Ketorolac and (-)-Epicatechin change retinal GFAP and NRF2 expression on hyperglycemic CD1 mice.

Our objective was to determine whether (-)-Epicatechin administered alone or simultaneously with topical Ketorolac decreased the relative expression of GFAP and modulated the response of Nrf2 in a mouse model with induced hyperglycemia. We found that GFAP and Nrf2 decreased in the groups that received treatments alone or simultaneous during 8 weeks; even when the effect on the Nrf2 was not pronounced, it showed a higher concentration when GFAP decreased. Our results suggest a protective effect of Ketorolac and (-) - Epicatechin, which seem to limit the preclinical retinal damage caused by inflammation in hyperglycemia.

Comparison of macular retinal sensitivity and its contribution to the foveal sensitivity between diabetic and non-diabetic patients with normal visual acuity / Comparación de la sensibilidad de la retina macular y su contribución a la sensibilidad de la fóvea entre pacientes diabéticos y no diabéticos con agudeza visual normal

Purpose: To compare the retinal sensitivity and evaluate its contribution to the foveal sensitivity in patients with and without diabetes who maintain normal visual acuity. Methods: Observational, descriptive, cross-sectional and prospective study in 20 subjects without diabetes (group 1) and 23 with type 2 diabetes mellitus (group 2) that had no ocular abnormalities. Retinal sensitivity was measured with the macular threshold test by the Humphrey's computerized perimeter. The mean sensitivity in each of the 16 points and the foveal sensitivity were compared between groups using the Mann-Whitney's U test; the correlation between retinal sensitivity and foveal sensitivity was analyzed by the Spearman's test and the contribution of each point to the foveal sensitivity was identified by multiple regression. Results: Sixty eyes were evaluated, 30 in group 1 and 30 in group 2; the mean foveal sensitivity was 34.77 ± 0.5dB in group 1 and 32.87 ± 0.6 in group 2. The highest sensitivity of the temporal visual field had an inferior paracentral location (point 3) in both groups. In the linear regression analysis, points which contributed to the foveal sensitivity were 1 in group 1 and points 7 and 15 in group 2. Conclusions: Subjects without diabetes have a significantly higher sensitivity in the temporal retina compared with those with diabetes; points with highest mean retinal sensitivity do not correspond to the central four. The reduced sensitivity in point 1 decreases the mean foveal sensitivity in subjects with diabetes, because this variable correlates with lower perimetry points

Objetivo: Comparar la sensibilidad de la retina y evaluar su contribución a la sensibilidad de la fóvea en pacientes con y sin diabetes con agudeza visual normal. Métodos: Estudio observacional, descriptivo, transversal y prospectivo en 20 sujetos no diabéticos (grupo 1) y 23 con diabetes mellitus tipo 2 (grupo 2) sin anomalías oculares. La sensibilidad de la retina se midió mediante la prueba de cuantificación del umbral macular realizada con campimetría computarizada Humphrey. La sensibilidad media en cada uno de los 16 puntos y la sensibilidad de la fóvea se compararon entre grupos mediante la prueba U de Mann Whitney; la correlación entre la sensibilidad de la retina y la sensibilidad de la fóvea se analizó mediante la prueba de Spearman, y la contribución de cada punto a la sensibilidad de la fóvea se identificó mediante regresión múltiple. Resultados: Se evaluaron sesenta ojos: 30 en el grupo 1, y 30 en el grupo 2; la media de la sensibilidad de la fóvea fue de 34,77 ± 0,5 dB en el grupo 1, y de 32,87 ± 0,6 en el grupo 2. La mayor sensibilidad del campo visual temporal tuvo una localización paracentral inferior (punto 3) en ambos grupos. En el análisis de regresión lineal, los puntos que contribuyeron a la sensibilidad de la fóvea fueron el punto 1 en el grupo 1, y los puntos 7 y 15 en el grupo 2. Conclusiones: Los sujetos no diabéticos tienen una sensibilidad significativamente mayor en la retina temporal en comparación a los sujetos diabéticos; los puntos con mayor sensibilidad media de la retina no corresponden a los cuatro centrales. La sensibilidad reducida en el punto 1 disminuye la sensibilidad de la fóvea en sujetos diabéticos, ya que esta variable guarda relación con los puntos perimétricos inferiores

Circularity of the foveal avascular zone and its correlation with parafoveal vessel density, in subjects with and without diabetes.

PURPOSE: To characterize the distribution of the foveal avascular zone circularity and its correlation with parafoveal vessel density, in subjects with and without diabetes. METHODS: Observational, descriptive, cross-sectional, and prospective study; subjects without diabetes (Group 1), with diabetes without retinopathy (Group 2), or with diabetic retinopathy (Group 3) were included. Means of foveal avascular zone circularity and parafoveal vessel density were compared between groups (Kruskal-Wallis) and their correlation was calculated with Spearman's Rho test. RESULTS: Seventy-seven eyes; central vessel density mean was higher in Group 1 than in Group 2 and higher in Group 2 than in Group 3; inner and complete vessel density means were also higher in Group 2 than in Group 3. The mean of the foveal avascular zone circularity did not differ between groups, and in Group 3 it had a positive correlation with central (0.45), inner (0.56), and complete (0.53) vessel densities. CONCLUSIONS: Circularity does not differ between subjects with diabetes, with and without retinopathy, and has only a low correlation with parafoveal vessel density in people with diabetic retinopathy, which does not allow anticipating a reduction of vessel density in this disease.

OBJETIVO: Caracterizar la distribución de la circularidad de la zona avascular foveal y su correlación con la densidad vascular perifoveal, en sujetos con y sin diabetes. MÉTODO: Estudio observacional, descriptivo, transversal y prospectivo; se incluyeron sujetos sin diabetes (Grupo 1), con diabetes sin retinopatía (Grupo 2) y con retinopatía diabética (Grupo 3). Los promedios de circularidad de la zona avascular foveal y de la densidad vascular parafoveal se compararon entre grupos (Kruskal-Wallis), y se calculó su correlación mediante la prueba Rho de Spearman. RESULTADOS: Se estudiaron 77 ojos. El promedio de la densidad vascular central fue mayor en el Grupo 1 que en el Grupo 2, y mayor en el Grupo 2 que en el Grupo 3. Los promedios de la densidad vascular interna y completa también fueron mayores en el Grupo 2 que en el Grupo 3. El promedio de la circularidad de la zona avascular foveal no difirió entre grupos, y en el Grupo 3 tuvo una correlación positiva con la densidad vascular central (0.45), interna (0.56) y completa (0.53). CONCLUSIONES: La circularidad no difiere entre sujetos con y sin diabetes, con y sin retinopatía, y solo tiene una baja correlación con la densidad vascular parafoveal en sujetos con retinopatía diabética, lo cual no permite anticipar una reducción de la densidad vascular en esta enfermedad.

Comparison of macular retinal sensitivity and its contribution to the foveal sensitivity between diabetic and non-diabetic patients with normal visual acuity.

PURPOSE: To compare the retinal sensitivity and evaluate its contribution to the foveal sensitivity in patients with and without diabetes who maintain normal visual acuity. METHODS: Observational, descriptive, cross-sectional and prospective study in 20 subjects without diabetes (group 1) and 23 with type 2 diabetes mellitus (group 2) that had no ocular abnormalities. Retinal sensitivity was measured with the macular threshold test by the Humphrey's computerized perimeter. The mean sensitivity in each of the 16 points and the foveal sensitivity were compared between groups using the Mann-Whitney's U test; the correlation between retinal sensitivity and foveal sensitivity was analyzed by the Spearman's test and the contribution of each point to the foveal sensitivity was identified by multiple regression. RESULTS: Sixty eyes were evaluated, 30 in group 1 and 30 in group 2; the mean foveal sensitivity was 34.77±0.5dB in group 1 and 32.87±0.6 in group 2. The highest sensitivity of the temporal visual field had an inferior paracentral location (point 3) in both groups. In the linear regression analysis, points which contributed to the foveal sensitivity were 1 in group 1 and points 7 and 15 in group 2. CONCLUSIONS: Subjects without diabetes have a significantly higher sensitivity in the temporal retina compared with those with diabetes; points with highest mean retinal sensitivity do not correspond to the central four. The reduced sensitivity in point 1 decreases the mean foveal sensitivity in subjects with diabetes, because this variable correlates with lower perimetry points.

The attempt to demolish the science and practice of preventive cardiovascular medicine. Part I. Addendum to the positioning around the diagnosis and treatment of dyslipidemias of ANCAM and the joint group of associated medical societies / El intento de demoler la ciencia y la práctica de la medicina cardiovascular preventiva. Parte I. Addendum al posicionamiento en torno al diagnóstico y tratamiento de las dislipidemias de la ANCAM y del grupo conjunto de sociedades médicas asociadas

Abstract: This manuscript is an addendum to the positioning around the diagnosis and treatment of dyslipidemias of ANCAM and the joint group of associated medical societies, already published. It is the first part of a wider reflection aimed on refute several of the theses and arguments of a group of clinicians and researchers who question the validity of the "cholesterol hypothesis", the usefulness and safety of statins and the most modern inhibitors of proprotein convertase of subtilisin/kexin type 9 (iPCSK9,) and the role of saturated fatty acids consumed in the usual diet in the atherosclerotic risk. This iconoclastic point of view is dangerous insofar as it undermines the scaffolding that supports the primary and secondary prevention of atherosclerosis. In this section of the manuscript, only the cholesterol hypothesis is discussed. The data of comparative zoology are reviewed, and several experimental animal models are analyzed, both supporting the link between cholesterol and the appearance and evolution of atherosclerotic lesions. The methodology and the results of the Study of the 7 Countries are defended and are exposed the numerous epidemiological, pathological, clinical and interventional evidences, which in our opinion give a solid sustenance to the cholesterol hypothesis. Based on this knowledge it is criticized the LDL cholesterol values currently considered adequate. Furthermore, the so-called residual risk is considered, as well as the conflicting evidence about the usefulness of statins in elderly patients.

Resumen: Este manuscrito es un apéndice del posicionamiento en torno al diagnóstico y tratamiento de las dislipidemias de la ANCAM y el grupo de las sociedades médicas asociadas, previamente publicado. Es la primera parte de un trabajo más amplio enfocado a refutar varias de las tesis y argumentos de un grupo de clínicos e investigadores que ponen en duda la validez de la "hipótesis del colesterol", la utilidad y seguridad de las estatinas y los más modernos inhibidores de la proproteína convertasa de la subtilisina/kexina tipo 9 (iPCSK9) y el papel de los ácidos grasos saturados consumidos en la dieta habitual en el riesgo ateroscleroso. Este punto de vista iconoclástico es peligroso porque socava el andamiaje que soporta la prevención primaria y secundaria de la aterosclerosis. En esta primera sección del manuscrito, se discute sólo la hipótesis del colesterol. Se revisan los datos de zoología comparada y se analizan varios modelos animales de experimentación, que apoyan la liga entre el colesterol y la aparición y evolución de las lesiones aterosclerosa. Se defienden la metodología y los resultados del estudio de los 7 países y se exponen las numerosas evidencias epidemiológicas, patológicas, clínicas e intervencionistas, que a nuestro juicio dan un sustento sólido a la hipótesis del colesterol. Se critican también, en base a ese conocimiento, los valores de colesterol LDL actualmente considerados adecuados, a la vez que se discute el llamado riesgo residual y las evidencias conflictivas acerca de la utilidad de las estatinas en pacientes ancianos.

Effect of Eicosapentaenoic Acid on Body Composition and Inflammation Markers in Patients with Head and Neck Squamous Cell Cancer from a Public Hospital in Mexico.

INTRODUCTION: Head and neck cancer patients are at high risk of anorexia-cachexia syndrome and literature shows that Eicosapentaenoic acid (EPA) could regulate it. We aim to determine the EPA effect on body composition and pro-inflammatory markers in patients with head neck cancer. MATERIALS AND METHODS: A randomized single-blind placebo-controlled clinical trial was conducted in patients with head and neck squamous cell cancer who received a polymeric diet with 2 g of EPA or a standard polymeric diet for six weeks before antineoplastic treatment. We assessed body composition by bioelectrical impedance analysis and determined IL-1ß, IL-6, TNF-α and IFN-γ, CRP, serum proteins, and blood count at baseline and at the end of the study. RESULTS: 32 patients received EPA (2 g/day) and 32 became controls. A decrease in serum levels of IL-1ß, IL-6, TNF-α, and IFN-γ was observed in the experimental group, as well as regulation of body weight (-0.3 ± 5.9 vs. -2.1 ± 3.7), lean body mass (-0.2 ± 3.8 vs. -1.3 ± 3.6), body fat mass (0.2 ± 3.5 vs. -1.2 ± 3.8), and quality of life (10 ± 33 vs. 5 ± 34). CONCLUSION: Supplementing with 2 g/day of EPA to head and neck cancer patient during antineoplastic treatment regulates serum pro-inflammatory cytokines, body weight, lean body mass, and improve quality of life.

Estimation of umbilical cord blood leptin and insulin based on anthropometric data by means of artificial neural network approach: identifying key maternal and neonatal factors.

BACKGROUND: Leptin and insulin levels are key factors regulating fetal and neonatal energy homeostasis, development and growth. Both biomarkers are used as predictors of weight gain and obesity during infancy. There are currently no prediction algorithms for cord blood (UCB) hormone levels using Artificial Neural Networks (ANN) that have been directly trained with anthropometric maternal and neonatal data, from neonates exposed to distinct metabolic environments during pregnancy (obese with or without gestational diabetes mellitus or lean women). The aims were: 1) to develop ANN models that simulate leptin and insulin concentrations in UCB based on maternal and neonatal data (ANN perinatal model) or from only maternal data during early gestation (ANN prenatal model); 2) To evaluate the biological relevance of each parameter (maternal and neonatal anthropometric variables). METHODS: We collected maternal and neonatal anthropometric data (n = 49) in normoglycemic healthy lean, obese or obese with gestational diabetes mellitus women, as well as determined UCB leptin and insulin concentrations by ELISA. The ANN perinatal model consisted of an input layer of 12 variables (maternal and neonatal anthropometric and biochemical data from early gestation and at term) while the ANN prenatal model used only 6 variables (maternal anthropometric from early gestation) in the input layer. For both networks, the output layer contained 1 variable to UCB leptin or to UCB insulin concentration. RESULTS: The best architectures for the ANN perinatal models estimating leptin and insulin were 12-5-1 while for the ANN prenatal models, 6-5-1 and 6-4-1 were found for leptin and insulin, respectively. ANN models presented an excellent agreement between experimental and simulated values. Interestingly, the use of only prenatal maternal anthropometric data was sufficient to estimate UCB leptin and insulin values. Maternal BMI, weight and age as well as neonatal birth were the most influential parameters for leptin while maternal morbidity was the most significant factor for insulin prediction. CONCLUSIONS: Low error percentage and short computing time makes these ANN models interesting in a translational research setting, to be applied for the prediction of neonatal leptin and insulin values from maternal anthropometric data, and possibly the on-line estimation during pregnancy.

(-)-Epicatechin improves mitochondrial-related protein levels and ameliorates oxidative stress in dystrophic δ-sarcoglycan null mouse striated muscle.

Muscular dystrophies (MDs) are a group of heterogeneous genetic disorders characterized by progressive striated muscle wasting and degeneration. Although the genetic basis for many of these disorders has been identified, the exact mechanism of disease pathogenesis remains unclear. The presence of oxidative stress (OS) is known to contribute to the pathophysiology and severity of the MD. Mitochondrial dysfunction is observed in MD, and probably represents an important determinant of increased OS. Experimental antioxidant therapies have been implemented with the aim of protecting against disease progression, but results from clinical trials have been disappointing. In this study, we explored the capacity of the cacao flavonoid (-)-epicatechin (Epi) to mitigate OS by acting as a positive regulator of mitochondrial structure/function endpoints and redox balance control systems in skeletal and cardiac muscles of dystrophic, δ-sarcoglycan (δ-SG) null mice. Wild-type or δ-SG null 2.5-month-old male mice were treated via oral gavage with either water (controls) or Epi (1 mg·kg(-1) , twice daily) for 2 weeks. The results showed significant normalization of total protein carbonylation, recovery of the glutathione/oxidized glutathione ratio and enhanced superoxide dismutase 2, catalase and citrate synthase activities with Epi treatment. These effects were accompanied by increases in the protein levels of thioredoxin, glutathione peroxidase, superoxide dismutase 2, catalase, and mitochondrial endpoints. Furthermore, we found decreases in heart and skeletal muscle fibrosis, accompanied by an improvement in skeletal muscle function, with treatment. These results warrant further investigation of Epi as a potential therapeutic agent to mitigate MD-associated muscle degeneration.

Inflammation and myocardial damage markers influence loss of residual renal function in peritoneal dialysis patients.

BACKGROUND: Residual renal function (RRF) has been identified as the most important component in dialysis adequacy and has a strong effect on clinical outcomes. This justifies any effort in understanding the mechanism behind the preservation or decline in RRF. The aim of this study was to analyze the possible association of components of cardio-renal syndrome with the rate of decline in RRF. METHODS: A retrospective cohort study was performed in a group of prevalent adult patients on continuous ambulatory peritoneal dialysis (CAPD). Patients were analyzed at baseline and after a 30-month follow-up. Evaluations included measurements of residual renal function, dialysis adequacy parameters, cardiovascular comorbidity, and measurements of biochemical markers of cardiovascular disease (CVD) and inflammation, as well as resting electrocardiography. RESULTS: We included 129 patients in the study who were divided into groups according to loss of RRF, considering the cut-off point as 100 mL/day of 24 h urine volume. At baseline, there were no differences between groups: patients who lost RRF showed low values of 24 h urine volume, higher levels of systolic blood pressure, N-terminal pro-brain natriuretic peptide (NT-proBNP), C-reactive protein (CRP), IL-6, and low values of serum albumin. In the multivariate analysis, age, albumin, CRP, and NT-proBNP were significant risk factors for the loss of RRF. CONCLUSIONS: Data indicate a close relationship between heart and kidney function where chronic kidney disease (CKD) affects and is an effect of, heart function, indicative of a bi-directional influence that leads to a vicious cycle, promoting deleterious effects on both systems.

Cardiovascular risk factors in a Mexican middle-class urban population: The Lindavista Study. Baseline data / Factores de riesgo cardiovascular en mexicanos de clase media: el estudio Lindavista. Datos basales

Introduction and objective: The aim of this communication is to describe the cardiovascular risk factors affecting a Mexican urban middle-class population. Methods: A convenience sample of 2602 middle class urban subjects composed the cohort of the Lindavista Study, a prospective study aimed to determine if conventional cardiovascular risks factors have the same prognosis impact as in other populations. For the baseline data, several measurements were done: obesity indexes, smoking, blood pressure, fasting serum glucose, total cholesterol, HDL-c, LDL-c and triglycerides. This paper presents the basal values of this population, which represents a sample of the Mexican growing urban middle-class. Results: The mean age in the sample was 50 years; 59% were females. Around 50% of the entire group were overweighed, while around 24% were obese. 32% smoked; 32% were hypertensive with a 20% rate of controlled pressure. 6% had diabetes, and 14% had impaired fasting glucose; 66% had total cholesterol ≥ 200mg/dL; 62% showed HDL-c levels <40mg/dL; 52% triglycerides > 150 mg/dL, and 34% levels of LDL-c ≥ 160 mg/dL. Half of the population studied had the metabolic syndrome. Conclusion: These data show a population with a high-risk profile, secondary to the agglomeration of several cardiovascular risk factors.

Introducción y objetivo: el objetivo de este comunicado es describir los factores de riesgo cardiovascular en la población urbana mexicana de clase media. Métodos: La cohorte del estudio Lindavista se compone de una muestra por conveniencia de 2,602 sujetos de clase media. El estudio es prospectivo y tiene como finalidad determinar si los factores de riesgo cardiovascular tienen el mismo factor pronóstico que en otras poblaciones. Para los datos basales, se hicieron varias determinaciones: índices de obesidad, consumo de tabaco, presión arterial, glucosa, colesterol total, c-HDL, c-LDL y triglicéridos en ayuno. Resultados: La media de edad fue de 50 años; el 59% fueron mujeres. Aproximadamente el 50% de la muestra presentó sobrepeso, mientras que el 24% eran obesos. El 32% fumaban, el 32% eran hipertensos con una tasa de control del 20%. El 6% tenían diabetes y el 14% resistencia a la insulina. El 66% tuvieron colesterol total ≥ 200 mg/dl; el 62% mostraron bajos niveles de c-HDL, el 52% triglicéridos > 150 mg/dl, y el 34% niveles de c-LDL ≥ 160 mg/dl. La mitad de la muestra tenía síndrome metabólico. Conclusión: Los datos revelan una población de alto riesgo cardiovascular debido a la aglomeración de diversos factores de riesgo.

Cardiovascular risk factors in a Mexican middle-class urban population. The Lindavista Study. Baseline data.

INTRODUCTION AND OBJECTIVE: The aim of this communication is to describe the cardiovascular risk factors affecting a Mexican urban middle-class population. METHODS: A convenience sample of 2602 middle class urban subjects composed the cohort of the Lindavista Study, a prospective study aimed to determine if conventional cardiovascular risks factors have the same prognosis impact as in other populations. For the baseline data, several measurements were done: obesity indexes, smoking, blood pressure, fasting serum glucose, total cholesterol, HDL-c, LDL-c and triglycerides. This paper presents the basal values of this population, which represents a sample of the Mexican growing urban middle-class. RESULTS: The mean age in the sample was 50 years; 59% were females. Around 50% of the entire group were overweighed, while around 24% were obese. 32% smoked; 32% were hypertensive with a 20% rate of controlled pressure. 6% had diabetes, and 14% had impaired fasting glucose; 66% had total cholesterol ≥ 200 mg/dL; 62% showed HDL-c levels<40 mg/dL; 52% triglycerides>150 mg/dL, and 34% levels of LDL-c ≥ 160 mg/dL. Half of the population studied had the metabolic syndrome. CONCLUSION: These data show a population with a high-risk profile, secondary to the agglomeration of several cardiovascular risk factors.

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.

A potential "tuning" role for the outer hair cells in children with language disorders.

The cochlear outer hair cells serve a tuning function, and any dysfunction of their electromotile response can be reflected in language disorders. Otoacoustic emissions can be used to determine any dysfunction of these cells. A set of clinical records was established to register the neurological and auditory functioning in 42 children, followed by assessment with the Wechsler Intelligence Scale for Children (WISC), the Initial Language Test (ILT), the Auditory and Phonetic Discrimination Evaluation (APDE), tests for measuring Brainstem Auditory Evoked Potential (BAEP) and Transient Otoacoustic Emissions (TOAE). Subjects were classified into 3 groups in this study: Control (C; n = 20), Syntactic Phonological Disorder (SPD; n = 17), and those with Phonological Disability (PD; n = 5). BAEP studies showed a clear response when all children were stimulated to 20 dB. TOAE responses displayed clear and significant differences with half-octave band reproducibility for both ears, the largest effect being observed in the right ear. The results that were compared using ANOVA tests, showed that cochlear processing affects the brain language function, playing a critical role in the language phonetic process.

Urban PM2.5 activates GAPDH and induces RBC damage in COPD patients.

During Chronic Obstructive Pulmonary Disease (COPD) progression, the intracellular antioxidant defence in RBCs must preserve the integrity of the plasmalemma through NADPH+ generation to obtain a sufficient number of reduced non-protein SH-groups. Here, we studied the activities of enzymes in RBCs that are related to glutathione metabolism under conditions of increasing oxidative stress, which are associated with COPD progression, by increasing cellular damage in vitro with PM2.5, a ROS generator. The study included 43 patients, who were separated according to their GOLD classification into moderate and severe groups, along with 11 healthy volunteers (HV). Blood samples were analysed for G6PD, GAPDH, GPx, and GR. The results showed significant decreases in the oxidation of the G6PD, GR and GPx proteins, resulting in decreased enzymatic activity. By contrast, an increase (p<0.05) in GAPDH was observed, suggesting a pool of ATP on the membrane. However, it is evident that RBCs are damaged during the progression of COPD, although their integrity is preserved, and they retain limited function, thus allowing patient survival without haemolysis.

Antioxidant supplementation has a positive effect on oxidative stress and hematological toxicity during oncology treatment in cervical cancer patients.

BACKGROUND AND AIM: Hematological toxicity and oxidative stress are common in cancer patients. Antioxidant supplementation has been shown to decrease oxidative stress, but there is still controversy on this topic. The aim of this study was to determine the effect of antioxidant supplementation on oxidative stress, hematological toxicity, and quality of life (QoL) in cervical cancer patients. METHODS: Randomized, single-blinded controlled trial in women with cervical cancer treated with radiotherapy and chemotherapy with cisplatin. Subjects were randomly assigned to receive antioxidant supplement or placebo supplement. Plasma concentrations of malondialdehyde, free carbonyls, and blood biometry were measured. EORTC quality of life questionnaire was applied before and after oncology treatment. Student's t test for independent samples and X (2) for categorical variables were performed. RESULTS: One hundred three patients were randomly assigned to receive treatment with antioxidants 49 (48 %) or placebo 54 (52.40 %). At the end of the oncology treatment, hemoglobin levels were maintained, and global QoL was better only in the supplemented group (p < 0.025). CONCLUSIONS: Antioxidant supplementation in patients treated with chemotherapy and radiotherapy apparently decreased oxidative stress, maintained hemoglobin levels, and improved QoL; however, more studies are needed to study the long-term effect of this intervention.

Obesity and metabolic syndrome: Future therapeutics based on novel molecular pathways

Obesity is a chronic disease, currently recognized as the triggering agent for the development of the metabolic syndrome. It is now accepted that obesity rises from an energy imbalance due to excessive food ingestion and insufficient physical activity. Mitochondria has an important role in energy balance and, interestingly, recent findings have found an association between obesity and mitochondrial dysfunction due to a defective network among regulator proteins such as peroxisome proliferator-activated receptors (PPARs), sirtuins (SIRTs), and PPAR coactivator 1 (..)

La obesidad es una enfermedad crónica que es considerada como el agente detonador para el desarrollo de síndrome metabólico. Se ha aceptado que la obesidad surge de un desbalance energético provocado por ingestión alimentaria excesiva y actividad física insuficiente. La mitocondria tiene un papel importante en tal balance energético e, interesantemente, se ha encontrado una asociación entre la obesidad y la disfunción mitocondrial debido a interacciones defectuosas entre ciertas proteínas reguladoras como los receptores activados por proliferado res de peroxisomas (PPAR), sirtuinas (SIRT) y el coactivador de PPAR (PGC-1 ).Estas moléculas se encuentran actualmente bajo una amplia investigación con miras a encontrar nuevos agentes que (..) (AU)

Caveolae and non-caveolae lipid raft microdomains of human umbilical vein endothelial cells contain utrophin-associated protein complexes.

Several studies have shown the importance of dystrophin-associated protein complex in the development of muscular dystrophies and dilated cardiomyopathy associated to vascular dysfunction. In vascular endothelium, dystrophin is substituted for utrophin (autosomal homolog of dystrophin); however, its role in this tissue is unknown. Therefore, it is important to obtain a more extensive knowledge of utrophin and its associated proteins in endothelial cells. In a previous study, we demonstrated the presence of utrophin-associated protein complex (UAPC) in human umbilical vein endothelial cells HUVEC, which interacts with caveolin-1 (Cav-1) and endothelial nitric oxide synthase (eNOS). Also, some of our observations suggested the presence of this complex in distinct membrane domains. Therefore, the aim of this study was to analyze the presence of the UAPC in caveolae and non-caveolae lipid rafts domains of HUVEC at baseline and with a mechanical stimulus. It was demonstrated, by subcellular fractionation and co-immunoprecipitation assays, the association of UAPC with Cav-1 and eNOS in caveolae domains, as well as its interaction with eNOS in non-caveolae lipid raft domains. Additionally, it was also observed that mechanical stress on endothelial cells induced activation and release of eNOS from both caveolae and non-caveolae lipid raft associated to UAPC. Together these results suggest that UAPC located in caveolae and non-caveolae lipid raft domains of HUVECs may have a mechanosensory function that could participate in the control of eNOS activity.

Anticonvulsant drugs, brain glutamate dehydrogenase activity and oxygen consumption.

Glutamate dehydrogenase (GDH, E.C. 1.4.1.3.) is a key enzyme for the biosynthesis and modulation of glutamate (GLU) metabolism and an indirect γ-aminobutyric acid (GABA) source, here we studied the effect of anticonvulsants such as pyridoxal phosphate (PPAL), aminooxyacetic acid (AAOA), and hydroxylamine (OHAMINE) on GDH activity in mouse brain. Moreover, since GLU is a glucogenic molecule and anoxia is a primary cause of convulsions, we explore the effect of these drugs on oxygen consumption. Experiments were performed in vitro as well as in vivo for both oxidative deamination of GLU and reductive amination of α-ketoglutarate (αK). Results in vitro showed that PPAL decreased oxidative deamination of GLU and oxygen consumption, whereas AAOA and OHAMINE inhibited GDH activity competitively and also inhibited oxygen consumption when αK reductive amination was carried out. In contrast, results showed that in vivo, all anticonvulsants enhanced GLU utilization by GDH and also decreased oxygen consumption. Together, results suggest that GDH activity has repercussions on oxygen consumption, which may indicate that the enzyme activity is highly regulated by energy requirements for metabolic activity. Besides, GDH may participate in regulation of GLU and, indirectly GABA levels, hence in neuronal excitability, becoming a key enzyme in seizures mechanism.

The structures and inhibitory effects of Buame [N-(3-hydroxy-1,3,5(10)-estratrien-17ß-yl)-butylamine] and Diebud [N,N'-bis-(3-hydroxy-1,3,5(10)-estratrien-17ß-yl)-1,4-butanediamine] on platelet aggregation.

Compounds with estrogenic effects that also inhibit platelet aggregation might be useful in reducing thrombotic events associated with estrogenic therapy. In this study, two aminoestrogens, Buame [N-(3-hydroxy-1,3,5(10)-estratrien-17ß-yl)-butylamine] and Diebud [N,N'-bis-(3-hydroxy-1,3,5(10)-estratrien-17ß-yl)-1,4-butanediamine], were synthesized and characterized using common analytical methods and spectrophotometric analyses. The location and orientation of these molecules on the estrogenic receptor α (ERα) were also evaluated. Platelet inhibitory effects were elucidated ADP-induced platelet aggregation and ADP- and collagen-induced ATP release. Molecular docking demonstrated that Buame can reach and bind to the ERα in the ligand binding domain (LBD) similar to 17ß-estradiol (co-crystallized ligand). On the other hand, Diebud binds only to the surface of ERα due to its high molecular volume compared to 17ß-estradiol and Buame.

Suplementación con antioxidantes no previene nefrotoxicidad por cisplatino en pacientes con cáncer cérvico uterino avanzado / Anti oxidant agent does not prevent nefro-toxicity in advance cervical cancer patients

En México el cáncer cérvico uterino al igual que en otros países de América representa un grave problema de salud pública. El tratamiento depende de su extensión; los estadios localmente avanzados son tratados con una combinación de quimioterapia con cisplatino y radioterapia. Ambas terapias utilizadas son consideradas oxidativas y por ello son capaces de influir en las toxicidades del propio tratamiento, el objetivo de este trabajo es determinar la eficacia de la suplementación con antioxidantes y su efecto sobre la prevención de la toxicidad renal por cisplatino. Ensayo clínico aleatorizado que incluyó a pacientes con cáncer cérvico uterino en estadios localmente avanzados cuyo tratamiento antineoplásico consistió en radioterapia y quimioterapia con cisplatino. Se asignó aleatoriamente a las pacientes a recibir un suplemento antioxidante diariamente o bien un placebo. Se determinó la función renal mediante la depuración de creatinina antes de iniciar el tratamiento y al término del mismo. Se realizaron pruebas t-Student inter e intra grupales a fin de determinar el efecto de la suplementación sobre los parámetros evaluados. No se encontraron diferencias estadísticamente significativas entre ambos grupos; en cambio, existió una disminución significativa en ambos grupos al finalizar el tratamiento. La suplementación con antioxidantes no es capaz de prevenir la toxicidad a nivel renal producida por la quimioterapia con cisplatino.

In Mexico, our country, the pathology of cervical cancer is a major public health issue, the same situation is present in other American countries. The treatment for this pathology depends on its extension; for locally advanced stages, a combination of radiotherapy and chemotherapy with cisplatin drug is common used. The both therapies are considered to be pro oxidative and this can be implied in the toxicities of the treatment. The objective of this work was to determine the efficacy of antioxidant supplementation on the prevention of cisplatin drug in the renal toxicity. We conducted a randomized clinical trial in the patients with locally advanced stage cervical cancer whose antineoplastic treatment consisted in radiation therapy and chemotherapy with the cisplatin drug. The patients were randomly assigned to receive either an antioxidant supplement or the placebo. We assessed renal function as creatinine clearance before and after concluding the oncologic treatment. We performed inter and intragroupal t-Student tests in order to determine the effect of the antioxidant supplementation on the evaluated parameters. No statistically significant differences we were found between the groups; however, there was a significant decrease in renal function in the both groups after finalizing the oncologic treatment. The antioxidant supplementation does not prevent the renal toxicity from the cisplatin drug chemotherapy.