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PubMed1992

Colchicine prevents kidney transplant amyloidosis in familial Mediterranean fever.

Twenty-one familial Mediterranean fever (FMF) patients who received a kidney transplant for terminal renal failure due to amyloidosis were studied retrospectively to evaluate the prophylactic effect of colchicine on graft amyloidosis. Proteinuria, highly suggestive of kidney transplant amyloidosis, developed in 11 patients within a median of 3 years after transplantation (range 0.5-10 years). In 10 patients, repeated urinalyses for protein were negative during a median of 5 years after transplantation (range 1-13). Patients who developed proteinuria or transplant amyloidosis received smaller colchicine doses than patients without proteinuria--mean 0.69 (range 0-1) versus 1.53 (range 1-2) milligrams per day (p = 0.0002), suggesting that colchicine prevents or delays development of transplant amyloidosis. This prophylactic effect of colchicine was complete at a dose of 1.5 mg/day or more and absent at a daily dose of 0.5 mg or less. In patients who received 1 mg/day, individual variability in the response to colchicine was observed. We conclude that the development of amyloidosis of the kidney transplant in FMF is inevitable at a colchicine dose lower than 1 mg/day, unpredictable at 1 mg/day and usually preventable with 1.5 mg/day or more.

Adolescent↗

PubMed1999

Direct effects of colchicine on myocardial function: studies in hypertrophied and failing spontaneously hypertensive rats.

-The aging spontaneously hypertensive rat (SHR) is a model in which the transition from chronic stable left ventricular hypertrophy to overt heart failure can be observed. Although the mechanisms for impaired function in hypertrophied and failing cardiac muscle from the SHR have been studied, none accounts fully for the myocardial contractile abnormalities. The cardiac cytoskeleton has been implicated as a possible cause for myocardial dysfunction. If an increase in microtubules contributes to dysfunction, then myocardial microtubule disruption by colchicine should promote an improvement in cardiac performance. We studied the active and passive properties of isolated left ventricular papillary muscles from 18- to 24-month-old SHR with evidence of heart failure (SHR-F, n=6), age-matched SHR without heart failure (SHR-NF, n=6), and age-matched normotensive Wistar-Kyoto rats (WKY, n=5). Mechanical parameters were analyzed before and up to 90 minutes after the addition of colchicine (10(-5), 10(-4), and 10(-3) mol/L). In the baseline state, active tension (AT) developed by papillary muscles from the WKY group was greater than for SHR-NF and SHR-F groups (WKY 5.69+/-1.47 g/mm2 [mean+/-SD], SHR-NF 3.41+/-1.05, SHR-F 2.87+/-0.26; SHR-NF and SHR-F P<0.05 versus WKY rats). The passive stiffness was greater in SHR-F than in the WKY and SHR-NF groups (central segment exponential stiffness constant, Kcs: SHR-F 70+/-25, SHR-NF 44+/-17, WKY 41+/-13 [mean+/-SD]; SHR-F P<0.05 versus SHR-NF and WKY rats). AT did not improve after 10, 20, and 30 minutes of exposure to colchicine (10(-5), 10(-4), and 10(-3) mol/L) in any group. In the SHR-F group, AT and passive stiffness did not change after 30 to 90 minutes of colchicine exposure (10(-4) mol/L). In summary, the data in this study fail to demonstrate improvement of intrinsic muscle function in SHR with heart failure after colchicine. Thus, in the SHR there is no evidence that colchicine-induced cardiac microtubular depolymerization affects the active or passive properties of hypertrophied or failing left ventricular myocardium.

Animals↗

PubMed1990

A controlled trial of colchicine to reduce the elastase load in the lungs of cigarette smokers with chronic obstructive pulmonary disease.

Current data suggest that emphysema in smokers is caused at least in part by the unrestrained action of neutrophil elastase on pulmonary tissues. Since colchicine reduces the secretion of enzymes from stimulated neutrophils, we designed a clinical trial to determine if colchicine could reduce the elastase load in the lungs or several putative indicators of elastin destruction. We carried out a prospective, double-blind, randomized, and placebo-controlled clinical trial. Outpatients seeking treatment for chronic obstructive pulmonary disease at the University of Texas Health Center at Tyler who met specific criteria were recruited into the study. A group of 46 cigarette smokers between 45 and 75 yr of age with chronic obstructive pulmonary disease (COPD) were studied. Colchicine or placebo was given orally in disguised capsules, 0.6 mg three times per day. Volunteers were placed on a baseline bronchodilator regimen of Theodur orally and albuterol by inhalation. Blood, urine, and bronchoalveolar lavage fluids were obtained after 1 wk of stabilization. The patients were then randomized and treated for 14 days with colchicine, and the measurements were repeated. Modifications in plasma elastin peptides and neutrophil elastase-generated fibrinopeptide A, urinary desmosines, and bronchoalveolar lavage fluid neutrophils or neutrophil elastase were the indicators of success or failure of the treatment. Pre- and posttreatment measurements in each patient and the difference between colchicine-treated and placebo-treated groups were compared. There were no statistically significant differences in either of the two types of analyses in any of the variables. We conclude that variables related to elastase load in the lungs were not modified by colchicine treatment. If a drug can be identified that is successful in modifying one of these variables, it would then have to be tested in a large-scale clinical trial in which the rate of decline in the FEV1.0 or mortality would be measured. The data presented here may provide useful information about the variability of key measurements of elastase load in the lungs and the breakdown of elastin and may aid investigators in designing similar trials in the future.

Aged↗

PubMed2004

Once-daily use of colchicine in children with familial Mediterranean fever.

Patients with familial Mediterranean fever routinely take daily multiple doses of colchicine to prevent acute attacks and to reduce the risk of amyloidosis. However, although there is no research in this regard in the literature, some clinicians believe that the use of colchicine in children as daily single dose may cause toxic side effects. The efficiency and the side effects of the administration of daily single dose versus daily multiple doses of colchicine were evaluated in the treatment of patients with familial Mediterranean fever. Thirty-nine patients being observed at Atatürk University Medical Faculty Pediatrics outpatient clinic with the diagnosis of familial Mediterranean fever were randomly divided into 2 groups. Group I consisted of 20 patients who continued taking colchicine in 2 or 3 divided doses daily as they did before the study. Group II comprised 19 patients who were given the total daily colchicine dose at 1 time. Patients were re-examined at 30-day intervals and both groups maintained this regimen for an average duration of 8 months. There was no difference between these 2 groups with respect to frequency of side effects, number of attacks, and acute phase response. Therefore, the daily colchicine dose can be given to children once daily.

Adolescent↗

PubMed1989

Immunocytochemical localization of angiotensinogen and cathepsins B, H, and L in rat hepatocytes, with special reference to degradation of angiotensinogen in lysosomes after colchicine.

We examined the effects of bilateral nephrectomy and colchicine treatment on localization and content of angiotensinogen and cathepsins B, H, and L in rat liver using immunohistochemistry, radioimmunoassay, and enzyme assay. Angiotensinogen content increased in the liver of colchicine-treated rats, whereas a clear-cut increase was not detected in the liver of nephrectomized rats. This tendency was consistent with the immunocytochemical results; only perivenous hepatocytes in control and nephrectomized rats were diffusely immunostained by anti-angiotensinogen, whereas perivenous and periportal hepatocytes of colchicine-treated rats were strongly immunostained. Enzyme assay revealed no significant change in activities of cathepsins B, H, and L in liver extracts under these experimental conditions. Immunocytochemical localization of these cysteine proteinases in hepatocytes after colchicine treatment was more widespread in the cytoplasm than that in the control hepatocytes. By electron microscopy, angiotensinogen was localized in smaller vesicles and some larger vesicles (lysosomes) of hepatocytes after colchicine treatment. Double immunostaining demonstrated co-localization of cathepsins B, H, and L with angiotensinogen in lysosomes. These results suggest that cathepsins B, H, and L play a role in the degradation of excess angiotensinogen in hepatocytes of rats after colchicine treatment.

Angiotensinogen↗

PubMed2004

Four children with colchicine poisoning.

Colchicine poisoning is a rare event. It is characterized by multiorgan involvement and by poor prognosis associated with overdose. In this article we present four children with colchicine poisoning to emphasize that colchicine poisoning has a large spectrum in childhood. The children's ages ranged between 1 year and 3.5 years. The ingested dosage of colchicine was between 0.37 and 1.72 mg/kg. Most of the findings of colchicine poisoning such as gastrointestinal symptoms, hepatotoxicity, cardiotoxicity, bone marrow suppression, hypocalcaemia and hair loss were diagnosed in our patients. Two children receiving 0.37 mg/kg and 1 mg/kg colchicine and admitted 13 and 19 hours after poisoning, respectively, died. Our findings suggest that in addition to amounts of the drug, mortality was also related to the duration between drug ingestion and admission to hospital.

Child, Preschool↗

PubMed1980

Effects of colchicine on the Golgi complex and GERL of cultured rat peritoneal macrophages and epiphyseal chondrocytes.

Thioglycollate-elicited rat peritoneal macrophages and epiphyseal chondrocytes were cultured in vitro, treated with colchicine, and then studied by electron-microscopic and cytochemical techniques. Colchicine, but not lumicolchicine, caused disappearance of cytoplasmic microtubules and breakup of the Golgi complex with spreading of its dictyosomes from a well defined juxtanuclear area throughout the cytoplasm. There was also an altered distribution of lysosomes, which oriented themselves close to the dictyosomes both in control and colchicine-treated cells. Further, the structure of the individual dictyosomes was changed, especially in the chondrocytes. GERL equivalents were observed in control cells but were difficult to detect after exposure to colchicine. Reaction product for thiamine pyrophosphatase was found in narrow cisternae on the inner side of the dictyosomes in control cells but in vacuole-like structures in colchicine-treated cells. Reaction product for acid phosphatase was present in GERL equivalents and lysosomes in control cells but mainly in lysosomes in colchicine-treated cells. Nevertheless, the total specific activities of these enzymes as well as of 5'-nucleotidase, a plasma membrane marker, remained unaffected by the drug treatment. These observations show that cytoplasmic microtubules play an important and, in many respects similar, cytoskeletal role in two so functionally diverse cell types as macrophages and chondrocytes. They are particularly important for the structural integrity of the Golgi complex, which in both cells is normally organized in the area around the centrioles, from which numerous microtubules radiate into the cytoplasm. The observations further suggest that GERL is an integrated part of the Golgi complex in these cells.

Animals↗

PubMed1979

Effect of colchicine on steroid secretion from rat adrenal gland.

To determine the influence of colchicine on adrenocortical function in vivo, we gave significant amounts subcutaneously to rats and observed the distribution to the anterior pituitary and adrenal glands. Corticosteroids in the serum and adrenal gland were increased remarkably by the administration of colchicine in a dose-dependent manner. Maximum elevation was achieved around 2.5 hours after the injection and continued for at least 4 hours. Maximum levels produced by the injection of 0.1 U/rat of adrenocorticotropic hormone, the latter producing temporary increases in corticosteroids in the serum and adrenal gland. A significant augmentation of corticosteroids in the serum and adrenal gland resulted when colchicine was administered 60 minutes prior to the injection of adrenocorticotropic hormone. The pattern of intracellular distribution of corticosteroids in the adrenal glands of rats given colchicine was the same as that seen in rats given adrenocorticotropic hormone. In the in vitro experiment, only high concentrations of colchicine such as 10(-3) M added to the incubation system of the adrenal quarters suppressed the release of corticosteroids from the adrenal gland. Thus, the continuous stimulation of the synthesis and secretion of adrenocortical hormone seen with the administration of colchicine may explain why this drug is effective in the treatment of gouty arthritis.

Adrenal Cortex Hormones↗

PubMed1981

The effect of bucolome on the biliary excretion of colchicine in the rat.

The biliary excretion of intravenously administered [14C]-colchicine was compared for 2 hr between control rats and rats treated with bucolome (5-n-butyl-1-cyclohexyl-2,4,6-trioxoperhydropyrimidine, 200 mg/kg, i.p.). In the first 10-min period after colchicine injection, the bile flow rate was 70 percent higher (p less than 0.01) in bucolome treated rats than in control rats. The bile flow rate in bucolome treated rats gradually decreased and 1 hr later, the difference between control and bucolome treated rats was no longer significant (p greater than 0.05). The percent of the administered colchicine dose recovered in the first 2 hr in bucolome treated rats given an i.v. injection of 70 or 700 micrograms/kg colchicine was significantly higher than in control rats. The difference was primarily due to the higher excretion rate in the former group in the first 10-min period. When the biliary radioactivity was examined by thin layer chromatography, it was found that the excretion of free colchicine was significantly increased in bucolome treated rats which accounted for the observed increase in the biliary excretion of radioactivity in bucolome treated rats. It was concluded that bucolome is effective in increasing the biliary excretion of free colchicine.

Animals↗

PubMedDate not supplied

Accidental overdose of insufflated colchicine.

An accidental overdose of colchicine by nasal insufflation occurred when the colchicine was mistaken for methamphetamine. Colchicine insufflation is not believed to be a common practice among drug abusers; however, its physical appearance was similar enough to methamphetamine for it to be mistaken for that drug of abuse. In this case a 29-year-old White man presented to the emergency room 3 days after he 'snorted' approximately 200mg of colchicine powder. The colchicine was used as a 'root stimulator' in gardening by the patient's brother and stored in the same cabinet as the methamphetamine. Within 24 hours of exposure the patient began experiencing gastrointestinal distress and myalgia, which eventually prompted him to seek medical attention. The clinical course included hypocalcaemia (69 mg/L--day 5), hypophosphataemia (10 mg/L--day 5) and thrombocytopenia (19 X 10(3)/mm3 - day 8), all of which are consistent with colchicine toxicity. The patient improved with supportive care and electrolyte replacement, and was discharged after an 8-day hospitalisation.

Adult↗

PubMed1997

Effect of colchicine and bisacodyl on rat intestinal transit and nitric oxide synthase activity.

BACKGROUND: Bisacodyl and colchicine affect smooth-muscle contractility, intestinal water, and electrolyte transport. Nitric oxide (NO) stimulates intestinal electrolyte secretion and has an important role as a mediator of intestinal motility. We therefore studied, in rats, the effects of these agents on nitric oxide synthase (NOS) activity and gastrointestinal transit. METHODS: Rats were treated with bisacodyl (10 mg/kg intragastrically) or colchicine (5 mg/kg intraperitoneally) with or without pretreatment with ketotifen (1 mg/kg intragastrically). Rats were killed after 1, 2, and 4 h. The intestine was isolated and rinsed, the mucosa scraped, and NOS activity determined. In all rats small-intestinal transit was measured 15 min after intragastric administration of charcoal. RESULTS: Bisacodyl (10 mg/kg) and colchicine (5 mg/kg) induced a significant decrease in jejunal NOS activity. Pretreatment with the mast cell stabilizer ketotifen, which has been shown to attenuate the increased permeability induced by NO inhibition, prevented the decrease in colonic and jejunal NOS activity induced by bisacodyl and colchicine. Bisacodyl and colchicine significantly decreased intestinal transit time. Their effect on transit time was similar to that induced by intravenous administration of NG-nitro-L-arginine methyl ester (10 mg/kg). CONCLUSIONS: It is suggested that the effect of bisacodyl and colchicine on intestinal transport is, at least partly, mediated through NO inhibition.

Animals↗

PubMed1998

In vitro release of colchicine using poly(phosphazenes): the development of delivery systems for musculoskeletal use.

A colchicine release system utilizing biodegradable poly(phosphazenes) was investigated in vitro for intra-articular administration. Polymer degradation and drug release studies were performed on colchicine-loaded poly(phosphazenes) containing either imidazolyl (I-PPHOS) or ethyl glycinato (EG-PPHOS) side chain substituents over a 21-day period. To study the effects of an implantable colchicine-PPHOS delivery system on local musculoskeletal tissue in vitro, osteoblast-like cells were grown on the matrices. Colchicine release was 20% for I-PPHOS and 60% for EG-PPHOS over the 21-day period. Release appeared to proceed through a combination of diffusional and degradative mechanisms. Environmental scanning electron microscopy (ESEM) studies revealed large pores in the drug-depleted devices in contrast to the control matrices without drug, which may have contributed to the release seen, especially with ethyl glycinato-containing matrices. Cell growth on matrices containing colchicine was significantly (p < 0.05) inhibited in contrast to growth on tissue culture polystyrene (TCPS) and EG-PPHOS matrices without drug. The in vitro cell kinetic data suggest that designs for in vivo studies must take into account possible toxicity of colchicine and the polymer matrix on local tissue. Biodegradable PPHOS systems are promising candidates for use as intra-articular delivery vehicles for drugs with potential for systemic toxicity.

3T3 Cells↗

PubMedDate not supplied

Use of colchicine to treat severe constipation in developmentally disabled patients.

BACKGROUND: Patients with severe developmental disabilities often have concurrent decreased neuromuscular tone of the gastrointestinal tract, which can lead to a weak gag reflex, esophageal reflux, aspiration, and severe intractable constipation. High doses of multiple laxatives are frequently needed to maintain bowel motility in these patients. Colchicine, a natural alkaloid that is primarily used for the treatment of acute attacks of gout, causes an increase in gastrointestinal motility by neurogenic stimulation. The purpose of this study was to determine whether daily colchicine administration can improve bowel function and reduce laxative use in profoundly disabled patients with severe, intractable constipation who currently require large doses of multiple laxatives. METHODS: Twelve developmentally disabled patients who required three or more different laxatives to manage their chronic constipation were selected to participate in a double-blind, crossover study. Eleven patients who completed the study received placebo treatment for 8 weeks and colchicine treatment for 8 weeks. The total number of bowel movements and the total number of laxatives used during each of the two 8-week periods were compared. RESULTS: Eight of 11 patients experienced an improved bowel pattern while on colchicine compared with placebo, as defined by an increase in total number of bowel movements or a decrease in total number of rectal laxatives used. No clinically important complications were related to use of colchicine. CONCLUSIONS: Colchicine appears to be a valuable adjunct in the management of severe intractable constipation. Larger, long-term studies are needed to confirm these preliminary results.

Adult↗

PubMed1976

Mechanisms of secretion: effects of colchicine and vincristine on composition and flow of milk in the goat.

Colchicine, the plant alkaloid, produced a dramatic decrease in milk flow when infused into the udder of the goat. The compound (1 to 5 mg) dissolved in 5 ml of water was inserted into one side of the under via the teat canal. Such treatments consistently caused a depression in milk yield from the infused side with maximum at 36 h and substantial reversal by 72 to 96 h. Milks from both the infused and uninfused sides of the udder were essentially normal in composition (fat, protein, and lactose). However, globulins and riboflavin were elevated in milks from the infused side. The plant alkaloid, vincristine, produced effects on milk secretion similar to those of colchicine but at dosages roughly one-tenth the latter. The two substances had no effect on the amount of milk from the uninfused side of the udder. Experiments employing [carbon-14] colchicine revealed that less than 20% of the infused colchicine is secreted in the milk. Both the secretion of fat globules and the emptying of secretory vesicles by the lactating cell are inhibited by colchicine indicating that a portion of the cell population is turned off from secretion. Plant substances such as colchicine and vincristine may at times limit yields of milk, especially in grazing ruminants.

Animals↗

PubMed1997

Colchicine versus prednisone as treatment of usual interstitial pneumonia.

OBJECTIVE: To assess the results with colchicine and prednisone as initial single-drug therapy in patients with usual interstitial pneumonia (UIP). MATERIAL AND METHODS: We reviewed the serial pulmonary function test results in 22 patients with typical clinical and high-resolution computed tomographic features of UIP who were treated with colchicine as initial single-agent therapy and compared them with a group of 22 historical patients with UIP of similar severity diagnosed by open-lung biopsy who were given prednisone as initial single-drug therapy. RESULTS: No significant difference was detected in the rate of decline of pulmonary function or in the time to "failure" between the two study groups. A trend was suggested for more rapid decline of pulmonary function in the prednisone-treated than in the colchicine-treated group. The design of this study does not allow distinction between a possible beneficial effect of colchicine and a possible adverse effect related to weaning from high-dose prednisone. Colchicine was well tolerated; few side effects other than mild diarrhea were noted in those patients able to take the drug long enough to return for pulmonary function testing at 3 months. In comparison, the side effects of prednisone were more serious and were not always reversible with cessation of therapy. CONCLUSION: This study lends further support to the assumption that colchicine may be a satisfactory and less hazardous substitute for prednisone in the treatment of patients with UIP.

Aged↗

PubMedDate not supplied

The role of colchicine in prevention of hepatic cirrhosis induced by carbon tetrachloride.

BACKGROUND/AIMS: The present study was undertaken to determine whether colchicine has a beneficial effect in the prevention of hepatic cirrhosis when it is given simultaneously with CCl4. METHODOLOGY: Wistar rats were employed as experimental animals and divided into 6 groups: Group I received saline solution, Group II, saline solution and mineral oil; Group III, colchicine (10 micrograms/100 g) and mineral oil; Group IV, colchicine (10 micrograms/100 g) and CCl4; Group V, colchicine (5 micrograms/100 g) and CCl4; and, Group VI received saline solution and CCl4. The effect of colchicine was evaluated by liver function tests, serum total proteins, electrolytes and histological evaluation. RESULTS: The results demonstrated higher values of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and total bilirubin in groups IV and V when compared with group VI (p < 0.05). No difference between group VI and groups IV and V was observed in histological evaluation, serum total proteins and electrolytes (p < 0.05). CONCLUSIONS: Colchicine, as given in this study, did not have any protective effect in the prevention of cirrhosis induced by carbon tetrachloride.

Animals↗

PubMed2002

Effect of colchicine and cytokines on MEFV expression and C5a inhibitor activity in human primary fibroblast cultures.

BACKGROUND: Familial Mediterranean fever is an autosomal recessive disease characterized by sporadic attacks of inflammation affecting the serosal spaces. The gene associated with FMF (MEFV), mainly expressed in neutrophils, was recently found to be expressed also in primary cultures of serosal origin (peritoneal and synovial fibroblasts). A C5a inhibitor, previously detected in normal serosal fluids, was recently identified in serosal cultures as well, and was found to be deficient in serosal fluids and cultures obtained from FMF patients. OBJECTIVE: To investigate the effect of colchicine (the main therapeutic agent for FMF patients) and certain inflammatory cytokines (IL-1 beta, TNF-alpha, IFN-alpha, IFN-gamma) on MEFV expression and C5a inhibitor activity in neutrophils and primary peritoneal fibroblast cultures. METHODS: Human primary peritoneal fibroblast cultures and neutrophils were studied for MEFV expression and C5a inhibitor activity, using reverse transcription-polymerase chain reaction and C5a-induced myeloperoxidase assay, respectively, in the presence and absence of colchicine and cytokines. RESULTS: MEFV expression in neutrophils was high and could not be induced further. Its expression in the peritoneal fibroblasts was lower than in neutrophils and could be induced using colchicine and cytokines parallel with induction of C5a inhibitor activity. Semi-quantitative RT-PCR assays enabled estimation of MEFV induction by the cytokines at 10-100-fold and could not be further increased by concomitant addition of colchicine. CONCLUSION: Serosal tissues, which are afflicted in FMF, express colchicine and cytokine-inducible MEFV and contain inducible C5a inhibitor activity. The relation between the ability of colchicine to induce MEFV and C5a inhibitor activity, and its efficacy in FMF treatment, require further investigation.

Antineoplastic Agents↗

PubMed2002

[Colchicine poisoning by accidental ingestion of the bulbs of Sandersonia aurantiaca: report of a case].

We report a case of colchicine poisoning in an 82-year-old woman. She had suffered from senile dementia and in her confused state ingested two bulbs of Sandersonia aurantiaca (Christmas-bells, Chinese lantern lily). She was admitted complaining of gastrointestinal symptoms, mainly severe watery diarrhea. The duration of her diarrhea was approximately 40 hours. On the 3rd day after ingestion, leukopenia and thrombocytopenia occurred. Although 50 micrograms of granulocyte-colony stimulating factor was administered from the 5th day to the 8th day, her white blood cell count did not increase and revealed nadir (100/microliter) on the 7th day. Her platelet count also revealed nadir on the 7th day. She died of respiratory failure in the early morning of the 9th day. The bulb of Sandersonia was found to contain colchicine at a concentration of 4.7 mg/g, and her serum level of colchicine was 6.3 ng/ml on the 6th day. Colchicine is an alkaroid extractable from the plants like Colchicum autumnale (meadow saffron, autumn crocus), and Gloriosa supra tuber. These plants belong to the lily family. Sandersonia aurantiaca also belongs to the lily family and we found that its bulb contained colchicine. To our knowledge, this is the first report of colchicine poisoning by Sandersonia aurantiaca.

Aged↗