Effect Of Colchicine Research Articles

The clinical black, white, and gray lessons.

This review examines recent contradictory large, well-controlled randomized control trials assessing the effects of omega-3 fatty acids and colchicine on cardiovascular (CV) outcomes. The Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT) and Statin Residual Risk Reduction with Epanova in high Cardiovascular Risk patients with Hypertriglyceridemia (STRENGTH) trial assessed the CV outcomes using high-dose omega-3 fatty acids in statin-treated patients with moderate hypertriglyceridemia and high-risk for CV disease with differing results. Similarly, Colchicine Cardiovascular Outcomes trial, (COLCOT) second Low Dose Colchicine (LoDoCo2), and Colchicine in patients with Acute Coronary Syndrome (COPS) assessed the CV outcomes using low-dose colchicine in patients with coronary artery disease with inconsistent results. These contradictory findings among studies assessing similar questions with the same drug or a drug within the same class challenge the scientific validity and clinical applicability of the derived conclusions. A comprehensive review revealed many differences between the trials, which could have contributed to observed divergent results. Consistent findings across multiple trials help strengthen the evidence for specific endpoints or sub-populations, and these findings must be included in guidelines. Large prospective cohort studies with diligent study protocols are warranted in the future to resolve unanswered dilemmas.

MORPHOLOGICAL AND GENETIC DIVERSITY ANALYSIS IN CALENDULA (CALENDULA OFFICINALIS L.) INFLUENCED BY MUTAGENIC EFFECT OF COLCHICINE

Calendula officinalis L. (pot marigold) is one of the main aromatic and medicinal plants with many uses in food and medicines. This study was carried out to demonstrate the efficiency of six colchicine concentrations (0.025, 0.05, 0.1, 0.2, 0.4 and 0.8 per cent, w/v) for Calendula improvement and induction of genetic variation. Colchicine treatments had a positive effect on the number of branches/plant, number of inflorescences, fresh and dry weight of inflorescences, inflorescence diameter, total soluble carbohydrates and β-carotene except for plant height, while seed germination and plant height were reduced. Estimation of heritability, genetic advance, genetic variability and selection of superior genotypes will be an important object in crop breeding and genetic improvement programs, and selection of genotypes with higher desirable characters. Heritability was high and ranged from 48.64 to 90.81, respectively (inflorescence diameter and plant height, respectively). Molecular markers based on a RAPD-PCR study elucidate the classification of induced Calendula mutants into two clusters. The coefficient of genetic diversity was estimated at 30%. A combination of morphological and physiological responses with molecular data contained in the various colchicine treatments illustrated the utility of RAPD-PCR as a method for identifying useful mutants and could be used to detect the colchicine effect significantly. Findings recommend the 0.05 per cent colchicine for efficient breeding calendula mutation and genetic improvement.

Efficacy and safety of colchicine for the prevention of major cardiovascular and cerebrovascular events in patients with coronary artery disease: a systematic review and meta-analysis on 12 869 patients

Abstract Aims The key role of inflammation in the pathogenesis of coronary artery disease (CAD) is an urgent call for innovative treatments. Several trials have proposed colchicine as a therapeutic option for secondary prevention in CAD patients but its utilization is hampered by fears about drug-related adverse events (DAEs) and conflicting evidences. The aim of this meta-analysis was to consolidate evidence on the efficacy and safety of colchicine for secondary prevention in patients with CAD. Methods and results A systematic search in electronic bibliographic databases of Medline, Scopus, Embase, and the Cochrane Library was performed to identify randomized controlled trials (RCTs) assessing the cardiovascular effects of colchicine in CAD patients, compared with placebo. Outcomes of interest were the occurrence of major adverse cardiovascular and cerebrovascular events (MACCE) and DAEs. Estimates were pooled using inverse-variance random-effects model. A total of 11 RCTs, including 12 869 patients, were identified as eligible. A total of 6501 patients received colchicine, while 6368 received placebo. After a median follow-up of 6 months (interquartile range, 1–16), patients receiving colchicine had a lower risk of MACCE [6% vs. 8.8%, relative risk (RR) = 0.67, 95% confidence interval (CI) 0.56–0.80, I2 = 19%], myocardial infarction (3.3% vs. 4.3%, RR = 0.76, 95% CI 0.61–0.96, I2 = 17%), coronary revascularization (2.9% vs. 4.2%, RR = 0.61, 95% CI 0.42–0.89, I2 = 40%), stroke (0.4% vs. 0.9%, RR = 0.48, 95% CI 0.30–0.77, I2 = 0%), hospitalization for cardiovascular cause (0.9% vs. 2.9%, RR = 0.32, 95% CI 0.12–0.87, I2 = 0%). Colchicine was associated with an increased risk of gastrointestinal DAEs (11% vs. 9.2%, RR = 1.67, 95% CI 1.20–2.34, I2 = 76%), myalgia (18% vs. 16%, RR = 1.16, 95% CI 1.02–1.32, I2 = 0%) and DAEs-related discontinuation (4.1% vs. 3%, RR = 1.54, 95% CI 1.02–2.32, I2 = 65%). However, gastrointestinal DAEs and discontinuation may be prevented with a lower daily dose. Colchicine did not increase the risk of cardiovascular death (0.7% vs. 1%, RR = 0.73, 95% CI 0.45–1.21, I2 = 14%), all-cause death (2% vs. 1.9%, RR = 1.01, 95% CI 0.71–1.43, I2 = 16%), or other DAEs. Conclusions The use of colchicine in patients with CAD is safe and efficacious for MACCE prevention.

Efficacy and safety of low-dose colchicine in patients with coronary disease: a systematic review and meta-analysis of randomized trials.

Recent randomized trials demonstrated a benefit of low-dose colchicine added to guideline-based treatment in patients with recent myocardial infarction or chronic coronary disease. We performed a systematic review and meta-analysis to obtain best estimates of the effects of colchicine on major adverse cardiovascular events (MACE). We searched the literature for randomized clinical trials of long-term colchicine in patients with atherosclerosis published up to 1 September 2020. The primary efficacy endpoint was MACE, the composite of myocardial infarction, stroke, or cardiovascular death. We combined the results of five trials that included 11 816 patients. The primary endpoint occurred in 578 patients. Colchicine reduced the risk for the primary endpoint by 25% [relative risk (RR) 0.75, 95% confidence interval (CI) 0.61-0.92; P = 0.005], myocardial infarction by 22% (RR 0.78, 95% CI 0.64-0.94; P = 0.010), stroke by 46% (RR 0.54, 95% CI 0.34-0.86; P = 0.009), and coronary revascularization by 23% (RR 0.77, 95% CI 0.66-0.90; P < 0.001). We observed no difference in all-cause death (RR 1.08, 95% CI 0.71-1.62; P = 0.73), with a lower incidence of cardiovascular death (RR 0.82, 95% CI 0.55-1.23; P = 0.34) counterbalanced by a higher incidence of non-cardiovascular death (RR 1.38, 95% CI 0.99-1.92; P = 0.060). Our meta-analysis indicates that low-dose colchicine reduced the risk of MACE as well as that of myocardial infarction, stroke, and the need for coronary revascularization in a broad spectrum of patients with coronary disease. There was no difference in all-cause mortality and fewer cardiovascular deaths were counterbalanced by more non-cardiovascular deaths.

The effect of Colchicine on Vicia faba and Chrysanthemum carinatum (L.) plants and their cytogenetical study

We have prepared various colchicine concentrations and applied them on seedling of Chrysanthemum carinatum (2n = 18) and seeds of Vicia faba (2n = 12). Colchicine-induced polyploidy was reported in Chrysanthemum carinatum (2n = 4x = 36) and Vicia faba (2n = 4x = 24) plants. This research explains the polyploidy in respective plants which successfully results in apparent morphological and cytological changes in polyploid plants compared to the control plants. Phenotypic characters exhibited that polyploid plants initially had slightly slower growth, stronger stems, thicker and larger leaves, larger flowers, and seeds and then increases abruptly. There was an increment in cytological characters such as cell size, chiasma frequency in polyploid plants as compared to the control plants. Growth patterns, morphology, pollen staining, and seed sets were recorded in this work. However, the main emphasis was laid on the behavior of chromosomes of isolated polyploids.

Sequential doxycycline and colchicine combination therapy in Covid-19: The salutary effects

Coronavirus virus disease 2019 (COVID-19) is a viral infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), actually considered as a global pandemic. The entry-point for SARS-CoV-2 is angiotensin converting enzyme 2 (ACE2) and dipeptidyl peptidase 4 (DPP4), which are highly expressed in the lung. Among other complications, COVID-19leads to fatal pneumonia, acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) due to development of cytokine storm (CS). The pathogenesis of SARS-CoV-2 infection depends on the viral load and human innate/adaptive immune response that are required for viral elimination in the first phase of COVID-19. However, an exaggerated immune response in the second phase of COVID-19 results in immune overreaction and CS-induced ALI and ARDS. Thus, in view of these considerations, we report here a series of five patients with COVID-19 pneumonia who developed ALI. In addition to the supportive therapy, the patients received doxycycline in the first week and doxycycline plus colchicine in the second week. Following sequential therapy with doxycycline and/or colchicine in patients with COVID-19 pneumonia, the patients had reduction of disease severity and symptoms with better clinical and radiological outcomes. However, it is tough to confirm the link between this therapeutic combination and recovery from COVID-19 pneumonia, as it is a small case-series report. Nevertheless, this study gives a rational for large-scale prospective studies to evaluate the dual sequential effect of doxycycline and colchicine on the COVID-19 severity. This case-series illustrated that use of colchicine: doxycycline combination is linked with marked improvements in the clinical, laboratory and radiological outcomes in patients with COVID-19 pneumonia. However, we cannot sketch any definitive conclusion from our observation, despite we hypothesize that this combination therapeutic regimen may attenuate and treat COVID-19. Further, namely prospective, randomized, and controlled clinical studies are recommended in this regard.

Investigation of molecular mechanisms underlying the antiproliferative effects of colchicine against PC3 prostate cancer cells

This work examined the cytotoxic effects of colchicine on PC3 cells and elucidated the possible underlying mechanisms of its cytotoxicity. The cells were exposed to colchicine at different concentrations ranging from 1 to 100 ng/mL for 24 h, and it showed considerable cytotoxicity with an IC50 value of 22.99 ng/mL. Mechanistic studies also exhibited that colchicine treatment results in cell cycle arrest at the G2/M phase as well as decreased mitochondrial membrane potential and increased early and late apoptotic cells. The apoptotic and DNA-damaging effects of colchicine have also been verified by fluorescence imaging and ELISA experiments, and they revealed that while colchicine treatment significantly modulated expression as increases in Bax, cleaved caspase 3, cleaved PARP, and 8-hydroxy-desoxyguanosine levels and as a decrease of BCL-2 protein expression. Besides, colchicine treatment significantly increased the total oxidant (TOS) level, which is a signal of oxidative stress and potential cause of DNA damage. Finally, the results of quantitative real-time PCR experiments demonstrated that colchicine treatment concentration-dependently suppressed MMP-9 mRNA expression. Overall, colchicine provides meaningful cytotoxicity on PC3 cells due to induced oxidative stress, reduced mitochondrial membrane potential, increased DNA damage, and finally increased apoptosis in PC3 cells. Nevertheless, further research needs to be conducted to assess the potential of colchicine as an anticancer drug for the treatment of prostate cancer.

AB020. A case report on cutaneous necrotizing vasculitis treated with colchicine in a Filipino adult male

Cutaneous necrotizing vasculitis is a condition characterized by vessel wall necrosis secondary to neutrophil infiltration classically presenting as palpable purpura on the lower extremities. Several etiologic agents have been identified but, literature showed that majority of cases have an unidentifiable cause. First-line pharmacologic management consists of systemic glucocorticoids with colchicine being used merely as second-line therapy. We report a case of a 59-year-old male with cutaneous necrotizing vasculitis treated with colchicine as monotherapy. This is the case of a 59-year-old male with a ten-day history of multiple discrete to confluent well-defined vesicles and bullae, some eroded with hemorrhagic exudates on the bilateral lower extremities, with accompanying round palpable purpura seen on the abdomen extending to the bilateral upper extremities. Skin biopsy was consistent with leukocystoclastic vasculitis. The patient completed 3-month treatment with colchicine 500 mcg twice daily with adjunct therapy of prednisone 20 mg once a day for 2 weeks tapered down by 5 mg. By 4th week of treatment, 50% improvement over the lesions were observed. By 3rd month of treatment, complete clearance was noted. This case highlights the effectiveness of colchicine as monotherapy for cases of cutaneous necrotizing vasculitis due to its action in suppressing granulocytic inflammatory reaction. Moreover, relative safety of colchicine is more favorable compared to the possible long-term side effects of systemic glucocorticoids. Especially for patients at risk for developing adverse effects to glucocorticoids, colchicine is a feasible yet often overlooked alternative treatment option compared to the conventional treatment with systemic glucocorticoids.

Can colchicine prevent acute myocardial infarction? Systematic review and meta-analysis

Introduction and objectives: The association between the use of colchicine and the incidence of acute myocardial infarction(AMI) is inconsistent. The main objective of this study was to evaluate the effect of colchicine on the incidence of AMI. Assessmentof the incidence of stroke and cardiovascular mortality were secondary endpoints.Methods: A meta-analysis of randomized studies that evaluated the use of colchicine in patients with atherosclerotic diseaseand reported cardiovascular events was performed, after searching the PubMed/MEDLINE, Embase, Scielo and CochraneControlled Trials databases. A fixed or random effects model were used depending on the heterogeneity observed.Results: Seven studies were selected for the analysis of the primary end point (5966 subjects in the colchicine arm and 5948patients in the control arm). This meta-analysis demonstrated that colchicine therapy was associated with a lower risk of AMI(OR: 0.76, 95% CI: 0.62-0.92; I2 = 15%). Likewise, a significant reduction in the incidence of stroke was observed without asignificant effect on cardiovascular mortality with pharmacological intervention.Conclusion: The use of colchicine in patients with atherosclerotic cardiovascular disease was associated with a significant reductionin the incidence of AMI. The incorporation of colchicine into the therapeutic arsenal of cardiovascular disease shouldbe considered by future clinical practice guidelines.

Pengaruh Konsentrasi Dan Lama Inkubasi Kolkisin Terhadap Duplikasi Kromosom Planlet Terung (Solanum melongena L.) Haploid Galur Aksesi Hasil Kultur Antera

The purpose of this study was to determine the effect of colchicine on chromosome duplication and to determine the best colchicine concentration and incubation time for haploid eggplant chromosome duplication results from anther culture. Laboratory experiments have been carried out at PT. East West Seed Indonesia, Benteng Village, Campaka District, Purwakarta from March to June 2020. With an altitude of 69 m above sea level. The environmental design used in this study was a completely randomized design consisting of 7 treatments and repeated 4 times. Colchicine treatment design A = Control, B = colchicine 0.05% 24 hours incubation, C = colchicine 0.05% 48 hours incubation, D = colchicine 0.1% 24 hours incubation, E = colchicine 0.1% 48 hours incubation, F = kolkisisn 0.15% incubation 24 hours, G = colchicine 0.15% incubation 48 hours. The responses observed were contamination, callous plantlets, rooted plantlets, live plantlets, haploid plantlets, double haploid plantlets, triploid plantets and unreadable ploidy check results. The results showed that the colchysis concentration and incubation time had an effect on the duplication of haploid eggplant plantlet chromosomes resulting from anther culture. And giving colchicine at a concentration of 0.05% with an incubation time of 48 hours and a colchicine concentration of 0.1% with an incubation time of 48 hours had a significant effect on the double haploid plantet of 23.44%.

Colchicine effects on the ploidy level and morphological characters of Katokkon pepper (Capsicum annuum L.) from North Toraja, Indonesia

BackgroundProductivity and quality of crops can be increased through polyploidy plants induced by colchicine. The use of colchicine has never been applied to Katokkon pepper, a local red pepper variety from North Toraja Indonesia. This pepper is characterized by its unique shape like the small-bell pod type of paprika and its strong spicy taste. Therefore, this study aimed to determine the effects of colchicine treatment on the ploidy level and morphological characters of Katokkon pepper. ResultsFlow cytometer analysis showed that all colchicine concentration treatments ranging from 0.025 to 0.1% with 24 h immersion time generated two plant groups based on their ploidy level; 50% of the total treatment plants was diploid while the rest plants were mixoploid. All colchicine treatment plants were significantly different in their width of stomata guard cells from the control plant. The effect of colchicine was also significantly on the plant height, thickness of fruit flesh, and the number of fruits per plant. ConclusionsThe results of this study showed that colchicine treatment had a significant effect on the ploidy level and several morphological characters of the Katokkon pepper. The colchicine treatment increased the number of fruits per plant and thicker flesh of fruits but reduced the size and weight of Katokkon pepper. Our findings provide essential information to obtain tetraploid Katokkon plants through colchicine treatment in further research. This study benefits as a preliminary step for increasing the productivity and quality of the local red peppers in Indonesia.

Beneficial effects of colchicine for moderate to severe COVID-19: a randomised, double-blinded, placebo-controlled clinical trial

ObjectiveTo evaluate whether the addition of colchicine to standard treatment for COVID-19 results in better outcomes.DesignWe present the results of a randomised, double-blinded, placebo-controlled clinical trial of colchicine for the...

Can colchicine prevent acute myocardial infarction? Systematic review and meta-analysis

Objective: The association between the use of colchicine and the incidence of acute myocardial infarction (AMI) is inconsistent. The main objective of this study was to evaluate the effect of colchicine on the incidence of AMI. Assessment of the incidence of stroke and cardiovascular mortality were secondary endpoints. Methods: A meta-analysis of randomized studies that evaluated the use of colchicine in patients with atherosclerotic disease and reported cardiovascular events was performed, after searching the PubMed/MEDLINE, Embase, Scielo and Cochrane Controlled Trials databases. A fixed or random effects model were used depending on the heterogeneity observed. Results: Seven studies were selected for the analysis of the primary end point (5966 subjects in the colchicine arm and 5948 patients in the control arm). This meta-analysis demonstrated that colchicine therapy was associated with a lower risk of AMI (OR: 0.76, 95% CI: 0.62-0.92; I2 = 15%). Likewise, a significant reduction in the incidence of stroke was observed without a significant effect on cardiovascular mortality with pharmacological intervention. Conclusion: The use of colchicine in patients with atherosclerotic cardiovascular disease was associated with a significant reduction in the incidence of AMI. The incorporation of colchicine into the therapeutic arsenal of cardiovascular disease should be considered by future clinical practice guidelines.

Adverse events of colchicine for cardiovascular diseases: a comprehensive meta-analysis of 14 188 patients from 21 randomized controlled trials.

Colchicine has an emerging role in the cardiovascular field, although, concerns for side effects, especially gastrointestinal, limit its prescription. We aimed at evaluating reported side effects of colchicine for cardiovascular indications. We performed a meta-analysis of published randomized controlled trials on colchicine for the treatment of cardiovascular diseases. Random-effects meta-analysis was used to assess the risk of adverse events and drug withdrawal. Publication bias was assessed using the Egger test, and meta-regression was performed to assess sources of heterogeneity. Among 14 188 patients, 7136 patients received colchicine while the other 7052 received placebo. The occurrence of any adverse event with colchicine was reported in 15.3 vs. 13.9% patients [relative risk (RR) 1.26, 95% confidence interval (CI) 0.96-1.64, P = 0.09]. Gastrointestinal events were reported in 16.1 vs. 12.2% (RR 2.16, 95% CI 1.50-3.12, P < 0.001), while diarrhea was reported in 12.5 vs. 8.1% (RR 2.77, 95% CI 1.55-4.94, P < 0.001). The risk of gastrointestinal events increased with daily dose and shorter treatment duration. Myalgias were observed in 21 vs. 18% patients (RR 1.16, 95% CI 1.02-1.32, P = 0.03). Other adverse events such as myotoxicity, hepatic adverse events, hematologic adverse events, cutaneous adverse events, infection or death were not increased by colchicine treatment. Colchicine discontinuation was reported in 4.8 vs. 3.4% patients (RR 1.54, 95% CI 1.20-1.99, P < 0.001). Colchicine is associated with increased risk of gastrointestinal events and myalgias, but not of other adverse events. The risk of gastrointestinal events may be avoided with lower dose (0.5 mg/daily) and is inversely related to treatment duration, possibly due to early drug discontinuation or drug tolerance.

Biochemical and Molecular Effects of Colchicine and Moringa Olifera on Thioacetamide Induced Liver Fibrosis in Rats

This study was conducted to investigate the effect of moringa olifera and colchicine on thioacetamide induced liver fibrosis in rats. One hundred and fife rats were randomly divided into equal seven groups of fifteen animals each for 60 days as follows: The first group (control) was kept on basal diet and water, the second group hepatotoxicity was induced by i.p injection of TAA (150 mg/kg of body weight, i.p.), for three times/week for two months and the third group was given colchicine (COL) orally with stomach tube (50 μ/kg day ) the fourth group was given MOEL( moringa olifera ethanolic leaves extract) also by stomach tube ( 400 mg/kg) ,the fifth group was given TAA(150 mg/kg) + COL(50 μ/kg day ), the six group was given TAA(150 mg/kg) +MOEL(400mg/kg), the seven group was given (TAA(150 mg/kg) + COL(50 μ/kg day )+ MOEL 400mg/kg) for 3times/week for 2 months. We studied liver fibrosis from three point of view biochemical effect, molecular effect and histopathological effect. Blood samples were collected and serum was separated for the determination of the following biochemical tests as liver enzymatic function ALT (Alanin aminotransferase),AST (Aspartateaminotransferase),GGT, ALP (Alkaline phosphatase ) , total protein ,albumin. The total antioxidant capacity (TAC), reduced glutathione (GSH) and malondialdehyde (MDA) in liver tissue homogenates, molecular view point as measuring BAX (bacl2associated X, Apoptosis Regulator) Bcla2 (B-celleymphoma 2) for detection apoptosis occurred then histopathological effect of liver fibrosis on liver tissue. The induction of TAA revealed a significant increase in liver enzymes, bilirubin, MDA, BAX, and a significant decrease in TP, Alb ,Bacl2 by p

Colchicine for the prevention of ischemic stroke: An updated meta-analysis of randomized clinical trials.

BACKGROUND:Inflammation is increasingly recognized as a target to reduce residual cardiovascular risk. Colchicine is an anti-inflammatory drug that was associated with improved cardiovascular outcomes. However, its effect on stroke reduction was not consistent across studies. Therefore, the aim of this study-level meta-analysis was to evaluate the influence of colchicine on stroke in patients with coronary artery disease (CAD).METHODS:Electronic databases were searched through October 2020, to identify randomized controlled trials using colchicine in patients with CAD. The incidence of clinical endpoints such as stroke, death, myocardial infarction (MI), study-defined major adverse cardiovascular events (MACE), and atrial fibrillation (AF) was compared between colchicine and placebo groups.RESULTS:A total number of 11,594 (5,806 in the colchicine arm) patients from 4 eligible studies were included in the final analysis. Stroke incidence was lower in the colchicine arm compared to placebo (rate ratio [RR] 0.48 [95% confidence interval [CI], 0.29–0.78], P = 0.003) whereby no significant difference was observed in the incidence of AF (odds ratio [OR] 0.86 [95% CI, 0.69–1.06], P = 0.16). Furthermore, a significant effect of colchicine on MACE [RR 0.65 (95% CI, 0.51–0.83), P = 0.0006] and MI (RR 0.65 (95% CI, 0.54–0.95], P = 0.02) was detected, with no influence on all-cause mortality (RR 1.04 [95% CI, 0.61–1.78], P = 0.88).CONCLUSIONS:This meta-analysis confirms a significant influence of colchicine on stroke in CAD patients. Despite its neutral effect on AF occurrence, other mechanisms related to plaque stabilization are plausible. The concept seems to be supported by contemporaneous MI reduction and posits that anti-inflammatory properties of colchicine may translate into a reduction of stroke risk.

Колхицин у пациентов с ишемической болезнью сердца: новые возможности снижения остаточного воспалительного риска

Inflammation plays an important role in atherosclerotic plaque destabilisation and the development of cardiovascular complications. Suppression of its activity in order to reduce residual inflammatory risk in atherosclerotic cardiovascular diseases remains an urgent and unresolved problem to the date. Over the recent years, evidence of the effectiveness of such an approach in secondary prevention of coronary heart disease has been obtained. The purpose of this review was to analyse modern literature on the effect of anti-inflammatory therapy with colchicine on the prognosis of patients with coronary heart disease. The review was carried out using the search for papers published in the PubMed and ClinicalTrials databases within the period from 2007 to 2021. The search was carried out using the keywords «colchicine», «inflammation», «atherosclerosis», «coronary heart disease» and «acute coronary syndrome». The anti-inflammatory and antiatherogenic effects of colchicine are discussed. The paper presents results of studies devoted to the use of colchicine in chronic and acute coronary syndrome, including the key ones LoDoCo2 (2020) and COLCOT (2019) which provided evidence of the effect of the drug on the disease outcome. The issues of safety and prospects of colchicine application in clinical practice for reduction of the residual inflammatory risk in patients with coronary heart disease are addressed.

Repurposing colchicine's journey in view of drug-to-drug interactions. A review.

Colchicine's medical evolution is historically bound to the Mediterranean basin, since remarkable researchers from this region underscored its valuable properties. With the passing of years colchicine became an essential pharmaceutical substance for the treatment of rheumatologic and cardiovascular diseases. In light of recent findings, the therapeutic value of colchicine has grown. In clinical practice, colchicine remains underutilized in view of its proven efficacy and safety. Its complex pharmacokinetics and multifaceted anti-inflammatory role remain under investigation. The current review addresses the safe administration of colchicine in view of key drug to drug interactions. Finally, we are briefly presenting colchicine's future potential applications.

GEF-H1 Is Required for Colchicine Inhibition of Neutrophil Rolling and Recruitment in Mouse Models of Gout.

Gout is a painful arthritic inflammatory disease caused by buildup of monosodium urate (MSU) crystals in the joints. Colchicine, a microtubule-depolymerizing agent that is used in prophylaxis and treatment of acute gout flare, alleviates the painful inflammatory response to MSU crystals. Using i.p. and intra-articular mouse models of gout-like inflammation, we found that GEF-H1/GEF-H1/AHRGEF2, a microtubule-associated Rho-GEF, was necessary for the inhibitory effect of colchicine on neutrophil recruitment. GEF-H1 was required for neutrophil polarization in response to colchicine, characterized by uropod formation, accumulation of F-actin and myosin L chain at the leading edge, and accumulation of phosphorylated myosin L chain, flotillin-2, and P-selectin glycoprotein ligand-1 (PSGL-1) in the uropod. Wild-type neutrophils that were pre-exposed to colchicine failed to roll or accumulate on activated endothelial monolayers, whereas GEF-H1 knockout (GEF-H1-/-) neutrophils were unaffected by treatment with colchicine. In vivo, colchicine blocked MSU-induced recruitment of neutrophils to the peritoneum and the synovium in wild-type mice, but not in GEF-H1-/- mice. Inhibition of macrophage IL-1β production by colchicine was independent of GEF-H1, supporting a neutrophil-intrinsic mode of action. Our results suggest that the anti-inflammatory effects of colchicine in acute gout-like inflammation can be accounted for by inhibition of neutrophil-rolling interactions with the inflamed vasculature and occurs through GEF-H1-dependent neutrophil stimulation by colchicine. These results contribute to our understanding of the therapeutic action of colchicine, and could inform the application of this drug in other conditions.

Effect of low-dose colchicine in acute and chronic coronary syndromes: A systematic review and meta-analysis.

Sparse evidence of the prognostic benefit of the anti-inflammatory drug colchicine in chronic and acute coronary syndromes (CCS/ACS) exists. We performed a systematic search of studies on CCS or ACS comparing colchicine vs. placebo and reporting data on cardiovascular outcomes (primary end points of each study) and/or changes in hs-CRP. Ten studies were selected: three on CCS (LoDoCo, LoDoCo2 and the CCS subgroup of COLCHICINE-PCI; total patient number=6256), three on ACS (COLCOT, COPS, ACS subgroup of COLCHICINE-PCI; n=5,654) and five (n=532) on hs-CRP changes from 1week to 12months, in CCS and/or ACS. In patients with CCS, colchicine reduced by 49% risk of a composite end point (hazard ratio [HR] 0.51, 95% confidence interval [CI] 0.32 to 0.81, P=.005). The favourable effect of colchicine on the risk of cardiovascular events did not change when excluding COLCHICINE-PCI from analysis (HR 0.51, 95% CI 0.25 to 1.03, P=.061). In patients with ACS, the use of colchicine tended to decrease the occurrence of the combined end point compared with placebo (HR=0.77, 95% CI 0.56 to 1.05, P=.100), and colchicine became significantly protective when removing COLCHICINE-PCI from analysis (HR=0.72, 95% CI 0.56 to 0.92, P=.009). Furthermore, colchicine tended to reduce the hs-CRP increase (standardized mean difference=-0.31, 95% CI -0.72 to 0.1, P=.133) compared with placebo. Colchicine therapy near halves the risk of cardiovascular events in CCS compared with placebo and is associated with a nonsignificant 23% risk reduction in ACS, together with a trend towards a greater reduction of hs-CRP.