Efficacy and safety of 0.5% colchicine cream versus 5% 5-fluorouracil cream in the treatment of cutaneous field cancerization: a randomized clinical trial

Abstract Background 5-Fluorouracil (5-FU) is a first-line drug to treat cutaneous field cancerization (CFC). There are few clinical trials with topical colchicine (COL). Objective To evaluate the effectiveness of 0.5% COL cream versus 5% 5-FU cream in the treatment of CFC. Method This was a randomized, open, self-controlled clinical trial. Forty-five patients (90 forearms), with three to ten actinic keratoses (AK) on each forearm, used 0.5% COL cream 2×/day for seven days on one forearm, and 5% 5-FU cream 2× /day, for 21 days, on the other forearm. The dosages were defined based on previous clinical trials for each drug. Adverse effects were evaluated after 14 days and outcomes after 90 days of inclusion. The primary outcome was complete AK clearance and the secondary outcomes were: partial clearance (≥50%), reduction in AK count, assessment of the Forearm Photoaging Scale (FPS), AK Severity Score (AKSS), and adverse effects. Results After 90 days, there was complete clearance of AK in 37% (95% CI 24%-49%) and partial clearance in 85% (95% CI 76%-93%) of the forearms treated with 5-FU,versus 17% (95% CI 7%-27%) and 78% (95% CI 66%-88%) for COL (p > 0.07). There was a percentage reduction of 75% in the AK count of the forearms treated with 5-FU (95% CI 66%-83%) and 64% in those treated with COL (95% CI 55%-72%). Regarding FPS and AKSS, there was improvement in both groups, with no difference regarding FPS (p = 0.654), and 5-FU superiority for AKSS (p = 0.012). Study limitations Single-center study. Conclusions 5-FU and COL are effective for treating CFC, with neither showing superiority regarding the reduction in AK counts.

Role of inflammation and evidence for the use of colchicine in patients with acute coronary syndrome.

Acute Coronary Syndrome (ACS) significantly contributes to cardiovascular death worldwide. ACS may arise from the disruption of an atherosclerotic plaque, ultimately leading to acute ischemia and myocardial infarction. In the pathogenesis of atherosclerosis, inflammation assumes a pivotal role, not solely in the initiation and complications of atherosclerotic plaque formation, but also in the myocardial response to ischemic insult. Acute inflammatory processes, coupled with time to reperfusion, orchestrate ischemic and reperfusion injuries, dictating infarct magnitude and acute left ventricular (LV) remodeling. Conversely, chronic inflammation, alongside neurohumoral activation, governs persistent LV remodeling. The interplay between chronic LV remodeling and recurrent ischemic episodes delineates the progression of the disease toward heart failure and cardiovascular death. Colchicine exerts anti-inflammatory properties affecting both the myocardium and atherosclerotic plaque by modulating the activity of monocyte/macrophages, neutrophils, and platelets. This modulation can potentially result in a more favorable LV remodeling and forestalls the recurrence of ACS. This narrative review aims to delineate the role of inflammation across the different phases of ACS pathophysiology and describe the mechanistic underpinnings of colchicine, exploring its purported role in modulating each of these stages.

Synthetic Tetraploid of Oncidium crispum Lodd. (Orchidaceae).

In ornamental plants, artificial polyploidization has enabled the creation of new cultivars. Due to their high commercial value in the international flower market and their ornamental characteristics, such as the shape, size, color, and durability of their flower, orchids have received great attention in studies of artificial polyploidization. Here we described the protocol used for polyploid induction in Oncidium crispum, an epiphyte species native of southeastern Brazil, of great ornamental interest and widely sold in flower shops. The species stands out for having inflorescence with large flowers, brown in color with yellow spots. In addition, O. crispum has great potential for use in genetic improvement programs since the species is widely used in interspecific crosses. Closed capsules containing mature O. crispum seeds were subjected to running sterilized water for 10 min and then to a 1.5% sodium hypochlorite solution for 10 min. Small portions of seeds were introduced into 50 mL of water-soluble fertilizer with macro- and micronutrients (B>M) plus 0.7% agar. Explants originating from seeds previously in vitro germinated were submitted to 0.05% and 0.1% of colchicine for 4 days and 8 days. Flow cytometry and chromosome counts confirmed that the protocol successfully produced synthetic polyploid plants.

Novel drug design and repurposing: An opportunity to improve translational research in cardiovascular diseases?

Drug repurposing is defined as the use of approved therapeutic drugs for indications different from those for which they were originally designed. Repositioning diminishes both the time and cost for drug development by omitting the discovery stage, the analysis of absorption, distribution, metabolism, and excretion routes, as well as the studies of the biochemical and physiological effects of a new compound. Besides, drug repurposing takes advantage of the increased bioinformatics knowledge and availability of big data biology. There are many examples of drugs with repurposed indications evaluated in in vitro studies, and in pharmacological, preclinical, or retrospective clinical analyses. Here, we briefly review some of the experimental strategies and technical advances that may improve translational research in cardiovascular diseases. We also describe exhaustive research from basic science to clinical studies that culminated in the final approval of new drugs and provide examples of successful drug repurposing in the field of cardiology.

Efficacy and safety of 0.5% colchicine cream versus 5% 5-fluorouracil cream in the treatment of cutaneous field cancerization: a randomized clinical trial.

BACKGROUND: 5-Fluorouracil (5-FU) is a first-line drug to treat cutaneous field cancerization (CFC). There are few clinical trials with topical colchicine (COL). OBJECTIVE: To evaluate the effectiveness of 0.5% COL cream versus 5% 5-FU cream in the treatment of CFC. METHOD: This was a randomized, open, self-controlled clinical trial. Forty-five patients (90 forearms), with three to ten actinic keratoses (AK) on each forearm, used 0.5% COL cream 2×/day for seven days on one forearm, and 5% 5-FU cream 2× /day, for 21 days, on the other forearm. The dosages were defined based on previous clinical trials for each drug. Adverse effects were evaluated after 14 days and outcomes after 90 days of inclusion. The primary outcome was complete AK clearance and the secondary outcomes were: partial clearance (≥50%), reduction in AK count, assessment of the Forearm Photoaging Scale (FPS), AK Severity Score (AKSS), and adverse effects. RESULTS: After 90 days, there was complete clearance of AK in 37% (95% CI 24%-49%) and partial clearance in 85% (95% CI 76%-93%) of the forearms treated with 5-FU,versus 17% (95% CI 7%-27%) and 78% (95% CI 66%-88%) for COL (p > 0.07). There was a percentage reduction of 75% in the AK count of the forearms treated with 5-FU (95% CI 66%-83%) and 64% in those treated with COL (95% CI 55%-72%). Regarding FPS and AKSS, there was improvement in both groups, with no difference regarding FPS (p = 0.654), and 5-FU superiority for AKSS (p = 0.012). STUDY LIMITATIONS: Single-center study. CONCLUSIONS: 5-FU and COL are effective for treating CFC, with neither showing superiority regarding the reduction in AK counts.

Observación de los efectos de la colchicina en el síndrome de insuficiencia respiratoria aguda por COVID-19 / Observation of the effects of colchicine in acute respiratory distress syndrome due to COVID-19

Resumen Introducción: El síndrome de dificultad respiratoria aguda por COVID-19 es un trastorno infeccioso viral de afección sistémica con predominio de síntomas respiratorios que en nuestro país se manifestó en un 16% la forma grave de la enfermedad, misma que requirió tratamiento en unidades de cuidados intensivos. Sin embargo, ante la sobre saturación de los servicios de salud en todos los niveles, se buscan opciones terapéuticas para frenar la progresión de la enfermedad y con ello evitar el requerimiento de estas unidades. Objetivo: Observar el efecto de la colchicina como terapia adyuvante al glucocorticoide, sobre los niveles de oxemia en pacientes con síndrome de dificultad respiratoria aguda por COVID-19 Material y métodos: Se revisaron expedientes clínicos del periodo de diciembre 2020 a marzo 2021 de donde se obtuvieron variables clínico-epidemiológicas de 408 pacientes para estadística descriptiva y analítica. Resultados: Se observó una mayor hospitalización de pacientes hombres en 65.9%, las comorbilidades más prevalentes fueron obesidad e hipertensión arterial los cuales aumentaban la probabilidad de enfermedad por COVID-19 con un OR de 1.7 y 2 veces respectivamente. El uso de colchicina como terapia adyuvante al glucocorticoide disminuyó la mortalidad en formas graves de la enfermedad (OR 0.17), aumentó la probabilidad de egreso por mejoría (OR 5.22) y disminuyó el requerimiento de traslados (OR 6.65). Por otra parte, se encontró que la ventilación en prono despierto es un factor protector en todos los grupos (OR 0.36).

Abstract Introduction: Acute respiratory distress syndrome by COVID-19 is a viral infectious disorder of systemic affection with a predominance of respiratory symptoms that in our country manifested itself in 16% of the severe form of the disease, which required treatment in care units. intensive. However, given the over-saturation of health services at all levels, therapeutic options are sought to slow the progression of the disease and thus avoid the need for these units. Objective: To observe the effect of colchicine as adjuvant therapy to glucocorticoid, on oxemia levels in patients with acute respiratory distress syndrome due to COVID-19. Material and methods: Clinical records from the period from December 2020 to March 2021 were reviewed, from which clinical-epidemiological variables of 408 patients were obtained for descriptive and analytical statistics. Results: A greater hospitalization of male patients was observed in 65.9%, the most prevalent comorbidities were obesity and arterial hypertension, which increased the probability of COVID-19 disease with an OR of 1.7 and 2 times, respectively. The use of colchicine as adjuvant therapy to the glucocorticoid decreased mortality in severe forms of the disease (OR 0.17), increased the probability of discharge due to improvement (OR 5.22) and decreased the need for transfers (OR 6.65). On the other hand, it was found that awake prone ventilation is a protective factor in all groups (OR 0.36).

Effects of colchicine on the prevention of AF recurrence after atrial ablation: a systematic review and meta-analysis.

BACKGROUND: Catheter ablation has become a widely accepted treatment for atrial fibrillation, but early recurrences remain a challenge, often attributed to inflammatory responses triggered during the procedure. This systematic review and meta-analysis aimed to evaluate the effectiveness of colchicine in preventing short-term AF recurrence post-ablation. METHOD: PubMed, Embase, and Cochrane Library were searched for studies comparing use of colchicine and placebo in patients after AF ablation. Outcomes included AF recurrence, GI side effects, and hospitalization. R program (version 4.3.2) was used for statistical analysis. Heterogeneity was assessed with I2 statistics. RESULTS: Five studies, including 1592 patients, were analyzed. Pooled results revealed no statistically significant decrease in AF recurrence (OR 0.74; 95% CI 0.48-1.12; p = 0.153) and pericarditis rates (OR 0.67; 95% CI 0.26-1.72; p = 0.403) with colchicine use. No significant difference in hospitalization rates was observed between colchicine and placebo groups (OR 1.00; 95% CI 0.63-1.59; p = 0.996). In addition, gastrointestinal side effects were notably higher in the colchicine group (OR 4.84; 95% CI 2.58-9.05; p < 0.001). CONCLUSION: Prophylactic use of colchicine after atrial ablation was not associated with a reduction in AF recurrence and pericarditis rates. In addition, there was no difference in the rate of all-cause hospitalization between the groups, and colchicine use was associated with gastrointestinal adverse events.

Efficacy and safety of 0.5% colchicine cream versus 5% 5-fluorouracil cream in the treatment of cutaneous field cancerization: a randomized clinical trial

Background: 5-Fluorouracil (5-FU) is a first-line drug to treat cutaneous field cancerization (CFC). There are few clinical trials with topical colchicine (COL). Objective: To evaluate the effectiveness of 0.5% COL cream versus 5% 5-FU cream in the treatment of CFC. Method: This was a randomized, open, self-controlled clinical trial. Forty-five patients (90 forearms), with three to ten actinic keratoses (AK) on each forearm, used 0.5% COL cream 2×/day for seven days on one forearm, and 5% 5-FU cream 2× /day, for 21 days, on the other forearm. The dosages were defined based on previous clinical trials for each drug. Adverse effects were evaluated after 14 days and outcomes after 90 days of inclusion. The primary outcome was complete AK clearance and the secondary outcomes were: partial clearance (≥50%), reduction in AK count, assessment of the Forearm Photoaging Scale (FPS), AK Severity Score (AKSS), and adverse effects. Results: After 90 days, there was complete clearance of AK in 37% (95% CI 24%­49%) and partial clearance in 85% (95% CI 76%­93%) of the forearms treated with 5-FU,versus 17% (95% CI 7%­27%) and 78% (95% CI 66%­88%) for COL (p > 0.07). There was a percentage reduction of 75% in the AK count of the forearms treated with 5-FU (95% CI 66%­83%) and 64% in those treated with COL (95% CI 55%­72%). Regarding FPS and AKSS, there was improvement in both groups, with no difference regarding FPS (p = 0.654), and 5-FU superiority for AKSS (p = 0.012). Study limitations: Single-center study.

Colchicine reduces the activation of NLRP3 inflammasome in COVID-19 patients.

OBJECTIVE: To evaluate whether colchicine treatment was associated with the inhibition of NLRP3 inflammasome activation in patients with COVID-19. METHODS: We present a post hoc analysis from a double-blinded placebo-controlled randomized clinical trial (RCT) on the effect of colchicine for the treatment of COVID-19. Serum levels of NOD-like receptor protein 3 (NLRP3) inflammasome products-active caspase-1 (Casp1p20), IL-1ß, and IL-18-were assessed at enrollment and after 48-72 h of treatment in patients receiving standard-of-care (SOC) plus placebo vs. those receiving SOC plus colchicine. The colchicine regimen was 0.5 mg tid for 5 days, followed by 0.5 mg bid for another 5 days. RESULTS: Thirty-six patients received SOC plus colchicine, and thirty-six received SOC plus placebo. Colchicine reduced the need for supplemental oxygen and the length of hospitalization. On Days 2-3, colchicine lowered the serum levels of Casp1p20 and IL-18, but not IL-1ß. CONCLUSION: Treatment with colchicine inhibited the activation of the NLRP3 inflammasome, an event triggering the 'cytokine storm' in COVID-19. TRIAL REGISTRATION NUMBERS: RBR-8jyhxh.

Síndrome de SAPHO en un adolescente con esclerodermia localizada: Reporte de Caso

El síndrome SAPHO es una enfermedad autoinflamatoria crónica que engloba una serie de manifestaciones cutáneas y osteoarticulares que incluyen sinovitis, acné, pustulosis, hiperostosis y osteítis. Se presenta el caso de un paciente masculino de 18 años de edad, con antecedente de esclerodermia localizada diagnosticada por biopsia hace 3 años, quien debutó con lesiones cutáneas y osteoarticulares 6 meses después de suspender tratamiento con metotrexate y colchicina, para dicho antecedente. Se reportó una resonancia magnética sugestiva de una sacroileítis con presencia de edema óseo; y la gammagrafía ósea reveló zonas de captación con imagen en cabeza de toro en articulación esternoclavicular, sugiriendo síndrome de SAPHO. Se decidió reincorporar el metotrexate y colchicina, evolucionando satisfactoriamente. No se encontraron reportes similares concomitando estas dos entidades que tienen como punto en común el tratamiento con los mismos fármacos.

SAPHO syndrome is a chronic autoinflammatory disease that encompasses a series of cutaneous and osteoarticular manifestations that include synovitis, acne, pustulosis, hyperostosis, and osteitis. We present the case of an 18-year-old male patient, with a history of localized scleroderma diagnosed by biopsy 3 years ago, who debuted with skin and osteoarticular lesions 6 months after discontinuing treatment with methotrexate and colchicine, for said history. An MRI suggestive of sacroiliitis with the presence of bone edema was reported, and bone scintigraphy revealed uptake areas with a bull's head image in the sternoclavicular joint, suggesting SAPHO syndrome. It was decided to reincorporate methotrexate and colchicine, evolving satisfactorily. No similar reports were found coexisting with these two entities that have treatment with the same drugs as a point in common.

In Vitro Polyploidization of Brassolaeliocattleya Hybrid Orchid.

The Cattleya (Orchidaceae-Laeliinae subtribe) intergeneric hybrids, such as Brassolaeliocattleya (Blc.), have great ornamental value, due to their compact-size, with large and high color diversity of flowers. Artificial induction of polyploidy brings agronomic, ornamental and genetic benefits to plants. Polyploidization efficiency depends on factors, such as the type of antimitotic, polyploidization method, concentrations, exposure times and type of explant. This study aimed to develop a protocol to polyploidize Blc. orchids, by testing two types of explants (seeds and protocorms), concentrations and exposure times to colchicine. The effects of colchicine on the in vitro development of explants were also investigated. The responses of explants to colchicine depended on the concentrations, exposure time and the interaction of these factors. Flow cytometric analysis evidenced high endopolyploidy and allowed the separation of polyploidized (4C, 8C and 16C peaks) from non-polyploidized (only 2C and 4C peaks) plants. The highest percentage of polyploid plants was regenerated from protocorms (16.4%) treated with colchicine instead of seeds (3.2%). Protocorms treated with colchicine at 500-750 µM for 18 h resulted in the best percentage of polyploidization. Additionally, in vitro natural polyploidization using protocorms was reported (11.5%). Cytological analyses allowed an estimation of the number of chromosomes of the parents (≡70), polyploidized (≡140) and non-polyploidized progeny (≡70).

Pediatric Recurrent Pericarditis: Appropriateness of the Standard of Care and Response to IL-1 Blockade.

OBJECTIVE: To analyze, in a cohort of pediatric patients with recurrent pericarditis undergoing anti-interleukin (IL)-1 treatment: the agent and dosing used as first-line treatment, the long-term efficacy of IL-1 blockers, the percentage of patients achieving a drug-free remission, and the presence of variables associated with drug-free remission. STUDY DESIGN: Data were collected from patients' charts. The annualized relapse rate (ARR) was used for evaluation of treatment efficacy, and bivariate logistic regression analysis was used for variables associated with drug-free remission. RESULTS: Fifty-eight patients, treated between 2008 and 2018, were included in the study (mean follow-up. 2.6 years). Of the 56 patients treated with first-line drugs, 14 not responsive patients were underdosed. Fifty-seven patients were treated with anakinra: the ARR before and during daily treatment was 3.05 and 0.28, respectively (P < .0001); an increase to 0.83 was observed after the reduction/withdrawal of treatment (P < .0001). The switch from anakinra to canakinumab (5 patients) was associated to an increase of the ARR (0.49 vs 1.46), but without statistical significance (P = .215). At last follow-up, only 9 of the 58 patients had withdrawn all treatments. With the limits of a retrospective study and the heterogeneity between the patients enrolled in the study, a shorter duration of treatment with anakinra was the only variable associated with drug-free remission. CONCLUSIONS: This study shows that most pediatric patients with recurrent pericarditis needing IL-1 blockade received an inadequate treatment with first-line agents. The effectiveness of anakinra is supported by this study, but few patients achieved drug-free remission. The different rate of response to anakinra and canakinumab may suggest a possible role of IL-1α in the pathogenesis of recurrent pericarditis.

Efficacy and safety of Ixekizumab vs. low-dose IL-2 vs. Colchicine vs. standard of care in the treatment of patients hospitalized with moderate-to-critical COVID-19: A pilot randomized clinical trial (STRUCK: Survival Trial Using Cytokine Inhibitors)

ABSTRACT Background: Cases of coronavirus disease 2019 (COVID-19) requiring hospitalization continue to appear in vulnerable populations, highlighting the importance of novel treatments. The hyperinflammatory response underlies the severity of the disease, and targeting this pathway may be useful. Herein, we tested whether immunomodulation focusing on interleukin (IL)-6, IL-17, and IL-2, could improve the clinical outcomes of patients admitted with COVID-19. Methods: This multicenter, open-label, prospective, randomized controlled trial was conducted in Brazil. Sixty hospitalized patients with moderate-to-critical COVID-19 received in addition to standard of care (SOC): IL-17 inhibitor (ixekizumab 80 mg SC/week) 1 dose every 4 weeks; low-dose IL-2 (1.5 million IU per day) for 7 days or until discharge; or indirect IL-6 inhibitor (colchicine) orally (0.5 mg) every 8 hours for 3 days, followed by 4 weeks at 0.5 mg 2x/day; or SOC alone. The primary outcome was accessed in the "per protocol" population as the proportion of patients with clinical improvement, defined as a decrease greater or equal to two points on the World Health Organization's (WHO) seven-category ordinal scale by day 28. Results: All treatments were safe, and the efficacy outcomes did not differ significantly from those of SOC. Interestingly, in the colchicine group, all participants had an improvement of greater or equal to two points on the WHO seven-category ordinal scale and no deaths or patient deterioration were observed. Conclusions: Ixekizumab, colchicine, and IL-2 were demonstrated to be safe but ineffective for COVID-19 treatment. These results must be interpreted cautiously because of the limited sample size.

Colchicina, perspectivas de un viejo amigo para la reumatología en la COVID-19: una revisión exploratoria / no

Introducción: La colchicina es ampliamente utilizada en enfermedades inflamatorias como la gota y la fiebre mediterránea familiar. Debido a su capacidad inmunomoduladora, podría tener un papel importante en el tratamiento de la COVID-19. Objetivo: Explorar la evidencia médica publicada hasta el 28 de diciembre del 2020, acerca de la eficacia y la seguridad de la colchicina en el tratamiento de pacientes con infección confirmada por SARS-CoV-2. Material y métodos: Revisión exploratoria de la literatura que incluyó PubMed y Scopus. Se tuvieron en cuenta registros de ensayos clínicos y publicaciones con datos empíricos (estudios observacionales y experimentales) en inglés y español. Resultados: Se encontraron 33 ensayos clínicos y 6 publicaciones empíricas: estudios de cohorte prospectivos (n = 2) y retrospectiva (n = 2), ensayo clínico aleatorizado (n = 1) y estudio casos y controles (n = 1). La suma de los participantes en los ensayos es de 46.324 individuos, el 73% (24/33) de los estudios recluta a la población de estudio y el 51% (17/33) son fase 3. Conclusiones: Un ensayo clínico respalda la disminución en marcadores inflamatorios pronósticos y el tiempo de estancia hospitalaria en la infección por SARS-CoV-2. Los ensayos clínicos en desarrollo ayudarán a esclarecer la eficacia y la seguridad de la colchicina para el manejo de pacientes con COVID-19.

Introduction: Colchicine is widely used to treat inflammatory diseases such as gout and Mediterranean fever. Due to its immunomodulatory capacity, it could play an important role in the treatment of COVID-19. Objective: To explore the current available medical evidence, published until 28 December 2020, regarding the efficacy and safety of colchicine in the treatment of patients with confirmed SARS-CoV-2 infection. Material and methods: Scoping review of the literature that included PubMed and Scopus. Records of clinical trials and publications with empirical data (observational and experimental studies) in English and Spanish were included. Results: A total of 33 clinical trials and 6 publications were found: prospective (n = 2) and retrospective (n = 2) cohort studies, randomised clinical trials (n = 1) and case-control studies (n = 1). The total number of participants in the trials is 46,324 individuals, 73% (24/33) of the studies are recruiting participants and 51% (17/33) are phase 3 studies. Conclusions: One clinical trial reports a decrease in prognostic inflammatory markers and length of hospital stay in SARS-CoV-2 infection. The ongoing clinical trials will clarify the efficacy and safety of colchicine for the management of patients with COVID-19.

Polyserositis as a Post-Covid-19 Complication.

INTRODUCTION: Polyserositis is described as inflammation with effusion of more than one serous membrane. There is very little published literature linking it to COVID-19 as a late complication. OBJECTIVE: Present and describe a case of post-COVID-19 polyserositis. METHODS: Data were collected from the medical record of a female patient admitted for fainting spells and marked weakness. The patient underwent a clinical evaluation, additional hematology, imaging and histopathology tests, and a surgical procedure. The new index, called the abdominal adipose deposit index, was obtained by multiplying the subcutaneous fat thickness by visceral fat thickness, both measured by ultrasound. A cutoff point was established that facilitated discernment of an unhealthy phenotype: normal weight but metabolically obese, a cardiometabolic risk factor. RESULTS: We present the case of a 57-year-old female patient admitted to hospital for fainting spells and marked weakness, four months after COVID-19 infection. She also had a history of obesity, asthma, type 2 diabetes mellitus and a cholecystectomy in December 1992 for gallstones. Clinical assessment revealed pericardial effusion and bilateral pleural effusion, in addition to a tumor-like lesion outside the pericardium, proximal to the right ventricular wall. A surgical procedure and findings from additional tests led to diagnoses of thymic remnants and polyserositis. CONCLUSIONS: This is a case of polyserositis in a post-COVID-19 patient. After other causes of polyserositis were ruled out, and since there is a likely physiological and pathogenic mechanism operating between the two diseases, the polyserositis was determined to be a late complication of COVID-19. To date, it is the second case reported in the world and the first reported in Cuba.

Validation of Reference Genes in a Population of Blueberry (Vaccinium corymbosum) Plants Regenerated in Colchicine.

For the first time we report the validation of reference genes in plants from a population of blueberry (Vaccinium corymbosum) clones cultured in vitro on a colchicine-supplemented medium. Nodal segment explants of the cultivar Duke were regenerated by organogenesis under different periods of colchicine 1 mg/L exposure (1, 2, 3, 5, 30 days). The clones selected for the study showed variability for phenotypic traits after 2 years of adaptation to field conditions, compared to plants of the donor genotype that were regenerated on a medium without colchicine. Vaccinium myrtillus (GAPDH) and Vaccinium macrocarpon (ATP1, NADH, RPOB and COX2) were used as reference genomes for primer design. The results show that colchicine treatments can cause genomic changes in blueberry plants. At the molecular level, exposure of plants to colchicine in early periods could promote an increase in gene expression of specific genes such as ATP1, COX2, GAPDH, MATK, NADH and RPOB. However, prolonged exposure (30 days) could decrease gene expression of the genes studied. For qPCR assays, the primers designed for ATP1, COX2, GAPDH and MATK genes showed high efficiency. In addition, the GAPDH, ATP1, NADH and COX2 genes showed high stability and could be recommended as potential reference genes for gene expression assays in Vaccinium.

The Role of Colchicine in Atherosclerosis: From Bench to Bedside.

Inflammation is a key feature of atherosclerosis. The inflammatory process is involved in all stages of disease progression, from the early formation of plaque to its instability and disruption, leading to clinical events. This strongly suggests that the use of anti-inflammatory agents might improve both atherosclerosis progression and cardiovascular outcomes. Colchicine, an alkaloid derived from the flower Colchicum autumnale, has been used for years in the treatment of inflammatory pathologies, including Gout, Mediterranean Fever, and Pericarditis. Colchicine is known to act over microtubules, inducing depolymerization, and over the NLRP3 inflammasome, which might explain its known anti-inflammatory properties. Recent evidence has shown the therapeutic potential of colchicine in the management of atherosclerosis and its complications, with limited adverse effects. In this review, we summarize the current knowledge regarding colchicine mechanisms of action and pharmacokinetics, as well as the available evidence on the use of colchicine for the treatment of coronary artery disease, covering basic, translational, and clinical studies.

In Silico Conformation of the Drug Colchicine into Tubulin Models and Acute Phytotoxic Activity on Cucumis sativus Radicles.

Many tests are used to determine the toxic activity of miscellaneous substances, and those that are simple, fast, and inexpensive are useful for screening compounds with applications in different fields. The Cucumis sativus root growth inhibition test is an example of acute toxicity determinations. On the other hand, colchicine has been used as a herbicide to generate polyploids in plant species finally reaching the environment; for this reason, colchicine could become a point of attention in ecotoxicology. This work established that Cucumis sativus, at the colchicine binding site (CBS) in tubulin, shares 100% similarity with humans. Colchicine was docked on seven Cucumis sativus computational models of the αß-tubulin heterodimer, allowing us to understand a possible conformation in tubulin to trigger its antimitotic effect. Furthermore, an in vitro phytotoxicity assay of colchicine-treated cucumber radicles indicated a hormetic-type concentration-dependent response with macroscopic changes in radicles and hypocotyl. These results support the highly preserved grade of tubulins in several species, and using microtubule inhibitors could require attention in ecotoxicological issues. The Cucumis sativus root growth test could help evaluate small molecules (colchicine analogs), chiefly by CBS interactions, a known druggable site, still a target in the search for antimitotic compounds.

Efficacy of Colchicine in the Treatment of COVID-19 Patients: A Systematic Review and Meta-Analysis.

OBJECTIVE: We assessed the efficacy of colchicine in COVID-19 patients through a systematic review. METHODS: Six databases were searched until March 2022 for studies assessing colchicine versus control in hospitalized patients with COVID-19. The primary outcome was mortality, and secondary outcome was length of hospitalization. Inverse variance and random effect meta-analyses were performed. The strength of evidence was assessed using GRADE. RESULTS: Nine studies (five randomized clinical trials (RCTs) and four non-randomized studies of intervention (NRSI); n = 13,478). Colchicine did not reduce mortality in comparison with the standard of care in RCTs (RR 0.99; 95%CI 0.90 to 1.10; p = 0.90); however, it did reduce mortality in NRSI studies (RR 0.45; 95%CI 0.26 to 0.77; p = 0.02). In the analysis of RCTs, colchicine did not reduce the length of hospitalization in comparison with the standard of care (MD: -2.25 days; 95%CI: -9.34 to 4.84; p = 0.15). Most studies were scored as having a high risk of bias. Quality of evidence was very low for primary and secondary outcomes. CONCLUSION: Colchicine did not reduce the mortality and length of hospitalization in comparison with the standard of care in hospitalized patients with COVID-19. The published evidence is insufficient and of very low quality to recommend treatment in patients with COVID-19.

Prescription Patterns of Drugs Given to Hospitalized COVID-19 Patients: A Cross-Sectional Study in Colombia.

The impact of COVID-19 prompted a race to find a treatment that would reduce its mortality. Most studies have not shown favorable results for many of these drugs, but they are still used. The aim as to determine the differences and similarities in the hospital pharmacological management of patients with COVID-19 according to sex, age group, and geographical region of Colombia, 2020-2021. Descriptive cross-sectional study was conducted on the prescription patterns of the medications given to patients diagnosed with COVID-19 treated in eight clinics in Colombia between 6 March 2020 and 31 May 2021. We performed a descriptive analysis of the sociodemographic, clinical, and pharmacological variables of the patients. A total of 8596 patients from 170 cities were identified, with a median age of 53.0 years and 53.3% of them men. A total of 24.3% required care in the intensive care unit, and 18.7% required invasive mechanical ventilation. The most commonly used drugs for the treatment of COVID-19 were systemic corticosteroids (63.6%), followed by colchicine (12.8%), azithromycin (8.9%), and ivermectin (6.4%). Corticosteroids, anticoagulants, colchicine, azithromycin, ivermectin, and hydroxychloroquine were prescribed more frequently in men, and their overall use increased with age. There were differences in prescriptions between geographic regions. The majority of patients were managed with medications included in the management guidelines. There were differences between sexes, age groups, and geographical regions.