Subject(s)
Humans , Male , Young Adult , Pulmonary Embolism/diagnostic imaging , Thrombosis/diagnostic imaging , Superior Vena Cava Syndrome/diagnostic imaging , Behcet Syndrome/diagnostic imaging , Anti-Bacterial Agents/therapeutic use , Anticoagulants/therapeutic use , Pulmonary Embolism/physiopathology , Pulmonary Embolism/drug therapy , Thrombosis/physiopathology , Thrombosis/drug therapy , Warfarin/therapeutic use , Superior Vena Cava Syndrome/physiopathology , Superior Vena Cava Syndrome/drug therapy , Prednisolone/therapeutic use , Diagnostic Imaging , Colchicine/analogs & derivatives , Colchicine/therapeutic use , Behcet Syndrome/physiopathology , Behcet Syndrome/drug therapy , Treatment Outcome , Tubulin Modulators/therapeutic useABSTRACT
ABSTRACT Objectives: To compare the response to tiocolchicine and verapamil injection in the plaque of patients with Peyronie's disease. Materials and Methods: Prospective, single-blind, randomized study, selecting patients who have presented Peyronie's disease for less than 18 months. Thiocolchicine 4mg or verapamil 5mg were given in 7 injections (once a week). Patients who had received any treatment for Peyronie's disease in the past three months were excluded. The parameters used were the International Index of Erectile Function (IIEF-5) score, analysis of the curvature on pharmaco-induced erections and size of the plaque by ultrasonography. Results: Twenty-five patients were randomized, 13 received thiocolchicine and 12 were treated with verapamil. Both groups were statistically similar. The mean curvature was 46.7° and 36.2° before and after thiocolchicine, respectively (p=0.019) and 50.4° and 42.08° before and after verapamil, respectively (p=0.012). The curvature improved in 69% of patients treated with thiocolchicine and in 66% of those who received verapamil. Regarding sexual function, there was an increase in the IIEF-5 from 16.69 to 20.85 (p=0.23) in the thiocolchicine group. In the verapamil group the IIEF-5 score dropped from 17.50 to 16.25 (p=0.58). In the thiocolchicine group, the plaque was reduced in 61% of patients. In the verapamil group, 8% presented decreased plaque size. No adverse event was associated to thiocolchicine. Conclusion: The use of thiocolchicine in Peyronie's disease demonstrated improvement on penile curvature and reduction in plaque size. Thiocolchicine presented similar results to verapamil in curvature assessment. No significant side effects were observed with the use of tiocolchicine.
Subject(s)
Humans , Male , Adult , Aged , Penile Induration/drug therapy , Vasodilator Agents/administration & dosage , Verapamil/administration & dosage , Colchicine/analogs & derivatives , Time Factors , Penile Erection/drug effects , Injections, Intralesional , Single-Blind Method , Colchicine/administration & dosage , Prospective Studies , Reproducibility of Results , Treatment Outcome , Middle AgedABSTRACT
New colchicine analogs have been synthesized with the aim of developing stronger potential anticancer activities. Among the analogs, CT20126 has been previously reported to show immunosuppressive activities. Here, we report that CT20126 also shows potential anticancer effects via an unusual mechanism: the modulation of microtubule integrity and cell cycle arrest at the G2/M phase before apoptosis. When we treated COS-7 cells with CT20126 (5 muM), the normal thread-like microtubules were disrupted into tubulin dimers within 10 min and thereafter repolymerized into short, thick filaments. In contrast, cells treated with the same concentration of colchicine exhibited microtubule depolymerization after 20 min and never underwent repolymerization. Furthermore, optical density (OD) analysis (350 nm) with purified tubulin showed that CT20126 had a higher repolymerizing activity than that of Taxol, a potent microtubule-polymerizing agent. These results suggest that the effects of CT20126 on microtubule integrity differ from those of colchicine: the analog first destabilizes microtubules and then stabilizes the disrupted tubulins into short, thick polymers. Furthermore, CT20126 induced a greater level of apoptotic activity in Jurkat T cells than colchicine (assessed by G2/M arrest, caspase-3 activation and cell sorting). At 20 nM, CT20126 induced 47% apoptosis among Jurkat T cells, whereas colchicine induced only 33% apoptosis. Our results suggest that the colchicine analog CT20126 can potently induce apoptosis by disrupting microtubule integrity in a manner that differs from that of colchicine or Taxol.
Subject(s)
Animals , Cattle , Humans , Acetylation/drug effects , Apoptosis/drug effects , COS Cells , Caspase 3/metabolism , Cell Division/drug effects , Chlorocebus aethiops , Colchicine/analogs & derivatives , Enzyme Activation/drug effects , G2 Phase/drug effects , Jurkat Cells , Microtubules/metabolism , Poly(ADP-ribose) Polymerases/metabolism , Tubulin/metabolism , Tubulin Modulators/chemistryABSTRACT
Colchicine has been shown to regulate the expression of inflammatory gene, but this compound possesses much weaker anti-inflammatory activity. In this study, we synthesized a new colchicine derivative CT20126 and examined its immunomodulatory property. CT20126 was found to have immunosuppressive effects by inhibiting lymphocyte proliferation without cytotoxicity and effectively inhibit the transcriptional expression of the inflammatory genes, iNOS, TNF-alpha, and IL-1beta, in macrophages stimulated by LPS. This effect was nearly comparable to that of cyclosporine A. This compound also significantly suppressed the production of nitric oxide and Th1-related pro-inflammatory cytokines, IL-1beta, TNF-alpha, and IL-2, with minimal suppression of Th2-related anti-inflammatory cytokines IL-4 and IL-10 in the sponge matrix allograft model. Moreover, administration of CT20126 prolonged the survival of allograft skins from BALB/c mice (H-2d) to the dorsum of C57BL/6 (H-2b) mice. The in vivo immune suppressive effects of CT20126 were similar to that of cyclosporine A. These results indicate that this compound may have potential therapeutic value for transplantation rejection and other inflammatory diseases.
Subject(s)
Animals , Female , Mice , Cell Line , Colchicine/analogs & derivatives , Cytokines/biosynthesis , Gene Expression Regulation/drug effects , Graft Survival/drug effects , Immunosuppression Therapy , Interleukin-1beta/genetics , Lipopolysaccharides/pharmacology , Lymphocyte Culture Test, Mixed , Mice, Inbred BALB C , Mice, Inbred C57BL , Nitric Oxide/biosynthesis , Nitric Oxide Synthase Type II/genetics , Skin Transplantation/immunology , Th1 Cells/drug effects , Th2 Cells/drug effects , Transplantation, Homologous , Tumor Necrosis Factor-alpha/geneticsABSTRACT
Background. The accummulation of collagen is a salient feature of chronic liver injury. The objetive of this study was to investigate and compare the therapeutic effectiveness of colchicine and one of its metabolites, colchiceine, to protect rats from developing liver injury and fibrosis. Methods. To accomplish this, the authors used a procedure developed by other to produce liver injury and firosis by chronic administration of CCl4 in rats. The effect of both compounds on collagen metabolism and liver injury was analyzed. Results. Althought both compounds prevented increase in collagen synthesis, animals treated with colchicine did not show a reduction in collagen content compared with animals treated with CCl4. On the other hand, the animals treated with colchiceine along with CCl4, showed a 50 percent reduction in hepatic collagen content as well as an improvement in histological architecture. Both compound, colchicine and colchiceine, increased the intracellular degradation of collagen in addition to increasing collagenase activity as compared to non-treated rats. However, collagenase activity was lower in animals treated with colchicine and colchiceine than in the fibrotic livers treated with CCl4. The changes in collagen metabolism correlated with changes in parameters of liver injury. Conclusions. In conclusion, the compound colchiceine may be recommended in the treatment of chronic liver diseases rather than its precursor, colchicine, due to the fact that it showed a lower accumulation of collagen content and has a better anti-fibrogenic effect than does colchicine