregnant (group E) mares after PGF2alpha treatment.

Abortion, Induced↗
PubMedDate not supplied

[Suicidal attempt with colchicine].

Colchicine is an alkaloid that has been successfully used for a long time in the treatment of acute gout episodes. It's efficacy lies in its inhibition of inflammation cell migration and in the action of specific cytokines, as well as of the production of lactic acid and deposition of uric acid in affected tissues. Colchicine toxicity is rare but may entail highly negative consequences for health unless a rapid gastric decontamination with stomach lavage and active carbon is carried out, and adequate support measures are taken as wellas appropriate hydration and electrolyte replacement. We present the case of a patient who was admitted to hospital after ingesting colchicine with suicidal intention. Colchicine inhibits cell division, which explains its distinct toxicity stages. The lack of proportion existing between ingested dose and clinical impact may result from concomitant treatment with other drugs or from peculiarities in its metabolism.

Adult↗
PubMedDate not supplied

Role of A-SAA in monitoring subclinical inflammation and in colchicine dosage in familial Mediterranean fever.

OBJECTIVES: 1) To compare the sensitivity of serum amyloid A protein (A-SAA) and other acute phase proteins (APPs) in determining subclinical inflammation in patients with familial Mediterranean fever (FMF) during an attack-free period; 2) to define those clinical, laboratory features that may modify the A-SAA level; and 3) to evaluate the effect of an increase in the colchicine dose on the A-SAA level. METHODS: A-SAA, CRP, ESR, fibrinogen and ferritin levels were measured in 183 patients [88 F, 95 M; median age 11.0 years (1.0-20.0)] with FMF during an attack-free period. Mutational analysis was available in 157 patients. The colchicine dose was increased in 26 randomly chosen patients with no attacks within the last year; laboratory studies were repeated at the end of the second month. RESULTS: During an attack-free period, the median A-SAA level was 74 (6-1,500) mg/L; other APPs were within normal ranges in 49-93% of the patients. Age, gender, age at onset, age at diagnosis, the duration of treatment and the frequency of attacks had no significant effect on the A-SAA level. Homozygous and compound heterozygous patients had higher A-SAA levels than heterozygous patients [129 mg/L (8-1,500) versus 29 mg/L (6-216); p < 0.005]. There was a dramatic decrease in the A-SAA level [from 244 mg/L (16-1,400) to 35.5 mg/L (8-1,120); p < 0.001] and an increase in the hemoglobin (1.89 +/- 0.10 mmol/L to 1.98 +/- 0.19 mmol/L; p < 0.005) after the increase in colchicine dose in 26 patients. CONCLUSION: Subclinical inflammation continues during an attack-free period in FMF patients. A-SAA was the best marker of subclinical inflammation. Patients who are homozygous or compound heterozygotes of MEFV mutations had higher A-SAA levels. An increase in the colchicine dose resulted in a dramatic decrease in A-SAA and an increase in hemoglobin level. These findings favor the use of A-SAA in drug monitoring.

Acute-Phase Proteins↗
PubMed1992

[Colchicine in toxic liver cirrhosis and primary biliary cirrhosis].

In animals, colchicine has been shown hepatoprotective, which is related to its anti-fibrotic and anti-inflammatory effect. In man, colchicine has been used for the treatment of alcoholic liver disease and primary biliary cirrhosis. Although controlled trials observed an improvement of liver function tests under colchicine, the survival rate in most studies was only slightly improved without reaching statistical significance. Therefore, at present, no final evaluation of colchicine for the treatment of alcoholic liver diseases and primary biliary cirrhosis can be given.

Animals↗