RESUMEN
A fundamental question in physiology is how hormones regulate the functioning of a cell or organ. It was therefore the aim of this study to investigate the effect(s) of BNP-32 on calcium handling by ventricular myocytes obtained from the rat left ventricle. We specifically tested the hypothesis that BNP-32 decreased the L-type calcium current (I(Ca,L)). Perforated patch clamp technique was used to record I(Ca,L) and action potential (AP) in voltage and current clamp mode, respectively. Myocyte shortening was measured using a photodiode array edge-detection system and intracellular calcium transients were measured by fluorescence photometry. Western blotting was used to determine the relative change in the expression of proteins. At the concentrations tested, BNP-32 significantly decreased cell shortening in a dose-dependent manner; increased the phase II slope of the AP by 53.0%; increased the APD(50) by 16.9%; reduced the I(Ca,L) amplitude with a 22.9% decrease in the peak amplitude and reduced Ca(2+)-dependent inactivation; increased the V(1/2) activation of the L-type calcium channel by 51.1% and decreased V(1/2) inactivation by 31.8%; and, intracellular calcium transient amplitude was significantly decreased by 32.0%, whereas the time to peak amplitude and T(1/2) were both significantly increased by 38.7% and 89.4% respectively. Sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2a) protein expression was reduced by BNP-32. These data suggest that BNP-32 regulates ventricular myocyte function by attenuating I(Ca,L), altering the AP and reducing SERCA2a activity and/or expression. This study suggests a novel constitutive mechanism for the autocrine action of BNP on the L-type calcium channel in ventricular myocytes.
Asunto(s)
Canales de Calcio Tipo L/efectos de los fármacos , Canales de Calcio Tipo L/metabolismo , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/fisiología , Péptido Natriurético Encefálico/farmacología , Animales , Electrofisiología , Técnicas In Vitro , Masculino , Modelos Cardiovasculares , Contracción Miocárdica/efectos de los fármacos , Técnicas de Placa-Clamp , Ratas , Ratas Wistar , ATPasas Transportadoras de Calcio del Retículo Sarcoplásmico/metabolismoRESUMEN
Half of all men with prolactin (PRL)-producing macroadenomas present with hypogonadism, decreased libido and impotence, and therefore require testosterone replacement. However, very little is known about the effect of testosterone on prolactinomas. We report a case of an 18-year-old obese man who presented with hypogonadism and hyperprolactinaemia and underwent a transphenoidal hypophysectomy after a computer tomography scan showed the presence of a suprasellar macroadenoma. On separate occasions, we documented a rise in PRL when testosterone replacement was started and a fall in PRL when testosterone replacement was stopped (r = 0.6090, P = 0.0095). Furthermore, imaging studies suggested the possibility of tumour re-growth after testosterone therapy. We hypothesize that the exogenous testosterone was aromatized to oestradiol, which stimulated the release of PRL by the anterior pituitary. This was supported by the increase in oestradiol levels after testosterone replacement, although statistical significance was not achieved due to the availability of only a few data points. This case highlights the need to be aware of testosterone-replacement-induced hyperprolactinaemia, an under-recognized complication of androgen replacement in this setting. The use of aromatase inhibitors together with testosterone-replacement therapy or the use of non-aromatizable androgens might be indicated in such patients. Taken together, this report and previous studies show that dopamine agonists apparently do not suppress the hyperprolactinaemia induced by testosterone replacement.
Asunto(s)
Adenoma/complicaciones , Hiperprolactinemia/inducido químicamente , Neoplasias Hipofisarias/complicaciones , Testosterona/efectos adversos , Adenoma/cirugía , Adolescente , Inhibidores de la Aromatasa/uso terapéutico , Agonistas de Dopamina/uso terapéutico , Estradiol/sangre , Humanos , Hipogonadismo/terapia , Hipofisectomía , Masculino , Obesidad/complicaciones , Neoplasias Hipofisarias/cirugía , Testosterona/sangreRESUMEN
Recent studies of inherited disorders of phosphate metabolism have shed new light on the understanding of phosphate metabolism. Phosphate has important functions in the body and several mechanisms have evolved to regulate phosphate balance including vitamin D, parathyroid hormone and phosphatonins such as fibroblast growth factor-23 (FGF23). Disorders of phosphate homeostasis leading to hypo- and hyperphosphataemia are common and have clinical and biochemical consequences. Notably, recent studies have linked hyperphosphataemia with an increased risk of cardiovascular disease. This review outlines the recent advances in the understanding of phosphate homeostasis and describes the causes, investigation and management of hypo- and hyperphosphataemia.
Asunto(s)
Hiperfosfatemia/etiología , Hipofosfatasia/etiología , Fosfatos/metabolismo , Enfermedad Crónica , Factor-23 de Crecimiento de Fibroblastos , Factores de Crecimiento de Fibroblastos/metabolismo , Homeostasis , Humanos , Hiperfosfatemia/terapia , Hipofosfatasia/terapia , Trasplante de Riñón/efectos adversos , Hormona Paratiroidea/metabolismo , Fosfatos/sangre , Fosfatos/orinaRESUMEN
BACKGROUND: It has been suggested that for the accurate measurement of calcium in urine, samples must be collected into bottles containing acid. Acidification poses risks to both patients and laboratory staff. Here we reappraise whether acidification is a preanalytical necessity. METHODS: Twenty-four-hour urine samples were collected from 133 patients into bottles without acid or preservatives. In a subset of 29 patients, 10 mL aliquots were prepared to test the effect on urine calcium of 0.1, 1.0 and 5.0 mol/L hydrochloric acid (HCl). Calcium was then measured immediately after acidification, after 12 h and seven days storage at 4 degrees C. In a separate study, urine calcium concentrations in paired control (non-acidified) and acidified (with 5 mol/L HCl) samples were compared in 133 patients. When available, we recorded the time from start of urine collection to time of analysis. Calcium was measured using the cresolphthalein complexone colorimetric endpoint assay on the Roche Modular system. RESULTS: There was no significant difference in the calcium concentration in the 29 cases studied between the varying acid concentrations tested compared with non-acidified urine (P = 0.987). Overall, in 133 patients there was no difference between control and acidified samples (P = 0.888). We found no correlation between basal urine pH and urine calcium at all time points studied. CONCLUSIONS: Our results suggest that the acidification of urine samples is not a preanalytical necessity for the measurement of urine calcium.
Asunto(s)
Ácidos/orina , Calcio/orina , Urinálisis/métodos , Química Clínica/métodos , Química Clínica/normas , Relación Dosis-Respuesta a Droga , Humanos , Ácido Clorhídrico/química , Concentración de Iones de Hidrógeno , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Temperatura , Factores de TiempoRESUMEN
OBJECTIVES: There is increasing evidence suggesting that adiponectin plays a role in the regulation of bone metabolism. DESIGN AND METHODS: This was a cross-sectional study of 34 post-menopausal women with and 37 without osteoporosis. All subjects had body mass index (BMI), bone mineral density (BMD), total-, high molecular weight (HMW)-adiponectin and their ratio, osteoprotegerin (OPG), a marker of bone resorption (betaCTX) and formation (P1NP) measured. RESULTS: We observed a positive correlation between BMI and BMD (r=0.44, p<0.001). When normalised for BMI, total-, HMW-adiponectin concentrations and HMW/total-adiponectin ratio were significantly lower in obese compared to lean subjects but there was no difference between those with or without osteoporosis. There were significant negative correlations between HMW/total-adiponectin ratio and BMI (r=-0.27, p=0.030) and with OPG (r=-0.44, p<0.001). CONCLUSIONS: Our data suggests that there is no significant difference in the circulating concentration of fasting early morning total- or HMW-adiponectin in post-menopausal women with or without osteoporosis. The correlation between HMW/total-adiponectin ratio and OPG may indicate that adiponectin could influence bone metabolism by altering osteoblast production of OPG thereby affecting osteoclasts mediated bone resorption.
Asunto(s)
Adiponectina/sangre , Índice de Masa Corporal , Huesos/metabolismo , Osteoporosis Posmenopáusica/sangre , Posmenopausia/sangre , Adiponectina/química , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Biomarcadores/sangre , Densidad Ósea , Colágeno Tipo I/sangre , Estudios Transversales , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Persona de Mediana Edad , Peso Molecular , Osteoporosis Posmenopáusica/metabolismo , Osteoprotegerina/sangre , Fragmentos de Péptidos/sangre , Péptidos/sangre , Procolágeno/sangreRESUMEN
BACKGROUND: We investigated the presence of interference in a patient who had an elevated CA19-9 concentration using the ADVIA Centaur but results within reference limits with ROCHE Modular Analytics E170 and Brahms KRYPTOR analysers. METHODS: We performed repeat analyses using the same (ADVIA Centaur) and alternate immunossays (Roche Modular Analytics E170 and Brahms KRYPTOR) on the patient's sample and investigated for known interferences. To determine the nature of the interference, we measured CA19-9 on the ADVIA Centaur after dilution experiments and after incubation with non-immune animal sera and in heterophilic blocking tubes (HBT). We also undertook polyethylene glycol precipitation, lectin inhibition experiments and gel filtration chromatography. RESULTS: A curvilinear response to dilution was observed with the ADVIA Centaur. Other known interferences were excluded. Treatment with HBT or non-immune animal sera did not give clinically different results from untreated samples. There was only 0.59% recovery after PEG precipitation in the sample from the case patient. Lectin reduced the assay signal in four patient samples (recovery=1.9-14.1%) but not in the case patient (recovery=106.2%). Gel filtration studies suggested the presence of a low molecular weight (approximately 100 kDa) interference in the case patient's serum. CONCLUSIONS: We report a novel mode of interference and show a non-CA19-9, low molecular-weight interference affecting the ADVIA Centaur CA19-9 immunoassay.