RESUMEN
OBJECTIVE: To examine physical activity (PA) thresholds affecting glucose, insulin and lipid concentrations and body fat composition in high-risk patients for type 2 diabetes (T2D). INTERVENTION: A total of 113 subjects of both genders having abnormal glucose levels in the oral glucose tolerance test were contacted. A total of 78 subjects with age 58.8±10.4 years and body mass index 31.7±5.3 kg m(-2) were randomly assigned to intervention and control groups. INTERVENTION consisted of a supervised walking (60 min three times weekly) for 3 months. All the subjects received standard care for PA and weight reduction and wore an accelerometer during the whole wakeful time. RESULTS: Over 80% of the daily steps clustered at an acceleration level of 0.3-0.7 g (2-3 km h(-1) of walking) and were 5870 in the intervention and 4434 in the control group (P<0.029). Between 0 and 3 months no significant changes were observed in fasting and 2-h glucose, body weight or maximal oxygen uptake. In contrast, changes in fasting and 2-h insulin (-3.4 mU l(-1), P=0.035 and -26.6, P=0.003, respectively), homeostasis model assessment-estimated insulin resistance (-1.0, P=0.036), total cholesterol (-0.55 mmol l(-1), P=0.041), low-density lipoprotein (LDL) cholesterol (-0.36 mmol l(-1), P=0.008) and visceral fat area (-5.5 cm(2), P=0.030) were significantly greater in the intervention than in control subjects. The overall effects of PA were analyzed by quartiles of daily steps of all subjects. There were significant reductions in total and LDL cholesterol and visceral fat area between the highest (daily steps over 6520) and the lowest quartile (1780-2810 daily steps). The changes associated with PA remained significant after adjustments of baseline, sex, age and body weight change. CONCLUSION: Habitual and structured PAs with the acceleration levels of 0.3-0.7 g and daily steps over 6520, equivalent to walking at 2-3 km h(-1) for 90 min daily, standing for the relative PA intensity of 30-35% of the maximal oxygen uptake, are clinically beneficial for overweight/obese and physically inactive individuals with a high risk for T2D.
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Glucemia/metabolismo , Diabetes Mellitus Tipo 2/prevención & control , Terapia por Ejercicio , Grasa Intraabdominal/metabolismo , Obesidad/prevención & control , Caminata , Pérdida de Peso , Diabetes Mellitus Tipo 2/metabolismo , Femenino , Finlandia , Prueba de Tolerancia a la Glucosa , Homeostasis , Humanos , Resistencia a la Insulina , Metabolismo de los Lípidos , Masculino , Persona de Mediana Edad , Obesidad/metabolismo , Conducta de Reducción del Riesgo , Encuestas y Cuestionarios , Resultado del TratamientoRESUMEN
BACKGROUND: NT-proXNP, a new natriuretic peptide analyte, incorporates information about the concentrations of both N-terminal pro-atrial and pro-brain natriuretic peptides (NT-proANP, NT-proBNP). We aimed to investigate whether NT-proXNP is a reliable indicator of the cardiac index (CI) and the hemodynamic state in neonates and infants undergoing an open heart surgery. METHODS: We enrolled 26 children under the age of 1 year into this prospective study. All patients underwent an elective cardiac operation with cardiopulmonary bypass (CPB) to achieve complete biventricular repair. Peri-operative hemodynamic parameters were assessed by transpulmonary thermodilution and natriuretic peptide levels were recorded. RESULTS: The NT-proXNP level correlated significantly with the simultaneously measured NT-proANP level (r=0.60, P<0.001), but more strongly with the NT-proBNP level (r=0.89, P<0.001) and the arithmetic sum of both (r=0.88, P<0.001). NT-proXNP had a strong correlation with CI (r=-0.85, P<0.001), the stroke volume index (r=-0.80, P<0.001) and the global ejection fraction (r=-0.67, P<0.009) throughout the post-operative period. Conventionally measured parameters such as heart rate, mean arterial pressure and pulse-pressure product exhibited weaker correlations with CI than NT-proXNP. Among laboratory values, creatinine levels correlated significantly with CI (r=-0.77, P<0.001) and NT-proXNP (r=0.76, P<0.001) during the post-operative period. A post-operative NT-proXNP level of 3079 pmol/l was diagnostic for CI <3 l/min/m(2) with 89% sensitivity and 90% specificity (area under the curve: 0.91 +/- 0.05). CONCLUSION: NT-proXNP is a good marker of cardiac output following pediatric cardiac surgery and might be a useful tool in the recognition of a low output state.
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Gasto Cardíaco/fisiología , Procedimientos Quirúrgicos Cardíacos , ADN Helicasas/metabolismo , Proteínas Nucleares/metabolismo , Biomarcadores , Creatinina/sangre , Electrocardiografía , Femenino , Cardiopatías Congénitas/cirugía , Frecuencia Cardíaca/fisiología , Ventrículos Cardíacos/cirugía , Hemodinámica/fisiología , Humanos , Lactante , Recién Nacido , Masculino , Periodo Posoperatorio , Estudios Prospectivos , Precursores de Proteínas/metabolismo , Volumen Sistólico/fisiología , Termodilución , Proteína Nuclear Ligada al Cromosoma XRESUMEN
SUMMARY: Regular impact exercise in premenopausal women caused positive osteogenic effects associated to low basal serum parathormone (PTH) but had no effects on bone turnover markers PINP or TRACP5b. The low serum basal PTH levels during impact exercise may be a sign of increased incorporation of calcium to bone. INTRODUCTION: This study aimed to determine the long-term effects of high-impact exercise on bone turnover and calciotropic hormones. METHODS: We performed a 12-month population-based, randomized, controlled exercise trial in 120 women (age 35-40 years) randomly assigned to an exercise group (EG; n = 60) or a control group (CG; n = 60). The exercise regimen consisted of supervised high-impact exercises three times per week. Daily impact loading was assessed by using an accelerometer. Bone turnover markers and calciotropic hormones were analyzed at 0, 6, and 12 months. RESULTS: Twelve months of impact exercise did not reveal any treatment effects in bone turnover markers PINP or TRAPC5b, whereas serum basal PTH decreased significantly more in the EG than in the CG (-11.2 vs. -2.2 pg/mL; p = 0.03). The change in PTH was dose dependent and most clearly seen in subjects with 96 to 130 daily impacts at 2.5 to 5.3 g (e.g., running or jumping). CONCLUSIONS: Regular impact exercise does not cause persistent alterations in bone turnover emphasizing necessity of continuous training to achieve bone benefits. Impact exercise training lowers the serum basal PTH levels and possibly enables greater difference between the basal PTH and transient exercise-induced PTH peaks leading to osteogenic effects.
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Huesos/metabolismo , Terapia por Ejercicio/métodos , Fosfatasa Ácida/sangre , Adulto , Biomarcadores/sangre , Densidad Ósea/fisiología , Femenino , Fémur/fisiología , Humanos , Isoenzimas/sangre , Actividad Motora/fisiología , Hormona Paratiroidea/sangre , Fragmentos de Péptidos/sangre , Premenopausia/metabolismo , Premenopausia/fisiología , Procolágeno/sangre , Fosfatasa Ácida Tartratorresistente , Tibia/fisiología , Soporte de Peso/fisiologíaRESUMEN
There are three members in the natriuretic peptide hormone family, atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP, brain natriuretic peptide), and C-type natriuretic peptide (CNP), that are involved in the regulation of blood pressure and fluid homeostasis. CNP is found principally in the central nervous system and vascular endothelial cells while ANP and BNP are cardiac hormones. ANP is synthesized mainly in the atria of the normal adult heart, while BNP is produced by both the atria and ventricles. The mechanisms controlling ANP release have been the subject of intense research, and are now fairly well understood. The major determinant of ANP secretion is myocyte stretch. Although much less is known about the factors regulating BNP release from the heart, myocyte stretch has also been reported to stimulate BNP release from both atria and ventricles. However, whether wall stretch acts directly or via factors such as endothelin- , nitric oxide, or angiotensin II liberated in response to distension has not been established. Recent studies show that by stimulating endothelin type A receptors endothelin plays an important physiological role as a mediator of acute-volume load-induced ANP secretion from atrial myocytes in conscious animals. In fact, endogenous paracrine/autocrine factors liberated in response to atrial wall stretch rather than direct stretch appears to be responsible for activation of ANP secretion in response to volume load, as evidenced by almost complete blockade of ANP secretion during combined inhibition of endothelin type A/B and angiotensin II receptors. Furthermore, under certain experimental conditions angiotensin II and nitric oxide may also exert a significant modulatory effect on stretch-activated ANP secretion. The molecular mechanisms by which endothelin-1, angiotensin II, and nitric oxide synergistically regulate stretch-activated ANP release are yet unclear.
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Angiotensina II/fisiología , Factor Natriurético Atrial/metabolismo , Endotelinas/fisiología , Óxido Nítrico/fisiología , Animales , Humanos , Estrés MecánicoRESUMEN
Stretching of atrial myocytes stimulates atrial natriuretic peptide (ANP) secretion, but the cellular processes linking mechanical distention to ANP release are unknown. We studied whether or not protein kinase C activation by phorbol ester affects atrial stretch-induced ANP secretion using the modified perfused rat heart preparation that enabled stepwise distention of the right atrium as an experimental model for stretch-stimulated ANP release. The increase in right atrial pressure (2.65 +/- 0.13 mm Hg) was accompanied by an increase in the perfusate immunoreactive ANP (IR-ANP) concentration (from 8.3 +/- 1.1 ng/5 min to 13.9 +/- 2.0 ng/5 min, P less than 0.05, n = 14). During stretch, a slight inotropic response was observed, while heart rate and perfusion pressure remained unchanged. Increase in right atrial pressure in the presence of a phorbol ester, 12-O-tetradecanoyl-phorbol-13-acetate (TPA), known to stimulate protein kinase C activity in heart cells, resulted in a significantly greater increase in the perfusate IR-ANP concentration than after vehicle infusion. The calculated ANP increase corresponding to the 2 mm Hg increase in the right atrial pressure was 1.52-fold in the control group and 1.84-fold when 10 nM TPA was infused (P less than 0.05). Infusion of TPA at a dose of 24 nM further increased the stretch-induced ANP release by causing 2.22-fold (P less than 0.01) increase in IR-ANP secretion. As judged by gel filtration chromatography, abnormal release of the large mol wt stored ANP could not account for the secretory response to phorbol ester. Additionally, a phorbol ester analog, 4 alpha-phorbol 12,13-didecanoate, which is incapable of binding to and activating protein kinase C, was inactive as an ANP secretagogue. In contrast, drugs known to increase the concentration of intracellular Ca2+ in myocytes, Bay K8644 (3 and 6 microns) and forskolin (0.14 microM), significantly inhibited the stretch-stimulated ANP release. This study shows that phorbol ester enhances atrial stretch-stimulated ANP secretion from the isolated perfused heart, suggesting that protein kinase C activity is positively coupled to the stretch-induced ANP release. The results further demonstrate the negative effect of increase in intracellular Ca2+ on stretch-induced ANP release.
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Factor Natriurético Atrial/metabolismo , Corazón/fisiología , Acetato de Tetradecanoilforbol/farmacología , Ácido 3-piridinacarboxílico, 1,4-dihidro-2,6-dimetil-5-nitro-4-(2-(trifluorometil)fenil)-, Éster Metílico/farmacología , Animales , Colforsina/farmacología , Atrios Cardíacos , Masculino , Estimulación Física , Radioinmunoensayo , Ratas , Ratas EndogámicasRESUMEN
To examine the role of intracellular signals in the regulation of atrial natriuretic peptide (ANP) release, the effects of endothelin (ET), a putative endogenous agonist for voltage-dependent Ca2+ channels on basal and atrial stretch-stimulated ANP release as well as on hemodynamic parameters (perfusion pressure, heart rate, contractile force) in isolated perfused rat hearts were studied. Infusion of ET (0.9 x 10(-9)-2.3 x 10(-9) M) alone for 30 min caused a dose-dependent sustained increase in the perfusate immunoreactive ANP (IR-ANP) concentration and coronary vasoconstriction. An initial inotropic response with a later decrease in the contractile force in response to ET was observed, while heart rate remained unchanged. A phorbol ester, 12-O-tetradecanoyl-phorbol-13-acetate (TPA), known to stimulate protein kinase-C activity, at a dose of 4.6 x 10(-8) M caused a gradual, slowly progressive increase in perfusate IR-ANP levels and a more rapid increase in perfusion pressure. ET, when infused in combination with TPA, enhanced IR-ANP secretion induced by the phorbol ester. When hearts from spontaneously hypertensive rats (SHR) were examined, the vasoconstrictor response to infusion of ET was greater than that in the normotensive Wistar-Kyoto (WKY) rats. Infusion of eguipressor doses of ET increased the release of IR-ANP in WKY rats, but had no effect on perfusate IR-ANP levels in SHR. To examine effects of ET on stretch-stimulated ANP release, the modified perfused rat heart preparation that enabled the stepwise distension of the right atrium was used. The increase in right atrial pressure (2.65 +/- 0.13 mm Hg) was accompanied by an increase in the perfusate IR-ANP concentration (from 8.3 +/- 1.1 to 13.9 +/- 2.0 ng/5 min; P less than 0.05; n = 15). The increase in right atrial pressure during the ET infusions resulted in a significantly greater increase in the perfusate IR-ANP concentration than vehicle alone. The calculated ANP increase corresponding to the 2-mm Hg increase in the right atrial pressure was 1.52-fold in the control group and 1.74-fold when 1.9 x 10(-9) M ET was infused (P less than 0.05). This study shows that ET stimulates both basal and atrial stretch-stimulated ANP secretion from the isolated perfused heart and suggests that ET is involved in the regulation of stretch-induced ANP release. The results further confirm the potent vasoconstrictor and cardiac effects of ET.
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Factor Natriurético Atrial/metabolismo , Miocardio/metabolismo , Péptidos/farmacología , Animales , Endotelinas , Endotelio Vascular/metabolismo , Corazón/fisiología , Atrios Cardíacos , Hemodinámica/efectos de los fármacos , Técnicas In Vitro , Contracción Miocárdica/efectos de los fármacos , Perfusión , Estimulación Física , Presión , Radioinmunoensayo , Ratas , Ratas Endogámicas SHR , Ratas EndogámicasRESUMEN
Endocardial cells, like endothelial cells, release nitric oxide (NO) and may play a role in modulating the contractility of cardiac muscle. We have studied the effects of NG-nitro-L-arginine methyl ester (L-NAME), a selective NO synthase inhibitor, on basal and volume expansion-induced secretion of two cardiac hormones, atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), in vivo. In conscious chronically cannulated rats, bolus injection of L-NAME at doses of 1, 3, and 10 mg/kg, iv, caused a dose-dependent increase in mean arterial pressure and sustained bradycardia, whereas right atrial pressure remained unchanged. The hemodynamic effects of L-NAME were reversed by simultaneous administration of L-arginine, a precursor of NO. Administration of 3 and 10 mg/kg L-NAME alone increased plasma levels of immunoreactive ANP (IR-ANP) from 30 +/- 5 to 52 +/- 9 pmol/liter and from 38 +/- 6 to 91 +/- 16 pmol/liter (P < 0.01), respectively, but had no effect on plasma levels of immunoreactive BNP (IR-BNP). The increase in plasma IR-ANP concentration in response to L-NAME infusions showed a positive linear correlation (P < 0.01) with the increase in mean arterial pressure and a negative correlation (P < 0.01) with the changes in heart rate. Acute volume expansion with 0.9% saline in conscious animals resulted in a 3.2-fold increase in plasma IR-ANP levels (from 35 +/- 7 to 113 +/- 15 pmol/liter; P < 0.01), but plasma IR-BNP levels did not change. In the rats pretreated with L-NAME, the relation between the changes from control in plasma IR-ANP and right atrial pressure shifted to the left; the absolute increases corresponding to the 3 mm Hg increase in right atrial pressure were 66 +/- 13, 76 +/- 15, 135 +/- 33, and 148 +/- 24 pmol/liter in the control and 1 mg/kg L-NAME, 3 mg/kg L-NAME-, and 10 mg/kg L-NAME-treated groups, respectively. The combined infusion of L-NAME and L-arginine attenuated the L-NAME-induced increase in ANP release. Our results show that L-NAME increases basal plasma IR-ANP levels and enhances stretch-induced ANP release, suggesting that secretion of ANP in response to volume load may be modulated by the locally released nitric oxide from the endothelium. Further, acute regulation of BNP secretion in response to inhibition of nitric oxide synthase and volume load differs from that of ANP.
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Arginina/análogos & derivados , Factor Natriurético Atrial/sangre , Hormonas/metabolismo , Miocardio/metabolismo , Proteínas del Tejido Nervioso/sangre , Óxido Nítrico/fisiología , Animales , Arginina/farmacología , Factor Neurotrófico Derivado del Encéfalo , Hemodinámica/efectos de los fármacos , Masculino , NG-Nitroarginina Metil Éster , Factores de Crecimiento Nervioso/sangre , Óxido Nítrico/antagonistas & inhibidores , Sustitutos del Plasma/farmacología , Ratas , Ratas Sprague-DawleyRESUMEN
A previously unknown melatonin metabolite was isolated by chloroform extraction and reverse phase HPLC from human and rat urine after administration of synthetic melatonin and characterized by mass spectroscopy and proton magnetic resonance spectroscopy to 1-acetyl-1,2,3,3a,8,8a-hexahydro-8a-hydroxy-5-methoxypyrrolo[2,3-b ]indole, a cyclic isomer of 2-hydroxymelatonin. This isolation was based on the fact that our melatonin antibody (a-MT-K1) cross-reacted against this novel metabolite at a level of 0.1% (melatonin 100%). In our HPLC program for indoles the cyclic 2-hydroxymelatonin eluted at 25 min, separately from synthetic indoles, between 6-hydroxymelatonin (19 min) and melatonin (35 min). In [3H] melatonin studies it was found to be present (at 25 min in our HPLC), accounting for 5% of the urinary metabolites of melatonin in the rat. Since beta-glucuronidase-arylsulfatase treatment of rat urine did not liberate the cyclic 2-hydroxymelatonin this would appear to be excreted into urine as the free form.
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Melatonina/análogos & derivados , Melatonina/metabolismo , Adulto , Animales , Cromatografía Líquida de Alta Presión , Femenino , Humanos , Isomerismo , Espectroscopía de Resonancia Magnética , Masculino , Espectrometría de Masas , Melatonina/orina , RatasRESUMEN
To evaluate the role of vasopressin in the regulation of atrial natriuretic peptide (ANP) secretion, the plasma, atrial, ventricular, and hypothalamic levels of ANP were measured in Long-Evans (LE) and vasopressin-deficient Brattleboro (DI) rats. Total atrial immunoreactive ANP (IR-ANP) as well as right auricular IR-ANP concentration were higher in the DI than in the LE rats, whereas no significant difference was noted in left auricular IR-ANP concentration. In the left ventricle of DI rats, the IR-ANP concentration was 82% greater than that in the LE rats, while no substantial difference was found in the right ventricular IR-ANP concentration between the strains. Normal LE rats had low levels of left ventricular ANP mRNA and barely detectable ANP mRNA in the right ventricle, DI rats showed a 3-fold greater ANP mRNA concentration in the left ventricle than age-matched LE controls, and ANP mRNA levels were also increased in the left auricle of DI rats. The hypothalamic IR-ANP content, but not the concentration, was significantly increased in the DI compared to the LE rats. Despite increased cardiac IR-ANP and ANP mRNA levels, plasma IR-ANP concentrations were similar in the conscious DI rats (97 +/- 9 pg/ml; n = 13) and the LE rats (95 +/- 8 pg/ml; n = 15). Volume expansion (1.1 ml/100 g BW of 0.9% saline, iv) increased right atrial pressure and caused a significant rise in plasma IR-ANP in both strains (P less than 0.01). Elevations of plasma IR-ANP concentrations caused by volume loading were comparable in LE and DI rats in either the absence or presence of exogenous vasopressin (5 ng/kg.min, iv), which, when infused alone, did not significantly influence the plasma IR-ANP concentration. However, the relation between the change in IR-ANP concentration and the change in right atrial pressure shifted to the left, and thus, for a given increase in right atrial pressure, a greater amount of IR-ANP was released in the vasopressin-treated rats than in the control animals. These results demonstrate that although acute volume expansion does not necessarily require endogenous vasopressin for the ANP secretory response, vasopressin increased the ability of volume expansion to induce ANP release, thus modulating the direct mechanical stimulus-induced ANP secretion. The increased left ventricular levels of immunoreactive ANP and augmentation of ANP mRNA levels in Brattleboro rats despite normal left ventricular weight to body weight ratio show that increased ANP gene expression may occur in the ventricles independently of hypertrophy.
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Factor Natriurético Atrial/metabolismo , Hipotálamo/metabolismo , Miocardio/metabolismo , Ratas Brattleboro/metabolismo , Ratas Mutantes/metabolismo , Vasopresinas/deficiencia , Animales , Factor Natriurético Atrial/sangre , Peso Corporal , Atrios Cardíacos , Ventrículos Cardíacos/anatomía & histología , Hemodinámica/efectos de los fármacos , Masculino , Tamaño de los Órganos , Sustitutos del Plasma/farmacología , ARN Mensajero/metabolismo , Radioinmunoensayo , Ratas , Ratas EndogámicasRESUMEN
Daily patterns of pineal function were studied in different seasons in 10 adult semidomesticated female reindeer and 5 prepubertal calves living in a natural arctic environment at latitude 69 degrees 10'N. Serum samples for melatonin RIA were collected every 4 h for 24 h in October (10 h of light, 14 h of darkness and 8 h of light, 16 h of darkness), December (24 h of darkness), March (13 h of light, 11 h of darkness), and June (24 h of light). A significant daily variation in serum melatonin levels was observed in the adult reindeer, with peak values (20-50 ng/liter) occurring during the night in autumn, winter, and spring, but not summer. The daytime values at 13 h (5-10 ng/liter) were constant throughout the year. Total daily amounts of melatonin, the duration of peak levels, and maximal concentrations were significantly lower in spring and summer than before the rut in autumn. The exposure of adult animals to artificial darkness from bright sunlight on August 1 and September 21 resulted in an immediate increase in serum melatonin concentrations. The 2-week-old calves had detectable serum melatonin levels, but no daily rhythm in the spring, whereas a rhythm was detectable by the first autumn, only to disappear unexpectedly during the first winter and return in the spring. At the age of 16 months, the calves had serum melatonin concentrations similar to those in the adults. Our present results show that the continuous illumination experienced during the summer abolished the normal daily melatonin rhythm. This does not seem to be related to organic changes in the pineal gland, since exposure to darkness during the summer increased melatonin levels. The highest melatonin secretion occurred in the autumn and was evidently associated with the rut. Similarly, the daily melatonin rhythm of an adult type observed in the calves at the age of 16 months may be related to the observation that most calves were in rut. Thus, a high rhythmical melatonin secretion appears to relate to puberty and the initiation of heat in female reindeer.
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Animales Recién Nacidos/sangre , Ritmo Circadiano/fisiología , Melatonina/sangre , Reno/sangre , Estaciones del Año , Animales , Femenino , Luz , Glándula Pineal/metabolismo , Glándula Pineal/fisiología , Radioinmunoensayo , Reno/fisiologíaRESUMEN
Urine samples from healthy adult subjects and patients who had received TRH orally were prepurified in SP-Sephadex-C-25 cation exchange chromatography, subjected to reverse phase high pressure liquid chromatography (HPLC) starting with 0.01 M ammonium acetate, pH 4, followed by 1%/min gradient of acetonitrile or isopropanol and assayed in a TRH RIA. Two TRH immunoreactive peaks (A and B) were detected by HPLC with an RP-8 column, peak A eluting at 4-10 min and B at 12-14 min. Serial dilutions of peak B produced a line parallel with synthetic TRH by RIA. Synthetic TRH added to urinary samples and urinary TRH immunoreactivity from TRH-treated patients were eluted at 12-14 min. These results suggest that peak B represents endogenous urinary TRH. Urinary TRH levels of eight normal human males and four females were 5.0 +/- 3.4 pg/ml and 5.2 +/- 1.2 pg/ml (mean +/- SD). These values are many times lower than those presented in previous studies.
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Hormona Liberadora de Tirotropina/orina , Adulto , Cromatografía Líquida de Alta Presión/métodos , Femenino , Humanos , Masculino , Valores de ReferenciaRESUMEN
The effects of heat exposure on plasma levels of GH and GHRH were studied in six younger (31-46 yr) and six older (49-66 yr) normal men. For the GHRH RIA, 2-mL plasma samples were purified on Sep-Pak C18 cartridges, from which the mean recovery of synthetic GHRH-(1-44) was 62 +/- 10% (+/- SD; n = 8). Heat exposure (15 min) in a Finnish sauna bath at an ambient temperature of 72 C, led to an increase in plasma GH levels from 2 to 5 micrograms/L (P less than 0.01) at 30 min in the younger men. Their rectal temperature had risen by 0.2 C at 15 min. Plasma immunoreactive GHRH increased from 9 to 36 ng/L (P less than 0.05) 5 min after heat exposure, and it gradually fell to the initial levels by 45 min. The older men did not have a significant increase in plasma GH or GHRH levels in response to the heat exposure. Reverse phase high pressure liquid chromatography studies of plasma immunoreactive GHRH suggested that the major circulating GHRH immunoreactivity was GHRH-(1-40). We conclude that heat exposure-stimulated GH release in young adult men is mediated by GHRH, but in older men, GHRH and GH responses do not occur.
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Hormona Liberadora de Hormona del Crecimiento/sangre , Calor , Adulto , Anciano , Envejecimiento/fisiología , Temperatura Corporal , Humanos , Masculino , Persona de Mediana Edad , Radioinmunoensayo , Baño de VaporRESUMEN
The serum and amniotic fluid concentrations of melatonin (MT) were measured by RIA during human labor in different conditions related to the type of delivery and the time of the day of delivery. Serum MT concentrations displayed a normal diurnal rhythm, resembling that of nongravid women; the mean concentration [163.8 +/- 149.6 (+/- SD) pmol/L] at night was significantly (P less than 0.001) higher than that during the day (31.4 +/- 16.3 pmol/L). The amniotic fluid MT concentration, which showed a significant positive correlation to the serum MT concentration (r = 0.625; P less than 0.01), also showed an obvious diurnal rhythm; the mean MT concentration was significantly (P less than 0.01) higher during the night [99.3 +/- 59.3 (+/- SD) pmol/L] than during the day (58.9 +/- 33.5 pmol/L). Reverse phase high pressure liquid chromatography confirmed that the amniotic fluid MT immunoreactivity eluated as synthetic MT. During the night the mean amniotic fluid MT concentration [99.3 +/- 59.3 (+/- SD) pmol/L] was significantly (P less than 0.01) lower than that in serum (178.9 +/- 189.6 pmol/L). The progress of delivery, estimated by cervical dilatation, did not affect serum MT concentrations. Induction of delivery by amniotomy and/or oxytocin, and operative delivery by cesarean section had no effect on serum MT concentrations. Human MT secretion does not seem to be influenced by the physical stress of labor or endocrine changes associated with parturition. The single factor regulating MT secretion during human delivery appears to be the time of day.
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Líquido Amniótico/metabolismo , Trabajo de Parto , Melatonina/metabolismo , Adulto , Ritmo Circadiano , Femenino , Humanos , Melatonina/fisiología , Embarazo , Radioinmunoensayo , Factores de TiempoRESUMEN
The effects of synthetic GHRH-(1-44) (1 microgram/kg, iv), clonidine (0.15 mg/m2, orally), L-dopa (0.5 g, orally), and insulin (0.1 IU/kg, iv) on plasma immunoreactive (ir) GHRH and GH levels were determined in normal men, aged 31-46 yr (n = 4-8). In addition, plasma ir-GHRH and GH concentrations were determined before and after the administration of clonidine in six younger men, aged 19-25 yr. GHRH was extracted from plasma using Sep-Pak C18 cartridges and measured with a mid-portion-specific GHRH antiserum. The mean plasma ir-GHRH and GH levels ranged from 9-11 ng/L and 0.5-1.5 microgram/L, respectively, in the older men during a 2-h control study. After GHRH administration, the mean plasma ir-GHRH concentration increased to a peak of 512.5 ng/L at 3 min and GH to a peak of 9.2 micrograms/L at 10 min. Clonidine resulted in a significant increase in mean plasma GH levels (P less than 0.05) in the younger men, but not in the older men. Plasma ir-GHRH concentrations did not change after clonidine. L-Dopa increased plasma ir-GHRH at 60 min (P less than 0.05) and GH at 60-120 min (P less than 0.05). Insulin-induced hypoglycemia increased plasma GH levels (to a mean of 23.8 micrograms/L at 60 min; P less than 0.001), whereas plasma ir-GHRH levels did not change. We conclude that the mechanisms of the various GH stimulation tests differ. Some GH responses, including those induced by insulin, do not appear to be mediated by GHRH.
Asunto(s)
Clonidina/farmacología , Hormona Liberadora de Hormona del Crecimiento/sangre , Hormona del Crecimiento/sangre , Insulina/farmacología , Levodopa/farmacología , Adulto , Hormona Liberadora de Hormona del Crecimiento/fisiología , Humanos , Masculino , Persona de Mediana Edad , Radioinmunoensayo , Valores de ReferenciaRESUMEN
The concentrations of melatonin in 112 preovulatory follicular fluid (FF) samples obtained from 60 women undergoing in vitro fertilization and 27 patients at laparotomy during a spontaneous cycle were measured by RIA and compared with those in peripheral serum. The circadian and seasonal variations in FF melatonin were also analyzed. The FF melatonin concentrations in stimulated (mean +/- SEM, 61.9 +/- 6.4 pmol/L) and spontaneous cycles (98.1 +/- 8.9 pmol/L) were significantly higher (P less than 0.005) than those in peripheral serum (25.4 +/- 1.2 and 38.6 +/- 1.8 pmol/L, respectively), and in the stimulated cycles there was a positive correlation between them. The FF melatonin concentration in the morning (58.9 +/- 3.8 pmol/L) was significantly higher (P less than 0.005) than that in the daytime (23.2 +/- 0.8 pmol/L), but the morning concentrations did not differ between the light and the dark seasons of the year, whereas the daytime values were higher (P less than 0.005) during the dark season (27.1 +/- 2.1 pmol/L) than during the light season (21.1 +/- 2.1 pmol/L). The FF melatonin concentration did not correlate with follicular volume, and FF and serum melatonin concentrations showed no significant correlation with the serum concentrations of estradiol, progesterone, testosterone, or PRL. There were also no differences between FF melatonin concentrations in aspirates with or without an ovum. In summary, significant circadian and circannual variations in high FF melatonin concentrations were found, which suggest that melatonin could potentially interfere with the regulation of reproduction in humans at the follicular level.
Asunto(s)
Ritmo Circadiano , Melatonina/análisis , Folículo Ovárico/análisis , Periodicidad , Cromatografía Líquida de Alta Presión , Transferencia de Embrión , Femenino , Fertilización In Vitro , Humanos , Melatonina/sangre , Estaciones del AñoRESUMEN
To elucidate the effects of alcohol on pineal rhythmicity, ethanol was administered in the evening in amounts usually consumed during social ingestion to nine healthy volunteers in a double blind, cross-over study. Plasma concentrations of melatonin, catecholamines (norepinephrine and epinephrine), and ethanol were measured by RIA, high pressure liquid chromatography, and gas chromatography before and for 12 h after the administration of 0, 0.5, and 1 g ethanol/kg wt. Plasma melatonin and catecholamines displayed expected diurnal rhythms, with peak values at 0300-0400 h for melatonin and trough values at 0100-0400 h for catecholamines. Intake of ethanol between 1900-1945 h inhibited the nocturnal melatonin secretion dose-dependently during the first half of the night, with no changes in urinary excretion of melatonin. The inhibition was 41% (P < 0.05) from the control at midnight for both ethanol doses, 33% (P < 0.05) at 0100 h, and 18% (P < 0.05) at 0200 h for the higher dose. In addition, the higher dose of ethanol increased plasma norepinephrine levels at 2000 and 2200 h (P < 0.01) until 0400 h (P < 0.05). Taking into account the involvement of melatonin in the regulation of sleep and diurnal rhythms, we suggest that ethanol-induced suppression of nocturnal melatonin secretion and an increase in noradrenergic activity may be closely associated with disturbances in sleep and performance.
Asunto(s)
Etanol/farmacología , Melatonina/metabolismo , Adulto , Ritmo Circadiano , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Epinefrina/sangre , Etanol/administración & dosificación , Etanol/sangre , Femenino , Humanos , Cinética , Masculino , Melatonina/sangre , Norepinefrina/sangre , Distribución AleatoriaRESUMEN
Previous studies on the effects of ethanol on circulating pituitary hormones have been carried out mostly during daytime when the secretion of these hormones is generally at a nadir. Therefore, we studied the effects of ethanol on the nocturnal secretion of GH, PRL, TSH, and thyroid hormones (protocol I, nine healthy subjects, five women) and on the TSH and PRL responses to synthetic TRH (protocol II, healthy subjects, four women). Ethanol was given in doses of 0, 0.5 or 1.0 g/kg of BW(protocol I) and 0 or 1.0 g/kg (protocol II) and ingested po at 1900-1945 h. In protocol I, plasma GH rose from 0.6 +/- 0.2 microgram/L (mean +/- SE) at 2200 h to 25.0 +/- 4.3 micrograms/L at 0100 h in control subjects and was almost completely inhibited at 4.5 +/- 1.7 micrograms/L at 0100 h in subjects receiving 1.0 g/kg ethanol (P < 0.01). In subjects receiving 0.5 g/kg ethanol, the inhibition was also significant (P < 0.01), plasma GH being 8.2 +/- 2.5 micrograms/L at 0100 h. Plasma GHRH was measured after solid phase separation in RIA, but it did not show any ethanol-related changes. Plasma PRL exhibited a clear diurnal rhythm in control subjects and rose from 77 +/- 16 at 1800 h to 248 +/- 62 micrograms/L at 0700 h (P < 0.01). The plasma PRL profile was not affected by ethanol. Plasma TSH was 1.4 +/- 0.2 mU/L at 1800-2200 h and rose to 2.3-2.4 mU/L for 0100-0700 h (P < 0.001) in the control subjects. Ethanol 1.0 g/kg suppressed plasma TSH to 1.4 +/- 0.2 mU/L (P < 0.05 at 0100 h and P < 0.01 at 0200 h). According to the area under the curve analyses, the suppression in the nocturnal TSH was 32% in the 0.5 g/kg group and 45% in the 1.0 g/kg group (P < 0.05 for both cases). Circulating free or total T3 and T4 did not show any statistically significant changes that could explain the ethanol-induced inhibition in the nocturnal TSH peak. In protocol II, synthetic TRH (1 microgram/kg BW) was given intravenously, and blood samples were collected before, at 20 and 60 min. TRH significantly stimulated plasma TSH and PRL, but ethanol (1.0 g/kg BW) had no effect on these responses. In conclusion, small amounts of ethanol have unexpectedly great effects on nocturnal surges of TSH, and especially on those of GH, that are apparently mediated by suprapituitary mechanisms. On the other hand, ethanol did not affect the nocturnal PRL surge. These inhibitory effects of ethanol may have unfavorable effects on growth and metabolism in adolescent drinkers.
Asunto(s)
Ritmo Circadiano , Etanol/farmacología , Hormona del Crecimiento/sangre , Prolactina/sangre , Hormonas Tiroideas/sangre , Tirotropina/sangre , Adulto , Estudios Cruzados , Método Doble Ciego , Etanol/administración & dosificación , Femenino , Humanos , Masculino , Hormona Liberadora de TirotropinaRESUMEN
Acid extracts of rat stomach and small intestine contained 8.6 +/- 3.7 and 39 +/- 15 ng/g of immunoreactive atrial natriuretic peptide (ANP). When studied by gel filtration and reverse-phase high-performance liquid chromatography, the stomach immunoreactivity consisted of multiple components, whereas the small intestine contained mostly proANP and ANP 1-28-like material. These findings indicate that ANP may have a role in the physiology of the gastrointestinal tract, e.g. in the regulation of water and electrolyte absorption.
Asunto(s)
Factor Natriurético Atrial/análisis , Sistema Digestivo/análisis , Animales , Cromatografía en Gel , Cromatografía Líquida de Alta Presión , Intestino Delgado/análisis , Masculino , Fragmentos de Péptidos/análisis , Precursores de Proteínas/análisis , Ratas , Ratas Endogámicas , Estómago/análisisRESUMEN
The effects of enalapril therapy on radionuclide ejection fraction and plasma N-terminal atrial natriuretic peptide were investigated in a randomized, double-blind, placebo-controlled study of 52 patients with acute myocardial infarction. The medication was begun intravenously within 24 hours of the onset of symptoms. At discharge and the end point of 6 months, the radiographic size of the heart was significantly smaller in patients receiving (n = 28) than in those not receiving (n = 24) enalapril therapy (p < 0.03 vs < 0.01). However, left ventricular ejection fraction decreased simultaneously from 50 +/- 10% to 47 +/- 11% in patients treated with enalapril, whereas it increased from 48 +/- 13% to 50 +/- 14% in control patients (p < 0.05 for the difference of the changes). The decrease in ejection fraction was most marked in the infarct-related region of the left ventricle (p < 0.01). During the in-hospital period, plasma N-terminal atrial natriuretic peptide was decreased in patients treated with enalapril, whereas it was increased in those treated with placebo with complicated acute myocardial infarction (p < 0.05). During the following 6 months, the differences remained insignificant. Early administration of enalapril significantly attenuated heart enlargement after myocardial infarction and probably improved hemodynamics during the acute phase of complicated infarction. The decrease in ejection fraction during recovery indicates an impairment of systolic function. The decrease in infarct-related regional ejection fraction suggests that the impairment may be due to poor healing of the infarction scar.
Asunto(s)
Factor Natriurético Atrial/sangre , Enalapril/uso terapéutico , Infarto del Miocardio/tratamiento farmacológico , Volumen Sistólico/efectos de los fármacos , Función Ventricular Izquierda/efectos de los fármacos , Anciano , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ventriculografía con Radionúclidos , Factores de TiempoRESUMEN
1. The effects of the selective alpha 2-adrenoceptor agonist, medetomidine, were assessed on plasma levels of immunoreactive atrial natriuretic peptide (IR-ANP), haemodynamics and on urine water and solute excretion in conscious, chronically cannulated, 7 month-old spontaneously hypertensive (SHR) and age-matched Wistar-Kyoto (WKY) rats, in order to examine the role of alpha 2-adrenoceptors in the control of ANP secretion. 2. A 60 min i.v. infusion of medetomidine (0.2 or 0.6 microgram kg-1 min-1) decreased heart rate dose-dependently in both strains. Medetomidine infusion (0.6 microgram kg-1 min-1) resulted in an increase in mean arterial pressure in WKY, whereas both doses decreased blood pressure in SHR. There was a slight increase in the right atrial pressure in both strains (WKY: +1.18 +/- 0.26 mmHg; SHR: +1.64 +/- 0.64 mmHg, NS) in response to infusion of 0.6 microgram kg-1 min-1 of medetomidine. 3. No differences were found in resting plasma IR-ANP levels between WKY (114 +/- 8 pg ml-1, n = 19) and SHR (117 +/- 10 pg ml-1, n = 21). Infusion of equibradycardic doses of medetomidine increased dose-dependently plasma IR-ANP levels in WKY, but did not affect the plasma IR-ANP concentration in SHR rats. 4. Despite the different effect of medetomidine on ANP release in WKY and SHR rats, i.v. administration of medetomidine affected renal excretory functions similarly in both strains; urine flow and sodium excretion increased and urine osmolality decreased significantly, while there was no consistent change in urinary potassium excretion. Urine osmolality decreased to hypo-osmotic levels during the infusion of 0.6 yg kg-1 min1 of medetomidine, suggesting a possible interaction between alpha 2-adrenoceptor stimulation and the vasopressin system. 5. These results show that the alpha 2-adrenoceptor agonist medetomidine increased plasma levels of ANP in WKY rats, probably through an increase in mean arterial and right atrial pressures, whereas the SHR had attenuated ANP release to alpha 2-adrenoceptor stimulation. Our findings, that medetomidine caused marked natriuretic and diuretic effects in both strains and that these effects on the excretory functions of the kidneys were not related to changes in plasma levels of IR-ANP, demonstrate that changes in plasma ANP levels alone do not account for the diuretic and natriuretic effect of alpha 2-agonists.