Fatty liver index as a predictor for type 2 diabetes in subjects with normoglycemia in a nationwide cohort study.

Our aim was to evaluate whether fatty liver index (FLI) is associated with the risk of type 2 diabetes (T2DM) development within the Spanish adult population and according to their prediabetes status; additionally, to examine its incremental predictive value regarding traditional risk factors. A total of 2260 subjects (Prediabetes: 641 subjects, normoglycemia: 1619 subjects) from the Di@bet.es cohort study were studied. Socio-demographic, anthropometric, clinical data and survey on habits were recorded. An oral glucose tolerance test was performed and fasting determinations of glucose, lipids and insulin were made. FLI was calculated and classified into three categories: Low (< 30), intermediate (30-60) and high (> 60). In total, 143 people developed diabetes at follow-up. The presence of a high FLI category was in all cases a significant independent risk factor for the development of diabetes. The inclusion of FLI categories in prediction models based on different conventional T2DM risk factors significantly increase the prediction power of the models when all the population was considered. According to our results, FLI might be considered an early indicator of T2DM development even under normoglycemic condition. The data also suggest that FLI could provide additional information for the prediction of T2DM in models based on conventional risk factors.

Supplementation with Phaseolus vulgaris Leaves Improves Metabolic Alterations Induced by High-Fat/Fructose Diet in Rats Under Time-Restricted Feeding.

Time-restricted feeding and food enriched in polyphenols are strategies to prevent or reduce metabolic disorders. Bean leaves (Phaseolus vulgaris L.) are a recognized source of polyphenolic compounds, whose effects on metabolic pathways are not well studied. We evaluated the combined effects of dietary supplementation with Phaseolus vulgaris leaves (10% w/w) (BL) and a 7-h daytime-restricted feeding protocol (RF) under a hypercaloric diet (high fat + high fructose) (HFFD) on the metabolic parameters related to glucose and lipid handling. Adult male Wistar rats were treated for 8 weeks with standard and HFFD diets with or without BL. The results showed that RF improved metabolic alterations induced by HFFD (e.g., hepatic steatosis, increased triacylglycerols, and serum lipoproteins). Supplementation with BL significantly enhanced this effect and downregulated the mRNA expression of carbohydrate and lipid metabolism genes in the liver. These results indicate that dietary supplementation with BL enhances the benefits elicited by RF.

Incidence of diabetes mellitus in Spain as results of the nation-wide cohort di@bet.es study.

Our aim was to determine the incidence of type 2 diabetes mellitus in a nation-wide population based cohort from Spain (di@bet.es study). The target was the Spanish population. In total 5072 people older than 18 years,were randomly selected from all over Spain). Socio-demographic and clinical data, survey on habits (physical activity and food consumption) and weight, height, waist, hip and blood pressure were recorder. A fasting blood draw and an oral glucose tolerance test were performed. Determinations of serum glucose were made. In the follow-up the same variables were collected and HbA1c was determined. A total of 2408 subjects participated in the follow-up. In total, 154 people developed diabetes (6.4% cumulative incidence in 7.5 years of follow-up). The incidence of diabetes adjusted for the structure of age and sex of the Spanish population was 11.6 cases/1000 person-years (IC95% = 11.1-12.1). The incidence of known diabetes was 3.7 cases/1000 person-years (IC95% = 2.8-4.6). The main risk factors for developing diabetes were the presence of prediabetes in cross-sectional study, age, male sex, obesity, central obesity, increase in weight, and family history of diabetes. This work provides data about population-based incidence rates of diabetes and associated risk factors in a nation-wide cohort of Spanish population.

Infrecuente complicación de páncreas ectópico: obstrucción intestinal por pseudoquiste pancreático en píloro / Infrequent complication of heterotopic pancreas: intestinal obstruction by pancreatic pseudocyst in pylorus

Resumen: Presentamos un caso un hombre de 53 años con antecedentes de reflujo gastroesofágico y pirosis con varias visitas al servicio de urgencias por vómitos, con antecedentes de consumo crónico de alcohol. La TC sin y con contraste endovenoso mostró a nivel del píloro una lesion ovoidea de paredes gruesas con captación similar al tejido pancreático, con un gran componente quístico bien delimitado que condiciona una obstrucción intestinal. La ecografía confirma la presencia de una lesión quística con ecos móviles en su interior. Tras la realización de antrectomía, el estudio histológico revela un pseudoquiste pancreático sobre páncreas ectópico, siendo esta presentación muy infrecuente, con pocos casos descritos hasta la fecha. Conclusión: Los hallazgos clínico-radiológicos con TC y US de páncreas ectópico pueden orientar el diagnóstico, aunque no son concluyentes. El diagnóstico definitivo se realiza mediante estudio histológico.

Abstract: A 53 year-old male with a past history of chronic alcohol intake, presents with an intestinal obstruction. A CT scan shows an ovoid tumor in pylorus with a great cystic component, thick wall and delimited rim, causing gastric retention. Its walls have similar enhancing pattern as the pancreatic tissue. Ultrasound revealed the presence of a cystic tumor with mobile echoes inside. After antrectomy the histological study reports pancreatic pseudocyst hosted in ectopic pancreas. This is an unusual presentation and only a few cases have been reported. Conclusion: The clinical and radiographic findings of ectopic pancreas are non-specific. Definitive diagnostic requires histological study.

Portable Pocket colposcopy performs comparably to standard-of-care clinical colposcopy using acetic acid and Lugol's iodine as contrast mediators: an investigational study in Peru.

OBJECTIVE: Our goal was to develop a tele-colposcopy platform for primary-care clinics to improve screening sensitivity and access. Specifically, we developed a low-cost, portable Pocket colposcope and evaluated its performance in a tertiary healthcare centre in Peru. DESIGN AND SETTING: Images of the cervix were captured with a standard-of-care and Pocket colposcope at la Liga Contra el Cáncer in Lima, Peru. POPULATION: Two hundred Peruvian women with abnormal cytology and/or human papillomavirus positivity were enrolled. METHODS: Images were collected using acetic acid and Lugol's iodine as contrast agents. Biopsies were taken as per standard-of-care procedures. MAIN OUTCOME MEASURES: After passing quality review, images from 129 women were sent to four physicians who provided a diagnosis for each image. RESULTS: Physician interpretation of images from the two colposcopes agreed 83.1% of the time. The average sensitivity and specificity of physician interpretation compared with pathology was similar for the Pocket (sensitivity = 71.2%, specificity = 57.5%) and standard-of-care (sensitivity = 79.8%, specificity = 56.6%) colposcopes. When compared with a previous study where only acetic acid was applied to the cervix, results indicated that adding Lugol's iodine as a secondary contrast agent improved the percent agreement between colposcopes for all pathological categories by up to 8.9% and the sensitivity and specificity of physician interpretation compared with pathology by over 6.0 and 9.0%, respectively. CONCLUSIONS: The Pocket colposcope performance was similar to that of a standard-of-care colposcope when used to identify precancerous and cancerous lesions using acetic acid and Lugol's iodine during colposcopy examinations in Peru. TWEETABLE ABSTRACT: The Pocket colposcope performance was similar to that of a standard-of-care colposcope when identifying cervical lesions.

Dolor lumbopélvico asociado a discapacidad durante el tercer trimestre de embarazo y su evolución posterior al parto / Lumbopelvic pain associated with disability during the third trimester of pregnancy and its evolution after delivery

RESUMEN El dolor lumbopélvico es una condición muy frecuente, afectando un 50 a 70% de las mujeres durante el embarazo. En la mayoría de los casos ha habido una recuperación al mes o 3 meses postparto. Sin embargo, estudios reportan que la mejoría es incompleta, pudiendo persistir o aumentar años posterior al parto. Esta condición puede causar limitaciones en la vida diaria, provocando algún grado de discapacidad que muchas veces no es abordado con la importancia que se merece. Objetivo Determinar la prevalencia de dolor lumbopélvico y su relación con el grado de discapacidad durante el tercer trimestre de embarazo y 3 meses postparto. Material y método Estudio observacional y cohorte prospectivo; la muestra son 81 mujeres estudiadas en su tercer trimestre de embarazo y 3 meses postparto atendidas durante 2014-2015 en el Departamento de Obstetricia & Ginecología, Clínica Las Condes. Se aplicó un cuestionario y el Índice de discapacidad Oswestry en ambas etapas y autoadministrada. El análisis de datos se realizó con STATA10.0. Resultados El 81,48% de las embarazadas presentaron dolor lumbopélvico, siendo más prevalente y con una asociación significativa en el tercer trimestre (72,84%, p<0,001). El 25,93% de las mujeres lo mantiene después del parto. Existe una asociación significativa entre dolor lumbopélvico y grado de discapacidad (p<0,001), específicamente con actividades de la vida diaria, actividad sexual y actividades domésticas. Conclusiones Existe una alta prevalencia de dolor lumbopélvico en el embarazo, y un porcentaje no menor lo mantiene postparto, y en ambos casos está asociado a un grado de discapacidad.

ABSTRACT Lumbopelvic pain is a very frequent condition that affects between 50 to 70% of pregnant women. In many cases have been a recovery over the month or three months postpartum. However, some studies showed an incomplete improvement, so it could persist or increase through years after childbirth. This condition can cause daily life limitations, it is provoking some disability grade, that many times it didn't understand with the importance that deserve. Aim To identify the lumbopelvic pain prevalence and the relation with disability grade during the third trimester of pregnancy and three months postpartum. Material and Methods Observational and prospective cohort study; the sample was 81 women studied in her third trimester of pregnancy and three months postpartum during 2014-2015 in the "Departamento de Obstetricia & Ginecologia de Clínica Las Condes". It applied a questionnaire and the Oswestry Disability Index in both stages and self-administered. Data analysis was using STATA 10.0 software. Results 81, 48% of pregnant showed lumbopelvic pain, there were being more prevalent and significantly associated with third trimester (72, 84%, p<0,001). 25, 93% of women maintained this condition postpartum. There is a significant association between lumbopelvic pain and disability grade (p<0,001), specifically with daily life, sexual and domestic activities. Conclusions There is a high prevalence of lumbopelvic pain during pregnancy, and not less percentage maintained this condition postpartum, that associated with a high disability grade.

Estenosis aórtica severa: nueva aproximación diagnóstica / Severe aortic stenosis: diagnosis approach

Estenosis aórtica (EA) es la enfermedad valvular más común referida para tratamiento quirúrgico. La ecocardiografía es el método de referencia para la evaluación de la severidad. La actual Guía Norteamericana define EA severa como un área valvular derivada por ecuación de continuidad (AVA) 1 cm2, área valvular indexada (Avaí) 0,6 cm2 / m2, gradiente medio de (MG) 40mmHg, y velocidad máxima (Vmax)> 4 m / s. La valoración ecocardiográfica de la EA es compleja, ya que depende de unas pocas mediciones críticas que son técnicamente demandantes, sujetas a errores y dependientes de metodologías de adquisición variable a través de las instituciones. Debe buscarse sistematización y estandarización de los enfoques metodológicos para las mediciones fundamentales de la válvula aórtica. Integrar la ecocardiografía con nuevas herramientas, como el score de calcio por CT y la RM tiene el potencial de hacer una plataforma más amplia para individualizar la severidad de la EA.

Aortic stenosis (AS) is the most common valvular disease referred for surgical treatment. Echocardiography is the state-of-the-art method of AS severity evaluation. Current US guidelines define severe AS as a continuity equation-derived valve area (AVA) 1 cm2, indexed valve area (AVAi) 0.6 cm2/m2, mean gradient (MG) 40mmHg, and peak velocity (Vmax) 4 m/s. Echocardiographic AS grading is complex since it relies on a few critical measurements that are technically demanding, subject to error and of variable acquisition methodology across institutions. Systematisationandstandardisationofmethodologicapproaches for fundamental echocardiographic aortic valve measurements must be sought. Integration of echocardiography with emerging independent tools such as CT valvular-calcium-load assessment and MRI has the potential of rendering a more comprehensive platform from which to individualise AS severity grading.

Analysis of the genotypic diversity of strains of Helicobacter pylori isolated from pediatric patients in Mexico.

Genotypic differences in Helicobacter pylori play an important role in infection. We characterized the diversity of the cagA, cagE, babA2, and vacA genes in H. pylori strains isolated from pediatric patients and the relationship between these genes and clinical disease. Additionally, we employed the Neighbor-net algorithm to predict the behavior of the genotypes of the strains isolated from patients. Of 93 patients analyzed, 32 were positive for infection. A total of 160 H. pylori strains (five isolates per positive patient) were analyzed. A total of 91% and 83% of strains possessed the cagA and cagE genes, respectively. For the vacA gene, 84% of strains possessed the s1 allele, 15% the s2 allele, 81% the m1 allele and 13.8% the m2 allele. The babA2 gene was present in 79% of strains. Infection with H. pylori strains with the vacA (s1m1) genotype was associated with risk of esophagitis and gastritis (p=0.0001). The combination of cagA and vacA (s1m1) was significantly associated with abdominal pain (p=0.002); however, EPIYA type was not significantly associated with abdominal pain. A total of 16 different genotypes were identified; the most common genotype was vacAs1m1cagA+cagE+babA2+ (47.5%). A total of 84% of pediatric patients were infected by at least two and up to five different genotypes. The network recovered two genotype groups (A: strains with vacAs1 and B: strains with vacAs2). The presence of multiple paths in the network suggests that reticulate events, such as recombination or reinfection, have contributed to the observed genotypic diversity.

Rehabilitación pelviperineal multimodal en pacientes con incontinencia fecal / Multimodal pelviperineal rehabilitation in patients with fecal incontinence

Fecal incontinence (FI) is associated with low self-esteem and quality of life. Nowadays, multimodal pelviperineal rehabilitation (MPPR) has become the preferred treatment. Purpose: To evaluate our results of multimodal pelviperineal rehabilitation (MPPR) in patients diagnosed with fecal incontinence (FI). Methods: Historic cohort study using a prospectively maintained database from patients with FI that underwent MPPR between years 1999 and 2012. FI was classified according to Jorge-Wexner´s scale, at the beginning (Winitial) and the end (Wfinal) of treatment. In July 2013 a survey was carried out to measure follow-up Wexner score (Wfollow-up) and pelvic muscle training. Statystical analysis was performed using Chi square test, Fisher Test, Mann-Whitney and Odds Ratio. Significant p value < 0.05. Results: One hundred and thirteen patients completed treatment, median age 67 years-old (r: 24-91) and 83 percent female. Median scores for Winitial and Wfinal were 9 points (r: 3-19) and 3 points (r: 0-13), respectively (p < 0.001). In July 2013, 68 (61 percent) patients were available for follow-up. Wexner score at the beginning, end and follow-up were as follows: 9 (i: 3-19), 3 (i:0-12) and 4 (i:0-19), respectively. There were significant differences between Winitial and Wfollow-up (p < 0.001), but not between Wfinal and Wfollow-up (p = 0.23). There were 20 patients (29 percent) who kept training their pelvic muscles and 48 (71 percent) who did it very rarely or did not do it at all. It was the latter group who showed an increased risk to obtain worst score in Wfollow-up (OR = 3.89; CI 95 percent: 1.26-11.9; p = 0.0175). Conclusion: FI patients treated with MPPR show good short and long-term results.

Introducción: La incontinencia fecal (IF) se asocia a menor calidad de vida en quienes la sufren. Actualmente, la rehabilitación pelviperineal multimodal (RPPM) es el tratamiento inicial de elección. Objetivo: Evaluar los resultados de la RPPM en pacientes con IF. Método: Estudio de cohorte histórica de pacientes con IF que recibieron RPPM entre 1999-2012. Se utilizó la escala de Jorge-Wexner para medir laIF, al inicio (Wi) y fin (Wf) del tratamiento. Se aplicó una encuesta en julio de 2013 para medir el Wexner de seguimiento (Ws) y mantención de ejercicios terapéuticos. Análisis estadístico: prueba de c2, prueba exacta de Fisher, Mann-Whitney y Odds Ratio. Significancia estadística p < 0,05. Resultados: Hubo 113 pacientes que completaron el tratamiento. La mediana de edad fue 67 años (i: 24-91) y 83 porciento género femenino. La mediana de Wi fue de 9 puntos (i: 3-19) y la mediana de Wf fue de 3 puntos (i: 0-13) (p < 0,001). Se logró contactar a 68 pacientes para el seguimiento, en ellos la mediana del puntaje de Wi, Wf y Wsfue de 9 (i: 3-19), 3 (i:0-12) y 4 (i:0-19), respectivamente. Hubo diferencia significativa entre Wi y Ws (p < 0,001), pero no entre Wf y Ws (p = 0,23). Veinte pacientes (29 por ciento) realizaron ejercicios terapéuticos regularmente y 48 (71 por ciento) nunca o raramente; este último grupo es factor de riesgo para obtener peores resultados (OR = 3,89; CI 95 porciento: 1,26-11,9; p = 0,0175). Conclusión: El tratamiento con RPPM en pacientes con IF tiene buenos resultados a corto y largo plazo.

Caracterización de las infecciones respiratorias en pacientes adultos oncológicos / Clinical characteristics of respiratory infections in patients with cancer

Introduction: Infections are common in oncology. Aim: To characterize respiratory infections in hospitalized adult cancer patients. Methods: Prospective, descriptive study of febrile adult patients in oncology at the Hospital Clínico Universidad Católica de Chile, between April 2008 and April 2009. Results: 187 episodes were evaluated. Clinical infection was recognized in 70% and 33 episodes (25%) were respiratory focus. Neoplastic disease corresponded to solid organ cancer in 77% of cases and 33% were admitted with febrile neutropenia. The upper respiratory tract infection accounted for 36% and low respiratory tract infection 65% of cases; 55% was pneumonia. Etiology of these was isolated in 39% (S. pneumoniae 2 cases, S. bovis 1, E. faecalis 1, P. jirovecii 2, S. maltophilia 1 and A. fumigatus 1). Hospital mortality for pneumonia was 22% and overall mortality 12%. Conclusions: Respiratory infections are a major focus in adult cancer patients, highlighting pneumonia. It carries high mortality and varied etiology.

Introducción: Las infecciones en oncología son frecuentes. Objetivo: Caracterizar las infecciones respiratorias en pacientes oncológicos hospitalizados. Métodos: Estudio descriptivo prospectivo de pacientes adultos oncológicos febriles en el Hospital Clínico de la Universidad Católica, entre abril de 2008 y abril de 2009. Resultados: Se evaluaron 187 episodios. Se identificó foco clínico en 70% y 33 episodios (25%) correspondieron a foco respiratorio. La patología oncológica correspondió a tumores de órgano sólido en 77% de los casos y el 33% ingresó con neutropenia febril. La infección respiratoria alta representó el 36% y baja un 65% de los casos; 55% fueron neumonía. De estos, se aisló el agente causal en un 39% (S. pneumoniae 2 casos, S. bovis 1, E. faecalis 1, P. jirovecii 2, S. maltophilia 1 y A. fumigatus 1). La letalidad en el hospital por neumonía fue 22% y la mortalidad general 12%. Conclusiones: La infección respiratoria es un motivo de consulta y hospitalización frecuente en pacientes oncológicos, destacando la neumonía. Conlleva elevada mortalidad y etiología variada.

Opiniones y creencias de embarazadas encontrol prenatal relacionadas con salud oral y embarazo / Opinion and beliefs of pregnancy women in prenatal control related to oral health and pregnant

Los procesos vitales son motivo de preguntas para la humanidad. La cultura popular da respuestas a éstas, no siempre científicamente, transformando las creencias en mitos. En salud oral, se cree que las embarazadas desarrollarían caries más fácilmente que la población general, considerándose normal que “por cada hijo se pierda un diente”, y mujeres embarazadas no desean recibir atención odontológica por el daño que podría producir al feto el uso de anestésicos locales, hecho importante ante la carencia de información del bajo riesgo que poseen para el paciente éstos procedimientos por algunos médicos, quienes rehusan someter a embarazadas a tratamientos dentales. La cultura tiene una profunda relación en el estilo de vida, sociabilización y autoayuda, mecanismos de intervención que serían cimientos que basan la promoción en salud. La investigación busca conocer las ideas que posee un grupo de embarazadas en control prenatal, en torno a la salud oral y el embarazo. Fue confeccionada una encuesta con 5 preguntas cerradas, aplicándose a 65 embarazadas seleccionadas aleatoriamente. La muestra fue obtenida por conveniencia. El 98% de las encuestadas cree que durante el embarazo es necesario consultar al odontólogo, el 60% cree que el embarazo produce caries y el 70% cree que el embarazo puede producir pérdida de piezas dentarias. Se requieren más esfuerzos en educación durante el control prenatal para entregar conocimientos adecuados a las embarazadas en relación a salud oral y embarazo, incluyendo el factor cultural, que les permita mejorarlas medidas de auto cuidado durante este período (AU)

Vital processes have created questions to humankind. People’s culture gives non-scientific response to some of it, changing beliefs into myths. Related to oral health, several cultures believe that pregnant women could suffer more frequently dental caries than general population, is considered normal that "by each one baby, mother lost a teeth", and some pregnant patients are not able to receive dental treatment, because this procedures could produce damages to fetus in develop; important situation considering absence of information that dental procedures expose to such a low risk to patients in some physicians, whom refuse authorize to pregnant women to receive dental treatment. Culture has a deep relationship to life styles, social relations and self-help; in these intervention mechanisms are based health promotion. The research seeks to know the ideas have a group of pregnant women in prenatal control related to oral health and pregnant. Was made a survey with 5 closed questions, applied to 65 pregnant woman randomly selected. 98% of women think that through pregnant period is necessary to visit a dentist, 60% believe that pregnant cause dental caries and 70% thinks that pregnant could cause lost of tooth. Mayor efforts in education, considering cultural factors, are required through prenatal control to improve knowledge as well as self care in oral health in these patients group (AU)

Hiperkalemia grave asociada a drogas que actúan sobre el sistema renina, angiotensina, aldosterona: Un problema que requiere atención: Caso clínico / Severe hyperkalemia associated to the use of losartan and spironolactone: Case report

Hyperkalemia is a complications of the use of angiotensin converting enzyme inhibitors, angiotensin receptor antagonists and aldosterone antagonists. These drugs are commonly used for the treatment of hypertension and cardiac failure. We report a 84 year-old female treated with losartan 50 mg/day and spironolactone 25 mg/day that presented with a hyperkalemia of 8.4 mEq/l and bradicardia, drowsiness and respiratory depression. She required hemodialysis and ventilatory assistance. She was discharged in good conditions five days after admission.

[Prevalence of celiac disease in diabetic children and adolescents]. / Prevalencia de enfermedad celíaca en niños y adolescentes diabéticos.

BACKGROUND: Celiac disease is more common in patients with insulin dependent diabetes than in the general population. AIM: To detect celiac disease in diabetic children and adolescents. PATIENTS AND METHODS: IgA antigliadin, IgG antireticulin and IgG antiendomysium antibodies were measured in 67 diabetic children (35 female), aged between 4 and 18 years old. RESULTS: Only one male adolescent, aged 18 years old, without gastrointestinal symptoms, had a significant elevation of antireticulin and antiendomysium antibodies. His intestinal biopsy showed subtotal villous atrophy, consistent with celiac disease. CONCLUSIONS: The prevalence of celiac disease in these diabetic children is 1:67 (1.5%). Similar figures have been reported elsewhere.

Zinc supplementation and growth of infants born small for gestational age.

To analyze the effect of zinc supplementation on postnatal growth of infants born small for gestational age, we selected 68 infants at birth and followed them monthly for 6 months. They were randomly assigned to a supplemented group (group S, n = 35) receiving 3 mg of Zn (acetate) per day, or to a placebo (group P, n = 33), in a double-blind study. Weight increments in group S were significantly higher than those in group P at 2 months (p < 0.003); z scores showed catch-up growth only in group S. Length increments were also greater in group S than in group P, ending at 6 months were 64.9 +/- 1.8 versus 63.4 +/- 3.5 cm (mean +/- SD; p < 0.01); changes in z scores for 6 months were -1.28 to -0.66 in group S and -1.43 to -1.47 in group P (p < 0.001). Weight-for-length improved similarly in both groups (z score, -2.2 to +0.2). The increase in weight-for-age was higher in group S girls (p < 0.034), ending at 6 months with -0.13 +/- 0.59, versus -0.52 +/- 0.62 in group S boys, -1.15 +/- 0.49 in group P girls, and -1.05 +/- 0.80 in group P boys (+/- SD). More infants in group P received cow milk-based formula before 4 months because of inadequate weight increments. An additive effect on weight increase was observed between Zn supplementation (p < 0.02), exclusive breast-feeding after 4 months of age (p < 0.001), and gender (p < 0.02). Plasma and hair Zn values showed a downward trend, less marked in group S than in group P. We conclude that Chilean infants born small for gestational age have better weight and linear growth during the first 6 months of life if they receive Zn supplementation.

Characterization of the alpha 1B-adrenergic receptors of chicken hepatocytes. Signal transduction and actions.

1. In chicken hepatocytes, alpha 1-adrenoceptor activation increased: (a) phosphatidylinositol labeling; (b) production of inositol trisphosphate; (c) cytosol calcium; and (d) phosphorylase activity. 2. Prazosin (Ki approximately 0.2-0.4 nM) was more potent in inhibiting these actions than 5-methyl-urapidil (Ki approximately 30-60 nM); these actions were sensitive to chlorethylclonidine suggesting the involvement of alpha 1B-adrenoceptors. 3. The stimulation of phosphoinositide turnover was insensitive to pertussis toxin. 4. In chicken liver membranes, [3H]prazosin binding sites (Bmax 872 fmol/mg protein) with high affinity for prazosin (KD 0.3 nM; Ki 0.4 nM) and lower affinity for 5-methyl-urapidil (Ki 46 nM) were detected, consistent with the presence of alpha 1B-adrenoceptors.

Activation of protein kinase C inhibits hormonal stimulation of the GTPase activity of Gi in human platelets.

The effect of 12-tetradecanoyl phorbol 13-acetate on the GTPase activity of Gi was investigated. Treatment with TPA did not alter basal GTPase activity of membranes or the stimulatory effect of prostaglandin E1 (putatively via Gs). In contrast, the phorbol ester markedly diminished stimulation of GTPase by agents whose receptors are coupled to Gi such as epinephrine (alpha-adrenergic action), platelet activating factor or thrombin. Pertussis toxin catalyzed ADP-ribosylation was also decreased in membranes from TPA-treated platelets as compared to the controls. It is suggested that the alteration in the hormonal activation of the GTPase activity of Gi is secondary to a perturbation in the receptor-Gi interaction.

Activation of protein kinase C alters the interaction of alpha 2-adrenoceptors and the inhibitory GTP-binding protein (Gi) in human platelets.

The effect of 12-tetradecanoyl phorbol 13-acetate (TPA) on the hormonal modulation of adenylate cyclase was studied. The effect of epinephrine (alpha 2-adrenergic action) was markedly diminished in membranes from TPA-treated platelets as compared to the controls. Interestingly, the inhibitory effect of guanylyl imido diphosphate (Gpp(NH)p) was not altered. Neither the number of alpha 2-adrenoceptors nor their affinity for [3H]yohimbine were affected by the treatment with TPA. In control platelets, 77% of the receptors were in a high-affinity state for epinephrine and 22% in a low-affinity state; Gpp(NH)p shifted the receptor affinity towards the low-affinity conformation. In membranes from TPA-treated platelets, the receptors were in the low-affinity state and no further decrease in affinity was induced by Gpp(NH)p. Our data suggest that activation of protein kinase C in platelets blocks the hormonal inhibition of adenylate cyclase by interfering with the receptor-Gi interaction.