Triptófano-5-hidroxilasa, transportador de serotonina y receptores serotoninérgicos en miocardiopatía dilatada.

BACKGROUND: Cardiomyocytes synthesize, utilize and reuptake serotonin, which is involved in the paracrine and autocrine modulation of heart activity and in the pathophysiology of some cardiovascular diseases. OBJECTIVE: To determine the expression of tryptophan-5-hydroxylase (TPH) 1 and 2, serotonin transporter protein (SERT) and serotonergic receptors in hearts with dilated cardiomyopathy (DCM) compared to controls. METHOD: A comparative study was performed in six tissue blocks of the left ventricular free wall (LVWL) and inter-ventricular septum from patients who died of DCM and six who died of no cardiovascular diseases (controls). Five slices from each block were obtained to determine the expression of TPH1 and TPH2, SERT and serotonergic receptors with antibodies specific for immunofluorescence. Immunofluorescence was analyzed by Student's t-test, accepting a significance level of p < 0.05. RESULTS: An increase in TPH1, TPH2, 5-HT2A and 5-HT2B receptors expression were observed in dilated structures compared to controls (p < 0.05). For dilated inter-ventricular septum, the 5-HT4 receptor increased its expression (p < 0.05), and SERT in PLVI compared to controls (p < 0.05). CONCLUSIONS: These results suggest that the increases observed in the expression of TPH, SERT, and serotonergic receptors in hearts with DCM compared to controls could play an important role in the pathophysiology of MCD in humans.

ANTECEDENTES: Los cardiomiocitos sintetizan, utilizan y recapturan serotonina, la cual participa en la modulación parácrina y autócrina de la actividad del corazón y en la fisiopatología de algunas enfermedades cardiovasculares. OBJETIVO: Determinar la expresión de triptófano-5-hidroxilasa (TPH) 1 y 2, transportador de serotonina (SERT) y receptores serotoninérgicos en corazones con miocardiopatía dilatada (MCD) en comparación con controles. MÉTODO: Estudio comparativo en seis bloques de la pared libre del ventrículo izquierdo (PLVI) y del septum interventricular de pacientes fallecidos por MCD y seis que murieron por enfermedades no cardiovasculares. Se obtuvieron cinco cortes de cada bloque para determinar la expresión de TPH1 y TPH2, SERT y receptores serotoninérgicos con anticuerpos específicos por inmunofluorescencia. La inmunofluorescencia fue analizada por la t de Student, aceptando un nivel de significancia de p < 0.05. RESULTADOS: Se observó un aumento en la expresión de TPH1 y TPH2 y en los receptores 5-HT2A y 5-HT2B en las estructuras dilatadas en comparación con las controles (p < 0.05). El receptor 5-HT4 aumentó su expresión en el septum interventricular dilatado (p < 0.05) y el SERT en la PLVI en comparación con los controles (p < 0.05). CONCLUSIONES: Estos resultados sugieren que los aumentos observados en las expresiones de TPH, SERT y receptores serotoninérgicos en corazones con MCD en comparación con controles podrían desempeñar un papel importante en la fisiopatología de la MCD en los humanos.

First-in-human experience of preload regulation with percutaneous transluminal caval flow regulation in heart failure with reduced ejection fraction patients.

AIMS: This study aims to investigate the acute haemodynamic effects of percutaneous transluminal flow regulation (PTCR®) with an inferior vena cava regulator balloon in heart failure patients. Preload reduction in heart failure has been achieved with high potency diuretics. However, no study has been conducted in humans to assess the effect of inferior vena cava intermittent occlusion for preload reduction. METHODS AND RESULTS: Six patients were included in the study: four men (55 ± 6 years old) and two women (63 ± 4 years old). Baseline evaluations included Doppler echocardiogram, coronary angiogram, and right heart catheterization. Caval balloon was kept inflated for 30 min, and right catheterization and control echocardiogram were performed while the balloon was still inflated. The balloon was then deflated and removed. Right haemodynamic variables were evaluated before balloon insertion and with the inflated balloon. The mean right atrial pressure decreased by 42.59% (P = 0.005); systolic right ventricular pressure decreased by 30.19% (P < 0.003); mean pulmonary arterial pressure decreased by 25.33% (P < 0.043); mean pulmonary capillary wedge pressure decreased by 31.37% (P > 0.016); and cardiac output increased by 9.92% (P < 0.175). CONCLUSIONS: The haemodynamic and echocardiographic changes obtained in our study using PTCR® suggest that this innovative approach can play a beneficial role in the heart failure treatment.

How intrauterine growth restriction due to nutritional stress changes the function of key proteins in brain serotonin metabolism during development.

This review aimed to describe and comment on how experimental intrauterine nutritional stress in animals produced some changes in tryptophan-5-hydroxylases (TPH) 1 and 2 in the brain and other key proteins such as plasma albumin, and how the intrauterine nutritional stress could produce long-lasting alterations in serotonin function in the brain of human infants.

El objetivo de esta revisión es describir y comentar cómo el estrés nutricional intrauterino experimental en animales produjo algunos cambios en las triptófano-5-hidroxilasas 1 y 2 en el cerebro y en otras proteínas clave, como la albúmina plasmática, y de qué manera el estrés nutricional intrauterino podría producir alteraciones duraderas en la función de la serotonina en el cerebro de lactantes.

Interaction of Thalassia testudinum Metabolites with Cytochrome P450 Enzymes and Its Effects on Benzo(a)pyrene-Induced Mutagenicity.

The aim of the present work was to evaluate the effects of Thalassia testudinum hydroethanolic extract, its polyphenolic fraction and thalassiolin B on the activity of phase I metabolizing enzymes as well as their antimutagenic effects. Spectrofluorometric techniques were used to evaluate the effect of tested products on rat and human CYP1A and CYP2B activity. The antimutagenic effect of tested products was evaluated in benzo[a]pyrene (BP)-induced mutagenicity assay by an Ames test. Finally, the antimutagenic effect of Thalassia testudinum (100 mg/kg) was assessed in BP-induced mutagenesis in mice. The tested products significantly (p < 0.05) inhibit rat CYP1A1 activity, acting as mixed-type inhibitors of rat CYP1A1 (Ki = 54.16 ± 9.09 µg/mL, 5.96 ± 1.55 µg/mL and 3.05 ± 0.89 µg/mL, respectively). Inhibition of human CYP1A1 was also observed (Ki = 197.1 ± 63.40 µg/mL and 203.10 ± 17.29 µg/mL for the polyphenolic fraction and for thalassiolin B, respectively). In addition, the evaluated products significantly inhibit (p < 0.05) BP-induced mutagenicity in vitro. Furthermore, oral doses of Thalassia testudinum (100 mg/kg) significantly reduced (p < 0.05) the BP-induced micronuclei and oxidative damage, together with an increase of reduced glutathione, in mice. In summary, Thalassia testudinum metabolites exhibit antigenotoxic activity mediated, at least, by the inhibition of CYP1A1-mediated BP biotransformation, arresting the oxidative and mutagenic damage. Thus, the metabolites of T. testudinum may represent a potential source of chemopreventive compounds for the adjuvant therapy of cancer.

Assessment of the cytotoxic potential of an aqueous-ethanolic extract from Thalassia testudinum angiosperm marine grown in the Caribbean Sea.

OBJECTIVES: Reported antioxidant, anti-inflammatory and neuroprotective properties for one aqueous-ethanolic extract from Thalassia testudinum which grows in the Caribbean Sea compelled us to explore about extract cytotoxic effects. METHODS: Cell viability was assayed on tumour (HepG2, PC12, Caco-2 and 4T1) and non-tumour (VERO, 3T3, CHO, MCDK and BHK2) cell lines. The extract effects upon primary cultures of rat and human hepatocytes and human lymphocytes were assayed. KEY FINDINGS: The extract exhibited cytotoxicity against cancer cells compared to normal cells, and the IC50 values were 102 µg/ml for HepG2, 135 µg/ml for PC12, 165 µg/ml for Caco-2 and 129 µg/ml for 4T1 cells after 48 h, whereas IC50 could not be calculated for normal cells. Additional data from a high-content screening multiparametric assay indicated that after 24-h exposure, the extract (up to 100 µg/ml) induced death in HepG2 cells through oxidative stress-associated mechanism, DNA damage and hypercalcaemia. Comet assay corroborated extract-induced DNA damage. CONCLUSIONS: Thalassia testudinum extract is more cytotoxic and produced more DNA damage on human hepatoma cells than to other non-tumour cells. A possible mechanism is suggested for extract-induced cytotoxicity based on oxidative stress, nuclear damage and hypercalcaemia in HepG2 cells. T. testudinum may be a source for antitumour agents.

In vitro modulation of the cytochrome P450 and ABCB1/P-glycoprotein activities of the aqueous extract of Allophylus cominia (L) Sw. leaves.

BACKGROUND: The aqueous extract of the Allophylus cominia (L) Sw (Sapindaceae) leaves has shown anti-diabetic, anti-obesity and anti-inflammatory properties. In the Caribbean region, it is typically used for the treatment of type-2 diabetes. METHODS: Considering the herb-drug interaction, the aim of this study was to evaluate the potential effects of the A. cominia extract on the cytochrome P450 (CYP) (rat hepatocyte model) and P-glycoprotein (P-gp) (4T1 cell line) systems. RESULTS: The extract did not decrease the cell viability after being assayed by the MTT test at up to 1500 µg/mL for 72 h. The exposure of the cultured rat hepatocytes to the product (up to 250 µg/mL) for 48 h increased the activities of CYP-1A2, 2C9, and 2E1 by 1.46-, 1.60-, and 1.51-fold, respectively, compared with the controls. The activities of CYP-2B6, 2D6, and 3A4 were not significantly altered, whereas the activity of P-gp decreased by 2- and 4-fold. In addition, the extracts at 100 and 200 µg/mL significantly increased doxorubicin cytotoxicity in these cells 24 h after treatment. CONCLUSIONS: The findings indicate that the A. cominia extract modulates the CYP and P-gp systems increasing sensitivity to doxorubicin. Further studies are necessary to evaluate the potential herb-drug interaction or chemosensitive properties.

Gas Chromatography-Mass Spectrometry Analysis of Ulva fasciata (Green Seaweed) Extract and Evaluation of Its Cytoprotective and Antigenotoxic Effects.

The chemical composition and biological properties of Ulva fasciata aqueous-ethanolic extract were examined. Five components were identified in one fraction prepared from the extract by gas chromatography-mass spectrometry, and palmitic acid and its ethyl ester accounted for 76% of the total identified components. Furthermore, we assessed the extract's antioxidant properties by using the DPPH, ABTS, and lipid peroxidation assays and found that the extract had a moderate scavenging effect. In an experiment involving preexposition and coexposition of the extract (1-500 µg/mL) and benzo[a]pyrene (BP), the extract was found to be nontoxic to C9 cells in culture and to inhibit the cytotoxicity induced by BP. As BP is biotransformed by CYP1A and CYP2B subfamilies, we explored the possible interaction of the extract with these enzymes. The extract (25-50 µg/mL) inhibited CYP1A1 activity in rat liver microsomes. Analysis of the inhibition kinetics revealed a mixed-type inhibitory effect on CYP1A1 supersome. The effects of the extract on BP-induced DNA damage and hepatic CYP activity in mice were also investigated. Micronuclei induction by BP and liver CYP1A1/2 activities significantly decreased in animals treated with the extract. The results suggest that Ulva fasciata aqueous-ethanolic extract inhibits BP bioactivation and it may be a potential chemopreventive agent.

El envejecimiento humano activo y saludable, un reto para el anciano, la familia, la sociedad / A healthy and active human aging process, a challenge for elderly, family and society

El aumento de la expectativa de vida de la población, unido al decrecimiento de la natalidad en los países desarrollados y algunos en vías en desarrollo, son responsables fundamentalmente del incremento acelerado de la población mayor de 65 años, uno de los principales problemas socioeconómicos que confrontan. Se precisa conocer urgente e integralmente el proceso de envejecimiento humano, que propiciará la adopción de medidas que faciliten a esta población la satisfacción de las condiciones económicas, sanitarias, sociales y espirituales, que garanticen el disfrute de una vejez activa y saludable. El objetivo de la presente comunicación es reiterar la importancia de esta cuestión de enorme repercusión política, socioeconómica, y cultural, que representa un desafío para el anciano, la familia, la sociedad y las instituciones gubernamentales, que de no enfrentarse adecuadamente, tendrá catastróficas consecuencias por su alto costo social y constituirá una violación de los derechos humanos a los ancianos

The increase of the population life expectancy and the decrease of births in developed and in some developing countries are responsible mainly of accelerated increase of the population aged over 65, one of the main existing socioeconomic problems. It is necessary to know in an urgent and integral way the human aging process, which will allow us to adopt measures giving to this population the meeting of economic, health, social and spiritual needs guaranteeing the enjoyment of an active and healthy old age. The objective of present communication is to reiterate the significance of this question of a huge politic, socioeconomic and cultural repercussion, which is a challenge for elderly, family and society and the government institutions what if it is not properly faced, will has catastrophic consequences due to its high social cost and will be a violation of human rights of old people

El síndrome metabólico, una epidemia silente / The metabolic syndrome, a silent epidemic

En el presente artículo se hace referencia a la definición, etiopatogenia, diagnóstico y tratamiento del síndrome metabólico, uno de los principales factores de riesgo de la aterosclerosis, caracterizado por alteraciones metabólicas que se expresan en un mismo individuo de forma simultánea o secuencial causados por la combinación de factores genéticos y ambientales asociados a un estilo de vida no saludable, en los que la resistencia a la insulina se considera el componente patogénico fundamental. Se enfatiza la necesidad de intensificar la realización de campañas educativas a la población relacionadas con la adopción de un estilo de vida saludable desde el nivel de atención primaria en salud fundamentalmente, que contribuyan a ganar conciencia en la percepción del riesgo del mismo desde edades tempranas de la vida, lo que indudablemente repercutirá en la disminución de la prevalencia, morbimortalidad y nefastas complicaciones ocasionada por el síndrome metabólico.

The present article makes reference to definition, pathogeny, diagnosis and treatment of metabolic syndrome, one of the main risk factors of atherosclerosis, characterized by metabolic disturbances simultaneously and sequential way expressed in the same subject due to combination of genetic and environmental factors associated with an unhealthy lifestyle, in which the insulin-resistance is considered the essential pathogenic component. It is emphasized the need to intensify the carrying out of educational campaigns to population related to adoption of healthy lifestyle from primary care levels mainly in health, contributing to become aware of risk perception from early ages of life with a future repercussion on decrease of prevalence, morbidity and mortality and on the harmful complications caused by the metabolic syndrome.

La hipertensión arterial primaria en edades tempranas de la vida, un reto a los servicios de salud / Primary high blood pressure in early ages in life a challenge for health services

La hipertensión arterial en Cuba, presenta una alta prevalencia y es el principal factor de riesgo de enfermedad coronaria del corazón, primera causa de muerte en nuestro país. En la fisiopatología de la hipertensión arterial, se encuentran involucrados factores genéticos tales como la heredabilidad, la agregación y segregación familiar, además de factores ambientales modificables, como la obesidad, el sedentarismo, el tabaquismo, el alcoholismo, ingestión de comidas con alto contenido de sal y grasas saturadas y otros. Investigaciones realizadas en niños aparentemente sanos han demostrado, que la hipertensión arterial primaria en edades tempranas de la vida, es más frecuente que lo que se cree. En el presente artículo hacemos referencia a algunos aspectos de la fisiopatología, prevención, diagnóstico, evaluación, control, tratamiento y pronóstico de la hipertensión arterial y se destaca la importancia estratégica de la medición frecuente de la presión arterial en niños y adolescentes supuestamente sanos con antecedentes patológicos paternos y/o maternos de hipertensión arterial, sobrepeso u obesidad, lo que tendrá un impacto positivo en la disminución de la prevalencia, morbimortalidad y complicaciones de esta deletérea enfermedad en la edad adulto.

Arterial hypertension presents in Cuba, a high prevalence and it is the main risk factor of coronary heart disease, who is the first cause of death . In the physiopathology of hypertension are involved genetic factors such as the heredability, family aggregation and segregation, besides the amendable environmental factors, as obesity, sedentary, smoke habit, alcoholism, foods ingestion with high content of salt and saturated fats and others. Recent investigations carried out in seemingly healthy children have demonstrated that the primary arterial hypertension in early ages of the life, it is more frequent than is believed. This article refers topics about the physiopathology, prevention, diagnostic, evaluation, control, treatment and prognostic of hypertension and emphasize the strategic importance of the frequent measurement the arterial blood pressure to children and adolescents with father and/or mother with hypertension history with overweight or obesity, that it will has a positive impact in the decrease of the prevalence, morbimortality and complications of this deleterious illness in the mature age.

Marcadores de estres oxidativo en pacientes hipertensos de una poblacion rural en provincia Habana / Oxidative stress markers in hypertensive patients from a rural population in Havana province

El metabolismo celular genera especies reactivas deletéreas que están implicadas en la biología vascular. Dada la posible participación de estas especies en la hipertensión arterial, nos propusimos estudiar algunos marcadores lipídicos y del metabolismo oxidativo en hipertensos de un año de evolución procedentes de una zona rural del municipio de Artemisa. Provincia Habana. La concentración de triglicéridos resultó superior en las mujeres hipertensas en comparación con las normotensas. La HDLc fue más baja en los hipertensos y no se observaron diferencias en los productos de la peroxidación lipídica, ni para la actividad de las enzimas antioxidantes superóxido dismutasa y catalasa. En correspondencia con el índice de masa corporal los pacientes hipertensos tenían sobrepeso. Los resultados presentados no sustentan el papel del estrés oxidativo en el desarrollo de la hipertensión arterial, al menos, en el grupo poblacional estudiado.

The cellular metabolism generates reactive deleterious species that are involved in vascular biology. Due to the possible participation of these species in arterial hypertension, we proposed ourselves to study some lipid markers and oxidative metabolism markers in hypertensives with one year of evolution from a rural zone of Artemisa municipality, Havana Province . The triglyceride concentration proved to be higher in hypertensive females compared with the normotensive. HDLc was lower among hypertensives and no differences were observed neither in the products of lipid peroxidation nor in the activity of the antioxidant enzymes such as superoxide dismutase and catalase. In correspondence with the body mass index, the hypertensive patients were overweight. The results showed did not support the role of oxidative stress in the development of arterial hypertension, at least in the population group under study.

Factores de riesgo, manifestaciones clínicas y tratamiento de la insuficiencia cardiaca en mayores de 65 años / Risk factors, clinical manifestations and treatment of heart failure in over 65 years-old patients

Se realizó un estudio poblacional en 10 consultorios de médicos de familia seleccionados al azar para conocer la etiología, los síntomas, signos y el tratamiento de la insuficiencia cardiaca en pacientes mayores de 65 años. Se entrevistaron y examinaron 805 casos, se recogieron enfermedades previas, síntomas y signos, y tratamientos utilizados en ese momento. A los que tenían 2 síntomas y signos o más, se les realizó ecocardiograma y si existía disfunción sistólica y/o diastólica se consideraron casos positivos de insuficiencia cardiaca. Los principales factores etiológicos (solos o asociados) fueron hipertensión arterial 75,7 por ciento y cardiopatía isquémica 61,3 por ciento; la combinación de disnea de esfuerzo y edemas de miembros inferiores fue la más frecuente (54 por ciento). Usaban diuréticos 55,1 por ciento, inhibidores de la enzima convertidora de angiotensina 42,5 por ciento, betabloqueadores 18,3 por ciento y digoxina 43,6 por ciento. La hipertensión arterial fue el principal factor etiológico. Hubo casos con insuficiencia cardiaca que estando ambulatorios, presentaron pocos síntomas. La mayoría no estaba recibiendo tratamiento adecuado.

A population-based study was carried out in ten randomly selected family physician` offices in order to find out the etiology, symptoms, signs and treatment of heart failure in over 65 years-old patients. Eight hundred and five cases were surveyed and examined, data on previous diseases, symptoms, signs and therapies at that moment were collected. Those patients with two or more symptoms and signs underwent echocardiogram and in case of systolic and/or diastolic dysfunction, they were classified as heart failure cases. The main etiological factors (single or associated) were blood hypertension in 75,7 percent of cases and ischemic cardiopathy in 61,3 percent; the combination of effort dyspnea and swollen low limbers was the most common (54 percent). Of the total number of patients, 55,1 percent used diuretics; 42,5 percent took angiotensin- converting enzyme inhibitors; 18,3 percent used beta blockers whereas 43,6 percent was prescribed Digoxin. Hypertension was the main etiological factor. There were cases of heart failure seen at outpatient service, but with few symptoms. Most of patients were not being properly treated.

Prevalencia y formas de insuficiencia cardíaca en mayores de 65 años / Prevalence and heart failure in over 65 years-old elders

Se realizó un estudio poblacional en 10 consultorios de médicos de familia seleccionados al azar, con el objetivo de conocer la prevalencia y formas de insuficiencia cardíaca en pacientes mayores de 65 años, del policlínico Marcio Manduley de Centro Habana. Fueron entrevistados y examinados 805 casos, de los cuales se recogieron síntomas y signos de insuficiencia cardíaca. A los que tenían 2 síntomas y signos o más, se les realizó ecocardiograma y si existía disfunción sistólica o diastólica, o ambas, se consideraron casos positivos de insuficiencia cardíaca. Se obtuvieron 2 síntomas y signos o más, en 111 casos, el ecocardiograma fue positivo de insuficiencia cardíaca en 87 de estos, o sea, la prevalencia total cardíaca fue 10,8 por ciento. Presentaron disfunción sistólica 18,4 por ciento, diastólica 42,5 por ciento y mixta 39,0 por ciento. Se concluyó que la prevalencia de insuficiencia cardíaca fue elevada. La presencia de insuficiencia cardíaca diastólica aislada debe ser buscada activamente.

A population-based study was carried out in 10 randomly selected family physician’s offices, with the objective of determining the prevalence and forms of heart failure in patients aged over 65 years seen at Marcio Manduley polyclinics in Centro Habana municipality. Eight hundred and five cases were interviewed and tested to collect heart failure symptoms and signs. Echocardiogram was performed in those who presented with two or more symptoms and signs; if there was systolic or diastolic dysfunction or both, these cases were considered positive to heart failure. One hundred and eleven cases showed two or more symptoms and signs, echocardiogram showed heart failure in 87 cases, that is, the total heart failure prevalence was 10.8 percent. 18.4 percent had systolic dysfunction, 42.5 percent diastolic and 39 percent both. It was concluded that heart failure prevalence was high. Isolated diastolic heart failure should be actively traced.

Evaluation of the effectiveness and tolerability of controlled-release diclofenac-potassium versus immediate-release diclofenac-potassium in the treatment of knee osteoarthritis.

UNLABELLED: Abstract. BACKGROUND: A controlled-release (CR) form of diclofenac-potassium has been developed, which delivers 100 mg over the course of 24 hours. This formulation is administered QD and provides steady plasmatic levels of the drug. OBJECTIVE: The aim of this study was to compare the effectiveness and tolerability of CR diclofenac-potassium versus the immediate-release (IR) formulation, when used for treatment of pain in patients with knee osteoarthritis. METHODS: This prospective, randomized, double-blind, comparative, multi-center, parallel-group study was conducted in male and female patients who had been previously diagnosed with knee osteoarthritis. Inclusion criteria included knee joint pain and ≥3 of the following: age >50 years, morning rigidity lasting <30 minutes, crackling in the joint, pain with applied pressure to the bones, bone hypertrophy, absence of articular heat, and a radiology status of I to III on the Kellgren-Lawrence scale. Patients were randomly divided into 1 of 2 equal-sized groups: 1 group received diclofenac-potassium IR 50 mg BID for 30 days and 1 group received diclofenac-potassium CR 100 mg QD for 30 days. Patients were assessed at baseline and again at 15 and 30 days after initiation of treatment with a physical examination, pain measurement via 100-mm visual analog scale (VAS), and Western Ontario McMaster (WOMAC) osteoarthritis index questionnaire. Adverse events (AEs) were assessed by direct interrogation, hematology controls, blood chemistry, hepatic tests, coagulation tests, and urine tests performed on patients before treatment initiation and on day 30. RESULTS: Sixty-five patients were screened and 62 patients (mean [SD]age, 61.8 [8.9] years; mean [SD] weight, 71.3 [12.4] kg; female sex, 55 [88.9%]) were included in the study; each study group had 31 patients. After 30 days, both products were equally effective in relieving pain, as measured by VAS (IR, 17.3 vs CR, 21.6; P = NS), and changes in the WOMAC score (IR, 14.5 vs CR, 19.2; P = NS). Significantly more patients in the IR group reported feeling better after 30 days than in the CR group (94% vs 76%; P = 0.002) and, according to the physician's opinion, significantly more patients treated with diclofenac-potassium IR felt better (97% vs 83%; P = 0.03). Significantly more patients in the IR group required rescue medication than those in the CR group (36% vs 26%; P = 0.03). In the CR group, 7 patients experienced AEs: 6 were gastrointestinal (ie, pyrosis, epigastralgia, dyspepsia) and 1 patient experienced increased arterial pressure. One patient from this group discontinued treatment due to a lack of efficacy. In the IR group, 6 patients experienced AEs (ie, tachycardia, epigastralgia, and pyrosis). One patient discontinued because of AEs, and 3 withdrew due to a lack of efficacy. CONCLUSION: Based on the results from this small study in a Venezuelan population, both IR and CR formulations of diclofenac-potassium have similar effectiveness and tolerability profiles.

La señal aterogénica temprana: estudio multinacional de 4 934 niños y jóvenes y 1 278 autopsias / The early atherogenic signal: a multinational study of 4 934 children and youth and 1 278 autopsies

Se presentaron los resultados de 5 investigaciones realizadas en niños y jóvenes, para demostrar que existen desde las primeras edades de la vida una serie de señales aterogénicas tempranas posibles de detectar; las que conocidas obligan a tomar medidas médicas y socioculturales que permitan evitar o retardar el desarrollo de la aterosclerosis. Se estudiaron niños y adolescentes entre 5 y 16 años de 6 escuelas de Ciudad de La Habana, 2 de Panamá, 1 de Concepción, Chile, y 3 de Itapetininga, Brasil. También se investigaron la aorta y la arteria coronaria derecha procedentes de las autopsias de un estudio multinacional dirigido por la Organización Mundial de la Salud, donde participaron 18 países de 4 continentes, se investigaron niños y jóvenes de edades entre 5 y 34 años, todos fallecidos por muerte violenta. Se presentaron los resultados de los estudios patomorfológicos y morfométricos, utilizando el sistema aterométrico . Se estudió el impacto de 3 factores de riesgo, hipertensión arterial, diabetes mellitus tipo 2 y tabaquismo en la producción de lesiones ateroscleróticas. Las conclusiones más relevantes fueron las siguientes: 1. Sí existen suficientes señales aterogénicas tempranas, como hipertensión arterial, obesidad, circunferencia de la cintura exagerada, el índice de masa corporal alterado, tabaquismo activo y pasivo, y los antecedentes patológicos familiares de padecer alguna enfermedad relacionada con la aterosclerosis. 2. Como elementos discriminatorios para la identificación de los niños y jóvenes en los distintos países las variables más relevantes fueron el peso corporal, la circunferencia de la cintura y los valores de tensión arterial sistólica y diastólica. 3. En los estudios de autopsia se pudo demostrar el incremento de áreas de íntima ocupada por lesiones ateroscleróticas con el progreso de la edad y el gran efecto que la hipertensión, la diabetes mellitus tipo 2 y el tabaquismo ejercen en el desarrollo de la aterosclerosis y la transformación de las estrías adiposas en placas fibrosas

Simple circuit to improve electric field homogeneity in contour-clamped homogeneous electric field chambers.

We redesigned contour-clamped homogeneous electric field (CHEF) circuitry to eliminate crossover distortion, to set identical potentials at electrodes of each equipotential pair and to drive pairs with transistors in emitter follower stages. An equipotential pair comprised the two electrodes set at the same potential to provide electric field homogeneity inside of the hexagonal array. The new circuitry consisted of two identical circuits, each having a resistor ladder, diodes and transistors. Both circuits were interconnected by diodes that controlled the current flow to electrodes when the array was energized in the 'A' or 'B' direction of the electric field. The total number of transistors was two-thirds of the total number of electrodes. Average voltage deviation from potentials expected at electrodes to achieve a homogeneous electric field was 0.06 V, whereas 0.44 V was obtained with another circuit that used transistors in push-pull stages. The new voltage clamp unit is cheap, generated homogeneous electric field, and gave reproducible and undistorted DNA band patterns.

Desarrollo de un modelo de aterosclerosis inducida por inmunocomplejos de forma activa en ratones BALB/CBJ / Development of an atherosclerosis model actively induced by immunocomplexes in BALB/CBJ mice

Se emplearon ratones isogénicos de la línea BALB/CBJ, de 6 semanas de edad y un régimen de agua y comida ad libitum. Estos se dividieron en 2 grupos, a uno de ellos se les realizó el esquema de inmunización de 0-1-4 semanas por vía intraperitoneal con la vacuna cubana anti hepatitis. El otro grupo fue el control y se inmunizó de la misma forma empleando el excipiente de la vacuna, sin el antígeno de superficie de la hepatitis B (AgsHB). El grupo tratado inhaló diariamente durante 1 mes humo de cigarillo. Después de cuantificar los Ac anti-HBs y la ausencia de estos en los controles, se llevaron a cabo 7 inmunizaciones con un intervalo de 5 d entre ellas por la vena caudal, se utilizó como inmunógeno en el grupo tratado AgsHB recombinante con una dosis que duplicó la concentración de anti-HBs de cada animal. Al grupo control se le suministró solución salina con la misma metodología que en el grupo tratado. Se determinó la presencia de inmunocomplejos circulantes en plasma. Se practicó eutanasia y se comprobó la presencia de lesiones ateroscleróticas de forma macroscópica y microscópica. Con los resultados obtenidos se concluyó que se logró obtener un modelo de aterosclerosis en ratones isogénicos BALB/CBJ por formación de inmunocomplejos de manera activa

Desarrollo de un modelo de aterosclerosis inducida por inmunocomplejos de forma pasiva en ratones BALB/CBJ transgénicos al antígeno de superficie de la hepatitis B / Development of an atherosclerosis model induced in a passive way by immunocomplexes in BALB/CBJ mice transgenic to the hepatitis B surface antigen

Se obtuvieron anticuerpos-HBs a partir del desarrollo de ascitis en ratones BALB/CBJ. Se emplearon 2 grupos de animales BALB/CBJ transgénicos al AgsHb, de 8 meses de edad y un régimen de agua y comida ad libitum. A un grupo se le inoculó Ac anti-HBs con una dosis doble a la de su concentración de AgsHb y al otro grupo se le inoculó solución salina. Se realizaron 7 inoculaciones con un intervalo de 5 d entre ellas por la vena caudal. Una semana después de la última inoculación se realizó extracción de sangre y se les determinó inmunocomplejos circulantes en plasma. Se les practicó eutanasia y se les extrajo las aortas donde se comprobó la formación de placas de ateromas de forma macroscópica por observación al estereoscopio y microscópicamente por tinción con hematosilina-eosina. A partir de estos resultados se concluyó que se logró un modelo de aterosclerosis en ratones BALB/CBJ Tg al AgsHb por formación de inmunocomplejos de forma pasiva

Aterosclerosis y muerte súbita: impacto patomorfológico y morfométrico de la hipertensión en las arterias coronarias / Atherosclerosis and sudden death: pathomorphological and morphometric impact of hypertension in coronary arteries

De un total de 237 necropsias de pacientes fallecidos por muerte súbita según los criterios de la Organización Mundial de la Salud en el Hospital Universitario "Dr. Carlos J. Finlay", 73 pacientes (30,8 porciento), 44 del sexo masculino y 29 del femenino, mayores de 15 años, padecían de hipertensión arterial. Se utilizaron como control 113 fallecidos (68 del sexo masculino y 45 del femenino) que murieron de causas no cardiovasculares y sin factores de riesgo aterogénico, y mostraron muy bajo nivel de aterosclerosis. Se estudiaron las principales arterias epicárdicas coronarias, derecha, descendente anterior y circunfleja izquierda. Se aplicó el sistema aterométricopara la caracterización patomorfológica y morfométrica de los tipos de lesiones ateroscleróticas. De los fallecidos con hipertensión arterial,73,97 porciento murió antes de llegar al hospital. De ellos 93,15 porciento presentó cardiomegalia con un peso promedio de los corazones mayor que 400 g. Las placas fibrosas y las graves fueron las más frecuentemente encontradas en este grupo. El total de la superficie intimal ocupada por el conjunto de las lesiones ateroscleróticas y los índices de obstrucción y estenosis aumentaron sus valores según la edad en los pacientes con hipertensión arterial