Molecular Detection of Gurltia paralysans by Semi-Nested PCR in Cerebrospinal Fluid and Serum Samples from Domestic Cats (Felis catus).

Gurltia paralysans is an angio-neurotropic metastrongyloid nematode that infects domestic and wild cats, invading the veins of the subarachnoid space of the spinal cord and mainly causing progressive paralysis of the pelvic limbs. The definitive diagnosis of feline gurltiosis can only be achieved by post-mortem examination that reveals the presence of the nematode in the spinal cord vein vasculature. An early diagnosis with conclusive results is required since laboratory and imaging findings are not sufficient. Therefore, the purpose of this study was to detect the presence of G. paralysans, via semi-nested PCR, in samples of cerebrospinal fluid (CSF) and the sera of domestic cats naturally infected with the parasite. A total of 12 cats with a diagnosis suggestive of feline gurltiosis were selected, and they underwent a complete neurological and imaging examination. DNA samples were analysed by semi-nested PCR, with universal (AaGp28Sa1/AaGp28Ss1) and specific (Gp28Sa3/Aa28Ss2) primers, for G. paralysans (G. paralysans 18S rRNA gene, partial sequence; ITS 1, 5.8S rRNA gene, and ITS 2, complete sequence; and 28S rRNA gene, partial sequence) and Aelurostrongylus abstrusus, obtaining amplifications of 356 and 300 bp, which indicated the presence or absence of nematode DNA, respectively. The presence of G. paralysans was detected in the CSF of four out of nine cats, and the sera of seven out of seven cats. In the sera analysis of five out of seven cats, a mixed infection with A. abstrusus was found, despite no alterations of the respiratory tract being observed during the necropsies. It is proposed that serum samples could be more effective than CSF in detecting the parasite by PCR analysis. Sequencing analysis showed high percentages of identity with G. paralysans, which indicated the feasibility of detection and the sensitivity/specificity of the method used, suggesting the implementation of semi-nested PCR as a routine diagnostic test for early and timely detection of feline gurltiosis.

Educación terapéutica en pacientes con diabetes y trastornos emocionales / Terapeutic education in patients with diabetes and emotional disorders

La diabetes mellitus (DM) se considera como un conjunto de trastornos metabólicos relacionados con la hiperglucemia, que requiere cambios en estilos de vida, en virtud de que no solo se afecta el estado físico, sino que requiere cambios que pueden influir en el estado emocional y psicosocial. Las personas con diabetes requieren de cuidados continuos orientados al control metabólico centrados en el empoderamiento, autocuidado y en la educación terapéutica para alcanzar metas y resultados orientados a minimizar la aparición de las complicaciones crónicas. Objetivo: analizar la importancia de la educación terapéutica en los pacientes con trastornos afectivos como depresión y ansiedad, asociados a la diabetes. Conclusión: la educación terapéutica como parte integral del tratamiento de la DM ha demostrado mejorar los síntomas asociados a depresión y ansiedad, lo cual podría adquirir un valor importante en el manejo de este grupo de pacientes(AU)

Diabetes mellitus (DM) is considered as a set of metabolic disorders related to hyperglycemia, which requires changes in lifestyle, because not only physical condition is affected, but it also requires changes that can influence emotional state and psychosocial. People with diabetes require continuous care oriented to metabolic control focused on empowerment, self-care and therapeutic education to achieve goals and results aimed at minimizing the occurrence of chronic complications. Objective: to analyze the importance of therapeutic education in patients with affective disorders such as depression and anxiety, associated with diabetes. Conclusion: therapeutic education as an integral part of the treatment of DM has been shown to improve symptoms associated with depression and anxiety, which could acquire an important value in the management of this group of patients(AU)

Reconsidering the Role of Cyclooxygenase Inhibition in the Chemotherapeutic Value of NO-Releasing Aspirins for Lung Cancer.

Nitric oxide-releasing aspirins (NO-aspirins) are aspirin derivatives that are safer than the parent drug in the gastrointestinal context and have shown superior cytotoxic effects in several cancer models. Despite the rationale for their design, the influence of nitric oxide (NO•) on the effects of NO-aspirins has been queried. Moreover, different isomers exhibit varying antitumor activity, apparently related to their ability to release NO•. Here, we investigated the effects and mode of action of NO-aspirins in non-small-cell lung cancer (NSCLC) cells, comparing two isomers, NCX4016 and NCX4040 (-meta and -para isomers, respectively). NCX4040 was more potent in decreasing NSCLC cell viability and migration and exhibited significant synergistic effects in combination with erlotinib (an epidermal growth factor receptor inhibitor) in erlotinib-resistant cells. We also studied the relationship among the effects of NO-aspirins, NO• release, and PGE2 levels. NCX4040 released more NO• and significantly decreased PGE2 synthesis relative to NCX4016; however, NO• scavenger treatment reversed the antiproliferative effects of NCX4016, but not those of NCX4040. By contrast, misoprostol (a PGE2 receptor agonist) significantly reversed the antiproliferative effect of NCX4040, but not those of NCX4016. Furthermore, misoprostol reversed the antimigratory effects of NCX4040. Overall, these results indicate that PGE2 inhibition is important in the mode of action of NO-aspirins.

Searching for Drug Synergy Against Cancer Through Polyamine Metabolism Impairment: Insight Into the Metabolic Effect of Indomethacin on Lung Cancer Cells.

Non-small cell lung cancer (NSCLC) is the most lethal and prevalent type of lung cancer. In almost all types of cancer, the levels of polyamines (putrescine, spermidine, and spermine) are increased, playing a pivotal role in tumor proliferation. Indomethacin, a non-steroidal anti-inflammatory drug, increases the abundance of an enzyme termed spermidine/spermine-N1-acetyltransferase (SSAT) encoded by the SAT1 gene. This enzyme is a key player in the export of polyamines from the cell. The aim of this study was to compare the effect of indomethacin on two NSCLC cell lines, and their combinatory potential with polyamine-inhibitor drugs in NSCLC cell lines. A549 and H1299 NSCLC cells were exposed to indomethacin and evaluations included SAT1 expression, SSAT levels, and the metabolic status of cells. Moreover, the difference in polyamine synthesis enzymes among these cell lines as well as the synergistic effect of indomethacin and chemical inhibitors of the polyamine pathway enzymes on cell viability were investigated. Indomethacin increased the expression of SAT1 and levels of SSAT in both cell lines. In A549 cells, it significantly reduced the levels of putrescine and spermidine. However, in H1299 cells, the impact of treatment on the polyamine pathway was insignificant. Also, the metabolic features upstream of the polyamine pathway (i.e., ornithine and methionine) were increased. In A549 cells, the increase of ornithine correlated with the increase of several metabolites involved in the urea cycle. Evaluation of the levels of the polyamine synthesis enzymes showed that ornithine decarboxylase is increased in A549 cells, whereas S-adenosylmethionine-decarboxylase and polyamine oxidase are increased in H1299 cells. This observation correlated with relative resistance to polyamine synthesis inhibitors eflornithine and SAM486 (inhibitors of ornithine decarboxylase and S-adenosyl-L-methionine decarboxylase, respectively), and MDL72527 (inhibitor of polyamine oxidase and spermine oxidase). Finally, indomethacin demonstrated a synergistic effect with MDL72527 in A549 cells and SAM486 in H1299 cells. Collectively, these results indicate that indomethacin alters polyamine metabolism in NSCLC cells and enhances the effect of polyamine synthesis inhibitors, such as MDL72527 or SAM486. However, this effect varies depending on the basal metabolic fingerprint of each type of cancer cell.

Educación nutricional en diabetes: una estrategia emergente en venezuela / Nutritional Diabetes Education: an emerging strategy in Venezuela

La Educación Terapéutica en Diabetes constituye una parte fundamental para el control adecuado de la diabetes, y dentro de esta la educación nutricional en Diabetes es fundamental, ya que permite el empoderamiento de los pacientes con herramientas nutricionales que le permitan de forma sencilla y agradable realizar cambios en el estilo de vida para controlar los niveles de glicemia y alcanzar los objetivos metabólicos. En Venezuela aún no se reconoce en las instituciones universitarias ni de salud a la Educación en Diabetes como una carrera profesional, pero varios grupos trabajan en conjunto para promover las herramientas y competencias educativas, en especial las relativas a la alimentación y nutrición. En este trabajo se presenta una perspectiva de los hallazgos más relevantes que sientan los principios nutricionales y educativos de la estrategia de Educación Nutricional en Diabetes en Venezuela, con el fin de que se pueda aplicar cada día más en el país a través de los educadores en diabetes, nutricionistas-dietistas y el resto de los profesionales de la salud(AU)

Therapeutic Education in Diabetes is a fundamental part for the adequate management of diabetes, and diabetes nutritional education is also fundamental, this allows the empowerment of patients with nutritional tools that allow them in a simple and pleasant way to make changes in lifestyle to control blood glucose levels and achieve metabolic goals. In Venezuela, Diabetes Education is still not recognized in the university or health institutions as a professional career, but several groups work together to promote educational tools and competencies, especially those related to food and nutrition. This paper presents a perspective of the most relevant findings that establish the nutritional and educational principles of the strategy of nutrition education in diabetes in Venezuela, so that it can be applied every day more in the country through educators in diabetes, Nutritionists-Dietitians and the rest of health professional(AU)

Gestión de la diabetes mellitus / Management of Diabetes Mellitus

La persona con diabetes mellitus se hace acreedora de participar activamente en la gestión de la diabetes mediante educación y prevención de los distintos procesos conducentes a optimizar conocimientos, recursos, habilidades y destrezas, aptitudes y valores para obtener metas de control metabólico que minimicen la aparición de complicaciones agudas y crónicas al menor costo y con la obtención de calidad de vida. La gestión, constituye un medio que define la capacidad para determinar y utilizar en forma racional los recursos humanos y materiales que intervienen en la consecución de la salud del individuo, gracias a distintas acciones prácticas que promueven el individuo, su grupo familiar y los proveedores de salud con el firme propósito de producir resultados óptimos, y alcanzar las metas propuestas. Objetivo: analizar la gestión de la diabetes como estrategia de prevención y tratamiento mediante una revisión de la literatura. Conclusión: incorporar la gestión de la diabetes mediante la participación activa de pacientes, la familia, la propia comunidad y profesionales sanitarios, convierte en un factor de eficacia y eficiencia. Dejar de tratar únicamente la enfermedad y fomentar la educación y promoción para la salud por medio del empoderamiento (empowerment), en el contexto de una condición clínica susceptible de mejorar mediante la educación participativa del individuo, para lograr el autocuidado, son metas plausibles en la actualidad(AU)

The person with diabetes mellitus should actively participate in the management of diabetes through education and prevention of various processes leading to optimize knowledge, resources, skills and values to obtain targets of metabolic control and minimize the appearance of its acute and chronic complications at a lower cost and obtaining quality of life. Management, is defined as the ability to determine and use rationally the human and material resources involved in achieving the health of the individual, through various practical actions that promote the individual, their families and health providers with the firm intention to produce optimum results, and achieve goals. Objective: To analyze the management of diabetes and prevention and treatment strategy by reviewing the literature. Conclusion: to incorporate diabetes management through active participation of patients, family, community and health professionals becomes a factor of effectiveness and efficiencyse(AU)

Prevalencia del síndrome metabólico / Prevalence of metabolic syndrome

Determinar la prevalencia del Síndrome Metabólico(SM) en una muestra de los habitantes del municipio Carrizal (Estado Bolivariano de Miranda, Venezuela) entre de marzo ­ junio 2013, según los criterios ATP III. Métodos: En un estudio observacional de campo, se evaluaron 52 sujetos de sexo masculino y femenino entre 18 y 74 años de edad en diferentes centros de salud del municipio Carrizal, los cuales firmaron previamente un consentimiento informado. A todos los participantes se les aplicó un test para determinar el riesgo de diabetes tipo 2 y de síndrome metabólico (Finnish Diabetes Risk Score) validado en población venezolana. Seguidamente respondían encuesta estructurada sobre antecedentes familiares, personales, factores de riesgo y estilos de vida. Acto seguido se les realizó análisis de sangre en ayuno (glucemia, triglicéridos, colesterol total y colesterol HDL), antropometría (peso, talla, circunferencias de cintura y porcentaje de grasa). El análisis estadístico se realizó mediante el software SPSS versión 14. Resultados: La Glucemia registrada en hombres fue de 116±53 mg/dl, en mujeres de 100±34mg/dl; hipertrigliceridemia en hombres 202±104mg/dl; en mujeres de 125±66 mg/dl; valor de colesterol HDL en hombres de 45±7 mg/dl, en mujeres 56±11 mg/dl; hipercolesterolemia en hombres 206 ±46 mg/dl, en mujeres 214 ±56; circunferencia de la cintura en hombres 113±13 cm, en mujeres 101±11 cm. Conclusiones: La prevalencia de SM fue de 41,8% en la muestra del municipio Carrizal, según los criterios ATP III, representando un alto riesgo de desarrollar enfermedades crónicas no transmisibles. Es fundamental, la intervención directa sobre los factores de riesgo del SM(AU)

To determine the prevalence of Metabolic Syndrome (MS ) in a sample of inhabitants of the municipality Carrizal ( Bolivarian State of Miranda, Venezuela ) within between March and June 2013 according to the ATP III criteria. Methods: In an field study, 52 male and female subjects around 18 and 74 years in different health centers in the municipality Carrizal, which previously signed informed consent were evaluated. All participants were administered a test to determine the risk of diabetes type 2 and metabolic syndrome (Finnish Diabetes Risk Score) validated in Venezuelan population. Then an answered structured survey on family, personal, risk factors and lifestyle history. Was taken Fasting blood tests (glucose, triglycerides, total cholesterol and HDL), anthropometry weight, height, waist circumference and body fat percentage). Statistical analysis was performed using SPSS version 14 software. RESULTS: Blood glucose recorded in men was 116 ± 53 mg / dl in women 100 ± 34mg / dl; hypertriglyceridemia in men 202 ± 104mg / dl ; in women 125 ± 66 mg / dl; value of HDL cholesterol in men aged 45 ± 7 mg / dl in women 56 ± 11 mg / dl; hypercholesterolemia in men 206 ± 46 mg / dl in women 214 ± 56; waist circumference in men 113 ± 13 cm, females 101 ± 11 cm . CONCLUSIONS: The prevalence of MS was 41.8 % in the sample of Carrizal Municipality, according to ATP III criteria, representing a high risk of developing chronic noncommunicable diseases. It is essential, direct intervention on risk factors of MS(AU)

Efecto del polimorfísmo factor XIII VAL34LEU sobre terapia trombólitica en pacientes con infarto agudo del miocardio con elevación del ST / Effect of factor XIII VAL34LEU polymorphism on thrombolytic therapy in patients with acute ST elevation myocardial infarction

Dos polimorfismos pueden tener un importante papel protector contra el infarto de miocardio, debido a que se asocian a una notable disminución de los niveles plasmáticos del factor VII y de la propensión a la trombosis. Objetivo: 1-. Determinar la presencia del polimorfismo Val34leu del Factor XIII en pacientes con infarto del miocardio que ingresan a la unidad de cuidados coronarios (UCC) del HMPC y reciben terapia trombolítica; 2-. Contrastar el efecto de la terapia trombolítica en pacientes con presencia de la mutación y aquellos que no la presentan. Métodos: Se realizó un estudio de campo, descriptivo y correlacional, desde mayo a septiembre del 2007, en la unidad de cuidados coronarios del HMPC-Caracas. La población fue seleccionada mediante criterios de AHA: SCA con elevación del ST, susceptibles a recibir terapia trombolítica. La muestra definitiva, quedo conformada por 30 pacientes. La eficacia de la fibrinólisis fue evaluada por criterios clínicos, electro cardiográfico y enzimático. Una disminución del ST mayor de 50 % a los 90 min y una elevación temprana de las enzimas cardiacas antes de las 12 h fueron considerados criterios de reperfusión. El ADN genómico fue evaluado mediante reacción en cadena de polimerasa. Resultados: El polimorfismo se presento en 39 % de los pacientes estudiados. Se demostró la asociación entre polimorfismo y niveles de fibrinógeno. Conclusiones: Los valores de fibrinógeno estaban disminuidos en la población con polimorfismo en comparación con la que no lo presentaba. La respuesta terapéutica a la terapia trombolítica se relaciono con el fibrinógeno(AU)

Two polymorphisms may have an important protective role against myocardial infarction, because it is associated with a significant decrease in plasma levels of factor VII and the propensity to thrombosis. Objective: 1 -. To determine the presence of Factor XIII Val34Leu polymorphism in patients with myocardial infarction admitted to coronary care unit (CCU) of the HMPC and receives thrombolytic therapy, 2 -. To compare the effect of thrombolytic therapy in patients with presence of the mutation and those without. Methods: We conducted a field study, descriptive, correlation, from May to September 2007 in the coronary care unit of HMPC-Caracas. The population was selected by AHA criteria: ST elevation ACS, likely to receive thrombolytic therapy. The final sample was composed of 30 patients. The effectiveness of fibrinolysis was assessed by clinical, electro cardiograph and enzyme. ST A decrease greater than 50% at 90 min and an early elevation of cardiac enzymes before 12 h reperfusion criteria were considered. DNA was assessed by polymerase chain reaction. Results: The polymorphism was present in 39% of the patients studied. Demonstrated the association between polymorphism and fibrinogen levels. Conclusions: Fibrinogen levels were decreased in the population with polymorphism in comparison with which it had not. The therapeutic response to thrombolytic therapy was associated with fibrinogen(AU)

Disfunción endotelial en pacientes diabéticos e hipertensos / Endothelial dysfunction in diabetic and hypertensive patients

La disfunción endotelial (DE) se considera en la actuali-dad una de las primeras manifestaciones de la enfermedad vascular y de la arteriosclerosis.Dado que los métodos diagnósticos de DE cada día son más numerosos e im-precisos se plantean la siguiente interrogante: Son útiles las hormonas endoteliales: Endotelina, Oxido nítrico (NO), Leptina, Proteína C Reactiva (PCR) y Moléculas de adhesión endotelial VCAM-1, como indicadores bio-químicas de DE en sujetos sanos, hipertensos y diabéticos tipo 2. Objetivo: 1-. Comprobar la utilidad de hormonas endoteliales, como indicadores bioquímicas de disfunción endotelial en sujetos sanos, hipertensos y diabéticos tipo 2. A los efectos, se diseño una investigación observacional de tipo analítico, correlacional y, transversal. La pobla-ción objeto del estudio fue de 75 pacientes seleccionados mediante criterios clínicos, los cuales se distribuyeron en 3 grupos de 25 pacientes, a saber: Sanos, diabéticos e hi-pertensos. A todos los pacientes se les midieron variables hemodinámicas no invasivas, antropométricas y bioquími-cas. Resultados: Al contrastar los indicadores endoteliales con presión arterial diastólica sólo VCAM-1, correlacionó de manera inversa y significativa, en el grupo sanos en condiciones basales. La variable hemodinámica no inva-siva que mejor correlaciona con hormonas endoteliales es la PAM. El VCAM-1 en pacientes diabéticos tipo 2 posee una excelente Sensibilidad: 92,0 y Especificidad: 96,0. Conclusión: VCAM- 1, resultó ser la prueba más sensible y específica para evaluar pacientes diabéticos tipo 2 con DE, asimismo, El VCAM-1 en pacientes hipertensos posee excelente Sensibilidad: 100,0 (IC-95%: 86,3 ­ 100,0) y Especificidad: 92,0 (IC-95%: 74,0 ­ 99,9) (AU)

Endothelial dysfunction (ED) is now considered one of the first manifestations of vascular disease and atheros-clerosis. Because of diagnostic methods are increasingly more numerous and imprecise pose the following question: endothelial hormones are useful: Endothelin, nitric oxide(NO), leptin, C-reactive protein (CRP) and endothelial adhesion molecules VCAM-1 as biochemical indicators of ED in healthy subjects and type 2 diabetic hypertensive. Objective: 1-. Test the usefulness of endothelial hormones as biochemical indicators of endothelial dysfunction in healthy subjects and type 2 diabetic hypertensive. For the purpose, we designed an observational analytic, corre-lational and cross. The purpose of the study population was 75 patients selected by clinical criteria, which were distributed in 3 groups of 25 patients, including: Healthy, diabetic and hypertensive. All patients underwent nonin-vasive hemodynamic variables measured, anthropometric and biochemical. Results: When comparing the endothe-lial indicators with diastolic blood pressure only VCAM-1, correlated inversely and significantly in the healthy group at baseline. The noninvasive hemodynamic variable that best correlates with endothelial hormones is the PAM. The VCAM-1 in type 2 diabetic patients has excellent sensitivity: 92.0, specificity: 96.0. Conclusion: VCAM-1, proved to be the most sensitive and specific test to assess type 2 diabetic patients with ED, also, the VCAM-1 in hypertensive patients has excellent sensitivity: 100.0and specificity: 92.0 (AU)

Determination of non-HDL cholesterol in diabetic and hypertensive patients.

Recently, it has been suggested that non-high-density lipoprotein (non-HDL) cholesterol measure is a useful evaluation tool to assess heart disease death risk. The non-HDL cholesterol is defined as the value between total cholesterol and HDL - total cholesterol, and it involves the different fractions of lipoproteins: low-density lipoprotein, intermediate-density lipoprotein, and very low density lipoprotein, including highly atherogenic lipoproteins as very low density lipoprotein remnants. The purpose of this study was to compare the values of non-HDL cholesterol as a cardiovascular risk marker in a control population, and one diabetic and hypertensive. It was demonstrated that the mean values of non-HDL cholesterol in the diseased groups were higher than the values from the control group, whereas the low-density lipoprotein showed no marked difference in high-risk patients. Non-HDL cholesterol has shown to be a quick and simple way to estimate the risk of developing cardiovascular disease.

Haemodynamical variables versus endothelial hormones in hypertensive and type 2 diabetic patients with endothelial dysfunction.

Leptin is a 167 aminoacid peptidic hormone secreted by adipose tissue. It works mainly in the hypothalamus at thirst signal, but given its closed connections with inflammatory and endothelial systems, also has been postulated that it may exert a regulatory control over blood pressure (BP), interacting with nitric oxide (NO) and C reactive protein (CRP). The cold pressor test (CPT) is a simple test that indirectly determines endothelial dysfunction. In this work, biochemical indicators (CRP, leptin, and NO) and hemodynamic indicators (systolic and diastolic BP) were performed and evaluated in hypertensive, type 2 diabetic, and control subjects during a single CPT for assessment of endothelial dysfunction. A total of 43 subjects, males and females aged 25 to 60 years and divided in three groups, 15 healthy volunteers, 13 hypertensive patients, and 15 patients with type 2 diabetes, were included in the study. A complete clinical history was obtained from each subject, and a complete physical examination, including an electrocardiogram was carried out. During the assay of 30 minutes, 0.9% saline was infused intravenously. CPT was performed to assess the cardiovascular reactivity at minute 15. The cardiovascular variables (systolic and diastolic BP) were measured in minute 0, 16, and 30. In addition, serum variables were obtained at the beginning and at the end of the experiment, and statistical analysis was performed. CPT caused in all subjects a significant increase of BP and pulse. There were no significant differences to CPR and leptin in any group, although we observed significant differences for NO (P < 0.05). Sensitivity and specificity for all biochemical variables resulted in nonsignificant statistical or clinical importance as markers of endothelial dysfunction; however, a positive association was found when leptin and NO were evaluated together (sensitivity: 0.2; specificity. 0.8). CRP, leptin, and NO did not shown any direct and significant association with the hemodynamic variables in this study, although a relationship was noted between NO according to group and biochemical variables when studied altogether.

Effects of metoclopramide and metoclopramide/dopamine on blood pressure and insulin release in normotensive, hypertensive, and type 2 diabetic subjects.

The objective is to determine cardiovascular and insulin release effects under metoclopramide (MTC) and dopamine (DA) infusion by using an acute comparative design with the intravenous infusion of both drugs. We evaluated 15 normal (normotensive and normoglycemic) subjects, 13 hypertensive, and 15 type 2 diabetic subjects. Subjects were submitted to an experimental design in which we first gave them a 0.9% saline solution for 30 minutes, and then administered MTC at 7.5 microg kg min through an intravenous infusion during a period of 30 minutes. Although subjects were receiving MTC, we added an intravenous infusion of DA at 1-3 microg kg min during 30 minutes. Blood pressure, heart rate, serum lipid profile, and insulin levels were measured. Sympathetic reactivity by the cold pressor test was also measured. In normotensive subjects, there was a systolic blood pressure and heart rate increase during MTC plus DA infusion. In subjects with diabetes mellitus there was a heart rate increase without changes in blood pressure during the MTC plus DA infusion period. In hypertensive subjects, MTC induced a significant decrease of systolic and diastolic blood pressure. During MTC plus DA period there was an increase of heart rate but no significant changes in blood pressure. During cold pressor test in both diabetic and hypertensive subjects, there were significant increases of both blood pressure and heart rate. Insulin serum levels increased in normotensive and hypertensive subjects but were attenuated in subjects with diabetes mellitus. We conclude that there is a pharmacologic interaction between MTC and DA, that the pressor effects of DA are due to activation to beta and alpha adrenergic receptors, and that the cardiovascular effects of DA in type 2 diabetic subjects are attenuated by a probable defect in sympathetic system and to endothelial dysfunction.

Metabolic and hemodynamic markers of endothelial dysfunction in patients with hypertension and patients with type 2 diabetes during the cold pressor test.

Leptin, a 167-amino acid peptidic hormone secreted by adipose tissue, acts mainly in the arcuate hypothalamus nucleus as a satiety signal, but given its closed connections with inflammatory and endothelial systems, a probable regulatory role in blood pressure (BP) control by interaction with nitric oxide (NO) and C-reactive protein (CRP) has also been described. The cold pressor test (CPT) is a simple test that indirectly determines endothelial dysfunction. In this work, biochemical indicators (CRP, leptin, and NO) and hemodynamic indicators (systolic and diastolic BP) were performed and evaluated in patients with hypertension, patients with type 2, and control subjects during a single CPT for assessment of endothelial dysfunction. A total of 43 subjects aged 25 to 60 years were divided into three groups: 15 healthy volunteers, 13 patients with hypertension, and 15 patients with type 2 diabetes were included in the study. A complete clinical history was obtained from each subject and a complete physical examination, including an electrocardiogram, was carried out. During the 30-minute assay, 0.9% saline solution was infused intravenously. CPT was performed to assess the cardiovascular reactivity at 15 minutes. The cardiovascular variables (systolic and diastolic BP) were measured at 0, 16, and 30 minutes. In addition, serum variables were extracted at the beginning and at the end of the experiment and statistical analysis was performed. CPT caused in all subjects a significant increase in BP and pulse. There were no significant differences in CRP or leptin in all groups, although we observed significant differences for NO (P < 0.05). Sensibility and specificity for all biochemical variables resulted in nonsignificant statistical or clinical importance as markers of endothelial dysfunction; however, a positive association was found when leptin and NO were evaluated together (sensibility, 0.2; specificity, 0.8). CRP, leptin, and NO did not show any direct or significant association with the hemodynamic variables in this study, although a relationship was observed in NO according to group and among biochemical variables when studied together.

Effect of drugs interacting with the dopaminergic receptors on glucose levels and insulin release in healthy and type 2 diabetic subjects.

Dopamine agonists play an important role in the regulation of the central nervous-cardiovascular, renal, and hormonal systems through stimulation of dopaminergic (DA1 and DA2) and alpha- and beta-adrenergic receptors. Several studies have shown that in fat and diabetic mice. The aim of the present study was to evaluate the interaction of the dopaminergic and endocrine systems by determining the effect of the dopaminergic antagonist, metoclopramide, and dopamine on insulin secretion and cardiovascular response by blockade and activation of dopamine receptors in healthy and type 2 diabetic subjects. Healthy subjects (n =15) and subjects with type 2 diabetes (n = 15) of both genders, aged 18 to 60 years, were recruited into this study. A comparative experimental design of 90 minutes was performed in which placebo (0.9% saline) was infused intravenously for the first 30 minutes followed by metoclopramide (7.5 microg/kg/min), a dopamine receptor antagonist for 30 minutes, and then metoclopramide (7.5 microg/kg/min) plus dopamine (0.5-3 microg/kg/min) for 30 minutes. The following clinical and biochemical parameters were measured at the beginning and then every 30 minutes of the experimental period (30', 60' and 90'): systolic-diastolic and mean arterial blood pressure, heart rate, serum glucose, insulin, triacylglycerides, and total cholesterol. Baseline glycosylated hemoglobin was measured and homeostasis model assessment for insulin resistance was calculated from insulin and glucose levels. Twelve-lead electrocardiograms were also obtained at these points. Dopamine infusion induced an increase in serum insulin, systolic blood pressure, and heart rate in healthy subjects but not in subjects with type 2 diabetes. Infusion of metoclopramide induced a hypotensive effect in healthy subjects, which was blunted by inclusion of dopamine in the infusion mixture. In subjects with diabetes, metoclopramide had no effect on blood pressure, but addition of dopamine raised systolic blood pressure. Neither metoclopramide nor dopamine altered significantly the lipid profile in healthy or diabetic subjects. Dopaminergic drugs increase serum insulin probably by interacting with dopaminergic receptors, but stimulation of beta-adrenergic receptors cannot be ruled out. Stimulation of cardiovascular dopamine receptors also caused modifications of hemodynamic parameters in healthy subjects, but apparently these receptors are attenuated in patients with type 2 diabetes probably as a result of endothelial dysfunction and alterations in the sympathetic nervous system sensitivity.