RESUMEN
Background: Some clinical dyslipidemia cases do not respond to statins, known as statin-resistant familial hypercholesterolemia (SR-FH), in which patients are under a high cardiovascular risk despite statin therapy. Therefore, novel therapeutic alternatives are required. Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) reduce cholesterol levels and cardiovascular disease risk, particularly in patients with SR-FH, where PCSK9i may differentially affect pro- and anti-inflammatory mediators depending on the clinical setting. Aim: To evaluate the effect of PCSK9i treatment on pro- and anti-inflammatory cytokines in patients with SR-FH. Methods: Before-after comparison, quasi-experimental, single-center study in patients with SR-FH. Blood samples were processed to obtain complete blood counts of glycated hemoglobin and serum lipid levels. Flow cytometry was performed to characterize baseline circulating M1- and M2-macrophages and monocytes. Multiplexing of plasma samples was used to compare plasma fraktaline, interleukins (ILs), monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor (TNF)-alpha. The endpoints were lower serum lipid levels and pro-inflammatory mediator modification. Results: Twenty patients with SR-FH, aged 58 years and most of them males, were included, with a mean body-mass index of 26.4 and showing ischemic heart disease and similar values of baseline M1- and M2-macrophages and monocytes. Six-month iPSCK-9 therapy considerably reduced LDLc, increased anti-inflammatory cytokine (IL-4), and modified pro-inflammatory cytokine (TNF-alpha and MCP-1) levels. No notable effects were observed for the other markers. Conclusion: PCSK9i therapy exerted subclinical anti-inflammatory and anti-atherogenic effects, indicating potential benefits for clinical outcomes.
RESUMEN
Trypanosoma cruzi is a parasite transmitted by the feces of triatomines. Many triatomine species are found in Mexico, and various T. cruzi variants have been isolated from these species, each showing very different virulence and cell tropism. The isolates were obtained from Meccus phyllosoma specimens in three localities in the state of Oaxaca, Mexico: Tehuantitla, Vixhana, and Guichivere. The virulence of each isolate was assessed by quantifying parasitemia, survival, and histopathologic findings. The lineage of each isolate was identified using the mini-exon gene. The expression of the tssa gene during infection was detected in the heart, esophagus, gastrocnemius, and brain. Our results show that the maximum post-infection parasitemia was higher for the Tehuantitla isolate. On genotyping, all isolates were identified as T. cruzi I. The amastigotes in the heart and gastrocnemius were verified for all isolates, but in the brain only for Tehuantitla and Vixhana. The tssa expression allowed us to detect T. cruzi isolates, for Tehuantitla, predominantly in the heart. For Vixhana, a higher tssa expression was detected in gastrocnemius, and for Guichivere, it was higher in the esophagus. Results show that virulence, tropism, and tssa expression can vary, even when the isolates are derived from the same vector species, in the same region, and at similar altitudes.
RESUMEN
OBJECTIVES: We aimed to determine whether parameters associated with adipose tissue (adipocyte density and the circulating concentrations of markers of adipose tissue pathology) predict cardiovascular risk (CVR) modification after metabolic surgery (MS). METHODS: We performed a case-control study of patients with morbid obesity who were candidates for MS. CVR was defined using flow-mediated dilation (FMD) and carotid intima media thickness (CIMT), which were measured during the 9 months following MS. Subgroups of CVR reduction were defined using the following cut-offs: CIMT 10% and/or a two-fold increase in FMD. RESULTS: We studied 40 patients with morbid obesity (mean age 44.5 years, 75% women, mean body mass index 46.4 kg/m2) and high prevalences of the metabolically unhealthy obesity phenotype, hypertension, and diabetes mellitus. A significant reduction in CVR was associated with lower vascular endothelial growth factor-A concentration (6.20 vs. 1.59 pg/mL, respectively), low adipocyte density in visceral adipose tissue (100 vs. 80 cells/field), low infiltration with CD68+ cells (18 vs. 8 cells/field) and higher concentrations of lipid peroxidation markers and malondialdehyde (313.7 vs. 405.7 ng/mL). CONCLUSION: The characteristics of adipose tissue and the circulating concentrations of markers of adipose pathology might represent useful predictors of the reduction in CVR following MS.Clinical trial registration number: NCT0356198 (https://clinicaltrials.gov).
Asunto(s)
Cirugía Bariátrica , Enfermedades Cardiovasculares , Tejido Adiposo/diagnóstico por imagen , Adulto , Enfermedades Cardiovasculares/etiología , Grosor Intima-Media Carotídeo , Estudios de Casos y Controles , Femenino , Factores de Riesgo de Enfermedad Cardiaca , Humanos , Masculino , Factores de Riesgo , Factor A de Crecimiento Endotelial VascularRESUMEN
Ulcerative colitis (UC) is a frequent type of inflammatory bowel disease, characterized by periods of remission and exacerbation. Gut dysbiosis may influence pathophysiology and clinical response in UC. The purpose of this study was to evaluate whether gut microbiota is related to the active and remission phases of pancolitis in patients with UC as well as in healthy participants. Fecal samples were obtained from 18 patients with UC and clinical-endoscopic evidenced pancolitis (active phase n = 9 and remission phase n = 9), as well as 15 healthy participants. After fecal DNA extraction, the 16S rRNA gene was amplified and sequenced (Illumina MiSeq), operational taxonomic units were analyzed with the QIIME software. Gut microbiota composition revealed a higher abundance of the phyla Proteobacteria and Fusobacteria in active pancolitis, as compared with remission and healthy participants. Likewise, a marked abundance of the genus Bilophila and Fusobacteria were present in active pancolitis, whereas a higher abundance of Faecalibacterium characterized both remission and healthy participants. LEfSe analysis showed that the genus Roseburia and Faecalibacterium were enriched in remission pancolitis, and genera Bilophila and Fusobacterium were enriched in active pancolitis. The relative abundance of Fecalibacterium and Roseburia showed a higher correlation with fecal calprotectin, while Bilophila and Fusobacterium showed AUCs (area under the curve) of 0.917 and 0.988 for active vs. remission pancolitis. The results of our study highlight the relation of gut dysbiosis with clinically relevant phases of pancolitis in patients with UC. Particularly, Fecalibacterium, Roseburia, Bilophila, and Fusobacterium were identified as genera highly related to the different clinical phases of pancolitis.
Asunto(s)
Bacterias/clasificación , Colitis Ulcerosa/microbiología , Colitis/microbiología , Disbiosis/microbiología , Heces/microbiología , Microbioma Gastrointestinal , Adulto , Bacterias/genética , Biodiversidad , ADN Bacteriano , Femenino , Voluntarios Sanos , Humanos , Complejo de Antígeno L1 de Leucocito/análisis , Masculino , ARN Ribosómico 16S , Índice de Severidad de la EnfermedadRESUMEN
Morphological characteristics and source of adipose tissue as well as adipokines may increase cardiometabolic risk. This study aimed to explore whether adipose tissue characteristics may impact metabolic and atherogenic risks. Subcutaneous Adipose Tissue (SAT), Visceral Adipose Tissue (VAT) and peripheral blood were obtained from obese patients submitted to bariatric surgery. Adipose tissue (morphometry), plasma adiponectin, TNF-α, resistin (multiplexing) and biochemical chemistry were analyzed; as well as endothelial dysfunction (Flow Mediated Dilation, FMD) and atherogenesis (Carotid Intima Media Thickness, CIMT). Subgroups divided by adipocyte size and source were compared; as well as correlation and multivariate analysis. Sixty patients 36.6% males, aged 44 years-old, BMI 46.7 kg/m2 were included. SAT's adipocytes showed a lower range of size expandability than VAT's adipocytes. Independent from their source, larger adipocytes were associated with higher glucose, lower adiponectin and higher CIMT. Particularly, larger adipocytes from SAT were associated with higher blood pressure, lower insulin and HDL-cholesterol; and showed positive correlation with glucose, HbA1c, systolic/diastolic values, and negatively correlated with insulin and adiponectin. VAT's larger adipocytes particularly associated with lower resistin and lower FMD values. Gender and Diabetes Mellitus significantly impacted the relation of adipocyte size/source with the metabolic and atherogenic risk. Multivariable analysis suggested hypertension-resistin-HbA1c interactions associated with SAT's larger adipocytes; whereas potential insulin-adiponectin associations were observed for VAT's larger adipocytes. Adipocyte morphology and source are differentially related with cardiometabolic and atherogenic risk in population with obesity, which are potentially affected by gender and Diabetes Mellitus.
Asunto(s)
Adipocitos/metabolismo , Aterosclerosis/metabolismo , Grasa Intraabdominal/metabolismo , Obesidad/metabolismo , Grasa Subcutánea/metabolismo , Adipocitos/patología , Adulto , Aterosclerosis/patología , Femenino , Humanos , Grasa Intraabdominal/patología , Masculino , Persona de Mediana Edad , Obesidad/patología , Factores de Riesgo , Grasa Subcutánea/patologíaRESUMEN
BACKGROUND: Inflammatory bowel disease (IBD) affects an estimated 1.6 million people in the United States with at least 70,000 new cases per year. In the last 15 years an increase in frequency of IBD cases from 0.30 cases per 100,000 person-years to 1.83 cases per 100,000 person-years has been reported in Mexico. Variables such as early hospitalization at diagnosis, low hemoglobin levels, high values of C-reactive protein (CRP), fecal calprotectin concentration and absence of mucosal healing during evolution define the prognosis of these patients. However, the distance a patient must travel in order to reach a specialized treatment center can become an impediment for a correct diagnosis and treatment, severely impacting the clinical outcome of such patients. METHODS: Observational, cross-sectional, retrospective study. Objective: In patients with IBD, determine the impact of distance between the residence and specialized treatment center on the general clinical outcome. Variables analyzed: sex, age, disease duration, average travel time, distance in kilometers between place of residence and specialized treatment center, Crohn´s Disease (CD) or Ulcerative Colitis (UC), and their respective severity classification scores, as well as number of hospital readmissions per year. The results were evaluated with ANOVA tests, univariate analysis had a 95% confidence index and a significant "p" determined as p < 0.05. RESULTS: The study included 66 patients (45 UC and 21 CD). Mean age 51.15± 17.5 years. The distance between residence and hospital was calculated and classified into 3 quartiles based on proximity: 750km (quartile 3). There was a higher risk among patients in the most distant quartile for the use of biological therapy (OR, 2.20; 95% CI, 0.23- 20.55) and surgery (OR, 2.76, 95% CI 0.49- 15.48). We observed a clear relationship between the number of hospital readmission and the distance quartiles with a p = 0.0047. CONCLUSION: We observed an impact between the distance of residence and specialized treatment center over the patient's clinical outcome. More readmissions, greater disease activity scores, more use of biological therapy and surgery were observed in patients who had to travel more than 750km from their home to their specialized treatment center compared to the other travel quartiles, this with a p = 0.0047.
RESUMEN
BACKGROUND: Sleep disorders occur recurrently in patients with inflammatory bowel disease (IBD). The relationship between poor sleep quality and IBD activity has been subject to scarce attention. Poor sleep quality could be considered a relevant extraintestinal manifestation and a potential marker of subclinical inflammation, which could increase the severity of inflammation and the risk of relapse, however, we do not have enough information to confirm this hypothesis. Objective: Describe the impact of IBD on the quality of sleep, in patients treated in a referral hospital. METHODS: Observational, analytical, and cross-sectional study. Patients with diagnosis of IBD treated at Centro Médico Nacional "20 de Noviembre" were evaluated. The Pittsburgh Sleep Quality Index (PSQI) was used to measure sleep quality. IBD activity was measured using the Harvey-Bradshaw index for Crohn's disease (CD) and the Mayo scale for Ulcerative Colitis (UC). RESULTS: A total of 51 patients were included, the Pittsburgh Sleep Index Questionnaire (PSQI) was performed, after informed consent was signed. Patients had a mean age of 52. Fifty five percent were female, 65% had UC. Biological therapy was administered to 70.5%. In CD 89% were in remission and 11% in moderate activity. In UC 48.5% were in remission, 45.5% had mild activity and 6% had moderate activity. Eighty percent of the patients did not use hypnotic drugs. Patients with UC in remission had a bad perception of sleep quality in 68%, quite good sleep quality in 18% and very good sleep quality in 12% with a PSQI of 10.5 ± 3.2. In patients with mild activity, the perception of sleep quality was very good in 6%, quite good in 46%, quite bad in 40% and very bad in 6%, with a PSQI of 8 ± 3.7. In patients with moderate activity, 100% had a rather bad perception of sleep quality with a PSQI of 11 ± 1.4. For CD in remission the perception of sleep was quite bad in 43%, quite good in 43%, very bad in 6% and very good in 6% with a PSQI of 9 ± 4.3. In patients with moderate activity 50% had a very bad sleep quality perception and 50% a fairly good sleep quality perception with a PSQI of 14 ± 4.2. CONCLUSION: In this study a statistically significant association was obtained between PSQI and the perception of sleep reported by the patients, with a p < 0.005. Further research is still needed to better characterize sleep disturbances in this population. Due to the sample size, a prospective, randomized study is required to confirm these findings. The present analysis has no conflict of interest.
RESUMEN
Critical limb ischemia (CLI) represents an advanced stage of the peripheral arterial disease. Angioplasty improves the blood flow to the lower limb; however, some patients irreversibly progress to limb amputation. The extent of vascular damage and the mechanisms of vascular repair are factors affecting post-angioplasty outcome. Mononuclear Progenitor Cells (MPCs) are reactive to vascular damage and repair, with the ability to reflect vascular diseases. The present protocol describes quantification of MPCs obtained from blood circulation from vessel close to the angioplasty site, as well as its relationship with endothelial dysfunction and its predictive ability for limb amputation in the next 30 days after angioplasty in patients with CLI.
Asunto(s)
Amputación Quirúrgica , Angioplastia , Isquemia/sangre , Leucocitos Mononucleares/patología , Extremidad Inferior/irrigación sanguínea , Células Madre/patología , Anciano , Amputación Quirúrgica/efectos adversos , Recolección de Muestras de Sangre , Endotelio/patología , Endotelio/fisiopatología , Femenino , Hemodinámica , Humanos , Isquemia/etiología , Isquemia/fisiopatología , Extremidad Inferior/fisiopatología , Masculino , Pronóstico , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
A basic question linked to differential patterns of gene expression is how cells reach different fates despite using the same DNA template. Since 5-hydroxymethylcytosine (5hmC) emerged as an intermediate metabolite in active DNA demethylation, there have been increasing efforts to elucidate its function as a stable modification of the genome, including a role in establishing such tissue-specific patterns of expression. Recently we described TET1-mediated enrichment of 5hmC on the promoter region of the master regulator of hepatocyte identity, HNF4A, which precedes differentiation of liver adult progenitor cells in vitro. Here, we studied the genome-wide distribution of 5hmC at early in vitro differentiation of human hepatocyte-like cells. We found a global increase in 5hmC as well as a drop in 5-methylcytosine after one week of in vitro differentiation from bipotent progenitors, at a time when the liver transcript program is already established. 5hmC was overall higher at the bodies of overexpressed genes. Furthermore, by modifying the metabolic environment, an adenosine derivative prevents 5hmC enrichment and impairs the acquisition of hepatic identity markers. These results suggest that 5hmC could be a marker of cell identity, as well as a useful biomarker in conditions associated with cell de-differentiation such as liver malignancies.
Asunto(s)
5-Metilcitosina/análogos & derivados , Diferenciación Celular/genética , Metilación de ADN/genética , Factor Nuclear 4 del Hepatocito/genética , Oxigenasas de Función Mixta/genética , Proteínas Proto-Oncogénicas/genética , 5-Metilcitosina/metabolismo , Desmetilación del ADN , Regulación del Desarrollo de la Expresión Génica/genética , Genoma/genética , Hepatocitos/metabolismo , Humanos , Regiones Promotoras Genéticas/genética , Células Madre/metabolismoRESUMEN
Major adverse cardiovascular events (MACEs) negatively impact the cardiovascular prognosis of patients undergoing coronary angioplasty due to coronary ischemic injury. The extent of coronary damage and the mechanisms of vascular repair are factors influencing the future development of MACEs. Intrinsic vascular features like the plaque characteristics and coronary artery complexity have demonstrated prognostic information for MACEs. However, the use of intracoronary circulating biomarkers has been postulated as a convenient method for the early identification and prognosis of MACEs, as they more closely reflect dynamic mechanisms involving coronary damage and repair. Determination of coronary circulating biomarkers during angioplasty, such as the number of subpopulations of mononuclear progenitor cells (MPCs) as well as the concentration of soluble molecules reflecting inflammation, cell adhesion, and repair, allows for assessment of future developments and the prognosis of MACEs 6 months post coronary angioplasty. This method is highlighted by its translational nature and better performance than peripheral blood circulating biomarkers regarding prediction of MACEs and its effect on the cardiovascular prognosis, which may be applied for risk stratification of patients with coronary artery disease undergoing angioplasty.
Asunto(s)
Angioplastia Coronaria con Balón/métodos , Biomarcadores/sangre , Enfermedad de la Arteria Coronaria/cirugía , Células Madre/metabolismo , Femenino , Humanos , Masculino , PronósticoRESUMEN
Background: Fecal calprotectin (FC) can be a valuable tool to optimize health care for patients with inflammatory bowel disease (IBD). The objective of this observational study was to determine the level of knowledge of the FC test in Mexican patients with IBD. Methods: A self-report questionnaire was distributed via Facebook to patients with IBD. The survey consisted of 15 questions in two categories: the first category assessed knowledge of IBD diagnosis, and the second category assessed knowledge of the FC test. Results: In total, 460 patients with IBD participated, of which 83.9% (386) had ulcerative colitis (UC) and 16.0% (74) had Crohn's disease (CD). Regarding IBD diagnosis, 41.9% of participants stated that they did not know of a non-invasive test for fecal matter to identify inflammation of the colon. Regarding the FC test, 57.5% (UC) and 58.1% (CD) stated that they did not know about the test. Additionally, 65.8% (UC) and 51.3% (CD) of participants stated that they had never received the FC test and 82.6% (UC) and 77.0% (CD) recognized that the FC test was difficult to access in their medical practice. Furthermore, 66% (UC) and 52.7% (CD) of participants noted that their specialist doctor had never suggested the FC test to them, yet 89.1% (UC) and 87.8% (CD) stated that they would prefer FC analysis for their IBD follow-up assessments. Conclusions: There is little knowledge of the FC biomarker among Mexican patients with IBD. This suggests the need for greater dissemination of its use and scope as a biomarker in IBD.
RESUMEN
The in vivo antifibrotic effect of a fucoidan extract (FE) from Sargassum fluitans Borgesen was evaluated in a carbon tetrachloride-induced liver damage model in rats over twelve weeks. Chemical analysis showed the FE to contain carbohydrates, sulfates, uronic acids, protein, phenols, and to have a molecular weight of ~60 kDa. Physiological, biochemical, histological and genetic assays were done. Daily oral administration of FE (50 mg/kg) reduced liver enzymatic activity, liver infiltration of inflammatory cells, collagen fiber deposition and gene expression cytokines such as interleukin beta 1 (IL-ß1), tumor necrosis factor alpha (TNF-α), transforming growth factor beta 1 (TGF-ß1), Smad-3, Smad-2, collagen 1 alpha 1 (col1α1) and tissue inhibitor of metalloproteinase 1 (TIMP-1). It also increased RNA expression of Smad-7 and metalloproteinase 2 and 9 (MMP2 and MMP9). The fucoidan extract exhibited an antifibrotic effect mediated by the inhibiting TGF-ß1/Smad pathway, as well as anti-inflammatory effects.
Asunto(s)
Cirrosis Hepática/tratamiento farmacológico , Extractos Vegetales/farmacología , Polisacáridos/química , Sargassum/química , Animales , Tetracloruro de Carbono/toxicidad , Intoxicación por Tetracloruro de Carbono/tratamiento farmacológico , Intoxicación por Tetracloruro de Carbono/genética , Intoxicación por Tetracloruro de Carbono/patología , Modelos Animales de Enfermedad , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Hígado/efectos de los fármacos , Cirrosis Hepática/inducido químicamente , Cirrosis Hepática/patología , Extractos Vegetales/química , Polisacáridos/farmacología , Ratas , Transducción de Señal/efectos de los fármacos , Proteínas Smad/genética , Proteína smad3/genética , Factor de Crecimiento Transformador beta/genética , Factor de Crecimiento Transformador beta1/genéticaRESUMEN
Resumen: La adiponectina es una hormona sensibilizadora a la insulina y antiinflamatoria secretada por el tejido adiposo que tiene un inmenso potencial como objetivo terapéutico de una multitud de enfermedades relacionadas con la obesidad, incluida la diabetes tipo 2, la aterosclerosis y las enfermedades cardiovasculares. El gen de la adiponectina se encuentra en el cromosoma 3q27, un locus de susceptibilidad para la diabetes tipo 2 y los trastornos metabólicos. El aumento de las concentraciones circulantes de adiponectina se asocia con reducción del síndrome metabólico y las reducciones son muy predictivas del riesgo de diabetes. Se han hecho grandes esfuerzos para comprender cómo pueden elevarse las concentraciones de adiponectina. El complejo procesamiento postraduccional y la secreción de adiponectina proporciona un área rica en la que puede desarrollarse la manipulación farmacológica para aumentar las concentraciones de adiponectina en humanos. Las concentraciones circulantes de adiponectina se incrementan con muchos fármacos de administración común, como las estatinas, los inhibidores de la enzima convertidora de angiotensina y las tiazolidinedionas, lo que da una oportunidad importante para conocer los mecanismos que subyacen a sus efectos. Esta revisión describe la relación que existe entre la obesidad, la diabetes tipo 2 y la adiponectina, se discuten las funciones específicas en los tejidos y las células de la adiponectina, con insistencia en la regulación de las vías de señalización de adiponectina, así como las posibles vías de señalización implicadas en la regulación metabólica.
Abstract: Adiponectin is an insulin-sensitizing and anti-inflammatory fat cell hormone that has immense potential as a therapeutic target for a multitude of obesity-associated diseases including type 2 diabetes, atherosclerosis and cardiovascular diseases. The adiponectin gene is located in chromosome 3q27, a susceptibility locus for type 2 diabetes and metabolic disorders. Increased circulating levels of adiponectin are associated with improvement in the metabolic syndrome and reductions are strongly predictive of diabetes risk. Extensive efforts have been made to understand how adiponectin levels can be elevated. The complex posttranslational processing and secretion of adiponectin provides a rich area where pharmacologic manipulation may be developed to increase adiponectin levels in humans. Circulating adiponectin levels are increased by many commonly used drugs, such as statins, angiotensin converting enzyme inhibitors, and thiazolidinediones providing an important opportunity to gain insight into the mechanisms underlying their effects. This review describes the relationship among obesity, type 2 diabetes and adiponectin, we discuss the specific functions in tissues and cells of adiponectin, with emphasis on the regulation of adiponectin signaling pathways, as well as possible pathways of signaling involved in metabolic regulation.
RESUMEN
Currently, there are no confident prognostic markers in patients with coronary artery disease (CAD) undergoing angioplasty. The present study aimed to explore whether basal coronary circulating Mononuclear Progenitor Cells (MPCs) and vascular injury biomarkers were related to development of major adverse cardiovascular events (MACEs) and may impact clinical prognosis. METHODS: The number of MPCs and soluble mediators such as IL-1ß, sICAM-1, MMP-9, malondialdehyde, superoxide dismutase and nitric oxide were determined in coronary and peripheral circulation. Prognostic ability for MACEs occurring at 6 months follow up was assessed by time-to-event and event free survival estimations. RESULTS: Lower coronary circulating MPCs subpopulations CD45+ CD34+ , CD45+ CD34+ CD133+ CD184+ , lower MMP-9 and higher sICAM-1 significantly associated with MACEs presentation and showed prognostic ability; while peripheral blood increase in malondialdehyde and decreased superoxide dismutase were observed in patients with MACEs. CONCLUSION: Coronary concentration of biomarkers related with vascular repair, such as MPCs subpopulations and adhesion molecules, may predict MACEs and impact prognosis in patients with CAD undergoing angioplasty; whereas peripheral pro-oxidative condition may be also associated.
Asunto(s)
Angioplastia , Biomarcadores/sangre , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/diagnóstico , Circulación Coronaria , Leucocitos Mononucleares/patología , Células Madre/patología , Anciano , Femenino , Humanos , Masculino , Pronóstico , SolubilidadRESUMEN
The present study aimed to compare echocardiography measurements of epicardial adipose tissue (EAT) thickness and other risk factors regarding their ability to predict adverse cardiovascular outcomes in patients with coronary artery disease (CAD). Outcomes of 107 patients (86 males, 21 females, mean age 63.6 years old) submitted to diagnostic echocardiography and coronary angiography were prospectively analyzed. EAT (measures over the right ventricle, interventricular groove and complete bulk of EAT) and left ventricle ejection fraction (LVEF) were performed by echocardiography. Coronary complexity was evaluated by Syntax score. Primary endpoints were major adverse cardiovascular events (MACE's), composite of cardiovascular death, myocardial infarction, unstable angina, intra-stent re-stenosis and episodes of decompensate heart failure requiring hospital attention during a mean follow up of 15.94 ± 3.6 months. Mean EAT thickness was 4.6 ± 1.9 mm; and correlated with Syntax score and body mass index; negatively correlated with LVEF. Twenty-three cases of MACE's were recorded during follow up, who showed higher EAT. Diagnostic ability of EAT to discriminate MACE's was comparable to LVEF (AUROC > 0.5); but higher than Syntax score. Quartile comparison of EAT revealed that measurement of the complete bulk of EAT provided a better discrimination range for MACE's, and higher, more significant adjusted risk (cutoff 4.6 mm, RR = 3.91; 95% CI 1.01-15.08; p = 0.04) than the other risk factors. We concluded that echocardiographic measurement of EAT showed higher predicting ability for MACE's than the other markers tested, in patients with CAD. Whether location for echocardiographic measurement of EAT impacts the diagnostic performance of this method deserves further study.
Asunto(s)
Tejido Adiposo/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Pericardio/diagnóstico por imagen , Anciano , Enfermedades Cardiovasculares/diagnóstico por imagen , Enfermedades Cardiovasculares/etiología , Angiografía Coronaria , Ecocardiografía , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Factores de RiesgoRESUMEN
One of the leading causes of death worldwide, cirrhosis, is a liver condition characterized by chronic necrosis, inflammation, and fibrosis. Hepatoprotective compounds, such as antioxidants, can prevent fibrosis. Macroalgae (seaweed) contain high amounts of antioxidant compounds and are plentiful; indeed, species such as Sargassum fluitans Borgesen (Phaeophyceae) carpet many beaches in the Caribbean Basin. An in vivo assay was done evaluating the possible hepatoprotective effect of a Sargassum fluitans ethanol extract. Two murine liver damage models were employed: acetaminophen (APAP) in Balb/c mice to induce acute damage; carbon tetrachloride (CCl4) in Wistar rats to induce chronic damage. Serum liver enzyme levels and relative liver weight were measured, and histopathological and immunohistochemical analyses of liver tissue sections were done. Both APAP and CCl4 significantly raised serum enzyme marker enzymes. Administration of 50 mg/kg S. Fluitans ethanol extract reduced this APAP- and CCl4-induced elevation to normal levels. This effect was corroborated by the extract's inhibition of inflammation and fibrosis in liver tissue observed in the histopathological analysis. The analyzed S. fluitans ethanol extract exhibited an in vivo hepatoprotective effect in acute and chronic liver injury models.
Asunto(s)
Enfermedad Aguda/terapia , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Enfermedad Crónica/terapia , Hígado/efectos de los fármacos , Extractos Vegetales/farmacología , Sustancias Protectoras/farmacología , Sargassum/química , Acetaminofén/farmacología , Adulto , Animales , Antioxidantes/farmacología , Tetracloruro de Carbono/farmacología , Etanol/química , Humanos , Inflamación/tratamiento farmacológico , Cirrosis Hepática/tratamiento farmacológico , Pruebas de Función Hepática/métodos , Ratones , Ratones Endogámicos BALB C , Ratas Wistar , Adulto JovenRESUMEN
Cirrhosis is a liver pathology originated by hepatocytes, Kupffer and hepatic stellate cells interactions and transformations. This pathology is associated with inflammation and fibrosis, originated by molecular signals secreted by immunological and parenchymal cells, such as cytokines and chemokines, like IL-1ß, IL-6, TNF-α or MCP-1, driven by Kupffer cells signals. As part of inflammation resolution, the same activated Kupffer cells contribute to anti-inflammatory effects with IL-10 and MMP-9 secretion. In a Wistar rat model, cirrhosis induced with CCl4 is characterized by increased inflammatory cytokines, IL-6, IL-1ß, MCP-1, and TNF-α, in plasma and liver tissue. The IFC-305 compound, an adenosine derivative salt, reverses the cirrhosis in this model, suggesting that immune mechanisms related to inflammation should be explored. The IFC-305 reduced inflammatory cytokines, supporting the anti-inflammatory effects induced by the elevation of IL-10, as well as the reduction of M1 inflammatory macrophages (CD11b/c+/CD163+) and the increase of M2 anti-inflammatory macrophages (HIS36+/CD11b+), measured by flow cytometry. Furthermore, the IFC-305 enhances the metabolic activity of arginase and moderates the inducible nitric oxide synthetase, evaluated through biochemical and immunohistochemical methods. These results contribute to understand the function of the IFC-305, which modulates the immune response in the Wistar rat model of CCl4-induced cirrhosis and support the hepatic protective action through an anti-inflammatory effect, mainly mediated by Kupffer cells.
Asunto(s)
Adenosina/análogos & derivados , Antiinflamatorios/uso terapéutico , Fibrosis/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Macrófagos/efectos de los fármacos , Adenosina/uso terapéutico , Animales , Arginasa/metabolismo , Antígeno CD11b/metabolismo , Antígeno CD11c/metabolismo , Tetracloruro de Carbono , Diferenciación Celular , Citocinas/metabolismo , Modelos Animales de Enfermedad , Fibrosis/inducido químicamente , Fibrosis/inmunología , Humanos , Inflamación/inducido químicamente , Inflamación/inmunología , Mediadores de Inflamación/metabolismo , Macrófagos/inmunología , Masculino , Óxido Nítrico Sintasa de Tipo II , Ratas , Ratas Wistar , Balance Th1 - Th2RESUMEN
The pathological characteristic of cirrhosis is scarring which results in a structurally distorted and dysfunctional liver. Previously, we demonstrated that Col1a1 and Pparg genes are deregulated in CCl4 -induced cirrhosis but their normal expression levels are recovered upon treatment with IFC-305, an adenosine derivative. We observed that adenosine was able to modulate S-adenosylmethionine-dependent trans-methylation reactions, and recently, we found that IFC-305 modulates HDAC3 expression. Here, we investigated whether epigenetic mechanisms, involving DNA methylation processes and histone acetylation, could explain the re-establishment of gene expression mediated by IFC-305 in cirrhosis. Therefore, Wistar rats were CCl4 treated and a sub-group received IFC-305 to reverse fibrosis. Global changes in DNA methylation, 5-hydroxymethylation, and histone H4 acetylation were observed after treatment with IFC-305. In particular, during cirrhosis, the Pparg gene promoter is depleted of histone H4 acetylation, whereas IFC-305 administration restores normal histone acetylation levels which correlates with an increase of Pparg transcript and protein levels. In contrast, the promoter of Col1a1 gene is hypomethylated during cirrhosis but gains DNA methylation upon treatment with IFC-305 which correlates with a reduction of Col1a1 transcript and protein levels. Our results suggest a model in which cirrhosis results in a general loss of permissive chromatin histone marks which triggers the repression of the Pparg gene and the upregulation of the Col1a1 gene. Treatment with IFC-305 restores epigenetic modifications globally and specifically at the promoters of Pparg and Col1a1 genes. These results reveal one of the mechanisms of action of IFC-305 and suggest a possible therapeutic function in cirrhosis. J. Cell. Biochem. 119: 401-413, 2018. © 2017 Wiley Periodicals, Inc.
Asunto(s)
Adenosina/análogos & derivados , Intoxicación por Tetracloruro de Carbono/tratamiento farmacológico , Epigénesis Genética/efectos de los fármacos , Cirrosis Hepática Experimental/tratamiento farmacológico , Adenosina/farmacología , Animales , Intoxicación por Tetracloruro de Carbono/genética , Intoxicación por Tetracloruro de Carbono/metabolismo , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Cadena alfa 1 del Colágeno Tipo I , Cirrosis Hepática Experimental/genética , Cirrosis Hepática Experimental/metabolismo , PPAR gamma/genética , PPAR gamma/metabolismo , Ratas , Ratas WistarRESUMEN
Objective To evaluate the relationship between pro-atherogenic biomarkers and epicardial adipose tissue (EAT) thickness in patients with cardiovascular risk factors. Methods Plasma nitric oxide (NO), soluble intercellular adhesion molecule-1 and malondialdehyde (MDA) levels, EAT thickness, flow-mediated dilation (FMD) and carotid intima media thickness (CIMT) were determined in patients aged >18 years who were referred for echocardiography for heart ischemia or non-ischemic diseases. Cardiovascular risk factors (Framingham score [FS] ≥ 20) were weighted. Results Hypertension, dyslipidaemia and type 2 diabetes mellitus were prevalent (≥55% of 40 patients). Patients with FS ≥ 20 ( n = 21) showed significantly higher EAT and CIMT values. Globally, MDA, CIMT, age, waist circumference, high-density lipoprotein cholesterol (HDL-C) and FS were associated with EAT thickness. EAT was significantly associated with NO in patients with FS ≥ 20. Significant differences in EAT thickness were found between patients stratified by NO value, FMD, age, smoking status, dyslipidaemia, type 2 diabetes mellitus and FS. An EAT-associated atherogenic risk (CIMT ≥ 1 mm) model was statistically significant when MDA and type 2 diabetes mellitus were included. Conclusion EAT thickness was associated with MDA, CIMT, age, waist circumference, HDL-C and FS globally, but with NO only in patients with FS≥20. EAT may be used to identify vascular damage stage, possibly influenced by MDA and type 2 diabetes mellitus.