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BACKGROUND: To help implement behavior change interventions (BCIs) it is important to be able to characterize their key components and determine their effectiveness. PURPOSE: This study assessed and compared the components of BCIs in terms of intervention functions identified using the Behaviour Change Wheel Framework (BCW) and in terms of their specific behavior change techniques (BCTs) identified using the BCT TaxonomyV1, across six behavioral domains and the association of these with cost-effectiveness. METHODS: BCIs in 251 studies targeting smoking, diet, exercise, sexual health, alcohol and multiple health behaviors, were specified in terms of their intervention functions and their BCTs, grouped into 16 categories. Associations with cost-effectiveness measured in terms of incremental cost-effectiveness ratio (ICER) upper and lower estimates were determined using regression analysis. RESULTS: The most prevalent functions were increasing knowledge through education (72.1%) and imparting skills through training (74.9%). The most prevalent BCT groupings were shaping knowledge (86.5%), changing behavioral antecedents (53.0%), supporting self-regulation (47.7%), and providing social support (44.6%). Intervention functions associated with better cost-effectiveness were those based on training (ßlow = -15044.3; p = .002), persuasion (ßlow = -19384.9; p = .001; ßupp = -25947.6; p < .001) and restriction (ßupp = -32286.1; p = .019), and with lower cost-effectiveness were those based on environmental restructuring (ß = 15023.9low; p = .033). BCT groupings associated with better cost-effectiveness were goals and planning (ßlow = -8537.3; p = .019 and ßupp = -12416.9; p = .037) and comparison of behavior (ßlow = -13561.9, p = .047 and ßupp = -30650.2; p = .006). Those associated with lower cost-effectiveness were natural consequences (ßlow = 7729.4; p = .033) and reward and threat (ßlow = 20106.7; p = .004). CONCLUSIONS: BCIs that focused on training, persuasion and restriction may be more cost-effective, as may those that encourage goal setting and comparison of behaviors with others.
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Terapia Conductista , Conductas Relacionadas con la Salud , Ejercicio Físico , Humanos , FumarRESUMEN
BACKGROUND: Smoking cessation improves physical health but it has been suggested that in vulnerable individuals it may worsen mental health. This study aimed to identify the short- and longer-term effects of stopping smoking on depression and anxiety in the general population and in those with a history of these disorders. METHOD: Sociodemographic and smoking characteristics, and mental and physical health were assessed using established measures in the ATTEMPT cohort, an international longitudinal study of smokers (n = 3645). Smokers who had stopped for at least 3 months or less than 3 months at the 12-month follow-up were compared with current smokers (n = 1640). RESULTS: At follow-up, 9.7% [95% confidence interval (CI) 8.3-11.2] of smokers had stopped for less than 3 months and 7.5% (95% CI 6.3-8.9) for at least 3 months. Compared with current smokers, prevalence of depression prescriptions obtained in the last 2 weeks was lower for those who had stopped for less than 3 months [odds ratio (OR) 0.37, 95% CI 0.14-0.96] or at least 3 months (OR 0.25, 95% CI 0.06-0.94) after adjusting for baseline prescription levels and confounding variables. Adjusted prevalence of recent depression symptoms was also lower for ex-smokers who had stopped for less than 3 months (OR 0.34, 95% CI 0.15-0.78) or at least 3 months (OR 0.24, 95% CI 0.09-0.67) than among continuing smokers. There was no change in anxiety measures in the general population or any increase in anxiety or depression symptoms in ex-smokers with a past history of these conditions. CONCLUSIONS: Smoking cessation does not appear to be associated with an increase in anxiety or depression and may lead to a reduced incidence of depression.
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Trastornos de Ansiedad/epidemiología , Trastorno Depresivo/epidemiología , Cese del Hábito de Fumar/estadística & datos numéricos , Adulto , Trastornos de Ansiedad/psicología , Canadá/epidemiología , Estudios de Casos y Controles , Estudios de Cohortes , Trastorno Depresivo/psicología , Femenino , Francia/epidemiología , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Prospectivos , Fumar/psicología , Cese del Hábito de Fumar/psicología , España/epidemiología , Reino Unido/epidemiología , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND/OBJECTIVE: Despite the increase in roll-your-own (RYO) cigarette consumption in many countries, very little is known about RYO smokers. In order to estimate the health risks inherent in RYO use, it is important to assess exposure to tobacco toxins in this group. Exposure is determined by a number of factors, including puffing behaviour, but so far this issue has not been addressed among RYO smokers. This study sought both to determine the feasibility of measuring puffing behaviour in this group, its reliability and validity, and to characterise puffing behaviour among RYO smokers compared with smokers of factory-made (FM) cigarettes. METHODS: At two visits, 24 hours apart, 131 FM and 29 RYO cigarette smokers provided saliva samples that were assayed for cotinine, a measure of nicotine intake and thus smoke exposure. Self-reported puffing behaviour of participants, as well as their demographic and smoking characteristics were also assessed. At the end of the first visit, smokers were shown how to use a portable smoking topography machine that measures puffing behaviour, the CReSSmicro, and asked to smoke all cigarettes with this machine until the second visit, when participants were asked to provide feedback on using the device. RESULTS: Both RYO and FM cigarette smokers reported that the CReSSmicro was easy to use; however, RYO cigarette smokers were more likely to have missing data, to reduce cigarette consumption and to indicate a change in their puffing behaviour because of the device. Machine-determined puffing behaviour was equally stable over time in both groups with similar ability to predict exposure; cotinine levels were related to machine but not to self-reported puffing parameters. Overall, RYO smokers appeared to puff cigarettes less hard but for longer than FM cigarette smokers. CONCLUSION: The measurement of puffing behaviour using a topography device is feasible but less practicable for RYO than FM cigarette smokers. Puffing parameters show comparable reliability and validity for both groups of smokers and reveal some differences in smoking topography dependent on the type of cigarette smoked.
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Ensayo de Materiales/instrumentación , Humo/análisis , Fumar/metabolismo , Adolescente , Adulto , Seguridad de Productos para el Consumidor , Cotinina/análisis , Estudios de Factibilidad , Femenino , Humanos , Exposición por Inhalación/análisis , Masculino , Ensayo de Materiales/métodos , Persona de Mediana Edad , Nicotina/análisis , Reproducibilidad de los Resultados , Saliva/química , Autorrevelación , Nicotiana/química , Adulto JovenRESUMEN
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is the fourth most common cause of death worldwide. It is caused primarily by cigarette smoking. Given its importance, it is remarkable that reliable national prevalence data are lacking for most countries. This study provides estimates of the national prevalence of COPD in England, the extent of under-detection of the disorder, and patterns of cigarette smoking, dependence, and motivation to stop smoking in those with the disease. METHODS: Data from 8215 adults over the age of 35 who participated in the Health Survey for England were analysed. Information was obtained on self-reported and cotinine validated smoking status, cigarette dependence, motivation to stop smoking, COPD defined by spirometry using joint American Thoracic Society and European Respiratory Society criteria, and self-reports of diagnosis with respiratory disorders. RESULTS: Spirometry-defined COPD was present in 13.3% (95% CI 12.6 to 14.0) of participants, over 80% of whom reported no respiratory diagnosis. Even among people with severe or very severe COPD by spirometric assessment, only 46.8% (95% CI 39.1 to 54.6) reported any diagnosed respiratory disease. A total of 34.9% (95% CI 32.1 to 37.8) of people with spirometry-defined COPD were smokers compared with 22.4% (95% CI 21.4 to 23.4) of those without, and smoking prevalence increased with disease severity. Smokers with spirometry-defined COPD were more cigarette dependent but had no greater desire to quit than other smokers. CONCLUSION: COPD is common among adults in England and is predominantly undiagnosed. In smokers it is associated with higher degrees of cigarette dependence but not with a greater motivation to stop smoking.
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Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Fumar/epidemiología , Tabaquismo/epidemiología , Adulto , Distribución por Edad , Anciano , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/etiología , Fumar/efectos adversos , Espirometría , Tabaquismo/complicacionesRESUMEN
Concern about a potentially increased risk of liver cancer associated to cyproterone acetate (CPA) treatment led to a postmarketing long-term surveillance study with historic accural of four groups of patients with sexual-hormonal disorders under treatment with CPA. The aim of the study was to provide a description of potential ADRs under CPA treatment with special emphasis on liver cancer. A long-term follow-up of 2506 patients was conducted. Six hundred and two persons were followed up retrospectively for longer than 10 years. In 16,721 patient-years of observation after the first CPA dose no malignant liver tumour was observed, whereas six would have been expected in this cohort. Seven incident, non-fatal benign liver tumours were found. Altogether 9.6% of a subset of 1685 patients with reported liver tests had, at some time, elevated liver enzymes. No cases were reported where CPA therapy had been discontinued due to severe liver disorder. We concluded from this active surveillance project, that CPA treatment is probably safe in the groups of patients followed up. Even though there was not a single case of liver cancer detected, the hypothesis of an elevated risk is being tested in an ongoing collaborative European case-control study which is examining the association of CPA use and primary hepatocellular cancer.
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A series of new positive inotropic agents was synthesized with the aim of combining the pharmacophores of the imidazolone-type phosphodiesterase (PDE) inhibitor enoximone and guanidine-type histamine H2 receptor agonists such as arpromidine. All compounds are para-substituted 4-benzoyl-5-alkyl-2-imidazolones. H2 agonism was incorporated by p-(hetero)arylalkyl substituents, in particular by an imidazolylpropyl guanidine group. In addition analogous ureas, cyanoguanidines, alkyl guanidine carboxylates, and amides were prepared. These functional groups were either directly attached to the phenyl ring or linked by an appropriate spacer. The compounds were screened for positive inotropic activity in the isolated electrically stimulated guinea pig papillary muscle and for inhibition of PDE III (cGMP-inhibited cAMP PDE, isolated from guinea pig heart). The cardiotonics obtained proved to be either PDE III inhibitors, some of them surmounting up to 3-fold the potency of enoximone, or pharmacological hybrids combining both PDE III inhibitor and histamine H2 receptor agonist activities. These hybrids were the most potent positive inotropic substances at the papillary muscle, probably due to their synergistic mechanism of action. The participation of histamine H2 receptors could be demonstrated in the papillary muscle preparation by pretreatment with the H2 antagonist famotidine (10 microM) as well as by further pharmacological experiments using isolated perfused hearts of guinea pigs and rats, isolated guinea pig right atria, adenylyl cyclase and H2 receptor binding assays. At equieffective concentrations the moderate PDE III inhibitor and histamine H2 agonist N1-(4-[(1,3-dihydro-5-methyl-2-oxo-3H-imidazol-4-yl)-carbonyl]phenyl)-N2 - [3-(1H-imidazol-4-yl)propyl]guanidine 65 and the 5-ethyl homologue 66 were about 2 and 10 times more potent than enoximone at the papillary muscle. Moreover, both compounds produced a 2.5-fold higher maximal response than the reference compound.
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3',5'-AMP Cíclico Fosfodiesterasas/antagonistas & inhibidores , Cardiotónicos/síntesis química , Guanidinas/síntesis química , Agonistas de los Receptores Histamínicos/síntesis química , Imidazoles/síntesis química , Inhibidores de Fosfodiesterasa/síntesis química , Animales , Cardiotónicos/farmacología , Fosfodiesterasas de Nucleótidos Cíclicos Tipo 3 , Guanidinas/farmacología , Cobayas , Agonistas de los Receptores Histamínicos/farmacología , Imidazoles/farmacología , Técnicas In Vitro , Masculino , Miocardio/enzimología , Inhibidores de Fosfodiesterasa/farmacología , Ratas , Ratas WistarRESUMEN
The localization of three key signal transduction components was indicated in rat heart tissue by immunocytochemical and histochemical experiment. It was shown that: 1. The M2 muscarinic receptors are localized along outer cell membranes and T-tubule membranes of cardiomyocytes but additionally at membranes of endothelial cells and fibroblasts. 2. Gia was found along outer cell membranes of cardiomyocytes and other cells of the heart and also inside the cells of the perinuclear space in close contact to the nuclei envelope and the endoplasmic reticulum membranes. Goa were found to be associated mainly in atrial tissue, especially at the nerval (neuronal) endings located among the cardiac muscle cells. This was shown in parallel incubation with specific neuronal antibody as a marker for these structures. 3. Adenylyl cyclase was localized along the sarcolemma and the T-tubule membranes in normal cardiomyocytes of rat and guinea pig hearts. Under ischemic conditions, the adenylyl cyclase was also seen in junctional sarcoplasmic reticulum membranes. The reasons for this changed localization need further elucidation. Binding of the adenylyl cyclase within the molecular structure of the membrane or variation of the marker penetration remain to be clarified.
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Adenilil Ciclasas/análisis , Proteínas de Unión al GTP/metabolismo , Miocardio/citología , Receptores Muscarínicos/análisis , Animales , Técnica del Anticuerpo Fluorescente , Proteínas de Unión al GTP/química , Cobayas , Inmunohistoquímica , Membranas Intracelulares/química , Microscopía Electrónica , Miocardio/ultraestructura , Ratas , Sarcolema/química , Transducción de Señal/fisiologíaRESUMEN
The PACAPs have been shown to be potent vasodilators in different animal species. Data in humans are still lacking. Therefore we investigated the effects of PACAP 38, PACAP 27 and VIP on isolated human and porcine coronary arteries (HCA and PCA). Our data show, that the PACAPs are endothelium-independent vasorelaxants, which in HCA are slightly more potent than VIP. The N-terminal shortened peptides PACAP 6-38 and PACAP 6-27 also show relatively potent vasorelaxant effects, acting as partial agonists. Glibenclamide, a selective inhibitor of ATP-sensitive potassium channels, partially reverses the effects of the PACAPs, indicating an involvement of these channels in the mechanism of action.
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Vasos Coronarios/efectos de los fármacos , Neuropéptidos/farmacología , Vasodilatadores/farmacología , Animales , Vasos Coronarios/citología , Endotelio Vascular/fisiología , Gliburida/farmacología , Humanos , Técnicas In Vitro , Polipéptido Hipofisario Activador de la Adenilato-Ciclasa , Bloqueadores de los Canales de Potasio , Canales de Potasio/metabolismo , Especificidad de la Especie , PorcinosRESUMEN
Localization of G proteins in the rat heart tissue was investigated using primary affinity-purified antibodies against synthetic peptides with amino acid sequences corresponding to alpha-subunits (alpha i common and alpha i 1, 2) of G proteins. Detection of immunoreactivity was performed with the peroxidase-anti-peroxidase complex (PAP), avidin-biotin complex (ABC) and fluorescein-labelled secondary antibodies for light microscopy and the protein A-gold technique for electron microscopy. In ventricles and atria, immunostaining for G proteins was detected in the sarcolemma and perinuclear space of cardiomyocytes. In endotheliocytes and fibroblasts, immunoreactivity was present also in the endoplasmic reticulum. All four immunocytochemical methods permit to demonstrate the same localization of G proteins in heart tissue. The ABC method and fluorescein labelled secondary antibodies technique showed the same sensitivity which is higher than that of the PAP method. Nomarski contrast microscopy enhanced the visualization of the final reaction product formed by the peroxidase reaction developed with diaminobenzidine in the ABC method. The results are discussed in terms of the role of G proteins in signal transduction via plasma membrane and membranes of the intracysternal space of the cell.
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Proteínas de Unión al GTP/análisis , Miocardio/química , Secuencia de Aminoácidos , Animales , Especificidad de Anticuerpos , Secciones por Congelación , Técnicas para Inmunoenzimas , Inmunohistoquímica , Microscopía Electrónica , Datos de Secuencia Molecular , Ratas , Ratas Wistar , Transducción de Señal , Adhesión del TejidoRESUMEN
In isolated rat hearts the calcium paradox, induced by perfusion for 3 minutes in the absence of calcium followed by perfusion for 10 minutes in the presence of calcium, depressed the activation of adenylyl cyclase by l-isoproterenol, NaF and forskolin. The characteristics of the beta-adrenoceptors and the activation of adenylyl cyclase by guanylyl imidodiphosphate were not changed. The findings suggest an uncoupling of beta-adrenoceptors from the catalytic site of the adenylate cyclase complex. Diltiazem, at 0.4 microM in the perfusion medium, greatly reduced the diminution of the activation of adenylate cyclase by isoproterenol and forskolin, and completely prevented the depression of the activation of adenylate cyclase by NaF. These effects may be due to interference by diltiazem with the mechanisms that promote an excessive influx of calcium into the heart during the calcium paradox.
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Adenilil Ciclasas/metabolismo , Calcio/metabolismo , Diltiazem/farmacología , Miocardio/metabolismo , Animales , Colforsina/farmacología , AMP Cíclico/metabolismo , Activación Enzimática/efectos de los fármacos , Isoproterenol/farmacología , Masculino , Perfusión , Ratas , Receptores Adrenérgicos beta/metabolismo , Fluoruro de Sodio/farmacologíaRESUMEN
The value of transaortal subvalvular myectomy after Morrow remains unclarified. We therefore analysed our results with HOCM with particular attention to the operation risk and the longterm results. 56 patients were treated at the Leipzig Heart Centre between January 1984 and August 1990 using the transaortic myectomy. In 16 patients an additional mitral valve replacement or -reconstruction was required. In 14 patients, other combined operations (aortic valve replacement, aortocoronary bypass) were indicated. In the postoperative observation period (up to 7 years; 141 patient-years; mean follow-up 4.2 yrs) detailed information was obtained at regular intervals about subjective complaints, ECG changes, left ventricular functional parameters and the weight of the heart muscle mass were recorded. The myectomy resulted in an alteration of the NYHA-class from 3.1 to 1.3 postoperatively (p < 0.05). The ventriculo-aortal pressure gradient reduced in the group myectomy (group I) from 69.2 +/- 5.2 to 23.3 +/- 2.7 mmHg postoperatively. In the myectomy+mitral valve repair group (group II) the intracavitary pressure gradient was even reduced to 11.7 +/- 2.2 Torr (p < 0.05). The Sokolov-Lyon-Index was 3.7 +/- 0.19 mV preoperatively and went down to 2.9 +/- 0.16 mV. The heart muscle mass decreased from 680 g to a postoperative value of 430 g (p < 0.05). The relation of BAR and calcium channel density of 0.5 +/- 0.1 in HOCM versus 0.9 +/- 0.08 in a control group (n = 6) proves the increased number of calcium channels in HOCM.
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Cardiomiopatía Hipertrófica/cirugía , Ecocardiografía Doppler , Ecocardiografía , Hemodinámica/fisiología , Complicaciones Posoperatorias/diagnóstico por imagen , Adolescente , Adulto , Anciano , Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/cirugía , Velocidad del Flujo Sanguíneo/fisiología , Cardiomiopatía Hipertrófica/diagnóstico por imagen , Cardiomiopatía Hipertrófica/mortalidad , Terapia Combinada , Puente de Arteria Coronaria , Femenino , Estudios de Seguimiento , Prótesis Valvulares Cardíacas , Humanos , Masculino , Persona de Mediana Edad , Válvula Mitral/diagnóstico por imagen , Válvula Mitral/cirugía , Complicaciones Posoperatorias/mortalidad , Tasa de SupervivenciaRESUMEN
UNLABELLED: Between 1/84 and 6/91 56 patients were treated for hypertrophic obstructive cardiomyopathy (HOCM): the Morrow technique alone was performed on 40 patients (group 1), in 16 patients (group 2) an additional replacement (n = 13) or reconstruction (n = 3) of the mitral valve was indicated. In a total of 14 cases coronary artery bypass grafting and aortic valve replacement was performed in addition. Postoperatively (mean follow-up 4.2 yrs, 141 patient-years) left-ventricular diastolic and systolic function parameters, heart muscle mass, ECG findings, and symptomatology were recorded and the ratios of beta-adrenoreceptor density to density of the calcium channel were measured. RESULTS: Pressure gradient decreased from 69.2 +/- 5.2 (group 1) and 75.1 +/- 4.8 (group 2) to 23.3 +/- 2.7 and 11.7 +/- 2.2 mmHg postoperatively. Likewise Sokolow-Lyon index decreased from 3.5 +/- 0.2/3.7 +/- 0.2 to 2.9 +/- 0.2/2.8 +/- 0.3. The quotient time-to-peak-velocity/left-ventricular-ejection-time decreased significantly in group 2 from 58.6 +/- 6.3 to 41.9 +/- 5.8 (p less than 0.05). The heart muscle mass, determined echocardiographically, decreased from 680g to 430g (p less than 0.05). Isovolumetric tension time, isovolumetric relaxation time, and E/A ratio at rest and after stress showed typical characteristics. Ca(++)-channel density was clearly raised in all patients, with no differences between the two groups being observable. We conclude from our results: The most marked improvements in clinical and left-ventricular functional parameters were experienced by patients in group 2 (myectomy+MVR).(ABSTRACT TRUNCATED AT 250 WORDS)
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Válvula Aórtica/cirugía , Cardiomiopatía Hipertrófica/cirugía , Válvula Mitral/cirugía , Adolescente , Adulto , Anciano , Cardiomiopatía Hipertrófica/mortalidad , Cardiomiopatía Hipertrófica/fisiopatología , Estudios de Seguimiento , Hemodinámica , Humanos , Persona de Mediana Edad , Complicaciones Posoperatorias/mortalidadRESUMEN
The irreversible loss of activity of the sarcolemma-localized beta-receptor-adenylyl cyclase system (beta-RAS) in myocardial ischemia is a well documented phenomenon. Alterations in the sarcolemma (SL) induced by reactive O2 species could be responsible for this loss. Therefore the influence of oxidation of SH-groups and lipid peroxidation induced by Fe2+/Vit. C on the beta-RAS activity was studied. During incubation of SL with Fe2+/Vit. C a transient enhancement followed by a continuous loss of the beta-RAS activity (isoprenaline-, NaF-, Gpp(NH)p-, forskolin-stimulated and basal activity) was observed. In contrast there occurred a continuous loss of SH-groups and lipid peroxidation, beginning immediately after the start of incubation. Loss of SH-groups and lipid peroxidation as well as changes in the beta-RAS did not take place in the presence of the antioxidant t-Butyl-4-hydroxyanisole (BHA) or the Fe(2+)-chelator EGTA. In view of the known ischemia-induced formation of reactive O2 species our results show that these powerful oxidants could contribute to the modulation of the beta-RAS during myocardial ischemia.
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Adenilil Ciclasas/metabolismo , Oxígeno/metabolismo , Receptores Adrenérgicos beta/metabolismo , Sarcolema/metabolismo , Animales , Ácido Ascórbico/metabolismo , Compuestos Ferrosos/metabolismo , Técnicas In Vitro , Peroxidación de Lípido/fisiología , Oxidación-Reducción , Compuestos de Sulfhidrilo/metabolismo , Porcinos , TiobarbitúricosRESUMEN
The subcellular localization of peptide antibodies against G-protein alpha subunits was studied by the indirect immunogold technique with Lowicryl K4M embedded rat cardiac tissue. Two antibodies were used. The alpha common peptide antibody recognizes the alpha subunits of Gs, Gi and Go. The alpha i common peptide antibodies recognize the alpha subunits of all Gi alpha subtypes (G1-3). Immunoreactivity against alpha common and alpha i common antibodies was found along the cell surface of cardiomyocytes and endothelial cells. No immunoreactivity was seen on sarcoplasmic reticulum membranes. T-tubule membranes showed a little reactivity. Distribution patterns obtained with alpha common and alpha i common antibodies were identical. Immunogold was seen in cardiocytes from both atria and ventricles. In light-microscopical studies with peroxidase-conjugated secondary antibodies, heavy immunostaining was seen in SA and AV nodes.
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Proteínas de Unión al GTP/análisis , Miocardio/química , Adenilil Ciclasas/análisis , Animales , Anticuerpos/análisis , Proteínas de Unión al GTP/inmunología , Inmunohistoquímica , Microscopía Electrónica , Miocardio/inmunología , Miocardio/ultraestructura , Ratas , Ratas EndogámicasRESUMEN
The activity of adenylyl cyclase (AC) is controlled by its interaction with receptor-regulated G proteins. The efficiency to form cyclic AMP is strongly influenced by the amount, the subspecies and function of these regulatory proteins. An impairment of AC function has been shown to occur in sarcolemmal preparations (SL) of hearts exposed to either local or global ischaemia. To examine the contribution of G protein function to this phenomenon, cholera toxin (CT)-catalysed ADP-ribosylation of Gs and pertussis toxin (PT)-catalysed ADP-ribosylation of G proteins have been investigated in SL of porcine hearts exposed to global ischaemia for 15-45 min. ADP-ribosylation by CT of an approximately 45 kDa polypeptide was 0.46 +/- 0.06 and ADP-ribosylation by PT of three 39-41 kDa polypeptides was 4.77 +/- 0.77 pmol mg-1 protein in SL of non-ischaemic myocardium. Whereas no change was observed in CT-catalyzed ribosylation after 30 min of ischaemia, there was a reduction in PT-catalyzed ADP-ribosylation to 3.7 +/- 0.35 pmol mg-1 protein after 30 min of ischaemia. Prolongation of ischaemia to 45 min did not reduce further ADP-ribosylation capacity. Quantitative immunoblotting of PT-sensitive G proteins suggests that the diminution of ADP-ribosylation occurred because of a loss of alpha-subunits of G0, Gi-1, and Gi-2 from sarcolemmal membranes.
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Enfermedad Coronaria/fisiopatología , Proteínas de Unión al GTP/análisis , Miocardio/química , Sarcolema/química , Adenosina Difosfato Ribosa/metabolismo , Toxina de Adenilato Ciclasa , Adenilil Ciclasas/metabolismo , Animales , Toxina del Cólera , Enfermedad Coronaria/enzimología , Immunoblotting , Técnicas In Vitro , Miocardio/enzimología , Toxina del Pertussis , Sarcolema/enzimología , Porcinos , Factores de Virulencia de BordetellaAsunto(s)
Ácido Ascórbico/farmacología , Compuestos Ferrosos/farmacología , Peroxidación de Lípido/efectos de los fármacos , Receptores Adrenérgicos beta/metabolismo , Sarcolema/metabolismo , Animales , Membrana Celular/metabolismo , Dihidroalprenolol/metabolismo , Miocardio/metabolismo , Receptores Adrenérgicos beta/efectos de los fármacos , Porcinos , TiobarbitúricosRESUMEN
In vitro studies have demonstrated that free radicals generated by Fe2+/Vit. C alter the beta-RAS function. SH-oxidation, peroxidation of sarcolemmal lipids and reaction of aldehydes (formed by lipid peroxidation) with the beta-RAS may contribute to this effect. In order to clarify the role of these reactions in respect to their ability to alter the beta-RAS function the time course of SH-oxidation, lipid peroxidation and formation of aldehyde reaction products has been studied. As result it is shown that SH-oxidation is nearly completed within 5 minutes and lipid peroxidation within 30 minutes after exposure to Fe2+/Vit. C. During this time period there was only a very small amount of aldehyde reaction products detectable. Therefore SH-oxidation and/or lipid peroxidation should be responsible for the activity loss of the beta-RAS.
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Adenilil Ciclasas/metabolismo , Ácido Ascórbico/farmacología , Compuestos Ferrosos/farmacología , Corazón/efectos de los fármacos , Miocardio/ultraestructura , Receptores Adrenérgicos beta/metabolismo , Sarcolema/metabolismo , Animales , Radicales Libres , Isoproterenol/farmacología , Cinética , Peroxidación de Lípido/efectos de los fármacos , Miocardio/metabolismo , Receptores Adrenérgicos beta/efectos de los fármacos , Sarcolema/efectos de los fármacos , Sarcolema/ultraestructura , PorcinosRESUMEN
The development of isometric tension of aortic rings from rats was tested after cumulative administration of BAY K 8644 before and after exposure of the aortic preparations for 15 or 60 minutes to IBMX (10(-4) M) or Db cAMP (3.10(-4) M). BAY K 8644 exhibits dose-dependent contractions of those aortic rings which have not been exposed or have been exposed for only 15 minutes to IBMX or Db cAMP. BAY K 8644 application, after an exposure time of 60 minutes of the aortic rings to either IBMX or Db cAMP, resulted in a dose-dependent relaxation. This relaxing effect is counteracted by elevation of KCl (15 mM) in bath solution but was not changed by norepinephrine. The results indicate that long time exposure of the aortic rings to compounds capable of elevating intracellular cAMP level might induce changes of Ca channel gating.
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1-Metil-3-Isobutilxantina/farmacología , Ácido 3-piridinacarboxílico, 1,4-dihidro-2,6-dimetil-5-nitro-4-(2-(trifluorometil)fenil)-, Éster Metílico/farmacología , Bucladesina/farmacología , Contracción Muscular/efectos de los fármacos , Músculo Liso Vascular/fisiología , Teofilina/análogos & derivados , Animales , Aorta/fisiología , AMP Cíclico/metabolismo , Dihidropiridinas/farmacología , Masculino , Músculo Liso Vascular/efectos de los fármacos , Norepinefrina/farmacología , Cloruro de Potasio/farmacología , Ratas , Ratas EndogámicasRESUMEN
Male Wistar rats were fed on a diet rich (13.3 J%) or poor (0.5 J%) in linoleic acid for 10 weeks. The inotropic and chronotropic effects of isoprenaline (100 ng) in isolated perfused hearts were reduced after a linoleic acid rich diet by 36% and 51%, respectively, with an accompanying reduction in isoprenaline-induced increase in the ventricular cAMP content. Moreover, the stimulation of adenylate cyclase in homogenates of ventricular tissue was diminished after linoleic acid rich diet. We postulate that the diminished adrenergic cardiac response after high vs. low linoleic acid diets could be due to alterations in the adenylate cyclase activity and cAMP formation.
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Grasas Insaturadas en la Dieta/farmacología , Frecuencia Cardíaca/efectos de los fármacos , Isoproterenol/farmacología , Ácidos Linoleicos/farmacología , Contracción Miocárdica/efectos de los fármacos , Animales , AMP Cíclico/metabolismo , Ventrículos Cardíacos/efectos de los fármacos , Técnicas In Vitro , Ácido Linoleico , Masculino , Miocardio/metabolismo , Perfusión , Ratas , Valores de ReferenciaRESUMEN
Cyclic AMP has been shown to play a significant regulatory role in a number of myocardial cell functions. The cAMP-forming adenylate cyclase complex is localized in the sarcolemmal membrane which is the major site of lipid peroxidation by oxygen-derived free radicals known to be increased in the ischemic myocardium. Adenylate cyclase function was found to be depressed in the ischemic myocardium but the specific biochemical mechanism responsible for this effect is still unknown. Therefore, the effect of free radical formation on adenylate cyclase was studied. Highly purified sarcolemmal membranes, exhibiting an NaF-stimulated activity of 3.46 +/- 0.65 nmol cAMP formed min-1 mg-1 of protein, were exposed to free radicals formation of which was induced by Fe++/ascorbate. A rapid loss of adenylate cyclase activation by 1-isoproterenol, NaF, and Gpp(NH)p has been observed. Concentration of malondialdehyde (MAD), a key intermediate in the formation of peroxides, was positively correlated to the rapid loss of adenylate cyclase activity. As result, adenylate cyclase was found to be highly susceptible to free radical-induced damage. It is thought that this effect might be one of the causes of the biochemical dearrangements contributing to the alteration of sarcolemmal membrane function in myocardial ischemia resulting in the reduction or loss of metabolic and contractile regulation of the heart.