Cytokine and T cell responses in post-chikungunya viral arthritis: A cross-sectional study.

OBJECTIVE: To define the relationship between chronic chikungunya post-viral arthritis disease severity, cytokine response and T cell subsets in order to identify potential targets for therapy. METHODS: Participants with chikungunya arthritis were recruited from Colombia from 2019-2021. Arthritis disease severity was quantified using the Disease Activity Score-28 and an Arthritis-Flare Questionnaire adapted for chikungunya arthritis. Plasma cytokine concentrations (interleukin (IL)-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, interferon-γ and tumor necrosis factor (TNF)) were measured using a Meso Scale Diagnostics assay. Peripheral blood T cell subsets were measured using flow cytometry. RESULTS: Among participants with chikungunya arthritis (N = 158), IL-2 levels and frequency of regulatory T cells (Tregs) were low. Increased arthritis disease activity was associated with higher levels of inflammatory cytokines (IL-6, TNF and CRP) and immunoregulatory cytokine IL-10 (p<0.05). Increased arthritis flare activity was associated with higher Treg frequencies (p<0.05) without affecting T effector (Teff) frequencies, Treg/Teff ratios and Treg subsets. Finally, elevated levels of IL-2 were correlated with increased Treg frequency, percent Tregs out of CD4+ T cells, and Treg subsets expressing immunosuppressive markers, while also correlating with an increased percent Teff out of live lymphocytes (p<0.05). CONCLUSION: Chikungunya arthritis is characterized by increased inflammatory cytokines and deficient IL-2 and Treg responses. Greater levels of IL-2 were associated with improved Treg numbers and immunosuppressive markers. Future research may consider targeting these pathways for therapy.

Novel Insights into the Cardioprotective Effects of the Peptides of the Counter-Regulatory Renin-Angiotensin System.

Currently, cardiovascular diseases are a major contributor to morbidity and mortality worldwide, having a significant negative impact on both the economy and public health. The renin-angiotensin system contributes to a high spectrum of cardiovascular disorders and is essential for maintaining normal cardiovascular homeostasis. Overactivation of the classical renin-angiotensin system is one of the most important pathophysiological mechanisms in the progression of cardiovascular diseases. The counter-regulatory renin-angiotensin system is an alternate pathway which favors the synthesis of different peptides, including Angiotensin-(1-7), Angiotensin-(1-9), and Alamandine. These peptides, via the angiotensin type 2 receptor (AT2R), MasR, and MrgD, initiate multiple downstream signaling pathways that culminate in the activation of various cardioprotective mechanisms, such as decreased cardiac fibrosis, decreased myocardial hypertrophy, vasodilation, decreased blood pressure, natriuresis, and nitric oxide synthesis. These cardioprotective effects position them as therapeutic alternatives for reducing the progression of cardiovascular diseases. This review aims to show the latest findings on the cardioprotective effects of the main peptides of the counter-regulatory renin-angiotensin system.

Novel Strategies to Improve the Cardioprotective Effects of Cardioplegia.

The use of cardioprotective strategies as adjuvants of cardioplegic solutions has become an ideal alternative for the improvement of post-surgery heart recovery. The choice of the optimal cardioplegia, as well as its distribution mechanism, remains controversial in the field of cardiovascular surgery. There is still a need to search for new and better cardioprotective methods during cardioplegic procedures. New techniques for the management of cardiovascular complications during cardioplegia have evolved with new alternatives and additives, and each new strategy provides a tool to neutralize the damage after ischemia/reperfusion events. Researchers and clinicians have committed themselves to studying the effect of new strategies and adjuvant components with the potential to improve the cardioprotective effect of cardioplegic solutions in preventing myocardial ischemia/reperfusion-induced injury during cardiac surgery. The aim of this review is to explore the different types of cardioplegia, their protection mechanisms, and which strategies have been proposed to enhance the function of these solutions in hearts exposed to cardiovascular pathologies that require surgical alternatives for their corrective progression.

Mechanisms of the Quorum Sensing Systems of Pseudomonas Aeruginosa: Host and Bacteria.

Quorum-sensing is a communication mechanism between bacteria with the ability to activate signaling pathways in the bacterium and in the host cells. Pseudomonas aeruginosa is a pathogen with high clinical relevance due to its vast virulence factors repertory and wide antibiotic resistance mechanisms. Due to this, it has become a pathogen of interest for developing new antimicrobial agents in recent years. P. aeruginosa has three major QS systems that regulate a wide gene range linked with virulence factors, metabolic regulation, and environment adaption. Consequently, inhibiting this communication mechanism would be a strategy to prevent the pathologic progression of the infections caused by this bacterium. In this review, we aim to overview the current studies about the signaling mechanisms of the QS system of P. aeruginosa and its effects on this bacterium and the host.

Effects of Metformin on Ischemia/Reperfusion Injury: New Evidence and Mechanisms.

The search for new drugs with the potential to ensure therapeutic success in the treatment of cardiovascular diseases has become an essential pathway to follow for health organizations and committees around the world. In June 2021, the World Health Organization listed cardiovascular diseases as one of the main causes of death worldwide, representing 32% of them. The most common is coronary artery disease, which causes the death of cardiomyocytes, the cells responsible for cardiac contractility, through ischemia and subsequent reperfusion, which leads to heart failure in the medium and short term. Metformin is one of the most-used drugs for the control of diabetes, which has shown effects beyond the control of hyperglycemia. Some of these effects are mediated by the regulation of cellular energy metabolism, inhibiting apoptosis, reduction of cell death through regulation of autophagy and reduction of mitochondrial dysfunction with further reduction of oxidative stress. This suggests that metformin may attenuate left ventricular dysfunction induced by myocardial ischemia; preclinical and clinical trials have shown promising results, particularly in the setting of acute myocardial infarction. This is a review of the molecular and pharmacological mechanisms of the cardioprotective effects of metformin during myocardial ischemia-reperfusion injury.

The Role of METTL3 in the Progression of Cardiac Fibrosis.

Cardiac fibrosis is known as the expansion of the cardiac interstitium through excessive deposition of extracellular matrix proteins; this process is performed by a multifunctional cell known as the cardiac fibroblast. After the myocardial injury, these cells are activated as a repair program, increase, and switch to a contractile phenotype, which is evidenced by an increase in alpha- smooth muscle actin. Likewise, there is an increase in type I and III collagen, which are considered profibrotic biomarkers. It is believed that one of the proteins involved in cardiac remodeling is METTL3, which is the enzyme responsible for N6-methyladenosine (m6A) methylation, the most common and abundant epigenetic modification of eukaryotic mRNA. This review focuses on recent studies in which the possible role of METTL3 in the progression of fibrosis has been demonstrated, mainly in cardiac fibrogenesis.

No todo lo que sibila es asma: revisión de tema / Not everything that wheezes is asthma

Las sibilancias se definen como sonidos pulmonares adventicios, continuos y de tono alto. Predominantemente las sibilancias son de naturaleza espiratoria, pero también pueden ser inspiratorias o bifásicas. Su etiología es secundaria a la obstrucción de flujo en vía aérea superior extratorácica, vía aérea superior intratorácica o vía aérea inferior. Se cree que las sibilancias se deben a las vibraciones de las paredes de las vías respiratorias ocluidas, inducidas por una velocidad reducida del flujo de aire. Cuando se perciben sibilancias sin inducir exhalación forzada es necesario estudiar la causa, realizando una historia clínica dirigida a las diversas etiologías y un examen físico que incluya la exploración torácica completa: inspección, palpación, percusión y auscultación. Ayudas diagnósticas como la radiografía de tórax, la espirometría pre y posbroncodilatador, la tomografía computarizada de tórax y la broncoscopia pueden ser necesarias. El objetivo de este artículo es demostrar que las sibilancias representan un hallazgo semiológico retador para el clínico, que obliga no solo a pensar en asma o en enfermedad pulmonar obstructiva crónica (EPOC) como posible causa.

Wheezing is defined as adventitious, continuous and high-tone lung sounds. Predominantly the wheezing is of an expiratory nature, but it can also be inspiratory or biphasic. Its etiology is secondary to flow obstruction in the extrathoracic and intrathoracic upper airway, or lower airway. It is believed that wheezing is due to vibrations of the walls of the occluded airways, induced by a reduced speed of air flow. When wheezing is perceived without inducing forced exhalation, it is necessary to study the cause, perform a medical history directed at the various etiologies and a physical health check that includes complete chest examination: Inspection, palpation, percussion, and auscultation. As diagnostic aids like chest x-ray, pre- and post-bronchodilator spirometry, computed tomography of the chest and bronchoscopy may be necessary. The objective of this article is demonstrate that wheezing represents a challenging clinical finding for the medical doctor and suggests that it is important to consider other causes in addition to Asthma or Chronic Obstructive Pulmonary Disease (COPD).

Potential of Angiotensin-(1-7) in COVID-19 Treatment.

The new coronavirus currently named SARS-CoV-2 was announced by the World Health Organization as the virus causing the COVID-19 pandemic. The pathogenesis of SARS-CoV-2 initiates upon contact of a structural spike protein with the angiotensin II-converting enzyme receptor, leading to the induction of inflammatory mechanisms and progression to severe disease in some cases. Currently, studies have emerged linking COVID-19 with angiotensin-(1-7), demonstrating the potential of angiotensin-(1-7)/Mas Receptor axis induction to control disease severity due to its antiinflammatory, vasodilator, antioxidant, antiproliferative, anticoagulant, antiangiogenic and fibrosis inhibitory effects. The renin angiotensin-system peptide Angiotensin-(1-7) shows a high therapeutic potential for COVID-19 mainly because of its ability to counteract the adverse effects caused in various organs due to angiotensin II-converting enzyme blockade. In light of these factors, the use of convalescent plasma conjugated therapy and Ang (1-7) agonists for the treatment of COVID-19 patients could be recommended. The differential expression of ACE2 and the varied response to SARSCoV- 2 are thought to be connected. According to several investigations, ACE2 antibodies and pharmacological inhibitors might be used to prevent viral entry. Given its capacity to eliminate the virus while ensuring lung and cardiovascular protection by regulating the inflammatory response, angiotensin-( 1-7) is expected to be a safe choice. However, more clinical evidence is required to clarify the therapeutic usage of this peptide. The aim of this review article is to present an update of scientific data and clinical trials on the therapeutic potential of angiotensin-(1-7) in patients with COVID-19.

Chronic urticaria associated with lung adenocarcinoma - a paraneoplastic manifestation: A case report and literature review.

BACKGROUND: Urticaria is one of the most common causes of emergency room visits. It is defined as an acute inflammatory dermatosis, characterized by localized degranulation of mast cells, with consequent dermal microvascular and formation of edematous and pruritic plaques called hives. Urticaria affects the skin and tissues of the superficial mucosa. Sometimes it is accompanied by angioedema, which is characterized by deeper edema of the dermis and subcutaneous cellular tissue known as the urticarial-angioedema syndrome. About 15%-25% of the general population has suffered at least one type of urticaria at some point during their lifetime and hyperpermeability estimated at 7.6%-16% and has experienced acute urticaria that is usually self-limited and spontaneously resolves without requiring medical attention. CASE SUMMARY: We present the case of a young male patient who was referred to our department with a clinical picture of 4 mo of pruritus associated with hives of variable sizes, irregular borders, with interlesional confluence, that were non-painful, without involvement of the palms and soles of the feet but with a tendency to progression in a generalized manner. He had multiple emergency room visits and poor response to antihistamines and systemic corticosteroids. Imaging studies demonstrated nodules in the lower lingula segment, at the level of the greater fissure and in the anterior contour of the left anterior basal segment associated with parahiliar adenopathies in the absence of findings suggestive of infectious or autoimmune etiology. Segmental lobectomy was performed by thoracoscopy with resection of a lung nodule in the lingula and biopsy of the para-aortic mediastinal ganglion. The histopathological report showed the presence of poorly differentiated invasive adenocarcinoma with a solid morphological and acinar pattern with immunohistochemical description of lung tissue that expresses strong positive and diffuse reaction for thyroid transcription factor 1 (TTF-1) with negativity to P40 for a histopathological diagnosis of malignant epithelial neoplasia with expression of infiltrating adenocarcinoma. Spontaneous chronic urticaria is considered possibly secondary to lung adenocarcinoma. CONCLUSION: Chronic spontaneous urticaria is considered a paraneoplastic dermatosis with a controversial association in the literature. In the presented case, a young patient presented with chronic refractory urticaria and after an exhaustive clinical work-up was found to have a diagnosis of poorly differentiated lung adenocarcinoma with high expression of TTF-1. According to the Curth criteria, the urticaria presented by the patient is related to the oncological diagnosis. In addition, the high expression of TTF-1 documented in this case could be acting as an autoantigen that would cause chronic spontaneous urticaria. Further research evaluating a causal relationship between the TFF-1 protein and urticaria in lung cancer is needed.

Novel Effects of Statins on Cancer via Autophagy.

Cancer is one of the main causes of death globally. Most of the molecular mechanisms underlying cancer are marked by complex aberrations that activate the critical cell-signaling pathways that play a pivotal role in cell metabolism, tumor development, cytoskeletal reorganization, and metastasis. The phosphatidylinositol 3-kinase/protein kinase-B/mammalian target of the rapamycin (PI3K/AKT/mTOR) pathway is one of the main signaling pathways involved in carcinogenesis and metastasis. Autophagy, a cellular pathway that delivers cytoplasmic components to lysosomes for degradation, plays a dual role in cancer, as either a tumor promoter or a tumor suppressor, depending on the stage of the carcinogenesis. Statins are the group of drugs of choice to lower the level of low-density lipoprotein (LDL) cholesterol in the blood. Experimental and clinical data suggest the potential of statins in the treatment of cancer. In vitro and in vivo studies have demonstrated the molecular mechanisms through which statins inhibit the proliferation and metastasis of cancer cells in different types of cancer. The anticancer properties of statins have been shown to result in the suppression of tumor growth, the induction of apoptosis, and autophagy. This literature review shows the dual role of the autophagic process in cancer and the latest scientific evidence related to the inducing effect exerted by statins on autophagy, which could explain their anticancer potential.

Mecanismos moleculares implicados en la etiopatogenia de la aterosclerosis coronaria asociada a la infección por Porphyromonas gingivalis / Molecular mechanisms involved in the ethiopathogenesis of coronary atherosclerosis associated with infection by Porphyromonas gingivalis

Resumen La aterosclerosis es una arteriopatía inflamatoria, crónica y progresiva que genera disfunción del endotelio vascular, estenosis y obstrucción de los vasos sanguíneos. Lidera las estadísticas relacionadas con enfermedades circulatorias y es la principal causa de cardiopatía isquémica. En el mundo representa la principal causa de muerte en la población general. Actualmente, las infecciones representan uno de los principales factores de riesgo emergentes asociados con la aterosclerosis. Varios estudios recientes han demostrado que la enfermedad periodontal está asociada a enfermedades cardiovasculares, que tienen como base la aterosclerosis; por tanto, la relación entre Porphyromonas gingivalis y aterosclerosis coronaria es un terreno activo de investigación en el ámbito global. El lipopolisacárido de la membrana externa y las gingipaínas de Porphyromonas gingivalis están vinculadas a los procesos inflamatorios que ocurren durante el proceso aterogénico. Por consiguiente, la infección periodontal producida por este microorganismo podría desencadenar mecanismos moleculares proinflamatorios involucrados en la etiopatogenia de la aterosclerosis coronaria. Esta revisión tiene como objetivo detallar, de manera minuciosa y precisa, los mecanismos celulares y moleculares implicados en la cardiopatía isquémica por ateromatosis coronaria asociada a la infección por Porphyromonas gingivalis.

Abstract Atherosclerosis is an inflammatory, chronic and progressive arteriopathy that generates vascular endothelial dysfunction with stenosis and obstruction of blood vessels. It is the main cause of circulatory diseases, especially ischemic heart disease. This pathology leads the statistics related to circulatory diseases and is the main cause of ischemic heart disease. Worldwide, atherosclerosis represents the leading cause of death in the general population. Currently, infections represent one of the main emerging risk factors associated with atherosclerosis, several recent studies have shown that periodontal disease is associated with cardiovascular diseases, based on atherosclerosis. The association between Porphyromonas gingivalis and coronary atherosclerosis is an active field of research at a global level. The outer membrane of lipopolysaccharide and the gingipains of Porphyromonas gingivalis are linked to the inflammatory processes that occur during the atherogenic process. Consequently, the periodontal infection caused by Porphyromonas gingivalis could be triggering proinflammatory molecular mechanisms involved in the etiopathogenesis of coronary atherosclerosis. This review aims to detail in a meticulous and precise way the cellular and molecular mechanisms involved in ischemic heart disease due to coronary atheromatosis associated with Porphyromonas gingivalis infection.

Recent Insights into COVID-19 in Children and Clinical Recommendations.

Pediatric coronavirus disease 2019 (COVID-19) and multisystem inflammatory syndrome in children (MIS-C) have been recognized in multiple countries globally. In this review, we provide recent insights into SARS-CoV-2 infection in children from epidemiological, clinical, and laboratory perspectives, including reports on the disease course and therapy. We highlight key features of SARS-CoV-2 infection in children, the relationship between MIS-C and Kawasaki disease, and summarize treatment guidelines for COVID-19 in children from institutional protocols from Colombia, case reports, recommendations based on expert consensus, and official statements from organizations such as the World Health Organization (WHO), United States Center for Disease Control (CDC), Colombian Association of Infectious Diseases, and the Colombian Society of Pediatrics. Finally, we discuss gaps in research with suggestions for future research on the pathogenesis underlying pediatric COVID-19.

Quorum Sensing Regulation as a Target for Antimicrobial Therapy.

Some bacterial species use a cell-to-cell communication mechanism called Quorum Sensing (QS). Bacteria release small diffusible molecules, usually termed signals which allow the activation of beneficial phenotypes that guarantee bacterial survival and the expression of a diversity of virulence genes in response to an increase in population density. The study of the molecular mechanisms that relate signal molecules with bacterial pathogenesis is an area of growing interest due to its use as a possible therapeutic alternative through the development of synthetic analogues of autoinducers as a strategy to regulate bacterial communication as well as the study of bacterial resistance phenomena, the study of these relationships is based on the structural diversity of natural or synthetic autoinducers and their ability to inhibit bacterial QS, which can be approached with a molecular perspective from the following topics: i) Molecular signals and their role in QS regulation; ii) Strategies in the modulation of Quorum Sensing; iii) Analysis of Bacterial QS circuit regulation strategies; iv) Structural evolution of natural and synthetic autoinducers as QS regulators. This mini-review allows a molecular view of the QS systems, showing a perspective on the importance of the molecular diversity of autoinducer analogs as a strategy for the design of new antimicrobial agents.

Sleep Disturbances are a Significant Predictor of Chikungunya Arthritis Flare Severity.

OBJECTIVE: The primary objective of this research was to explore the link between sleep and flare pain associated with chikungunya virus (CHIKV) infection. The secondary objective was to investigate if cytokines and T regulatory (Treg) cells have an influence on this relationship. METHODS: A cross-sectional study was performed using data collected in Barranquilla, Colombia, which enrolled patients with and without chronic arthritis with a history of chikungunya infection. Flare severity was measured by a version of the Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) flare questionnaire adapted for CHIKV arthritis, including metrics for pain, difficulty with physical activity, fatigue, stiffness and difficulty maintaining social activities due to arthritis that contribute to flare severity. In addition, four sleep disturbance items, five inflammatory cytokine levels, four anti-inflammatory cytokine levels, and six Treg levels were measured. Then, multivariable linear regression models were used to test the direct and indirect effects of flare-pain on sleep disturbance, and to determine whether this relationship was mediated by cytokines or Tregs. Finally, the SAS CALIS procedure was used to test path models showing possible causal effects with mediators and confounds. RESULTS: The analysis showed that sleep disturbance is positively correlated with CHIKV arthritis flare pain, and that it is a significant predictor of flare severity after adjusting for demographic variables, cytokine, and T cell levels. Further, neither T cells nor cytokines mediate the pain/sleep relationship in CHIKV arthritis. CONCLUSION: There is a strong association between sleep disturbance and arthritis flare pain and severity; however, this relationship is not mediated by cytokines or T cells. Since this study is unable to determine causation, further research is needed to determine the mechanism underlying the relationship between sleep disturbances and CHIKV arthritis flares.

Novel Targets of Metformin in Cardioprotection: Beyond the Effects Mediated by AMPK.

Ischemic heart disease is the main cause of death globally. In the heart, the ischemia/reperfusion injury gives rise to a complex cascade of molecular signals, called cardiac remodeling, which generates harmful consequences for the contractile function of the myocardium and consequently heart failure. Metformin is the drug of choice in the treatment of type 2 diabetes mellitus. Clinical data suggest the direct effects of this drug on cardiac metabolism and studies in animal models showed that metformin activates the classical pathway of AMP-activated protein kinase (AMPK), generating cardioprotective effects during cardiac remodeling, hypertrophy and fibrosis. Furthermore, new studies have emerged about other targets of metformin with a potential role in cardioprotection. This state of the art review shows the available scientific evidence of the cardioprotective potential of metformin and its possible effects beyond AMPK. Targeting of autophagy, mitochondrial function and miRNAs are also explored as cardioprotective approaches along with a therapeutic potential. Further advances related to the biological effects of metformin and cardioprotective approaches may provide new therapies to protect the heart and prevent cardiac remodeling and heart failure.

Distribution of polymorphism rs693 of ApoB gene in a sample of Colombian Caribbeans / Distribución del polimorfismo rs693 en el gen de la apolipoproteína B en una muestra caribeños colombianos

Abstract Introduction: Several studies have reported that the single nucleotide polymorphism rs693 of Apo lipoprotein B gene is associated with high levels of plasma lipids and high body mass index, which are risk factors for cardiovascular diseases. The distribution of this single nucleotide polymorphism and its association with the phenotype depend on the genetic background of each population. Objective: To evaluate the distribution of single nucleotide polymorphism rs693 and its association with lipid profile and body mass index in a sample of Colombian Caribbeans. Methods: 108 non-related adult subjects of both gender were included in this study. Body mass index and lipid profile that included total cholesterol, triglycerides, Low Density Lipoprotein and High Density Lipoprotein were determined. The single nucleotide polymorphism rs693 was determined by Polymerase Chain Reaction/Restriction Fragment Length Polymorphism from genomic DNA followed by digestion with the restriction enzyme XbaI. The chi-square test was used to analyze the genotype distribution of rs693 and the genotype-phenotype association was evaluated through different inheritance model. Results: The genotype frequencies for single nucleotide polymorphism rs693 were CC (45.0%), TT (16.5%) and CT (38.5%). The allele frequencies were C (64.0%) and T (36.0%). The single nucleotide polymorphism was in Hardy-Weinberg equilibrium in the studied sample. No association of the single nucleotide polymorphism rs693 with lipid profile nor the body mass index was found (p >0.05). Conclusion: There is no significant association between single nucleotide polymorphism rs693 and body mass index nor lipid profile, in a sample of Colombian Caribbeans.

Resumen Introducción: Varios estudios han informado que el polimorfismo de un solo nucleótido rs693 del gen de la apolipoproteína B se asocia con altos niveles de lípidos plasmáticos e índice de masa corporal, los cuales son factores de riesgo para enfermedades cardiovasculares. La distribución de este polimorfismo y su asociación con el fenotipo dependen del antecedente genético de cada población. La población caribeña colombiana es producto de la mezcla de tres grupos étnicos principales: africano, amerindio y caucásico. Objetivo: Evaluar la distribución del polimorfismo rs693 y su asociación con el perfil lipídico y el índice de masa corporal en una muestra de sujetos caribeños colombianos. Métodos: Fueron incluidos en este estudio 108 sujetos adultos de ambos sexos y no relacionados. Se determinaron el índice de masa corporal y el perfil lipídico; de éste se incluyó colesterol total, triglicéridos, lipoproteínas de baja densidad y lipoproteína de alta densidad. El polimorfismo rs693 se determinó mediante Reacción en Cadena de la Polimerasa del ADN genómico seguida por digestión con la enzima de restricción XbaI. Se utilizó la prueba de ji cuadrado para analizar la distribución del genotipo de rs693 y se evaluó la asociación genotipo-fenotipo a través de diferentes modelos de herencia. Resultados: Las frecuencias genotípicas para rs693 fueron CC (45.0%), TT (16.5%) y TC (38.5%). Las frecuencias alélicas fueron C (64.0%) y T (36.0%). El polimorfismo rs693 estaba en equilibrio de Hardy-Weinberg en la muestra estudiada y no presentó asociación con el perfil lipídico ni con el índice de masa corporal (p >0.05). Conclusión: No existe asociación significativa del polimorfismo rs693 con el índice de masa corporal ni con el perfil lipídico en una muestra de caribeños colombianos.

Enfermedades cardiovasculares y cáncer: ¿dos entidades mutuamente relacionadas? / Cardiovascular diseases and cancer: ¿mutually related entities?

Resumen: Las enfermedades cardiovasculares y el cáncer son enfermedades crónicas transmisibles culturalmente, y las dos causas principales de mortalidad en el mundo. Además del gran impacto sobre la mortalidad y morbilidad, estas enfermedades han mostrado un alto grado de relación entre ellas debido, entre otras razones, a que comparten factores de riesgo y mecanismos biológicos. La alta incidencia de enfermedad cardiovascular en pacientes con cáncer es un fenómeno conocido que ha orientado el desarrollo del campo interdisciplinario de la cardio-oncología. Sin embargo, en la última década han surgido evidencias que muestran el papel que desempeñan las enfermedades cardiovasculares en el desarrollo de cáncer. Un estudio reciente publicado por Meijers y cols, en agosto de 2018 en Circulation, mostró que la insuficiencia cardiaca post-infarto del miocardio contribuye significativamente al desarrollo del cáncer de colón, apoyando lo obtenido en estudios epidemiológicos anteriores. Este estudio también sugiere que el crecimiento tumoral podría producirse por factores secretados por el corazón insuficiente abriendo un amplio grupo de posibilidades de investigación en lo que sería un nuevo campo de la medicina cuyo propósito sería el desarrollo de nuevas estrategias para el seguimiento y tratamiento del cáncer en pacientes con enfermedades cardiovasculares. El presente artículo revisa los factores de riesgo, y mecanismos celulares y moleculares, que son comunes en las enfermedades cardiovasculares y el cáncer, la contribución del trabajo de Meijers y cols hacia un mayor entendimiento de la interrelación entre estas patologías y las perspectivas futuras con respecto a los nuevos hallazgos.

Abstracts: Cardiovascular diseases and cancer are culturally transmitted chronic diseases and the two main causes of death globally. In addition to their high morbidity and mortality, these diseases are closely related, due to their common risk factors and biological mechanisms. The high incidence of cardiovascular diseases in cancer patients is widely known phenomenon, which has oriented the development of the interdisciplinary field of cardio-oncology Nonetheless, there is emerging evidence in the last decade suggesting a potential role for cardiovascular diseases in the onset of cancer. A recent publication by Meijers et al in the scientific cardiovascular journal Circulation showed that heart failure significantly contributes to tumor growth, confirming previous epidemiological findings suggesting this hypothesis. Moreover, this study indicates that tumor growth may be stimulated by the secretion of factors from the failing heart, opening a wide spectrum of research areas in what may be suggested as a new field in medicine that would seek to develop new strategies to treat and prevent cancer in patients with cardiovascular diseases. This article will review shared risk factor and common cellular and molecular pathways in cardiovascular diseases and cancer, the contribution of Meijers et al to a better understanding of the connection of these diseases and future perspectives in light of the new evidence.

Distribution of polymorphism rs693 of ApoB gene in a sample of Colombian Caribbeans.

INTRODUCTION: Several studies have reported that the single nucleotide polymorphism rs693 of Apo lipoprotein B gene is associated with high levels of plasma lipids and high body mass index, which are risk factors for cardiovascular diseases. The distribution of this single nucleotide polymorphism and its association with the phenotype depend on the genetic background of each population. OBJECTIVE: To evaluate the distribution of single nucleotide polymorphism rs693 and its association with lipid profile and body mass index in a sample of Colombian Caribbeans. METHODS: 108 non-related adult subjects of both gender were included in this study. Body mass index and lipid profile that included total cholesterol, triglycerides, Low Density Lipoprotein and High Density Lipoprotein were determined. The single nucleotide polymorphism rs693 was determined by Polymerase Chain Reaction/Restriction Fragment Length Polymorphism from genomic DNA followed by digestion with the restriction enzyme XbaI. The chi-square test was used to analyze the genotype distribution of rs693 and the genotype-phenotype association was evaluated through different inheritance model. RESULTS: The genotype frequencies for single nucleotide polymorphism rs693 were CC (45.0%), TT (16.5%) and CT (38.5%). The allele frequencies were C (64.0%) and T (36.0%). The single nucleotide polymorphism was in Hardy-Weinberg equilibrium in the studied sample. No association of the single nucleotide polymorphism rs693 with lipid profile nor the body mass index was found (p >0.05). CONCLUSION: There is no significant association between single nucleotide polymorphism rs693 and body mass index nor lipid profile, in a sample of Colombian Caribbeans.

INTRODUCCIÓN: Varios estudios han informado que el polimorfismo de un solo nucleótido rs693 del gen de la apolipoproteína B se asocia con altos niveles de lípidos plasmáticos e índice de masa corporal, los cuales son factores de riesgo para enfermedades cardiovasculares. La distribución de este polimorfismo y su asociación con el fenotipo dependen del antecedente genético de cada población. La población caribeña colombiana es producto de la mezcla de tres grupos étnicos principales: africano, amerindio y caucásico. OBJETIVO: Evaluar la distribución del polimorfismo rs693 y su asociación con el perfil lipídico y el índice de masa corporal en una muestra de sujetos caribeños colombianos. MÉTODOS: Fueron incluidos en este estudio 108 sujetos adultos de ambos sexos y no relacionados. Se determinaron el índice de masa corporal y el perfil lipídico; de éste se incluyó colesterol total, triglicéridos, lipoproteínas de baja densidad y lipoproteína de alta densidad. El polimorfismo rs693 se determinó mediante Reacción en Cadena de la Polimerasa del ADN genómico seguida por digestión con la enzima de restricción XbaI. Se utilizó la prueba de ji cuadrado para analizar la distribución del genotipo de rs693 y se evaluó la asociación genotipo-fenotipo a través de diferentes modelos de herencia. RESULTADOS: Las frecuencias genotípicas para rs693 fueron CC (45.0%), TT (16.5%) y TC (38.5%). Las frecuencias alélicas fueron C (64.0%) y T (36.0%). El polimorfismo rs693 estaba en equilibrio de Hardy-Weinberg en la muestra estudiada y no presentó asociación con el perfil lipídico ni con el índice de masa corporal (p >0.05). CONCLUSIÓN: No existe asociación significativa del polimorfismo rs693 con el índice de masa corporal ni con el perfil lipídico en una muestra de caribeños colombianos.

Protection of the myocardium against ischemia/reperfusion injury by angiotensin-(1-9) through an AT2R and Akt-dependent mechanism.

Angiotensin-(19), a peptide of the non-classical renin angiotensin system, has been shown to prevent and revert hypertension and cardiac hypertrophy. We hypothetized that systemic delivery of angiotensin-(1-9) following myocardial infarction will also be protective and extend to provide protection during reperfusion of the ischemic heart. Adult Sprague Dawley rats were subjected to left anterior descending artery ligation and treated with angiotensin-(1-9) via osmotic mini-pump for 2 weeks in the presence or absence of Mas receptor or AT2R antagonists (A779 and PD123319, respectively). Myocardial death and left ventricular function were evaluated after infarction. Infarct size and functional parameters were determined in isolated rat hearts after global ischemia/reperfusion in the presence of angiotensin-(1-9) plus receptor antagonists or Akt inhibitor at reperfusion. in vitro, neonatal rat ventricular cardiomyocytes underwent simulated ischemia/reperfusion and angiotensin-(1-9) was co-incubated with A779, PD123319 or Akt inhibitor. Systemic delivery of angiotensin-(1-9) significantly decreased cell death and improved left ventricular recovery after in vivo myocardial infarction. Perfusion with the peptide reduced the infarct size and improved functional recovery after ex vivo ischemia/reperfusion. In vitro, angiotensin-(1-9) decreased cell death in isolated neonatal rat ventricular cardiomyocytes subjected to simulated ischemia/reperfusion. The cardioprotective effects of angiotensin-(1-9) were blocked by PD123319 and Akti VIII but not by A779. Angiotensin-(1-9) limits reperfusion-induced cell death by an AT2R- and Aktdependent mechanism. Angiotensin-(1-9) is a novel strategy to protect against cardiac ischemia/reperfusion injury.

Novel Therapies Targeting Cardioprotection and Regeneration.

Cardiovascular disease is the leading cause of death worldwide. The heart is susceptible to pathologies that impact the myocardium directly, such as myocardial infarction and consequent heart failure, as well as conditions with indirect cardiac effects, such as cancer treatment-related cardiotoxicity. As the contractile cells of the heart, cardiomyocytes are essential for normal cardiac function. Various stress stimuli may result in transient damage or cell death in cardiomyocytes through apoptosis, necrosis or maladaptive autophagy. Moreover, cardiomyocytes are unable to regenerate; thus, lost cells are replaced with fibrotic tissue, with a potentially severe impact on myocardial function. Several therapeutic agents and strategies to reduce cardiomyocyte damage are currently available. This manuscript reviews the state of the art regarding novel cardioprotective endogenous peptides, such as neuregulin-1, angiotensin-(1-9), growth/differentiation factor-11, growth/differentiation factor- 15 and insulin-like growth factor-1. We discuss their protective effects and therapeutic potential in cardiovascular diseases and the current challenges to harnessing their full cardioprotective power. We also explore targeting of exosomes as a cardioprotective approach along with the therapeutic potential of cardiac regeneration strategies. Further advances associated with these molecules and cardioprotective approaches may provide more effective therapies to attenuate or prevent cardiomyocyte death, thereby preserving the myocardium.