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Colchicine for persistent constipation after total abdominal colectomy with ileorectostomy for colonic inertia.

Severe constipation caused by colonic inertia may be associated with a generalized gastrointestinal dysmotility syndrome. Patients with severe constipation pose a significant challenge in terms of management. Failure of medical therapy usually leads to surgery in the form of a subtotal colectomy. Most patients develop diarrhea after the surgery, but a subgroup of patients continue to experience constipation. We report the case of such a patient who underwent a total abdominal colectomy and ileorectostomy for intractable constipation. He continued to have constipation after the surgery that was responsive only to a gallon of bowel-cleansing solution. A treatment trial of colchicine was partially unsuccessful when used on its own, but a combination of colchicine and a lesser dose of Colyte was found to be effective in maintaining regular bowel movements.

Adult↗

Effect of colchicine on circulating and myocardial neutrophils and on infarct size in a canine model of ischemia and reperfusion.

Myocardial injury after ischemia/reperfusion has been attributed in part to the effects of neutrophils. We examined whether colchicine, a potent and rapid inhibitor of neutrophils, may reduce inflammatory leukocytosis, prevent postischemic myocardial neutrophil accumulation, and reduce infarct size (IS). Twenty-four dogs were randomized to either a control (saline administration) or a colchicine (1 mg/kg intravenously, i.v.) group. Anesthetized open-chest dogs underwent 120-min coronary artery occlusion followed by 6-h reperfusion. Determinants of IS [area-at-risk (AAR) and collateral flow] and IS were measured in 22 dogs (11 in each group). We evaluated neutrophil toxicity by measuring ex vivo production of reactive oxygen species by chemiluminescence. Myocardial localization and accumulation of neutrophils were histologically evaluated by independent observers. The number of circulating neutrophils (p < 0.01), neutrophil cytotoxicity (p < 0.05), and neutrophil myocardial accumulation after 6-h reperfusion (p = 0.006) were reduced in treated dogs. Left ventricular (LV) peak rate of pressure increase was similar in both groups during ischemia /reperfusion. However, whereas collateral blood flow and AAR, the main determinants of IS, were similar in control and treated dogs, there was no reduction in IS: 37.1 +/- 7% of AAR in controls and 37.4 +/- 8% in treated dogs. Despite marked reduction of neutrophil toxicity and postischemic myocardial neutrophil accumulation, no myocardial protection could be detected in this dog model.

Animals↗

A correlation between in vivo and in vitro effects of the microtubule inhibitors colchicine, parbendazole and nocodazole on myxamoebae of Physarum polycephalum.

The effects of the microtubule inhibitors colchicine, parbendazole and nocodazole on the growth of myxamoebae of Physarum polycephalum were closely paralleled by the effects of these drugs on the assembly in vitro of purified amoebal microtubule protein. Colchicine at 100 microM did not inhibit amoebal growth and did not inhibit formation, or depolymerization, of amoebal microtubules. The benzimidazole carbamate derivatives nocodazole and parbendazole were very effective in both inhibiting growth and inhibiting the assembly in vitro of amoebal microtubule protein. Parbendazole was the most effective.

Benzimidazoles↗

Remission of recalcitrant epidermolysis bullosa acquisita (EBA) with colchicine monotherapy.

A 42-year-old woman with widespread recalcitrant epidermolysis bullosa acquisita (EBA) responded well to colchicine monotherapy after attempts to control her disease with other modalities failed. These included dapsone, tetracycline, prednisolone, and combination of cyclophosphamide/azathioprine with dexamethasone 'pulse therapy'. The useful role of colchicine in controlling some difficult cases of EBA, a therapeutically problematic condition, is stressed.

Adult↗

Colchicine in the treatment of the cutaneous manifestations of Behçet's disease.

Five patients with Behçet's disease were satisfactorily treated with colchicine. Oral aphthosis, erythema nodosum-like lesions and genital erosions improved greatly within a month as did laboratory findings. We believe colchicine to be the first choice in the management of the cutaneous and ocular lesions of Behçet's disease.

Adult↗

Effects of potassium iodide, colchicine and dapsone on the generation of polymorphonuclear leukocyte-derived oxygen intermediates.

The effects of potassium iodide, colchicine and dapsone on the in vitro generation of polymorphonuclear leukocyte (PMN)-derived oxygen intermediates were investigated. These three drugs have beneficial effects on those conditions in which PMNs play an important pathogenetic role. Three oxygen intermediates, superoxide anion (O2-), hydrogen peroxide (H2O2), hydroxyl radical (OH.) and chemiluminescence were included in assay studies. Dose response studies were performed with therapeutic doses of the drugs (10 microM--mM). We found that both potassium iodide and dapsone significantly suppressed the generation of oxygen intermediates, except for O2-. Colchicine decreased OH. production. Our results show tha these agents to some extent exert their anti-inflammatory effects by interfering with the PMN-dependent production of oxygen intermediates, thus conferring protection from auto-oxidative tissue injury. This may account for their clinical efficacy in many PMN-mediated dermatological diseases.

Anions↗

Delayed pressure urticaria, objective evaluation of a variable disease using a dermographometer and assessment of treatment using colchicine.

A randomized double-blind placebo controlled trial of colchicine in the treatment of 13 patients with delayed pressure urticaria enabled us to assess some of the variables in this disorder. We have modified a previously described method of pressure testing using a calibrated dermographometer and shown a pressure induced papular dose response curve. Assessment of disease activity was based on the number of pressure weals which occurred, the size of delayed pressure induced papules using a dermographometer calibrated at 9.75 x 10(5) pascals for five separate time periods on the back and estimations of erythrocyte sedimentation rate and the acute phase protein levels. We have been unable to show a therapeutic effect using colchicine 0.5 mg bd for I week.

Adult↗

The maintenance of colchicine-arrested metaphases in plants requires protein synthesis.

With the aim of finding out factors involved in chromosomal condensation, the kinetics of both metaphase accumulation and the subsequent formation of restitution nuclei in the presence of 1 mM colchicine have been analyzed in Allium cepa L. meristems. Restitution nuclei are formed by decondensation of the chromosomes from the c-mitoses and the reformation of nuclear envelopes around them. The study has been carried out in control conditions as well as in conditions which either inhibit protein synthesis (1 microgram/ml cycloheximide) or modify the accuracy of transcription (by near ultraviolet light irradiation under anoxia of cells with bromosubstituted-DNA). The results suggest that the high condensation of chromosomes observed in colchicine-arrested metaphases depends on sustained synthesis of protein, and that the DNA regions coding for such proteins are transcribed not before late prophase. By using cells, the genome of which has been partially bromosubstituted, fed bromodeoxyuridine during different fractions of this S period, it could be inferred that the coding regions for the proteins involved in chromosome condensation are probably multiple since they replicate throughout the whole S period.

Allium↗

Destruction of sensitized erythrocytes by human monocytes in vitro: effects of cytochalasin B, hydrocortisone and colchicine.

The purpose of this study was to characterize the destruction of sensitized erythrocytes by human blood monocytes in vitro. The incubation in vitro of human monocytes with 51Cr-labelled human erythrocytes sensitized with IgG rhesus alloantibodies anti-D (EAIgG anti-D) resulted in release of 51Cr from the erythrocytes (lysis) as well as uptake of 51Cr-labelled erythrocytes by the monocytes (phagocytosis). The lysis of EAIgG anti-D by monocytes was not dependent on phagocytosis, because cytochalasin B, which inhibited phagocytosis of EAIgG, enhanced lysis. In contrast, hydrocortisone and colchicine inhibited lysis, but had no effect on phagocytosis. These agents did not affect binding of EAIgG anti-D to monocytes. The effect of these agents on lysis corresponded to their effect on release of lysosomal enzymes by monocytes. The release of lysosomal enzymes, when induced by EAIgG anti-D, was, likewise, enhanced by cytochalasin B and inhibited by hydrocortisone and colchicine. A significant correlation was found between lysosomal enzyme release and lysis. Together, these results strongly suggest that lysosomal enzymes, released by the monocytes when incubated with anti-D-sensitized erythrocytes, are responsible for the cytotoxic activity of these cells towards sensitized erythrocytes. The action of these enzymes only occurs over a short range, probably at the site of attachment of the erythrocyte, because only erythrocytes that were bound to the monocytes were lysed. The finding of other investigators that removal of monocytes from suspensions of human mononuclear leucocytes results in a strong reduction in the cytotoxic activity of these leucocytes towards sensitized erythrocytes in vitro. was confirmed.

Colchicine↗

Use of colchicine in the treatment of Behçet's disease.

To date, various treatment modalities have failed to produce consistent improvement in patients having Behçet's disease. Recent reports in the literature, however, have shown promising results with the use of colchicine. Our patient, an 18-year-old white woman, satisfied the 1977 Istanbul Conference criteria for Behçet's disease by exhibiting ocular inflammation and a five-year history of severe, recurrent oral and vaginal ulcerations. She was treated with 0.6 mg of colchicine orally twice daily, and at the end of two weeks of treatment, the oral lesions had completely resolved, and the vaginal ulcers were reduced in diameter and depth to at least one half. Within one month all oral and vaginal ulcers were completely healed.

Adolescent↗

A quantitative analysis of tubulin-colchicine binding to microtubules.

The binding of the tubulin-colchicine complex to microtubules has been studied in conditions where copolymerisation, as observed by Sternlicht and Ringel [J. Biol. Chem. 254, 10540-10550 (1979)], is negligible. The binding is shown to be rapid and reversible, in contrast with assumptions found in the literature. The binding constant was determined by a quantitative analysis of the concentration dependence of growth inhibition. The binding constant is of the same order of magnitude as the equilibrium constant of growth for tubulin. The temperature dependence was also studied and the Van't Hoff plot was found to be biphasic with an exothermic part at temperatures lower than 30 degrees C. A molecular model is presented for the interpretation of the copolymerisation observed by Strenlicht and Ringel. When a large excess of colchicine was added to microtubules, only a small phase of dissociation was observed. The new end state was metastable, as further dissociation could not be reversed. This is in conflict with a pure head-to-tail polymerisation mechanism, but in agreement with the recent observations of Bergen and Borisy [J. Cell Biol. 84, 141-150 (1980)], that head-to-tail polymerisation contributes only a small fraction of the total polymerisation.

Animals↗

Induction of casein synthesis by prolactin and inhibition by progesterone in the pseudopregnant rabbit treated by colchicine without any simultaneous variations of casein mRNA concentration.

Prolactin injected into pseudopregnant rabbits induced casein synthesis and it provoked an accumulation of casein mRNA and of ribosomal RNA. Colchicine, which has been shown to block the prolactin signal, totally prevented the accumulation of beta-casein mRNA, when injected with the hormone. However, the drug did not hamper the initiation of casein synthesis and the accumulation of ribosomal RNA. The effect of prolactin injected with colchicine on casein synthesis was totally abrogated by progesterone administered simultaneously and it was essentially unmodified by glucocorticoids. These results suggest that prolactin controls casein gene expression by supporting the accumulation of casein mRNAs and by stimulating the translation of these mRNAs, through independent mechanisms. Progesterone which is known to prevent the accumulation of casein mRNAs is also a potent inhibitor of casein mRNA translation whereas glucocorticoids exert their effect essentially by favouring the accumulation of casein mRNA but not by modifying their translation efficiency.

Animals↗

A quantitative description of microtubule formation in the presence of tubulin-colchicine.

The overall polymerization of microtubule protein in the presence of tubulin-colchicine is described by competition between an intrinsically unaltered nucleation process and the process of propagation inhibited by the binding of tubulin-colchicine to the microtubule ends. The inhibition of propagation can be quantified with the binding constant previously determined [Lambeir and Engelborghs (1980) Eur. J. Biochem. 109, 619-624]. A quantitative description of the competition between nucleation and propagation follows from the kinetic theory of Oosawa. Comparison of several subsequent cycles of polymerization/depolymerization shows that a fraction of cold-stable complexes are formed. An equilibrium derivation is presented which shows the enhanced nucleation upon binding of inhibiting proteins, by the increase of the nucleation parameter A [Oosawa and Asakura (1975) Thermodynamics of the Polymerization of Protein, Academic Press, London, New York]. The kinetic and equilibrium derivations presented here are generally applicable to all capping factors, e.g. some of the actin-binding proteins.

Animals↗

Disparate effects of monensin and colchicine on intracellular processing of secretory proteins in cultured rat hepatocytes.

We have studied the biosynthesis and intracellular processing of three major secretory proteins, albumin, alpha 1-protease inhibitor and alpha 2u-globulin, in cultured rat hepatocytes. The effect of secretion-blocking agents, monensin, a monovalent ionophore, and the microtubule-affecting agents colchicine and taxol was determined. In the control cells, alpha 1-protease inhibitor, a glycoprotein, was first synthesized as an endoglycosidase-H-sensitive form with Mr 51 000, and then processed to two endoglycosidase-H-resistant forms having Mr 51 000 and 56 000, the latter of which was secreted into the medium. Initially synthesized proalbumin was converted with chase to serum-type albumin, while no pro-type precursor was identified for alpha 2u-globulin. In the cells treated with colchicine or taxol, in which secretion was greatly inhibited, the fully processed alpha 1-protease inhibitor and albumin accumulated and were finally secreted into the medium. In the monensin-treated cells, however, most of the newly synthesized alpha 1-protease inhibitor and albumin were not processed to the final mature forms, resulting in accumulation of two 51 000-Mr forms and proalbumin, respectively. Moreover in treated cells, proalbumin and the endoglycosidase-H-resistant alpha 1-protease inhibitor were finally secreted into the medium. Such an effect was not caused by NH4Cl which also inhibited the secretion and is known to exert the similar effect as monensin on the receptor-mediated endocytosis pathway. Based on these results, the use of monensin may prove valuable for more detailed analysis of intracellular processing of various proteins.

Albumins↗

A study of colchicine tubulin complex by donor quenching of fluorescence energy transfer.

The utility of collisional quenching of energy donors in fluorescence energy transfer is described. In multi-donor single acceptor systems, which contain different classes of donors (as distinguished by their accessibility towards a collisional quencher), donor quenching may be used to assess the fraction of energy transfer from each class of donor. The tubulin-colchicine complex was used as a donor-acceptor system to show that two inaccessible tryptophans are at or near the colchicine binding site.

Acrylamide↗

Effects of colchicine and phenothiazine on biliary excretion of organic anions in rats.

Vesicular transport inhibitors have been reported to inhibit biliary excretion of some organic anions, suggesting that vesicular transport has a role in intracellular transport of these compounds. However, these inhibitors are substrates for P-glycoprotein. To examine whether P-glycoprotein has a role in canalicular transport of organic anions in addition to the canalicular multispecific organic anion transporter, we studied the effect of colchicine, a vesicular transport inhibitor, and phenothiazine to increase P-glycoprotein expression on biliary excretion of various organic anions in rats. Colchicine treatment slightly but significantly inhibited biliary excretion of indocyanine green, dinitrophenyl-glutathione and pravastatin, and had no effect on biliary excretion of sulphobromophthalein and dibromosulphophthalein. Phenothiazine treatment did not affect biliary excretion of indocyanine green and pravastatin, but it increased biliary sulphobromophthalein-glutathione excretion. In conclusion, the present findings suggest that P-glycoprotein plays an additive role on biliary excretion of some organic anions in addition to the canalicular multispecific organic anion transporter.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

A case of non-specific interstitial pneumonia effectively treated with a combination of prednisolone and colchicine, in which granulation tissue was extensive.

A 56-year-old woman was admitted for interstitial pneumonia, and subsequently diagnosed with idiopathic non-specific interstitial pneumonia with a bronchiolitis obliterans organizing pneumonia pattern, on the basis of clinical and surgical lung biopsy findings. Histological findings revealed diffuse thickness of alveolar walls accompanied by lymphocyte infiltration and fibrosis in the lobules. In addition to those findings, granulation tissue was extensive. Although initial symptom and CT improvement occurred following high-dose prednisolone therapy, the CT did not show further improvement and her serum KL-6 level began increasing again as prednisolone was reduced. With the addition of colchicine therapy, clinical and CT findings improved remarkably and a further reduction of the prednisolone dose was achieved. This case suggests that the combination of colchicine and corticosteroids may be an effective therapy for non-specific interstitial pneumonia.

Anti-Inflammatory Agents↗