RESUMEN
A monolithically integrated low linewidth optical comb is demonstrated by gain switching of a three-section laser device. The device consists of a slave and master section separated by a shared slotted mirror section. Wavelength tunability has been demonstrated by varying the electrical bias of each section. The number of comb lines is shown to almost double with the addition of optical injection from the master section into the slave. The unmodulated device has a full width half max linewidth of â¼ 500 kHz, while the comb line set were measured to be â¼ 600 kHz, with little degradation as a result of gain switching. The FSR (free spectral range) of the demonstrated comb is 4 GHz, which is tunable within the bandwidth of the device, with a central wavelength of 1580.3 nm.
RESUMEN
BACKGROUND: Inflammation is a critical process contributing to heart failure (HF). We hypothesized that IL-33/ST2 pathway, a new mechanism regulated during cardiac stress, may be involved in the functional worsening of end-stage HF patients, candidates for left ventricular assist device (LVAD) implantation, and potentially responsible for their outcome. METHODS: IL-33, ST2, and conventional cytokines (IL-6, IL-8, and TNF-α) were determined in cardiac biopsies and plasma of 22 patients submitted to LVAD implantation (pre-LVAD) and compared with (1) control stable chronic HF patients on medical therapy at the moment of heart transplantation without prior circulatory support (HT); (2) patients supported by LVAD at the moment of LVAD weaning (post-LVAD). RESULTS: Cardiac expression of ST2/IL-33 and cytokines was lower in the pre-LVAD than in the HT group. LVAD determined an increase of inflammatory mediators comparable to levels of the HT group. Only ST2 correlated with outcome indices after LVAD implantation. CONCLUSIONS: IL-33/ST2 and traditional cytokines were involved in decline of cardiac function of ESHF patients as well as in hemodynamic recovery induced by LVAD. IL-33/ST2 pathway was also associated to severity of clinical course. Thus, a better understanding of inflammation is the key to achieving more favorable outcome by new specific therapies.
Asunto(s)
Citocinas/fisiología , Insuficiencia Cardíaca/etiología , Corazón Auxiliar , Mediadores de Inflamación/fisiología , Interleucinas/fisiología , Receptores de Superficie Celular/fisiología , Femenino , Insuficiencia Cardíaca/inmunología , Insuficiencia Cardíaca/terapia , Trasplante de Corazón , Humanos , Proteína 1 Similar al Receptor de Interleucina-1 , Interleucina-33 , Masculino , Persona de Mediana Edad , Transducción de SeñalRESUMEN
BACKGROUND: Piperacillin, unlike other antibiotics, rarely causes immediate allergic reactions. Only two cases related to occupational exposure are reported in the literature. OBJECTIVES: Adoption of new methods for diagnosis of occupational allergy to drugs. METHODS: An atopic nurse, aged 30 years, was referred to our hospital for an allergic work-related reaction to piperacillin. The patient had suffered two successive episodes with immediate cutaneous reaction, angioedema and dyspnoea after preparing piperacillin. Almost four years previously she had suffered from similar symptoms after taking amoxicillin. She was submitted to a clinical examination and a routine allergic test, performing also specific IgE (Phadia Pharmacia ImmunoCap) and BAT (Basophil Activation Test) for Beta-lactam antibiotics. RESULTS: A positive response to piperacillin was observed in our case using BAT a new non-invasive and safe method, that proved useful for diagnosis of allergy. Moreover, we observed a change from an allergic reaction for therapeutic use of amoxicillin to a work-related adverse reaction to another beta-lactam, piperacillin. CONCLUSIONS: In previous clinical cases cutaneous and specific challenge tests were performed for diagnosis. At present, availability of an in vitro test, such as BAT may provide new diagnostic opportunities, and a useful tool for studying clinical cases other than, in perspective, monitoring exposed workers. Preventive measures were taken in the workplace to lower the risk of sensitization and allergic response. The nurse was transferred to a well controlled job.
Asunto(s)
Angioedema/diagnóstico , Antibacterianos/efectos adversos , Prueba de Desgranulación de los Basófilos , Hipersensibilidad a las Drogas/diagnóstico , Enfermeras y Enfermeros , Enfermedades Profesionales/diagnóstico , Piperacilina/efectos adversos , Adulto , Angioedema/inducido químicamente , Angioedema/inmunología , Hipersensibilidad a las Drogas/inmunología , Femenino , Humanos , Inmunoglobulina E/sangre , Enfermedades Profesionales/inducido químicamente , Enfermedades Profesionales/inmunología , Valor Predictivo de las Pruebas , Sensibilidad y Especificidad , Pruebas CutáneasRESUMEN
Drug reactions in pharmaceutical industry workers represent a quiet different problem in terms of evaluation and job ability, if related to hospitalized patients with adverse reaction to drug administration. The modern approach of GRADE (Grading Recommendation Assessment Development and Evaluation) was applied to 8 workers who had suspected occupational drug reactions, and were clinically examined in order to exclude any possible adverse event. Such a method allows to draw the relationship between adverse reaction to drugs, aetiology, risk evaluation and clinical events. Therefore, the adverse events are classified in type A (incongruous exposure), type B (hypersensitivity reactions) and not A not B (not work related). Both medical history/clinical evaluation and GRADE seem to give a correct view of the single case. Moreover, a high score suggests an occupational pathology, whilst low scores for evidence of drug reaction and occupational risk can avoid the use of diagnostic procedures.
Asunto(s)
Hipersensibilidad a las Drogas/diagnóstico , Enfermedades Profesionales/diagnóstico , Técnicas y Procedimientos Diagnósticos , HumanosRESUMEN
UNLABELLED: Baker's asthma is one of the most commonly reported occupational lung diseases in countries, and is characterized by rhinitis, bronchial hyperresponsiveness, and reversible airflow obstruction. The development of a mouse model could be useful in order to characterize the development and progression of baker's asthma. RESULTS: Experimental studies evidenced that flour dust elicits neutrophilic inflammation in a tlr4-independent manner, suggesting that endotoxin is not playing a role in the inflammatory response to flour dust. Moreover, bakery flour dust and dust extract significantly enhance pre-existing allergic asthma in OVA sensitized and challenged mice. CONCLUSIONS: Bakery flour dust is strongly pro-inflammatory, can cause non-allergic airway inflammation, and can enhance allergen-mediated airway inflammation.
Asunto(s)
Alérgenos/inmunología , Asma/inducido químicamente , Hiperreactividad Bronquial/inducido químicamente , Polvo , Harina/efectos adversos , Animales , Asma/inmunología , Asma/patología , Hiperreactividad Bronquial/inmunología , Hiperreactividad Bronquial/patología , Modelos Animales de Enfermedad , Polvo/inmunología , Inflamación/inmunología , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Neutrófilos/inmunología , Ovalbúmina/inmunología , Sistema Respiratorio/inmunología , Receptor Toll-Like 4/inmunologíaRESUMEN
BACKGROUND: Hairdressers are exposed to irritants and allergenic compounds that may cause contact dermatitis, rhinitis and asthma. OBJECTIVES: In this paper we describe the case of a female, age 33 years, who developed contact dermatitis after 10 years of exposure to ammonium persulfate. METHODS: After 7 months of progressively extensive and persistent skin lesions, respiratory symptoms appeared that were related to the occupational exposure (on-off test). SIDAPA and specific occupational patch test for hairdressers and occupational challenge with ammonium persulfate were performed. Clinical parameters of inflammation, ECP (eosinophil cationic protein) and exhaled nitric oxide (FeNO) were detected before and after the specific bronchial challenge. RESULTS: The patch test was positive to ammonium persulfate (++), and bronchial challenge for ammonium persulfate showed a significant late response (FEV1 decrease--33%). Both FeNO and ECP showed a significant increase after 24 hours. Dermatitis, urticaria and angioedema occurred on the uncovered skin due to airborne contact. Topic steroids and anti-histaminic drugs resolved the clinical symptoms. CONCLUSIONS: Bronchial challenge is, in fact, considered to be the gold standard for the diagnosis of occupational asthma, although new inflammatory parameters can contribute to the diagnosis and can be useful for monitoring after a specific inhalation test with occupational agents. The described case summarizes the evolution from contact dermatitis to inhalation allergy, suggesting the occurrence of an allergic "march" for occupational allergy.
Asunto(s)
Sulfato de Amonio/efectos adversos , Asma/inducido químicamente , Peluquería , Blanqueadores del Pelo/efectos adversos , Enfermedades Profesionales/inducido químicamente , Rinitis Alérgica Perenne/inducido químicamente , Adulto , Contaminantes Ocupacionales del Aire , Angioedema/inducido químicamente , Angioedema/tratamiento farmacológico , Antialérgicos/uso terapéutico , Asma/diagnóstico , Asma/tratamiento farmacológico , Pruebas Respiratorias , Pruebas de Provocación Bronquial , Dermatitis Profesional/diagnóstico , Dermatitis Profesional/tratamiento farmacológico , Dermatitis Profesional/etiología , Errores Diagnósticos , Progresión de la Enfermedad , Femenino , Reflujo Gastroesofágico/diagnóstico , Humanos , Óxido Nítrico/análisis , Enfermedades Profesionales/diagnóstico , Enfermedades Profesionales/tratamiento farmacológico , Pruebas del Parche , Rinitis Alérgica Perenne/diagnóstico , Rinitis Alérgica Perenne/tratamiento farmacológico , Urticaria/inducido químicamente , Urticaria/tratamiento farmacológicoRESUMEN
BACKGROUND: Baker's asthma is one of the most commonly reported occupational lung diseases in countries where fresh bread is baked daily in large quantities, and is characterized by rhinitis, bronchial hyperresponsiveness, and reversible airflow obstruction. Epidemiological studies have identified pre-existing atopy as an important risk factor for developing baker's asthma, yet the aetiology and pathogenesis of baker's asthma remain poorly understood. OBJECTIVE: We sought to develop a mouse model of baker's asthma that could be used to characterize the development and progression of baker's asthma. METHODS: We were unable to sensitize mice to bakery flour dust or flour dust extract. We assessed total inflammatory cells, cellular differential, total serum IgE and the pro-inflammatory cytokine response to oropharyngeally instilled bakery flour dust or flour dust extract by itself or in the context of ovalbumin (OVA) sensitization and challenge. RESULTS: Both bakery flour dust and flour dust extract consistently elicited a neutrophilic inflammation in a Toll-like receptor 4-independent manner; suggesting that endotoxin is not playing a role in the inflammatory response to flour dust. Moreover, bakery flour dust and dust extract significantly enhance the inflammatory response in OVA-sensitized and challenged mice. CONCLUSIONS: Bakery flour dust and flour dust extract are strongly pro-inflammatory and can cause non-allergic airway inflammation and can enhance allergen-mediated airway inflammation.
Asunto(s)
Asma/inducido químicamente , Polvo , Harina/efectos adversos , Enfermedades Profesionales/inducido químicamente , Animales , Asma/inmunología , Asma/patología , Lavado Broncoalveolar , Citocinas/inmunología , Modelos Animales de Enfermedad , Polvo/inmunología , Inmunoglobulina E/inmunología , Lipopolisacáridos/inmunología , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Neutrófilos/inmunología , Enfermedades Profesionales/inmunología , Enfermedades Profesionales/patología , Ovalbúmina/inmunología , Receptor Toll-Like 4/fisiologíaRESUMEN
BACKGROUND: Exposure to nickel sulphate, other than contact dermatitis, can potentially cause respiratory symptoms. Although few cases of occupational rhinitis and asthma are reported in literature, a prolonged exposure can determine sensitization and evolution to respiratory symptoms. OBJECTIVES: Clinical evaluation of a case of occupational rhinitis and asthma due to nickel sulphate. METHODS: A female worker, aged 43 years, has been occupationally exposed to nickel for 22 years. After 1 year she experienced asthma, apparently not work related. She treated the respiratory symptoms for many years, but a slow and progressive increase of the disease was observed. During the last five years a straight relationship between work and symptoms was observed. On-off test was positive. The diagnosis of occupational respiratory disease was based on the work-related symptoms and the specific nasal challenge test result. RESULTS: An early response was observed with nasal symptoms (score 4), increase of anterior nasal airflow resistance (33%), severe dyspnea, haematic eosinophilia, and fall in FEV-1 of 18%. CONCLUSIONS: The prolonged exposure to nickel determined impairment of respiratory function. Nasal challenge, more safe and useful than bronchial challenge, can be considered gold standard for the diagnosis of occupational rhinitis and asthma due to occupational allergens.
Asunto(s)
Níquel/efectos adversos , Enfermedades Profesionales/etiología , Hipersensibilidad Respiratoria/etiología , Adulto , Femenino , HumanosRESUMEN
BACKGROUND: Latex is a relevant occupational and environmental allergen, strongly related to the extensive use of natural rubber products. OBJECTIVES: Threshold Limit Values have to be identified, as well as biocompatible materials in order to avoid sensitization or appearance of allergic symptoms. METHODS: In this paper we consider the main methods, which have been used to detecting latex allergens for environmental monitoring of airborne and latex products. RESULTS: We report our experience in such afield, and our approach to the latex problem, suggesting that quantification of allergens, which is currently applicable according to well standardized methods, should be adopted by manufacturers, agency and consumer organization.
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Alérgenos/análisis , Monitoreo del Ambiente/métodos , Guantes Quirúrgicos , Hipersensibilidad al Látex/diagnóstico , Látex/análisis , Material Particulado/análisis , Femenino , Humanos , Hipersensibilidad al Látex/etiología , Medición de RiesgoRESUMEN
BACKGROUND: Baker's asthma is related to wheat flour exposure and to other cereal dust exposure. OBJECTIVES: The cockroach is considered a significant allergen and can occasionally trigger asthma in bakery workers. METHODS: The case of a 33-year-old male, suffering from asthma in the workplace with previous equivocal tests for cereal dust was investigated Clinical assessment of the worker consisted of cutaneous and blood screening for common and occupational allergens, including cockroach. The subject was monitored for aspecific bronchial reactivity and peak flow in a cockroach disinfected workplace, and these data were compared to data obtained after previous workplace exposure. RESULTS: The worker was not allergic to wheat and other cereal dusts or alpha-amylase, but was sensitized to cockroach. His asthmatic symptoms disappeared, and bronchial reactivity varied after a long period outside the bakery workplace. PEF monitoring, that had showed diurnal variability > 20% and differences between working and non-working periods, demonstrated both normal values and daily variations less than 10% when he returned to the cockroach disinfected workplace. CONCLUSIONS: The cockroach is a common allergen, however no case of work-related baker's asthma due to the cockroach has been previously described. Clinical history and analysis of the allergens at the workplace must direct the clinical approach of the investigators, in order to correctly evaluate the subject and enable him/her to resume work.
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Alérgenos/efectos adversos , Asma/inmunología , Cucarachas , Enfermedades Profesionales/inmunología , Exposición Profesional/efectos adversos , Adulto , Animales , Humanos , MasculinoRESUMEN
The present study characterizes for the first time a GSH specific transporter in a human intestinal epithelial cell line (I407). GSH metabolism is very important for the antioxidant and detoxifying action of intestine and for the maintenance of the luminal thiol-disulfide ratio involved in regulation mechanisms of the protein activity of epithelial cells. GSH level decreases have been related to physio-pathological alterations either of intestine or other organs. GSH specific transport systems have been identified in membranes of various cell types of rat, mice and rabbit. The presence of a Na+-independent transport system of GSH is confirmed by the similar behaviour of GSH uptake time-courses when Na+ in extracellular uptake medium was replaced with choline+ or K+ as well as by kinetic saturation and by the trans-stimulation effect on GSH uptake in GSH preloaded cells. Moreover, this transporter is activated when cations are present in extracellular medium and it is affected by membrane potential changes with an increase in GSH uptake values when membrane depolarization occurs. The present results also show a remarkable affinity and specificity of this transporter for GSH; in fact, Km value is very low (90 +/- 20 microM) and only compounds strictly related to GSH structure, such as GSH S-conjugates and GSH-ethyl ester, inhibit GSH uptake in 1407 cells. Finally, a possible hormonal control and modulation by the thiol-disulfide status of GSH transporter activity is suggested.
Asunto(s)
Proteínas Portadoras/metabolismo , Glutatión/metabolismo , Mucosa Intestinal/metabolismo , Intestino Delgado/metabolismo , Animales , Transporte Biológico , Colina/metabolismo , Cromatografía Líquida de Alta Presión , Humanos , Potenciales de la Membrana , Proteínas de Transporte de Membrana , Ratones , Potasio/metabolismo , Conejos , Ratas , Sodio/metabolismoRESUMEN
BACKGROUND: The benefits of vessel recanalization in acute myocardial infarction (AMI) are limited by reperfusion damage. In animal models, adenosine limits reperfusion injury, reducing infarct size and improving ventricular function. The aim of this study was to evaluate the safety and feasibility of adenosine adjunct to primary PTCA in AMI. METHODS AND RESULTS: Fifty-four AMI patients undergoing primary PTCA were randomized to intracoronary adenosine or saline. The 2 groups were similar for age, sex, and infarct location. Adenosine administration was feasible and well tolerated. PTCA was successful in all patients and resulted in TIMI 3 flow in all patients given adenosine and in 19 given saline (P<0.05). The no-reflow phenomenon occurred in 1 adenosine patient and in 7 saline patients (P=0.02). Creatine kinase was lower in the adenosine group, and a Q-wave MI developed in 16 adenosine patients and in 23 saline patients (P=0.04). Sixty-four percent of dyssynergic segments improved in the adenosine group and 36% in the saline group (P=0. 001). Function worsened in 2% of dysynergic segments in the adenosine group and in 20% in the saline group (P=0.0001). Adverse cardiac events occurred in 5 patients in the adenosine group and in 13 patients in the saline group (P=0.03). CONCLUSIONS: Intracoronary adenosine administration is feasible and well tolerated in AMI. Adenosine adjunct to primary PTCA ameliorates flow, prevents the no-reflow phenomenon, improves ventricular function, and is associated with a more favorable clinical course.
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Adenosina/administración & dosificación , Angioplastia Coronaria con Balón , Infarto del Miocardio/terapia , Vasodilatadores/administración & dosificación , Adenosina/efectos adversos , Anciano , Vasos Coronarios/efectos de los fármacos , Vasos Coronarios/fisiopatología , Electrocardiografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/fisiopatología , Resultado del Tratamiento , Vasodilatadores/efectos adversosRESUMEN
OBJECTIVES: The aim of this study was to investigate coronary vasodilator reserve and metabolism in myocardium subtended by angiographically normal arteries remote from ischemia. BACKGROUND: After infarction, structural and functional changes occur in remote myocardium often subtended by normal arteries. Whether changes occur in regions remote from ischemic but noninfarcted myocardium is unknown. METHODS: Coronary vasodilator reserve was measured with positron emission tomography in 12 patients with single-vessel disease using intravenous dipyridamole (0.56 mg/kg for 4 min). In another 10 patients, simultaneous arterial/great cardiac vein catheterization was performed during atrial pacing to measure myocardial metabolism in regions subtended by diseased or normal arteries. RESULTS: Basal myocardial blood flow in stenosis-related regions was comparable to that in remote regions but was lower after dipyridamole administration (1.73 +/- 0.91 vs. 2.89 +/- 0.93 ml/min per g, p < 0.01), giving coronary vasodilator reserve values of 1.80 +/- 0.82 and 2.73 +/- 0.89 (p < 0.01). In normal control subjects, basal myocardial blood flow was 0.92 +/- 0.13 and 3.67 +/- 0.94 ml/min per g in the basal state and after dipyridamole (both p < 0.05 vs. values in remote regions), and coronary vasodilator reserve was 4.07 +/- 0.98 (p < 0.01) vs. values in remote regions). During pacing there was net lactate release in diseased regions (-18 +/- 27%, p < 0.05 vs. values in remote regions and control subjects) and extraction in remote regions (38 +/- 17%) and in normal control subjects (26 +/- 11%). Glucose and alanine extraction were increased in diseased (8 +/- 6% and 6 +/- 6%) and remote regions (6 +/- 3% and 4 +/- 3%), compared with values in normal control subjects (2 +/- 3% and -1 +/- 3%, both p < 0.05 vs. diseased and remote regions). CONCLUSIONS: Coronary vasodilator reserve is reduced and glucose and alanine metabolism is abnormal in regions subtended by normal arteries remote from ischemic but noninfarcted myocardium.
Asunto(s)
Enfermedad Coronaria/fisiopatología , Vasos Coronarios/fisiopatología , Miocardio/metabolismo , Vasodilatación/fisiología , Anciano , Angina de Pecho/diagnóstico por imagen , Angina de Pecho/fisiopatología , Cateterismo Cardíaco , Enfermedad Crónica , Angiografía Coronaria , Circulación Coronaria , Enfermedad Coronaria/diagnóstico por imagen , Dipiridamol , Ventrículos Cardíacos/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Tomografía Computarizada de Emisión/métodosRESUMEN
OBJECTIVES: The aim of the study was to evaluate whether adenosine infusion can induce production of active renin and angiotensin II in human coronary circulation. BACKGROUND: Adenosine can activate angiotensin production in the forearm vessels of essential hypertensive patients. METHODS: In six normotensive subjects and 12 essential hypertensive patients adenosine was infused into the left anterior descending coronary artery (1, 10, 100 and 1,000 microg/min x 5 min each) while active renin (radioimmunometric assay) and angiotensin II (radioimmunoassay after high performance liquid chromatography purification) were measured in venous (great cardiac vein) and coronary arterial blood samples. In five out of 12 hypertensive patients adenosine infusion and plasma samples were repeated during intracoronary angiotensin-converting enzyme inhibitor benazeprilat (25 microg/min) administration. Finally, in adjunctive hypertensive patients, the same procedure was applied during intracoronary sodium nitroprusside (n = 4) or acetylcholine (n = 4). RESULTS: In hypertensive patients, but not in control subjects, despite a similar increment in coronary blood flow, a significant (p < 0.05) transient increase of venous active renin (from 10.7 +/- 1.4 [95% confidence interval 9.4 to 11.8] to a maximum of 13.8 +/- 2.1 [12.2 to 15.5] with a consequent drop to 10.9 +/- 1.8 [9.7 to 12.1] pg/ml), and angiotensin II (from 14.6 +/- 2.0 [12.7 to 16.5] to a maximum of 20.4 +/- 2.7 [18.7 to 22.2] with a consequent drop to 16.3 +/- 1.8 [13.9 to 18.7] pg/ml) was observed under adenosine infusion, whereas arterial values did not change. Calculated venous-arterial active renin and angiotensin II release showed a strong correlation (r = 0.78 and r = 0.71, respectively; p < 0.001) with circulating active renin. This adenosine-induced venous angiotensin II increase was significantly blunted by benazeprilat. Finally, both sodium nitroprusside and acetylcholine did not affect arterial and venous values of active renin and angiotensin II. CONCLUSIONS: These data indicate that exogenous adenosine stimulates the release of active renin and angiotensin II in the coronary arteries of essential hypertensive patients, and suggest that this phenomenon is probably due to renin release from tissue stores of renally derived renin.
Asunto(s)
Adenosina/farmacología , Angiotensina II/sangre , Circulación Coronaria/efectos de los fármacos , Hipertensión/fisiopatología , Renina/sangre , Acetilcolina/farmacología , Adulto , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Benzazepinas/farmacología , Cateterismo Cardíaco , Circulación Coronaria/fisiología , Relación Dosis-Respuesta a Droga , Femenino , Antebrazo/irrigación sanguínea , Hemodinámica/efectos de los fármacos , Humanos , Infusiones Intraarteriales , Flujometría por Láser-Doppler , Masculino , Persona de Mediana Edad , Nitroprusiato/farmacología , Sistema Renina-Angiotensina/efectos de los fármacos , Sistema Renina-Angiotensina/fisiologíaRESUMEN
OBJECTIVES: The present study was designed to investigate which characteristics of anginal symptoms or exercise test results could predict the favorable anti-ischemic effect of the beta-adrenergic blocking agent metoprolol and the calcium antagonist nifedipine in patients with stable angina pectoris. BACKGROUND: The characteristics of anginal symptoms and the results of exercise testing are considered of great importance for selecting medical treatment in patients with chronic stable angina pectoris. However, little information is available on how this first evaluation may be used to select the best pharmacologic approach in individual patients. METHODS: In this prospective multicenter study, 280 patients with stable angina pectoris were enrolled in 25 European centers. After baseline evaluation, consisting of an exercise test and a questionnaire investigating patients' anginal symptoms, the patients were randomly allocated to double-blind treatment for 6 weeks with either metoprolol (Controlled Release, 200 mg once daily) or nifedipine (Retard, 20 mg twice daily) according to a parallel group design. At the end of this period, exercise tests were repeated 1 to 4 h after drug intake. RESULTS: Both metoprolol and nifedipine prolonged exercise tolerance over baseline levels; the improvement was greater in the patients receiving metoprolol (p < 0.05). Multivariate analysis revealed that low exercise tolerance was the only variable associated with a more favorable effect within each treatment group. Metoprolol was more effective than nifedipine in patients with a lower exercise tolerance or with a higher rate-pressure product at rest and at ischemic threshold. None of the characteristics of anginal symptoms or exercise test results predicted a greater efficacy of nifedipine over metoprolol. CONCLUSIONS: The results of a baseline exercise test, but not the characteristics of anginal symptoms, may offer useful information for selecting medical treatment in stable angina pectoris.
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Angina de Pecho/tratamiento farmacológico , Metoprolol/uso terapéutico , Nifedipino/uso terapéutico , Angina de Pecho/diagnóstico , Preparaciones de Acción Retardada , Método Doble Ciego , Electrocardiografía , Prueba de Esfuerzo/efectos de los fármacos , Tolerancia al Ejercicio/efectos de los fármacos , Femenino , Humanos , Masculino , Metoprolol/administración & dosificación , Persona de Mediana Edad , Análisis Multivariante , Nifedipino/administración & dosificación , Valor Predictivo de las Pruebas , Estudios Prospectivos , Encuestas y CuestionariosRESUMEN
Coronary hemodynamics, myocardial metabolism and left ventricular function at rest and after incremental atrial pacing were evaluated in 12 patients with stress-induced angina and ST segment depression, angiographically normal coronary arteries and no evidence of spasm, generally labeled as syndrome X, and in 10 normal subjects. At baseline study, great cardiac vein flow was comparable in patients and control subjects. During pacing, an equivalent rate-pressure product was reached in the two groups, but the slope of the relation between rate-pressure product and great cardiac vein flow was significantly less steep in patients than in normal subjects (0.0027 vs. 0.0054 ml/mm Hg.beat, p less than 0.001). Nevertheless, the left ventricular ejection fraction was comparable in both groups at rest (66 +/- 6% vs. 71 +/- 7%, p = NS) and during pacing (71 +/- 7% vs. 66 +/- 5%, p = NS). At baseline study, myocardial glucose extraction was more efficient in patients with syndrome X (p less than 0.05), but net myocardial exchange of pyruvate and alanine was, respectively, smaller and greater than in control subjects. Lactate was extracted to a similar extent in the two groups and in no instance was net lactate release observed during pacing or recovery. During pacing and recovery, patients with syndrome X showed net pyruvate release, unlike the control subjects in whom net pyruvate exchange was positive. In addition, patients with syndrome X continued to show net myocardial extraction of alanine during spacing and recovery, whereas normal subjects produced alanine throughout the study. Myocardial carbohydrate oxidation increased significantly during maximal pacing in normal subjects but not in patients, in whom it always remained below (p less than 0.01) the concurrent rate of myocardial uptake of carbohydrate equivalents (glucose, lactate, pyruvate, alanine). Myocardial energy expenditure was significantly lower in patients than in control subjects at maximal rate-pressure product levels (p less than 0.01). The metabolic pattern in patients with syndrome X therefore is not consistent with classic ischemia, although differences in the net exchange of circulating substrates (glucose, pyruvate, alanine) can be demonstrated. Thus, in patients with syndrome X, the symptoms, electrocardiographic signs and impairment in the increase in great cardiac vein flow during pacing coexist with preserved global and regional left ventricular function and myocardial energy efficiency.
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Angina de Pecho/fisiopatología , Estimulación Cardíaca Artificial , Angiografía Coronaria , Circulación Coronaria/fisiología , Miocardio/metabolismo , Angina de Pecho/diagnóstico , Electrocardiografía , Metabolismo Energético/fisiología , Prueba de Esfuerzo , Femenino , Humanos , Persona de Mediana Edad , Consumo de Oxígeno , Síndrome , Función Ventricular Izquierda/fisiologíaRESUMEN
OBJECTIVES: This study was designed to investigate whether combination therapy with metoprolol and nifedipine provides a greater anti-ischemic effect than does monotherapy in individual patients with stable angina pectoris. BACKGROUND: Combination therapy with a beta-adrenergic blocking agent (which reduces myocardial oxygen consumption) and a dihydropyridine calcium antagonist (which increases coronary blood flow) is a logical approach to the treatment of stable angina pectoris. However, it is not clear whether, in individual patients, this combined therapy is more effective than monotherapy. METHODS: Two hundred eighty patients with stable angina pectoris were enrolled in a double-blind trial in 25 European centers. Patients were randomized (week 0) to metoprolol (controlled release, 200 mg once daily) or nifedipine (Retard, 20 mg twice daily) for 6 weeks; placebo or the alternative drug was then added for a further 4 weeks. Exercise tests were performed at weeks 0, 6 and 10. RESULTS: At week 6, both metoprolol and nifedipine increased the mean exercise time to 1-mm ST segment depression in comparison with week 0 (both p < 0.01); metoprolol was more effective than nifedipine (p < 0.05). At week 10, the groups randomized to combination therapy had a further increase in time to 1-mm ST segment depression (p < 0.05 vs. placebo). Analysis of the results in individual patients revealed that 7 (11%) of 63 patients adding nifedipine to metoprolol and 17 (29%) of 59 patients (p < 0.0001) adding metoprolol to nifedipine showed an increase in exercise tolerance that was greater than the 90th percentile of the distribution of the changes observed in the corresponding monotherapy + placebo groups. However, among these patients, an additive effect was observed only in 1 (14%) of the 7 patients treated with metoprolol + nifedipine and in 4 (24%) of the 17 treated with nifedipine + metoprolol. CONCLUSIONS: The mean additive anti-ischemic effect shown by combination therapy with metoprolol and nifedipine in patients with stable angina pectoris is not the result of an additive effect in individual patients. Rather, it may be attributed to the recruitment by the second drug of patients not responding to monotherapy.
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Antagonistas Adrenérgicos beta/uso terapéutico , Angina de Pecho/tratamiento farmacológico , Bloqueadores de los Canales de Calcio/uso terapéutico , Metoprolol/uso terapéutico , Nifedipino/uso terapéutico , Antagonistas Adrenérgicos beta/administración & dosificación , Angina de Pecho/diagnóstico , Angina de Pecho/fisiopatología , Bloqueadores de los Canales de Calcio/administración & dosificación , Método Doble Ciego , Quimioterapia Combinada , Electrocardiografía , Prueba de Esfuerzo , Tolerancia al Ejercicio/efectos de los fármacos , Femenino , Humanos , Masculino , Metoprolol/administración & dosificación , Persona de Mediana Edad , Nifedipino/administración & dosificaciónRESUMEN
OBJECTIVE: The aim of the study was to evaluate the effects of adenosine on renal blood flow in humans. METHODS: Eleven normotensive patients (mean age 53 +/- 11 years) with normal renal angiograms were enrolled in the study. Arterial blood pressure, one ECG lead and arterial renal blood flow velocity, by intravascular Doppler catheter, were monitored throughout the procedure. Incremental doses (10(-5), 10(-4), 10(-3), 2 x 10(-3), 5 x 10(-3), 10(-2), 10(-1), 1 mg) were selectively injected, at 5-min intervals, in a renal artery. RESULTS: Adenosine administration had no significant effects on blood pressure, heart rate and atrio-ventricular conduction. A progressive reduction in renal blood flow velocity (from 16.36 +/- 1.9 to 3.9 +/- 0.8 cm/s, P < 0.0001) was observed. Following adenosine the decrease of flow velocity was immediate and its duration was proportional to dosage (from 0.5 +/- 0.4 s at 10(-5) mg to 31 +/- 6.5 s at 1 mg). Renal angiography, repeated in four patients during flow velocity decrement, showed no changes in vessel diameter. CONCLUSIONS: Exogenous adenosine-induced a marked and transient reduction in renal blood flow in man. This effect suggests that adenosine or its metabolites may be directly implicated in rapid and powerful mechanisms of cardiac output redistribution. Thus endogenous adenosine could have a role in regulating renal blood flow in physiological and pathological situations like strenuous exercise, hemorrhage shock and cardiac failure.
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Adenosina/farmacología , Circulación Renal/efectos de los fármacos , Vasodilatadores/farmacología , Femenino , Humanos , Riñón/diagnóstico por imagen , Masculino , Persona de Mediana Edad , RadiografíaRESUMEN
A comprehensive analysis on glutathione metabolism in rat cerebral cortex synaptosomes as a function of age was performed. All different glutathione system components (GSH, GSSG, total GSH, and GSH redox index) changed significantly only during aging. GSH, total GSH, and GSH redox index decreased by about 40%, 24%, and 52%, respectively, while GSSG showed a remarkable increase of about 60%. On the contrary, some GSH-related enzyme activities showed characteristic changes both during growth and aging. GSH peroxidase and GSH-S-transferase activities significantly increased both during growth and aging, GSH reductase and gamma-glutamylcysteine synthetase activities showed lower levels only during aging, while glucose-6-phosphate dehydrogenase activity did not change throughout the life of the rat. The results obtained suggest an increase of the oxidative status due to a reduced antioxidant capacity of the GSH system in the synaptosomal compartment during aging. The main cause of these metabolic modifications is a lowering of the rates of both GSSG reduction to GSH and GSH synthesis. Moreover, an irreversible loss of GSH as GSH-S-conjugates due to a high detoxification mechanism during aging is also possible. These alterations in glutathione metabolism, found mainly during aging in rat cerebral cortex synaptosomes may contribute to clarify some aspects of cerebral diseases.
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Envejecimiento/metabolismo , Corteza Cerebral/crecimiento & desarrollo , Corteza Cerebral/metabolismo , Glutatión/metabolismo , Sinaptosomas/metabolismo , Animales , Corteza Cerebral/ultraestructura , Masculino , Proteínas del Tejido Nervioso/metabolismo , Oxidación-Reducción , Ratas , Ratas WistarRESUMEN
We measured glutathione (GSH) metabolism in normal NIH/3T3 fibroblasts, and in cells transformed by the oncogenes sis, erbB, src, ras, dbl, and raf.erbB,src,ras and raf, but not sis and dbl transformants, showed increased level of total and reduced GSH as compared with normal NIH/3T3 fibroblasts; oxidized GSH was elevated only in src- and ras-transformed cells. Increased total GSH content was associated with decreased activity of the synthetic enzyme gamma-glutamylcysteine synthetase, and oxidized GSH level with increased activity of GSH reductase. These data suggest that GSH synthesis was selectively enhanced in cells transformed by specific oncogenes, with resulting down-regulation of its synthetic enzyme; alterations of GSH metabolism appeared to be peculiar of transformation by specific oncogenes, and not trivial epiphenomena of neoplastic transformation. Oncogenic transformants that presented elevated level of GSH were also those reported to be resistant to antineoplastic drugs and ionizing radiations, thus confirming a possible link between altered GSH metabolism and resistance to antineoplastic treatment.