RESUMEN
BACKGROUND & AIMS: We present the 7-year follow-up analysis in overweight children and adolescents, who had participated originally in a randomized control trial of a lifestyle intervention. We compared them to an untreated population-based control group to demonstrate the effectiveness of the intervention. METHODS: Degree of overweight (BMI-SDS) was determined in 32 overweight children (mean age 11.5 ± 1.5yrs, 65.6% females, mean BMI 23.7 ± 1.5 kg/m2) at onset of intervention (T0), end of 6-month intervention (T1), 12 months (T2) and 7 years after end of intervention (T3). A total of 76 overweight children derived from a representative national population survey served as control group. RESULTS: The participants in the intervention group reduced significantly their BMI-SDS between T0-T1 (mean ± standard deviation -0.28 ± 0.28, p < 0.001) and demonstrated no significant changes between T1-T2 (mean ± standard deviation -0.10 ± 0.34) and between T2-T3 (median +0.07; interquartile range: -0.54-0.62). BMI-SDS at T3 was significantly (p = 0.015) lower compared to T0. At T3, 46.8% of the participants in the intervention were normal-weight. The reduction in BMI-SDS between T0-T3 was significantly (p = 0.043) greater in the intervention group (median -0.26; interquartile range -0.87-0.23 BMI-SDS) compared to the control group (mean ± standard deviation -0.05 ± 0.77). CONCLUSIONS: The lifestyle intervention led to a significant reduction of overweight in the 7-year follow-up period. This decrease in BMI-SDS was significantly greater than the changes in BMI-SDS in a control group. This study is registered at clinicaltrials.gov (NCT00422916).
Asunto(s)
Terapia Conductista/métodos , Ejercicio Físico , Terapia Familiar/métodos , Estilo de Vida , Educación del Paciente como Asunto/métodos , Obesidad Infantil/terapia , Niño , Femenino , Estudios de Seguimiento , Humanos , Masculino , Resultado del TratamientoRESUMEN
In a randomised controlled study (n=34 intervention group, n = 32 control group) the effects of a 6-month outpatient training for overweight but not obese children and adolescents (BMI > 90(th) ≤ 97(th) percentile) were assessed up to 12 months after the end of intervention. BMI-SDS reduction was the main outcome. The results show that the lifestyle intervention "Obeldicks light" is effective to reduce overweight, as well as blood pressure and several other risk parameters in overweight children. Effects are stable over a 12 months period.
Asunto(s)
Terapia Conductista/estadística & datos numéricos , Dietoterapia/estadística & datos numéricos , Promoción de la Salud/estadística & datos numéricos , Sobrepeso/epidemiología , Sobrepeso/prevención & control , Adolescente , Salud del Adolescente/estadística & datos numéricos , Índice de Masa Corporal , Niño , Salud Infantil/estadística & datos numéricos , Preescolar , Terapia Combinada/estadística & datos numéricos , Femenino , Estilo de Vida Saludable , Humanos , Análisis de Intención de Tratar , Sobrepeso/diagnóstico , Conducta de Reducción del Riesgo , Resultado del TratamientoRESUMEN
Health behaviours are influenced by gender-specific conceptions and norms of the society. These conceptions and norms are changing over time. The aim of this analysis is to describe gender differences in health behaviour of adolescents and to interpret these gender differences in terms of theories of social construction.We used the national German data of the Health-Behaviour in School-aged Children (HBSC) studies conducted in the years 2001/02, 2005/06 und 2009/10 with respect to the following health behaviours: tobacco use, binge drinking, diet, fruit and vegetable consumption, daily breakfast and physical activity. We describe the difference in frequencies between girls and boys and used a series of logistic regressions to test the significance of the gender difference in health behaviours with survey year as the predictor.There is only a small difference -between girls and boys with respect to tobacco use and binge drinking. For binge drinking girls nearly converge with the figures of boys. Relatively stable gender differences over time are existing for diet, nutrition and physical activity.From a theoretical gender perspective it might be possible that with respect to risky behaviours like tobacco use and alcohol consumption a clear gender specific connotation has changed over time. In other words risk behaviours become less important in presenting oneself as masculine. A gender sensible development of preventive interventions should consider the changes over time of gender-related -social constructions.
Asunto(s)
Conducta Alimentaria , Conductas Relacionadas con la Salud , Encuestas Epidemiológicas/tendencias , Estilo de Vida , Adolescente , Consumo Excesivo de Bebidas Alcohólicas/epidemiología , Consumo Excesivo de Bebidas Alcohólicas/tendencias , Estudios Transversales , Femenino , Alemania , Humanos , Estudios Longitudinales , Masculino , Actividad Motora , Asunción de Riesgos , Factores Sexuales , Fumar/epidemiología , Fumar/tendencias , Valores SocialesRESUMEN
BACKGROUND & AIMS: Lifestyle interventions address primarily obese children, while interventions tailored to overweight but not obese children are scarce. The effectiveness of the lifestyle intervention "Obeldicks light" based on physical activity training, nutrition education, and behavior counseling for overweight children and their parents has been demonstrated by a randomized controlled trial. Here, we present the 12 months follow-up analysis of these children after end of intervention. METHODS: Degree of overweight (BMI and SDS-BMI), waist circumference, skinfold thickness, bioimpedance analyses (BIA), and blood pressure were determined in 76 overweight (BMI>90(th)≤97(th) percentile) children (mean age 11.8 ± 1.8years, 67% females, mean BMI 24.3 ± 1.9 kg/m(2)) participating in the evaluation study of "Obeldicks light" at onset of intervention (T0), end of 6 months intervention (T1), 6 months after end of intervention (T2) and 12 months after end of intervention (T3). Comparisons were performed on an intention-to-treat approach. RESULTS: The drop-out rate was 4% in the intervention period and additional 3% during follow-up. The children reduced significantly (p < 0.001) their SDS-BMI in the intervention period between T0 and T1 (-0.27 ± 0.23; p < 0.001). This SDS-BMI reduction remained stable at T2 (T0-T2:-0.26 ± 0.31; p < 0.001) and T3 (T0-T3:-0.26 ± 0.39; p < 0.001). SDS-BMI reductions were independent from age and gender. Body fat measured by skinfold thickness and BIA, waist circumference, and blood pressure decreased significantly in the intervention period and remained stable in the follow-up period as well. CONCLUSIONS: The lifestyle intervention "Obeldicks light" was effective in reducing degree of overweight, fat mass, waist circumference, and blood pressure both at end of intervention and in a 12 months follow-up period.
Asunto(s)
Estilo de Vida , Sobrepeso/terapia , Adiposidad , Adolescente , Terapia Conductista , Presión Sanguínea , Índice de Masa Corporal , Niño , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Análisis de Intención de Tratar , Masculino , Actividad Motora , Ciencias de la Nutrición/educación , Sobrepeso/dietoterapia , Pacientes Desistentes del Tratamiento , Educación del Paciente como Asunto , Circunferencia de la Cintura , Pérdida de PesoRESUMEN
BACKGROUND & AIMS: Randomized controlled trials (RCT) have demonstrated the effectiveness of lifestyle interventions in obese children. However, the effectiveness of interventions for overweight, but no obese children has not been demonstrated yet by RCTs. METHODS: A total of 66 overweight (BMI>90th< or =97th percentile) children (mean age 11.5+/-1.6 years, 58% females, mean BMI 23.4+/-1.5kg/m(2)) were randomized into a control group (CG) (n=32; no intervention for a duration of 6 months) or intervention group (IG) (n=34; 6 months intervention "Obeldicks light" based on physical activity, nutrition education, and behaviour counselling). BMI, waist circumference, skinfold thickness, bioimpedance analyses, blood pressure, physical activity based on questionnaires, and three-day-weighed dietary records were determined at baseline (T0) and 6 months (T1) later. Degree of overweight was calculated as BMI-SDS. Comparisons were performed on an intention-to-treat approach. RESULTS: The drop-out rate was 3% in IG and 16% in CG. At T1, 94% of the children in IG decreased their BMI-SDS and 24% of them were normal weight. The changes between T0 and T1 in BMI-SDS differed significantly (p<0.001) between IG and CG (CG: +0.05+/-0.19 BMI-SDS; IG: -0.26+/-0.22 BMI-SDS). Similar findings were observed for blood pressure, waist circumference, skinfold thickness, and fat mass based on bioimpedance analyses. In the IG, energy, fat and sugar intake decreased significantly between T0 and T1, while no significant changes were observed in the CG. CONCLUSIONS: The lifestyle intervention was associated with an improvement of dietary patterns and was effective in reducing degree of overweight, fat mass, waist circumference, and blood pressure.
Asunto(s)
Estilo de Vida , Sobrepeso/terapia , Adiposidad , Adolescente , Presión Sanguínea , Índice de Masa Corporal , Niño , Conducta Infantil/psicología , Terapia Combinada , Consejo , Dieta , Impedancia Eléctrica , Terapia Familiar , Conducta Alimentaria/psicología , Femenino , Humanos , Masculino , Actividad Motora , Ciencias de la Nutrición/educación , Sobrepeso/dietoterapia , Sobrepeso/psicología , Grosor de los Pliegues Cutáneos , Circunferencia de la CinturaRESUMEN
Oxidative stress, the imbalance between production of reactive oxygen species and the cellular detoxification of these reactive compounds, is believed to be involved in the pathology of various diseases. Several biomarkers for oxidative stress have been proposed to serve as tools in toxicological and ecotoxicological research. Not only may exposure to various pro-oxidants create conditions of cellular oxidative stress, but hyperoxic conditions may also increase the production of reactive oxygen species. The objective of the current study was to determine the extent to which differences in oxygen partial pressure would affect biomarkers of oxidative stress in a primary culture of hepatocytes from rainbow trout (Oncorhynchus mykiss). Membrane integrity, metabolic activity, levels of total and oxidized glutathione (tGSH/GSSG) was determined, as well as mRNA expression levels of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GSSG-R), gamma-glutamyl-cystein synthetase (GCS) and thioredoxin (TRX). The results show that different biomarkers of oxidative stress are affected when the cell culture is exposed to atmospheric oxygen, and that changes such as increased GSSG content and induction of GSSG-R and GSH-Px can be reduced by culturing the cells under lower oxygen tension. Oxygen tension may thus influence results of in vitro based cell research and is particularly important when assessing parameters in the antioxidant defence system. Further research is needed to establish the magnitude of this effect in different cellular systems.
Asunto(s)
Estrés Oxidativo/efectos de los fármacos , Oxígeno/farmacología , Animales , Catalasa/efectos de los fármacos , Catalasa/metabolismo , Membrana Celular/efectos de los fármacos , Membrana Celular/metabolismo , Células Cultivadas , Glutatión/efectos de los fármacos , Glutatión/metabolismo , Glutatión Peroxidasa/efectos de los fármacos , Glutatión Peroxidasa/metabolismo , Glutatión Reductasa/efectos de los fármacos , Glutatión Reductasa/metabolismo , Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Oncorhynchus mykiss , Oxígeno/administración & dosificación , Presión Parcial , Superóxido Dismutasa/efectos de los fármacos , Superóxido Dismutasa/metabolismoRESUMEN
As more salmon gene expression data has become available, the cDNA microarray platform has emerged as an appealing alternative in ecotoxicological screening of single chemicals and environmental samples relevant to the aquatic environment. This study was performed to validate biomarker gene responses of in vitro cultured rainbow trout (Oncorhynchus mykiss) hepatocytes exposed to model chemicals, and to investigate effects of mixture toxicity in a synthetic mixture. Chemicals used for 24h single chemical- and mixture exposures were 10 nM 17alpha-ethinylestradiol (EE2), 0.75 nM 2,3,7,8-tetrachloro-di-benzodioxin (TCDD), 100 microM paraquat (PQ) and 0.75 microM 4-nitroquinoline-1-oxide (NQO). RNA was isolated from exposed cells, DNAse treated and quality controlled before cDNA synthesis, fluorescent labelling and hybridisation to a 16k salmonid microarray. The salmonid 16k cDNA array identified differential gene expression predictive of exposure, which could be verified by quantitative real time PCR. More precisely, the responses of biomarker genes such as cytochrome p4501A and UDP-glucuronosyl transferase to TCDD exposure, glutathione reductase and gammaglutamyl cysteine synthetase to paraquat exposure, as well as vitellogenin and vitelline envelope protein to EE2 exposure validated the use of microarray applied to RNA extracted from in vitro exposed hepatocytes. The mutagenic compound NQO did not result in any change in gene expression. Results from exposure to a synthetic mixture of the same four chemicals, using identical concentrations as for single chemical exposures, revealed combined effects that were not predicted by results for individual chemicals alone. In general, the response of exposure to this mixture led to an average loss of approximately 60% of the transcriptomic signature found for single chemical exposure. The present findings show that microarray analyses may contribute to our mechanistic understanding of single contaminant mode of action as well as mixture effects, but that its use in screening of complex environmental samples will need to be further evaluated.
Asunto(s)
Etinilestradiol/toxicidad , Expresión Génica/efectos de los fármacos , Hepatocitos/efectos de los fármacos , Compuestos Heterocíclicos/toxicidad , Oncorhynchus mykiss/genética , Contaminantes Químicos del Agua/toxicidad , Animales , Cartilla de ADN/química , Regulación hacia Abajo , Sinergismo Farmacológico , Perfilación de la Expresión Génica/veterinaria , Análisis de Secuencia por Matrices de Oligonucleótidos/veterinaria , Oncorhynchus mykiss/fisiología , Análisis de Componente Principal , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Toxicogenética , Regulación hacia ArribaRESUMEN
Brominated flame retardants (BFRs) leak out in the environment, including the aquatic one. Despite this, sublethal effects of these chemicals are poorly investigated in fish. In this study, a screening of selected biomarkers in juvenile rainbow trout (Oncorhynchus mykiss) and feral eelpout (Zoarces viviparus) was performed after exposure to hexabromocyclododecane (HBCDD) and tetrabromobisphenol A (TBBPA). Rainbow trout was injected intraperitoneally (i.p.) with HBCDD or TBBPA. Two out of four short-term experiments with HBCDD showed an increase in the activity of catalase. A 40% increase in liver somatic index (LSI) could be observed after 28 days. HBCDD did also seem to have an inhibitory effect on CYP1A's activity (ethoxyresorufin-O-deethylase (EROD)). A putative peroxisome proliferating activity of the compound was investigated without giving a definite answer. HBCDD did not seem to be estrogenic or genotoxic. TBBPA increased the activity of glutathione reductase (GR) after 4, 14 and 28 days in rainbow trout suggesting a possible role of this compound in inducing oxidative stress. The compound did not seem to be estrogenic. TBBPA seemed to compete with the artificial substrate ethoxyresorufin in vitro, during the EROD assay. In eelpout, only one 5 days in vivo experiment was performed. Neither of the compounds gave rise to any effect in this fish. This was the first screening of sublethal effects of the two chemicals in fish, using high doses. Our results indicate that there is a need for further studies of long-term, low-dose effects of these two widely used flame retardants.
Asunto(s)
Retardadores de Llama/toxicidad , Hidrocarburos Bromados/toxicidad , Oncorhynchus mykiss/metabolismo , Perciformes/metabolismo , Bifenilos Polibrominados/toxicidad , Animales , Western Blotting , Catalasa/metabolismo , Citocromo P-450 CYP1A1/metabolismo , Citosol/enzimología , Ensayo de Inmunoadsorción Enzimática , Cromatografía de Gases y Espectrometría de Masas , Glutatión Reductasa/metabolismo , Hidrocarburos Bromados/química , Hígado/efectos de los fármacos , Hígado/enzimología , Microsomas Hepáticos/enzimología , Tamaño de los Órganos , Bifenilos Polibrominados/química , Espectrofotometría Ultravioleta , Factores de TiempoRESUMEN
The expression of protein tyrosine phosphatase epsilon (PTPepsilon) was studied in human tissues and blood cells. High mRNA expression was observed in peripheral blood leucocytes, particularly in monocytes and granulocytes which revealed at least four distinct transcripts. In lymphocytes, PTPepsilon expression was induced after 12-O-tetradecanoylphorbol-13-acetate (TPA) or antigen-receptor stimulation, indicating that PTPepsilon plays a role in the events taking place after antigen engagement. Previously, PTPepsilon has been shown to be involved in regulating voltage-gated potassium channel activity, insulin-receptor signalling and Janus kinase-signal transducers and activators of transcription (STAT) signalling. Transfection of cells with different PTPepsilon constructs and activator protein-1 reporter gene indicates that the catalytic activity of PTPepsilon is involved in the regulation of the mitogen-activated protein kinase cascade. In particular, the extracellular signal-regulated kinases (ERK1/2) were shown to be inhibited in both phosphorylation status and enzymatic activity after overexpression of PTPepsilon. Thus, PTPepsilon emerges as a phosphatase with a potential to regulate the ERK1/2 pathway either directly or indirectly through its catalytic activity.
Asunto(s)
Leucocitos/enzimología , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Proteínas Tirosina Fosfatasas/genética , Secuencia de Aminoácidos , Animales , Línea Celular , Femenino , Expresión Génica/efectos de los fármacos , Células HL-60 , Humanos , Células Jurkat , Leucocitos/efectos de los fármacos , Masculino , Ratones , Proteína Quinasa 3 Activada por Mitógenos , Datos de Secuencia Molecular , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Proteínas Tirosina Fosfatasas Clase 4 Similares a Receptores , Homología de Secuencia de Aminoácido , Acetato de Tetradecanoilforbol/farmacología , Distribución TisularRESUMEN
The objective of this study was to determine the calcitonin (CT) hormone reserve in different severity of atrophic autoimmune thyroiditis (AAT). Forty-eight female patients with AAT were divided into four groups based on basal and peak thyrotropin (TSH) values (after oral thyrotropin-releasing hormone [TRH], free triiodothyronine (FT3) and free thyroxine (FT4) ranging from normal in group 1 to overt hypothyroidism in group 4. All had thyroid antibodies. The control group comprised euthyroid females of comparable age, without thyroid antibodies. Basal CT and CT response to calcium infusion (area under the curve) were investigated as parameters of CT reserve. Basal CT was lower in groups 2 to 4 of patients with AAT (compared to controls), but the difference was not significant. Stimulated CT levels were lower (p < 0.05) in all groups of patients compared to controls, with markedly reduced CT-secretory reserve in group 4. Thyroid antibody concentrations and, basal and postinfusion calcium levels were not significantly different among the various groups. In conclusion CT deficiency (especially stimulated values) occurs in AAT and is more severe in hypothyroid patients than in earlier stages of AAT.
Asunto(s)
Calcitonina/sangre , Glándula Tiroides/patología , Tiroiditis Autoinmune/sangre , Tiroiditis Autoinmune/patología , Administración Oral , Adulto , Atrofia , Calcio/farmacología , Femenino , Humanos , Persona de Mediana Edad , Valores de Referencia , Tirotropina/sangre , Hormona Liberadora de Tirotropina/uso terapéutico , Tiroxina/sangre , Triyodotironina/sangreRESUMEN
1. The effect of the nitric oxide synthesis inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) was investigated on stress- and morphine-induced prolactin (PRL) secretion in vivo in male rats, by use of a stress-free blood sampling and drug administration method by means of a permanent indwelling catheter in the right jugular vein. 2. Three doses of L-NAME were tested (1, 10 and 30 mg kg-1) and were given intraperitoneally one hour before blood sampling; control rats received saline. After the first blood sample, rats received an initial intravenous injection of morphine (3, 6 or 12 mg kg-1) or were subjected to immobilization stress. In the case of a morphine administration, rats received a second dose of morphine (3, 6 or 6 mg kg-1, respectively) 90 min later, when tolerance had developed, while rats subjected to immobilization stress received 6 mg kg-1 morphine 90 min after onset of stress. 3. L-NAME had no effect on basal plasma PRL concentration. However, it potentiated acute morphine-induced PRL secretion and attenuated the subsequent tolerance in a dose-dependent way. Immobilization stress-induced PRL secretion was inhibited dose-dependently by L-NAME, as was its subsequent tolerance to morphine; however, in this case, in a reversed dose-dependent way. 4. When the highest dose of morphine (12 mg kg-1) was combined with the highest dose of L-NAME pretreatment (30 mg kg-1), all rats showed a dramatic potentiation of the morphine-induced PRL rise compared to controls. Moreover, all of these rats died within 90 min after the administration of morphine. 5. These results show that NO plays a role in the acute opioid action on PRL release during stress as well as in the development of tolerance to the opioid effect, and some possible mechanisms are discussed.
Asunto(s)
Inhibidores Enzimáticos/farmacología , Morfina/farmacología , NG-Nitroarginina Metil Éster/farmacología , Narcóticos/farmacología , Óxido Nítrico Sintasa/antagonistas & inhibidores , Prolactina/metabolismo , Estrés Fisiológico/metabolismo , Animales , AMP Cíclico/fisiología , Masculino , Ratas , Ratas WistarRESUMEN
1. The effect of the nootropic drug, piracetam on stress- and subsequent morphine-induced prolactin (PRL) secretion was investigated in vivo in male rats, by use of a stress-free blood sampling and drug administration method by means of a permanent indwelling catheter in the right jugular vein. 2. Four doses of piracetam were tested (20, 100, 200 and 400 mg kg-1), being given intraperitoneally 1 h before blood sampling; control rats received saline instead. After a first blood sample, rats were subjected to immobilization stress and received morphine, 6 mg kg-1, 90 min later. 3. Piracetam had no effect on basal plasma PRL concentration. 4. While in the non-piracetam-treated rats, stress produced a significant rise in plasma PRL concentration, in the piracetam-pretreated rats PRL peaks were attenuated, especially in the group given 100 mg kg-1 piracetam, where plasma PRL concentration was not significantly different from basal values. The dose-response relationship showed a U-shaped curve; the smallest dose had a minor inhibitory effect and the highest dose had no further effect on the PRL rise. 5. In unrestrained rats, morphine led to a significant elevation of plasma PRL concentration. After the application of immobilization stress it lost its ability to raise plasma PRL concentration in the control rats, but not in the piracetam-treated rats. This tolerance was overcome by piracetam in a significant manner but with a reversed dose-response curve; i.e. the smaller the dose of piracetam, the higher the subsequent morphine-induced PRL peak. 6. There is no simple explanation for the mechanism by which piracetam induces these contradictory effects. Interference with the excitatory amino acid system, which is also involved in opiate action, is proposed speculatively as a possible mediator of the effects of piracetam.
Asunto(s)
Morfina/farmacología , Narcóticos/farmacología , Nootrópicos/farmacología , Piracetam/farmacología , Prolactina/sangre , Estrés Psicológico/metabolismo , Animales , Relación Dosis-Respuesta a Droga , Tolerancia a Medicamentos , Inmovilización , Masculino , Naloxona/farmacología , Antagonistas de Narcóticos/farmacología , Ratas , Ratas WistarRESUMEN
A new method using traditional hybridization methodology, coupled with the new magnetic particle technology, has been developed for DNA purification, specifically for sequencing applications. The method is similar to the reverse hybridization blot system; however, a specific oligonucleotide probe was attached to the paramagnetic particle instead of a sheet membrane. The target DNA containing the complementary sequence of the probe hybridizes to the probe that is attached to the bead and is then magnetically removed from solution, washed and collected. This system eliminates the need of organic extractions and precipitation/concentration steps. The entire hybridization-purification system can be done in a 1.5-ml microcentrifuge tube making the method ideal for automation. M13 phage clones were purified with this method, both by manual means and by using the CATALYST 800 Molecular Biology LabStation fitted with a prototype magnetic station, and then sequenced. DNA sequencing results obtained with this system were reproducible and gave excellent length of read with low background.
Asunto(s)
Secuencia de Bases , ADN/aislamiento & purificación , Magnetismo , Moldes Genéticos , Colifagos/genética , Sondas de ADN , ADN Viral/aislamiento & purificación , Técnicas Genéticas , Operón Lac , Microesferas , Datos de Secuencia MolecularRESUMEN
We have examined the effects of dopamine on prolactin gene expression using quantitative in-situ hybridization histochemistry in different pituitary cell (sub)populations separated according to their density on a discontinuous Percoll gradient. Administration of dopamine resulted in a drastic reduction in hybridization of 35S-labelled DNA probe complementary to prolactin mRNA in total pituitary cells and in lactotrophs with low density. In contrast, dopamine significantly stimulated mRNA accumulation in prolactin-secreting cells with high density compared with other cell layers. The combined use of Percoll gradient and quantitative in-situ hybridization is a valuable and sensitive method with which to examine prolactin-secreting cell response to a given stimulation. Prolactin-secreting cells with high and low density clearly show functional heterogeneity in their response to dopamine.
Asunto(s)
Dopamina/fisiología , Expresión Génica/fisiología , Adenohipófisis/fisiología , Prolactina/genética , ARN Mensajero/análisis , Animales , Células Cultivadas , Femenino , Hibridación de Ácido Nucleico , Adenohipófisis/citología , Prolactina/metabolismo , Ratas , Ratas EndogámicasRESUMEN
A 41-year-old man with clinical Cushing's syndrome and intermittent central ACTH hypersecretion for a period of 9 1/2 years follow-up is described. Episodes of biochemical and clinical remission alternated with periods of florid Cushing's disease, characterized by circadian hyperpulsatile ACTH and cortisol secretion. Responses to metyrapone and inhibition of ACTH and cortisol hypersecretion after high dose dexamethasone during active phases of the disease favored a central origin of ACTH hypersecretion, confirmed by simultaneous bilateral venous sampling of the sinus petrosus inferior. Prolonged clinical remission followed near total anterior hypophysectomy. However, on anatomopathological examination of the pituitary neither corticotroph cell hyperplasia nor a microadenoma could be documented. The possibility of a functional ACTH hypersecretion is discussed.
Asunto(s)
Síndrome de Cushing , Glándulas Suprarrenales/metabolismo , Hormona Adrenocorticotrópica/metabolismo , Hormona Adrenocorticotrópica/fisiología , Adulto , Síndrome de Cushing/fisiopatología , Síndrome de Cushing/cirugía , Humanos , Hidrocortisona/metabolismo , Hipofisectomía , Masculino , Periodicidad , Adenohipófisis/cirugíaRESUMEN
The effects of restraint stress and opiates on prolactin secretion in male rats have been measured. Both induced a short-lived increase in prolactinaemia. Experimental evidence indicates that both opioids and restraint stress bring about their actions by the activation of opioid receptors. When restraint stress was followed by administration of the specific kappa-agonist bremazocine, a second prolactin peak was observed. In contrast, morphine (predominantly a mu-agonist) lost its prolactin-stimulating capacity when given after a period of restraint stress. This indicates cross-tolerance between restraint stress and morphine. Tolerance was overcome when the dose of morphine was doubled, and an increase in prolactin secretion could again be obtained. The cross-tolerance phenomenon argues that a common opioid receptor is involved in morphine- and restraint stress-stimulated prolactin release. In another set of experiments, in which morphine administration replaced restraint stress as a means of inducing tolerance, a second rise in prolactinaemia was seen only with bremazocine and not with a further administration of morphine. This suggests a morphine (mu) receptor-specific development of tolerance. Two consecutive administrations of bremazocine also produced tolerance, in this case for the kappa-receptor. This illustrates the rapid and receptor-specific development of tolerance for the prolactin-releasing capacity of opioid compounds.
Asunto(s)
Tolerancia a Medicamentos/fisiología , Morfina/farmacología , Prolactina/metabolismo , Receptores Opioides/fisiología , Estrés Psicológico/fisiopatología , Animales , Benzomorfanos/farmacología , Relación Dosis-Respuesta a Droga , Haloperidol/farmacología , Masculino , Prolactina/sangre , Ratas , Ratas EndogámicasRESUMEN
Fentanyl, a selective mu opioid receptor agonist, administered intravenously, influences growth hormone secretion in conscious male rats. A dose-response study demonstrated that the maximum growth hormone release was obtained with 10 micrograms/kg while higher doses were less or not effective. MR-2266 (6 mg/kg i.v.), a mu and kappa opioid receptor antagonist, and bremazocine (0.1 mg/kg i.v.) a mu opioid receptor antagonist with kappa agonistic properties, both potently inhibited the growth hormone response to fentanyl (10 micrograms/kg i.v.). In contrast, the effect of fentanyl on growth hormone release was not blocked in rats treated with either ICI-154129 (30 mg/kg i.v. or 150 micrograms/kg intracerebroventricularly a selective delta opioid receptor antagonist, or U-50488 (10 mg/kg i.v.), a specific kappa opioid receptor agonist. These results suggest that opioid receptors of the mu type are involved in the fentanyl-induced growth hormone release.
Asunto(s)
Fentanilo/farmacología , Hormona del Crecimiento/metabolismo , Receptores Opioides/fisiología , 3,4-Dicloro-N-metil-N-(2-(1-pirrolidinil)-ciclohexil)-bencenacetamida, (trans)-Isómero , Animales , Benzomorfanos/farmacología , Relación Dosis-Respuesta a Droga , Encefalina Leucina/análogos & derivados , Encefalina Leucina/farmacología , Fentanilo/administración & dosificación , Masculino , Antagonistas de Narcóticos , Pirrolidinas/farmacología , Ratas , Ratas Endogámicas , Receptores Opioides muRESUMEN
The effects of systemic administration of the selective dopamine1 receptor agonist fenoldopam and the selective dopamine2 receptor agonist quinpirole on blood pressure and regional haemodynamics were investigated in anaesthetized normotensive Wistar rats. Both compounds produced dose-dependent reductions in blood pressure. Mesenteric and renal blood flow were enhanced by fenoldopam, but reduced by quinpirole. Hindquarter blood flow was not modified by fenoldopam, but was increased by quinpirole. The calculated vascular resistances were reduced by both compounds in the three vascular beds. The effects of fenoldopam were antagonized by SCH 23390 but SCH 23390 did not affect those of quinpirole. The effects of quinpirole, but not those of fenoldopam, were antagonized by domperidone. Hexamethonium abolished the effects of quinpirole without affecting those of fenoldopam. These results indicate that the hypotensive effects of fenoldopam and quinpirole are due to stimulation of postsynaptic dopamine1 and neuronal dopamine2 receptors, respectively, resulting in differential regional haemodynamic effects.
Asunto(s)
Antihipertensivos , Benzazepinas/farmacología , Presión Sanguínea/efectos de los fármacos , Ergolinas/farmacología , Hemodinámica/efectos de los fármacos , Animales , Fenoldopam , Quinpirol , Ratas , Receptores Dopaminérgicos/efectos de los fármacos , Resistencia Vascular/efectos de los fármacosRESUMEN
The inhibitory effect of beta-endorphin (EP) or other opioids on TSH secretion is, in contrast to their stimulating properties on PRL release, still a matter of debate. In the present study a dose of 1 microgram beta-EP injected intracerebroventricularly (IVT) in unstressed conscious male rats, though highly effective on PRL release, did not affect basal TSH levels, nor the TRH-induced TSH secretion. The previously reported inhibition of TSH release by opioids may therefore be an effect only seen when pharmacological doses are used.
Asunto(s)
Hormona Liberadora de Tirotropina/fisiología , Tirotropina/metabolismo , betaendorfina/fisiología , Animales , Masculino , Prolactina/sangre , Ratas , Tirotropina/sangreRESUMEN
Intravenously administered bombesin lowered basal PRL levels in conscious male rats and prevented the morphine, bremazocine and stress-induced PRL secretion. The same dose of bombesin had no effect on PRL levels in alpha-methyl-p-tyrosine pretreated rats and did not affect haloperidol-stimulated PRL release. These results show that bombesin given intravenously acts as an inhibitor of PRL secretion and suggests that it does not act on the lactotrope itself but rather by an increase of the inhibitory dopaminergic tone.