Advanced Oxidative Protein Products Had a Diagnostic Accuracy for Identifying Chronic Kidney Disease in Adult Population.

Chronic Kidney Disease (CKD) is a serious public health problem. Hyperglycemia stimulates the production of reactive oxygen species that cause oxidative damage to proteins. AOPPs constitute a group of oxidized dityrosine-containing proteins that are generated during periods of oxidative stress. They have proved to be a valuable early marker of oxidative tissue damage and active mediators of inflammation associated with the uremic state. To analyze if advanced oxidative protein products (AOPPs) have diagnostic accuracy for identifying chronic kidney disease (CKD) in the adult population. We conducted a diagnostic test validation study in 302 adults ≥20 years old, of both sexes, with and without T2D. After obtaining informed consent, a comprehensive clinical history, anthropometric measurements (weight, BMI) and blood pressure were recorded. Glucose, cholesterol, triglyceride, HDL-c, LDL-c and AOPPs were determinates. Glomerular filtration rate (GFR) was calculated using Cockcroft-Gault (C-G) corrected by body surface area (BSA, mL/min/1.73 m2), CKD-EPI and MDRD equations to identify five stages of CKD. This study follows the Standards for Reporting Diagnostic Accuracy Studies (STARD). The median value of AOPPs was 198.32 µmol/L (minimum-maximum value: 113.48-522.42 µmol/L). The group with patients diagnosed with T2D exhibited higher concentrations (median: 487.39 µmol/L) compared to the non-diabetic group (median: 158.50 µmol/L, p = 0.0001). The selected cut-off point was ≥200 µmol/L using the closest to the median value of AOPPs with sensitivity and specificity as follows: C-G: sensitivity 96.58%; specificity 80%; likelihood ratio: 4.83; CKD-EPI: sensitivity 95.76%; specificity 79.89%; likelihood ratio: 4.76; MDRD: sensitivity 86.55%; specificity: 73.22%; likelihood ratio: 3.23. A difference was observed between AOPPs and chronic kidney disease stage. This study provides evidence that AOPPs ≥ 200 µmol/L have diagnostic accuracy in identifying stage 4-5 CKD by C-G, MDRD and CKD-EPI equations in adults with and without T2D.

Prevalence and characterization of undiagnosed arterial hypertension in the eastern zone of Mexico.

Arterial hypertension is considered a public health problem with severe consequences at an individual and public health levels. However, there is a lack of information regarding its characterization in Mexico. The objective of this study is to estimate the proportion of undiagnosed arterial hypertension (UAH) and the overall prevalence and clinical management of arterial hypertension within the Eastern Zone of Mexico. Additionally, we explore associated factors related with both UAH and uncontrolled arterial hypertension. We obtained information from the May Measure Month (MMM) 2019 study. People were asked for cardiovascular risk factors and blood pressure was measured according to the protocols of the European Society of Hypertension (ESH). Data from 5901 subjects were extracted: 76.04% from the Eastern Zone of the State of Mexico. The overall prevalence of hypertension was 32.4% (95% CI 31.2-33.6). From all subjects living with hypertension, 28.3% had UAH, 22.1% had previous diagnosis but were untreated; 29.3% were treated but had uncontrolled hypertension. Younger men adults living in the State of Michoacán had increased proportion of UAH and untreated hypertension. We observed that male sex, age, obesity, living at Michoacán were risk factors for UAH. Finally, male sex, diabetes, and living at Michoacán were related risk conditions for having uncontrolled arterial hypertension. In summary, there is a high proportion of UAH in Easter Zone of Mexico. Younger adults had higher proportion of UAH and untreated hypertension profiles. Efficient actions are required to make a timely diagnosis in the young adult population to prevent long-term complications.

Behavior of Eosinophil Counts in Recovered and Deceased COVID-19 Patients over the Course of the Disease.

Knowledge about the immune responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, particularly regarding the function of eosinophils, has been steadily emerging recently. There exists controversy regarding the implications of eosinophils in the coronavirus disease 2019 (COVID-19)'s pathology. We report a retrospective cohort study including the comparison of leukocyte counts in COVID-19 patients, considering the outcomes of recovery (n = 59) and death (n = 60). Among the different types of leukocytes, the eosinophil counts were those that showed the greatest difference between recovered and deceased patients. Eosinopenia (eosinophil count < 0.01 × 109/L) was more frequently observed in deceased than recovered patients (p = 0.0012). The eosinophil counts more rapidly increased and showed a greater proportion over the course of the disease in the recovered than deceased patients. Furthermore, the estimated survival rate was greater in patients without eosinopenia than in patients with eosinopenia (p = 0.0070) during hospitalization. Importantly, recovered but not deceased patients showed high negative correlations of the eosinophils with the neutrophil-to-lymphocyte ratio (NLR) and neutrophil counts at Day 9 of the onset of clinical symptoms (p ≤ 0.0220). Our analysis suggests that eosinopenia may be associated with unfavorable disease outcomes and that the eosinophils have a beneficial function in COVID-19 patients, probably contributing by controlling the exacerbated inflammation induced by neutrophils.

Glycogen Synthase Kinase 3ß Modulates the Inflammatory Response Activated by Bacteria, Viruses, and Parasites.

Knowledge of glycogen synthase kinase 3ß (GSK3ß) activity and the molecules identified that regulate its function in infections caused by pathogenic microorganisms is crucial to understanding how the intensity of the inflammatory response can be controlled in the course of infections. In recent years many reports have described small molecular weight synthetic and natural compounds, proteins, and interference RNA with the potential to regulate the GSK3ß activity and reduce the deleterious effects of the inflammatory response. Our goal in this review is to summarize the most recent advances on the role of GSK3ß in the inflammatory response caused by bacteria, bacterial virulence factors (i.e. LPS and others), viruses, and parasites and how the regulation of its activity, mainly its inhibition by different type of molecules, modulates the inflammation.

[Creatinin as predictor value of mortality in patients with acute coronary syndrome]. / Creatinina sérica como pronóstico de mortalidad en pacientes con síndrome coronario agudo.

BACKGROUND: Cardiovascular diseases have become the leading cause of death worldwide. OBJECTIVE: To estimate serum creatinine (Cr) as a prognostic value of mortality in patients with Acute Coronary Syndrome (ACS), which was admitted to the shock room in the emergency department (ED). MATERIAL AND METHODS: A transversal, prospective study, which included 95 patients with ACS who were admitted to the shock room. The following variables were studied: laboratory tests with Cr, cardiovascular risk factors (CVRF), days of hospital stay, service to which it was derived and discharge condition (alive or dead). Statistical analysis was through SPSS v. 23. RESULTS: The diagnosis of admission was ACS without ST elevation (NSTE-ACS), 72.6%; and Acute Myocardial Infarction with ST elevation (STEMI), 27.4%. The 63.2% were discharged alive, 13.7% transferred to a third level hospital and 23.2% died. There was a difference in the level of Cr between living and deceased (p = 0.0001). CONCLUSIONS: CR on admission of the patient with SCA provides prognostic information for mortality, and can be established as a prognostic marker of easy access and available in the ED.

INTRODUCCIÓN: las enfermedades cardiovasculares se han convertido en la principal causa de muerte a nivel mundial. OBJETIVO: estimar la creatinina (Cr), sérica como valor pronóstico de mortalidad en pacientes con síndrome coronario agudo (SCA) que ingresaron a sala de choque en el servicio de urgencias (SU). MATERIAL Y MÉTODOS: estudio prospectivo, transversal, que incluyó a 95 pacientes con SCA ingresados en sala de choque. Se estudiaron las siguientes variables: estudios de laboratorio con Cr, factores de riesgo cardiovascular (FRCV), días de estancia hospitalaria, servicio al que se derivó y condición de egreso (vivo/ muerto). El análisis estadístico fue mediante SPSS v. 23. RESULTADOS: el diagnóstico de ingreso fue de SCA sin elevación del ST (SCASEST), 72.6%; e infarto agudo al miocardio con elevación del segmento ST (IAMCEST), 27.4%. Egresaron vivos el 63.2%, fueron trasladados a hospital de tercer nivel el 13.7% y falleció el 23.2%. Se encontró una diferencia en el nivel de Cr entre vivos y fallecidos (p = 0.0001). CONCLUSIONES: la Cr al ingreso del paciente con SCA proporciona información pronostica para mortalidad, y se puede establecer como un marcador pronóstico de acceso fácil y disponible en el SU.

Data mining of digitized health records in a resource-constrained setting reveals that timely immunophenotyping is associated with improved breast cancer outcomes.

BACKGROUND: Organizations that issue guidance on breast cancer recommend the use of immunohistochemistry (IHC) for providing appropriate and precise care. However, little focus has been directed to the identification of maximum allowable turnaround times for IHC, which is necessary given the diversity of hospital settings in the world. Much less effort has been committed to the development of digital tools that allow hospital administrators to monitor service utilization histories of their patients. METHODS: In this retrospective cohort study, we reviewed electronic and paper medical records of all suspected breast cancer patients treated at one secondary-care hospital of the Mexican Institute of Social Security (IMSS), located in western Mexico. We then followed three years of medical history of those patients with IHC testing. RESULTS: In 2014, there were 402 breast cancer patients, of which 30 (7.4% of total) were tested for some IHC biomarker (ER, PR, HER2). The subtyping allowed doctors to adjust (56.7%) or confirm (43.3%) the initial therapeutic regimen. The average turnaround time was 56 days. Opportune IHC testing was found to be beneficial when it was available before or during the first rounds of chemotherapy. CONCLUSIONS: The use of data mining tools applied to health record data revealed that there is an association between timely immunohistochemistry and improved outcomes in breast cancer patients. Based on this finding, inclusion of turnaround time in clinical guidelines is recommended. As much of the health data in the country becomes digitized, our visualization tools allow a digital dashboard of the hospital service utilization histories.

Copeptin Plasma Levels are Associated with Decline of Renal Function in Patients with Type 2 Diabetes Mellitus.

BACKGROUND: Chronic kidney disease (CKD) is a leading complication of type 2 diabetes mellitus (T2DM) and is considered as a public health problem. Copeptin is a surrogate marker of arginine vasopressin (AVP) system and is proposed as a biomarker of decline renal function. OBJECTIVE: Evaluate whether plasma copeptin levels may be used as a biomarker of decline renal function in patients with T2DM. RESEARCH DESIGN AND METHODS: A total of 480 patients with T2DM and different stages of CKD were included. Plasma levels of copeptin, cystatin-C, and other biochemical parameters were measured. The correlation between copeptin and glomerular filtration rate (GFR), estimated based on plasma cystatin-C levels, was investigated. RESULTS: Plasma copeptin levels were gradually increased from the stage 1-5 of CKD in the patients with T2DM. In univariate linear regression analysis, high plasma levels of copeptin were associated with lower GFR (Standardized ß = -0.535, R2 = 0.287, p <0.0001). This association remained significant even after being adjusted for glucose levels and years of T2DM diagnosis, mean blood pressure, pharmacological treatment, gender, and age. CONCLUSIONS: The results show that high plasma copeptin levels are associated with the decline of renal function in patients with T2DM and, therefore, copeptin may be considered as a biomarker of renal function. Further evaluation of plasma copeptin levels to predict morbidity and mortality of T2DM patients, with or without CKD, has been taken into our consideration.

Productos avanzados de oxidación proteica (PAOP) y su relación con los factores de riesgo cardiovascular en jóvenes aparentemente sanos / Advanced oxidation protein products and their relationship with cardiovascular risk factors in young apparently healthy people

Introducción: Los productos avanzados de oxidación proteica (PAOP) son un marcador para estimar estrés oxidativo en proteínas plasmáticas. El estrés oxidativo se considera un factor de riesgo cardiovascular (FRCV), relacionado con el aumento de presión arterial y la dislipidemia. Este trabajo tuvo por objetivo evaluar la asociación entre las concentraciones plasmáticas de PAOP y los FRCV en adultos jóvenes aparentemente sanos. Métodos: Estudio transversal comparativo prospectivo en 120 estudiantes de la Facultad de Químico Farmacobiología de la UMSNH, a los que se les determinó IMC, presión arterial, así como PAOP, glucosa, colesterol total, lipoproteínas (de alta, baja y muy baja densidad) y triglicéridos. Resultados: Los grupos de jóvenes con y sin FRCV presentaron diferencias significativas respecto a IMC, cintura, grasa corporal (p<0,05) y perfil lipídico (p<0,0001). Se presentaron cifras más altas de PAOP en el grupo de jóvenes con 3 y 4 FRCV (F: 4,651; p=0,002). Los PAOP correlacionaron negativamente con el colesterol LDL (r=-0,364; p=0,0001). Conclusiones: Se identificó que las concentraciones de PAOP se ven incrementadas conforme aumentan los FRCV en los jóvenes, por lo que estos podrían considerarse un factor importante de riesgo debido a que su depósito en la placa de ateroma favorece el proceso aterogénico y así el desarrollo de enfermedades cardiovasculares. La cuantificación de PAOP contribuye a la determinación indirecta del estado oxidativo en el organismo. El estudio del estado metabólico y oxidativo de jóvenes de aspecto saludable es de importancia en la prevención de enfermedades cardiovasculares en etapas posteriores de la vida, sin embargo, se requieren estudios longitudinales para estudiar su evolución (AU)

Introduction: Advanced oxidation protein products (AOPPs) are used as a marker to estimate oxidative stress in plasma proteins. Oxidative stress is considered a factor of cardiovascular risk (CVRF) related to increased blood pressure, and dyslipidaemia. The aim of this study was to evaluate the association between plasma AOPPs and CVRF in apparently healthy young adults. Methods: A prospective cross-sectional study was conducted on 120 students of the Faculty of Chemical-Pharmacobiology of the UMSNH. Body mass index (BMI) and blood pressure were determined. A blood specimen was also collected to quantify AOPPs, glucose, total cholesterol, lipoproteins (high, low, and very low density), and triglycerides. Results: Differences were observed in the groups with and without CVRF, with significant differences in BMI, waist, body fat (P<.05), and lipid profile (P<.0001). AOPPs were higher in the group of young people with three and four CVRF (F: 4.651; P=.002). A negatively correlation was found between AOPPs and LDL cholesterol (r=-0.364; P=.0001). Conclusions: It was observed that AOPPs concentrations are increased as CVRF increase in young adults. Thus, this could be considered an important risk factor, because their deposition in the atherosclerotic plaque favours the atherogenic process, and thus the development of cardiovascular disease. Quantification of AOPPs contributes to the indirect determination of oxidative status in the body. The study of metabolic and oxidative state of apparently healthy young adults is important in the prevention of cardiovascular disease in later life. More longitudinal studies are required to study its evolution (AU)

Advanced oxidation protein products and their relationship with cardiovascular risk factors in young apparently healthy people. / Productos avanzados de oxidación proteica (PAOP) y su relación con los factores de riesgo cardiovascular en jóvenes aparentemente sanos.

INTRODUCTION: Advanced oxidation protein products (AOPPs) are used as a marker to estimate oxidative stress in plasma proteins. Oxidative stress is considered a factor of cardiovascular risk (CVRF) related to increased blood pressure, and dyslipidaemia. The aim of this study was to evaluate the association between plasma AOPPs and CVRF in apparently healthy young adults. METHODS: A prospective cross-sectional study was conducted on 120 students of the Faculty of Chemical-Pharmacobiology of the UMSNH. Body mass index (BMI) and blood pressure were determined. A blood specimen was also collected to quantify AOPPs, glucose, total cholesterol, lipoproteins (high, low, and very low density), and triglycerides. RESULTS: Differences were observed in the groups with and without CVRF, with significant differences in BMI, waist, body fat (P<.05), and lipid profile (P<.0001). AOPPs were higher in the group of young people with three and four CVRF (F: 4.651; P=.002). A negatively correlation was found between AOPPs and LDL cholesterol (r=-0.364; P=.0001). CONCLUSIONS: It was observed that AOPPs concentrations are increased as CVRF increase in young adults. Thus, this could be considered an important risk factor, because their deposition in the atherosclerotic plaque favours the atherogenic process, and thus the development of cardiovascular disease. Quantification of AOPPs contributes to the indirect determination of oxidative status in the body. The study of metabolic and oxidative state of apparently healthy young adults is important in the prevention of cardiovascular disease in later life. More longitudinal studies are required to study its evolution.

BNP predicts mortality of cardiovascular disease in patients with end-stage renal disease treated / BNP predictor de mortalidad cardiovascular en pacientes con enfermedad renal crónica terminal

BACKGROUND: Mortality for cardiovascular disease (CVD) in patients with chronic kidney disease (CKD) is higher. In the end-stage renal disease (ESRD) the mortality is 20 times greater in comparison with general population. Natriuretic peptides, particularly type-B natriuretic peptide (BNP) have been studied as potential markers of risk of cardiovascular (CV) mortality. The aim of this paper is to determine whether BNP acts as a prognostic marker for CV mortality in patients with ESRD. METHODS: We studied 53 patients with ESRD prevalent in peritoneal dialysis without clinical evidence of heart failure at baseline was studied. The impact of variables was performed with linear regression model. The probability of survival was estimated by Kaplan-Meir analysis and the difference between survivals between groups with log-rank test according the levels of BNP. Adjusted hazard ratios were calculated with Cox proportional hazards analysis. RESULTS: BNP strongly predicts CVD mortality. The Cox regression model showed that BNP is a predictor of death from CVD. Patients with high levels of BNP were at increased risk of death. Several pathophysiological mechanisms not well defined are involved. CONCLUSIONS: BNP predicts CVD mortality in patients with ESRD. Serum measurement of this peptide can be useful for risk stratification in these patients and adjust treatment.

INTRODUCCIÓN: la mortalidad por enfermedad cardiovascular (ECV) en pacientes con enfermedad renal crónica (ERC) es alta. En la población con ERC terminal (ERCT) la mortalidad es hasta 20 veces mayor en comparación a la población general. Los péptidos natriuréticos, especialmente el péptido natriurético tipo-B (BNP), han sido estudiados como posibles marcadores de riesgo de mortalidad por ECV. El objetivo de este trabajo es determinar si el BNP actúa como un marcador pronóstico para mortalidad por ECV en pacientes con ERCT. MÉTODOS: se estudiaron 53 pacientes con ERCT prevalentes en diálisis peritoneal sin evidencia clínica de insuficiencia cardiaca al inicio del estudio. El impacto de las variables se realizó con el modelo de regresión lineal. La probabilidad de sobrevida fue estimada con el análisis de Kaplan-Meier y la diferencia entre grupos con el test de Log-Rank, acorde a los niveles de BNP dividido en tertiles. La asociación de riesgo fue calculada con el análisis proporcional de Cox ajustado. RESULTADOS: el BNP fuertemente predice la mortalidad por ECV. El modelo de regresión de Cox mostró que el BNP es un predictor de muerte por ECV. Pacientes con niveles altos de BNP tuvieron mayor riesgo de muerte. Varios mecanismos fisiopatológicos no bien definidos están involucrados. CONCLUSIONES: el BNP predice la mortalidad por ECV en pacientes con ERCT. La medición sérica de este péptido puede ser útil para la estratificación de riesgo en estos pacientes y ajustar el plan terapéutico

Blood pressure rhythmicity in patients with end stage chronic kidney disease: bromocriptine effect / Ritmicidad de la presión arterial en pacientes con enfermedad renal crónica terminal: efecto de bromocriptina

BACKGROUND: The aim of this paper was to characterize the blood pressure CR in patients with end stage chronic kidney disease (ESCKD) before and after treatment with bromocriptine compared to healthy volunteers. METHODS: Fifteen patients and nine healthy volunteers were included. Both groups underwent ambulatory 24 hours blood pressure (24 h ABPM). Patients received 2.5 mg every 8 hours of bromocriptine for eight weeks, at the end of the treatment 24 h ABPM was repeated; blood pressure CR was compared before and after treatment and with healthy volunteers. The CR was identified by the method of Cosinor. RESULTS: 64% of volunteers showed a 24 h CR, against 27% of patients (p < 0.05). After the treatment with bromocriptine 40% of patients showed RC 24 h. The mean arterial pressure decreased from 129 ± 1 mmHg to 106 ± 1 mmHg. A 12 h rhythm was identified in 45% of volunteers and 73% of patients before treatment (p < 0.05) against 60% at the end (p < 0.001), with no statistical difference with volunteers. CONCLUSIONS: The CR in blood pressure is altered in ESCKD and could be restored with bromocriptine. 12 hours rhythmicity was identified predominantly in patients with ESCKD; this rhythm was also present in the healthy volunteers.

INTRODUCCIÓN: el propósito de este estudio es caracterizar el ritmo circadiano (RC) de la presión arterial en pacientes con enfermedad renal crónica terminal (ERCT) en tratamiento con diálisis peritoneal continua ambulatoria (DPCA) antes y después del tratamiento con bromocriptina (BEC) comparándolos con voluntarios sanos. MÉTODOS: se incluyeron 15 pacientes del servicio de Nefrología y 9 voluntarios sanos. Se les realizó monitoreo ambulatorio de presión arterial de 24 horas (MAPA). Los pacientes recibieron 2.5 mg de BEC cada 8 hora durante ocho semanas, al final del tratamiento se repitió el MAPA; el RC de la presión arterial se comparó antes y después del tratamiento y con los voluntarios. Resultados: el 64% de los voluntarios exhibieron RC de 24 horas, frente al 27% de los pacientes (p < 0.05). Después del tratamiento con BEC, el 40% de pacientes mostraron RC de 24 h. El mesor de la presión arterial media disminuyó de 129 ± 1 mmHg a 106 ± 1 mmHg (p < 0.05). Se identificó un ritmo de 12 h en 45% de los voluntarios y en el 73% de los pacientes antes del tratamiento (p < 0.05) frente a 60% al final (p < 0.001), sin diferencia estadística con los voluntarios. CONCLUSIONES: el RC de la presión arterial esta alterado en la IRCT y se restableció con BEC. La ritmicidad de 12 h predominó en los pacientes con ERCT, también presente en los voluntarios sanos.

Thyroid disorders among dialysis patients / Alteraciones tiroideas en pacientes en diálisis

The thyroid gland and the kidney are closely related. Thyroid hormones (TH) contribute to the homeostasis of the human being through complex interactions of fluids and electrolytes, protein synthesis, etc. The effects on the kidney of TH may be pre renal or direct actions. Decreasing glomerular filtration (GF) this balance especially in advanced stages of chronic kidney disease (CKD) is altered. CKD is linked to alterations in TH levels and/or metabolism, resulting in a high prevalence of subclinical hypothyroidism and low free triiodothyronine (FT3) syndrome. These alterations are linked in micro inflammation, endothelial damage, cardiac abnormalities, and high mortality. In this study, we describe the most common thyroid abnormalities reported in CKD with dialytic stage approach.

La glándula tiroides y el riñón están estrechamente relacionados. Las hormonas tiroideas (HT) contribuyen en la homeostasis del ser humano a través de complejas interacciones de líquidos y electrolitos, síntesis de proteínas, etc. Los efectos de las HT sobre el riñón pueden ser pre-renales o directos. Está demostrado que al disminuir la filtración glomerular (FG) se altera este equilibrio, sobre todo en estadios avanzados de la enfermedad renal crónica (ERC). La ERC está vinculada con alteraciones en los niveles de HT y/o su metabolismo, lo que resulta en una alta prevalencia de hipotiroidismo subclínico y el síndrome de T3 libre baja. Estas alteraciones están relacionadas con micro inflamation, daño endotelial, alteraciones cardiacas y alta mortalidad. El presente estudio, describe las alteraciones tiroideas más frecuentes reportadas en ERC con enfoque en la etapa dialítica.

[Consensus on Systemic Arterial Hypertension In México]. / Consenso de Hipertensión Arterial Sistémica en México.

This Consenso Nacional de Hipertensión Arterial Sistémica (National Consensus on Systemic Arterial Hypertension) brings together experiences and joint work of 79 specialists who have been in contact with the patient affected by systemic arterial hypertension. All concepts here presented were outlined on the basis of the real world practice of Mexican hypertensive population. The consensus was developed under strict methodological guidelines. The Delphi technique was applied in two rounds for the development of an appropriate statistical analysis of the concepts exposed by all the specialists, who posed key questions, later developed by the panel of experts of the Hospital de Cardiología, and specialists from the Centro Médico Nacional. Several angles of this illness are shown: detection, diagnosis, pathophysiology, classification, treatment and prevention. The evidence analysis was carried out using PRISMA method. More than 600 articles were reviewed, leaving only the most representative in the references. This document concludes with practical and useful recommendations for the three levels of health care of our country.

Este Consenso Nacional de Hipertensión Arterial Sistémica reúne las experiencias y el trabajo conjunto de 79 especialistas que han estado en contacto con el paciente que padece hipertensión arterial sistémica. Todos los conceptos aquí presentados se plantearon con base en la práctica del mundo real de la población hipertensa de México. El consenso se desarrolló bajo lineamientos metodológicos estrictos. La técnica de Delphi se aplicó en dos vueltas para el desarrollo de un análisis estadístico apropiado de los conceptos vertidos por todos los especialistas con preguntas clave que desarrolló el panel de expertos del Hospital de Cardiología y especialistas del Centro Médico Nacional. Se presentan los aspectos de detección, diagnóstico, fisiopatología, clasificación, tratamiento y prevención. El análisis de la evidencia en la literatura se hizo utilizando el método de PRISMA para análisis de evidencia. Se revisaron más de 600 artículos y se dejaron en la bibliografía solo los más representativos. Este documento concluye con recomendaciones prácticas y de utilidad para los tres niveles de atención en salud de nuestro país.

Myeloperoxidase is associated with insulin resistance and inflammation in overweight subjects with first-degree relatives with type 2 diabetes mellitus.

BACKGROUND: Family history of type 2 diabetes mellitus (T2DM) is one of risk factors for that in future a subject can develop diabetes. Insulin resistance (IR) is important in the pathogenesis of T2DM. There is evidence that oxidative stress plays an important role in the etiology and/or progression of diabetes. Myeloperoxidase (MPO) participates in developing of inflammation. The objective was to investigate if MPO is associated with IR and inflammation in individuals with first-degree relatives of T2DM. METHODS: Cross-sectional study in 84 overweight individuals with family history of T2DM divided in two groups according to IR, group with IR (homeostasis model assessment [HOMA] ≥2.5; n=43) and control group (CG; HOMA <2.5; n=41). Complete clinical history and a venous blood sample were collected for measuring glucose and lipids profile, insulin, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), MPO, glutathione reductase (GRd), glutathione peroxidase, and superoxide dismutase. RESULTS: MPO, TNF-α, and IL-6 were higher in patients with IR than in CG (MPO: 308.35 [190.85 to 445.42] vs. 177.35 [104.50 to 279.85], P=0.0001; TNF-α: 13.46 [10.58 to 18.88] vs. 9.39 [7.53 to 11.25], P=0.0001; IL-6: 32.93 [24.93 to 38.27] vs. 15.60 [12.93 to 26.27]; P=0.0001, respectively). MPO was associated with IR (rho de Spearman=0.362, P=0.001). In the analysis of lineal regression, MPO predicts IR (ß, 0.263; t, 2.520; P=0.014). In the univariate analysis, MPO had an odds ratio of 9.880 for risk of IR (95% confidence interval, 2.647 to 36.879). CONCLUSION: MPO had relation with IR and inflammation parameters in overweight subjects with first-degree relatives of T2DM. We need studies on a casual relationship and molecular mechanisms among the increased serum MPO levels, inflammation markers, and IR.

Modulation of the inflammatory response of bovine mammary epithelial cells by cholecalciferol (vitamin D) during Staphylococcus aureus internalization.

Vitamin D is an immunomodulator that exerts anti-inflammatory effects. In this work, the effects of cholecalciferol, a vitamin D precursor, on the inflammatory response of bovine mammary epithelial cells (bMECs) during the internalization of Staphylococcus aureus were analyzed. Cholecalciferol and S. aureus inhibited TLR2 mRNA expression, but cholecalciferol differentially modulated the TLR2 membrane abundance. In fact, 50 nM cholecalciferol inhibited the TLR2 membrane abundance in bMECs infected with S. aureus, and this concentration also exerted the highest inhibitory effect on internalization. Cholecalciferol down-regulated the mRNA expression of TNF-α and IL-1ß and up-regulated that of RANTES and IL-10 but did not modify IL-6 and IL-8 expression. S. aureus strongly induced the mRNA expression of TNF-α, RANTES and IL-10 and inhibited IL-8 expression. Interestingly, cholecalciferol pre-treatments inhibited the bacterial-induced expression of TNF-α, IL-1ß, RANTES and IL-10. In conclusion, cholecalciferol differentially regulates the inflammatory response of bMECs during S. aureus internalization and may be an effective innate immunity modulator in mammary gland tissues.

Factors associated with early platelet activation in obese children.

OBJECTIVE: To investigate the factors associated with platelet activation in obese children. DESIGN: Cross-sectional study. SETTING: Department of Pediatrics of Regional Hospital N∘ 1 of Mexican Institute of Social Security in Morelia, Michoacán, Mexico. PARTICIPANTS: 79 obese and 64 non-obese children between the ages of 5 and 10 years. MAIN OUTCOMES MEASURES: Obese children (body mass index [BMI] >85 in growth curves for Centers for Disease Control/National Center for Health Statistics), and the control group of 64 non-obese children (percentile <85), % body fat, platelet activation was assessed by sP-selectin. Other measures were leptin, uric acid (UA), von Willebrand Factor (vWF), plasminogen activator inhibitor (PAI-1), lipid profile, and glucose. RESULTS: Obese children displayed higher plasma sP-selectin, leptin, PAI-1, and vWF than non-obese children. In the univariate logistic regression analysis, leptin, vWF, UA, and high density lipoprotein (HDL), but not with PAI-1, were factors associated with platelet activation. By stepwise linear regression analysis adjusted by sex and age, the best predictor variables for platelet activation were leptin (ß:0.381; t:4.665; P=0.0001), vWF (ß:0.211; t:2.926; P=0.004), UA (ß:0.166; t:2.146; P=0.034), and HDL (ß:-0.215; t:-2.819; P=0.006). CONCLUSIONS: Obese children have a higher risk of developing early platelet activation. Factors associated with platelet activation were Leptin, vWF, UA, and HDL. Further studies involving larger numbers of patients over a longer duration are needed to understand the possible molecular mechanism underlying the association between leptin, vWF, and UA and endothelial activation and/or endothelial damage/dysfunction in obese children and its influence in cardiovascular disease in adults.

Effects of dopamine on leptin release and leptin gene (OB) expression in adipocytes from obese and hypertensive patients.

BACKGROUND: A reduction of dopaminergic (DAergic) activity with increased prolactin levels has been found in obese and hypertensive patients, suggesting its involvement as a pathophysiological mechanism promoting hypertension. Similarly, leptin action increasing sympathetic activity has been proposed to be involved in mechanisms of hypertension. The aim of this study was to analyze the effects of DA, norepinephrine (NE), and prolactin on leptin release and leptin gene (OB) expression in adipocytes from obese and hypertensive patients. METHODS: Leptin release and OB gene expression were analyzed in cultured adipocytes from 16 obese and hypertensive patients treated with DA (0.001, 0.01, 0.1, and 1.0 µmol/L), NE (1.0 µmol/L), insulin (0.1 µmol/L), and prolactin (1.0 µmol/L), and from five nonobese and normotensive controls treated with DA (1 µmol/L), NE (1 µmol/L), insulin (0.1 µmol/L), and prolactin (1.0 µmol/L). RESULTS: A dose-related reduction of leptin release and OB gene messenger ribonucleic acid expression under different doses of DA was observed in adipocytes from obese hypertensive patients. Whereas prolactin treatment elicited a significant increase of both leptin release and OB gene expression, NE reduced these parameters. Although similar effects of DA and NE were observed in adipocytes from controls, baseline values in controls were reduced to 20% of the value in adipocytes from obese hypertensive patients. CONCLUSION: These results suggest that DAergic deficiency contributes to metabolic disorders linked to hyperleptinemia in obese and hypertensive patients.

Cardiovascular and renal effects of bromocriptine in diabetic patients with stage 4 chronic kidney disease.

OBJECTIVE: The objective of this study was to investigate the effect of bromocriptine (BEC) on left ventricular mass index (LVMI) and residual renal function (RRF) in chronic kidney disease (CKD) patients with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: A 6-month double-blind randomized controlled trial was conducted in 28 patients with T2D and stage 4 CKD with increased LVMI. Fourteen patients received BEC (2.5 mg, initially 1 tablet with subsequent increase to three times a day) and 14 received a placebo (PBO; initially 1 tablet with subsequent increase to three times a day). Cardiovascular changes were assessed by monitoring 24 h ambulatory blood pressure, two-dimensional-guided M-mode echocardiography, and N-terminal brain natriuretic peptide (NT-proBNP) plasma levels. RRF was evaluated by creatinine clearance and cystatin-C plasma levels. RESULTS: Both BEC and PBO groups decreased blood pressure-but the effect was more pronounced in the BEC group. Average 24 h, diurnal and nocturnal blood pressures, and circadian profile showed improved values compared to the PBO group; LVMI decreased by 14% in BEC and increased by 8% in PBO group. NT-proBNP decreased in BEC (0.54 ± 0.15 to 0.32 ± 0.17 pg/mL) and increased in PBO (0.37 ± 0.15 to 0.64 ± 0.17 pg/mL). Creatinine clearance did not change in the BEC group and decreased in the PBO group. CONCLUSIONS: BEC resulted in a decrease on blood pressure and LVMI. BEC also prevented the progression of CKD while maintaining the creatinine clearance unchanged.

Genetic damage in patients with chronic kidney disease, peritoneal dialysis and haemodialysis: a comparative study.

Patients with chronic kidney disease (CKD) have signs of genomic instability and, as a consequence, extensive genetic damage, possibly due to accumulation of uraemic toxins, oxidative stress mediators and other endogenous substances with genotoxic properties. We explored factors associated with the presence and background levels of genetic damage in CKD. A cross-sectional study was performed in 91 CKD patients including pre-dialysis (CKD patients; n = 23) and patients undergoing peritoneal dialysis (PD; n = 33) or haemodialysis (HD; n = 35) and with 61 healthy subjects, divided into two subgroups with the older group being in the age range of the patients, serving as controls. Alkaline comet assay and cytokinesis-block micronucleus assay in peripheral blood lymphocytes were used to determine DNA and chromosome damage, respectively, present in CKD. Markers of oxidative stress [malondialdehyde (MDA), advanced glycation end products (AGEs), thiols, advanced oxidation protein products and 8-hydroxy-2'-deoxyguanosine] and markers of inflammation (C-reactive protein, interleukin-6 and tumour necrosis factor alpha) were also measured. Micronucleus (MN) frequency was significantly higher (P < 0.05) in the CKD group (46±4‰) when compared with the older control (oC) group (27.7±14). A significant increase in MN frequency (P < 0.05) was also seen in PD patients (41.9±14‰) versus the oC group. There was no statistically significant difference for the HD group (29.7±15.6‰; P = NS) versus the oC group. Comet assay data showed a significant increase (P < 0.001) of tail DNA intensity in cells of patients with CKD (15.6±7%) with respect to the total control (TC) group (11±1%). PD patients (14.8±7%) also have a significant increase (P < 0.001) versus the TC group. Again, there was no statistically significant difference for the HD group (12.5±3%) compared with the TC group. Patients with MN values in the upper quartile had increased cholesterol, triglycerides, AGEs and MDA levels and lower albumin levels. Multiple logistic regression analysis showed that male gender, diabetes and treatment modality were independently associated with higher levels of DNA damage. Our results suggest that oxidative stress, diabetes, gender and dialysis modality in CKD patients increased DNA and chromosome damage. To confirm these data, prospective clinical trials need to be performed.