Ghrelin suppresses glucose-stimulated insulin secretion and deteriorates glucose tolerance in healthy humans.

OBJECTIVE: The orexigenic gut hormone ghrelin and its receptor are present in pancreatic islets. Although ghrelin reduces insulin secretion in rodents, its effect on insulin secretion in humans has not been established. The goal of this study was to test the hypothesis that circulating ghrelin suppresses glucose-stimulated insulin secretion in healthy subjects. RESEARCH DESIGN AND METHODS: Ghrelin (0.3, 0.9 and 1.5 nmol/kg/h) or saline was infused for more than 65 min in 12 healthy patients (8 male/4 female) on 4 separate occasions in a counterbalanced fashion. An intravenous glucose tolerance test was performed during steady state plasma ghrelin levels. The acute insulin response to intravenous glucose (AIRg) was calculated from plasma insulin concentrations between 2 and 10 min after the glucose bolus. Intravenous glucose tolerance was measured as the glucose disappearance constant (Kg) from 10 to 30 min. RESULTS: The three ghrelin infusions raised plasma total ghrelin concentrations to 4-, 15-, and 23-fold above the fasting level, respectively. Ghrelin infusion did not alter fasting plasma insulin or glucose, but compared with saline, the 0.3, 0.9, and 1.5 nmol/kg/h doses decreased AIRg (2,152 +/- 448 vs. 1,478 +/- 2,889, 1,419 +/- 275, and 1,120 +/- 174 pmol/l) and Kg (0.3 and 1.5 nmol/kg/h doses only) significantly (P < 0.05 for all). Ghrelin infusion raised plasma growth hormone and serum cortisol concentrations significantly (P < 0.001 for both), but had no effect on glucagon, epinephrine, or norepinephrine levels (P = 0.44, 0.74, and 0.48, respectively). CONCLUSIONS: This is a robust proof-of-concept study showing that exogenous ghrelin reduces glucose-stimulated insulin secretion and glucose disappearance in healthy humans. Our findings raise the possibility that endogenous ghrelin has a role in physiologic insulin secretion, and that ghrelin antagonists could improve beta-cell function.

Acute administration of unacylated ghrelin has no effect on Basal or stimulated insulin secretion in healthy humans.

Unacylated ghrelin (UAG) is the predominant ghrelin isoform in the circulation. Despite its inability to activate the classical ghrelin receptor, preclinical studies suggest that UAG may promote β-cell function. We hypothesized that UAG would oppose the effects of acylated ghrelin (AG) on insulin secretion and glucose tolerance. AG (1 µg/kg/h), UAG (4 µg/kg/h), combined AG+UAG, or saline were infused to 17 healthy subjects (9 men and 8 women) on four occasions in randomized order. Ghrelin was infused for 30 min to achieve steady-state levels and continued through a 3-h intravenous glucose tolerance test. The acute insulin response to glucose (AIRg), insulin sensitivity index (SI), disposition index (DI), and intravenous glucose tolerance (kg) were compared for each subject during the four infusions. AG infusion raised fasting glucose levels but had no effect on fasting plasma insulin. Compared with the saline control, AG and AG+UAG both decreased AIRg, but UAG alone had no effect. SI did not differ among the treatments. AG, but not UAG, reduced DI and kg and increased plasma growth hormone. UAG did not alter growth hormone, cortisol, glucagon, or free fatty acid levels. UAG selectively decreased glucose and fructose consumption compared with the other treatments. In contrast to previous reports, acute administration of UAG does not have independent effects on glucose tolerance or β-cell function and neither augments nor antagonizes the effects of AG.

Niveaux de vigilance pendant et après une exposition à la lumière vive durant la nuit

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Évaluation de trois solutions épidurales pour l'analgésie en chirurgie cardiaque à coeur battant

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Duelo, ansiedad y depresión en familiares de pacientes en una unidad de cuidados paliativos a los dos meses de la pérdida

Aim: This study is going to assess the prevalance of prolonged grief diagnoses and it will evaluate the severity of the symptoms of depression, anxiety and complicated grief two months after a loved one is lost. We also intend to study which variables associated with the risk of grief could be more decisive when diagnosing it, its symptoms and the consequent emotional distress.Method: A total of 66 families of patients in the Palliative Care Unit (PCU) at Hospital San Cecilio in Granada have been evaluated. Measurements were taken two months after the death. This investigation has explored the existing emotional distress using the following questionnaires: Beck Depression Inventory (BDI-II), Beck Anxiety Inventory (BAI), Inventory of Complicated Grief (ICG) and Prolongued Grief Disorder (PG-12).Results: The results show that 33.3% and 21.21% of the sufferers had high levels of depression and clinical anxiety two months after the death. The prevalence of prolongued grief diagnoses, according to the PG-12, is 10.6% and 53.03% of the participants showed symptoms of complicated grief according to the ICG. Additionally, statistically significant differences are found in the sufferers with and without a prolongued grief diagnosis and scores in the ICG and BDI-II. The family’s financial situation is linked to the presence of symptoms of anxiety and depression and complicated grief, with the most determining variable being the risk of grief. Finally, the greater the age of the deceased and the longer the time spent in the PCU is linked to fewer symptoms of grief. However, important links have been found between the sufferers who have experienced stressful critical events prior to losing their loved one, with symptoms of depression, anxiety and complicated grief.Conclusions: The high numbers of cases of symptoms of complicated grief and levels of anxiety and clinical depression two months after a death suggests that early interventions should be carried out in those individuals with greater vulnerability.

Hormonal changes related to paternal and alloparental care in common marmosets (Callithrix jacchus)

The physiological mechanisms of parental and alloparental care in cooperatively breeding nonhuman primate species such as the common marmoset (Callithrix jacchus) are poorly known. In this study, we examined prolactin and cortisol plasma levels of fathers and older offspring of both sexes, with and without previous experience in infant carrying, around parturition and during infant carrying. Blood samples were collected from fathers and older offspring and prolactin and cortisol were measured by RIA and EIA, respectively. Prolactin levels of both caretakers were not influenced by infant’s birth, previous experience or proximity to parturition. However, prolactin levels increased in both caretakers while in physical contact with infants and also with the number of infants being carried in older offspring. These findings suggest that increased prolactin seems to be mainly due to physical effort rather than a physiological trigger of paternal and alloparental care in common marmosets. Cortisol levels were higher for experienced fathers shortly before parturition which could act to reinforce affiliative bonds between breeding males and females at this time or in the ability of males to detect the proximity of the parturition or both

Avaliação da fidedignidade dos ensaios de esteróides fecais realizados no Laboratório de Medidas Hormonais do Departamento de Fisiologia da UFRN

NASCIMENTO, H. G. ; FERNANDES, L. C. ; SOUSA, M. B. C. . Avaliação da fidedignidade dos ensaios de esteróides fecais realizados no Laboratório de Medidas Hormonais do Departamento de Fisiologia da UFRN. Publica , v. 2, p. 39-48, 2006.

Une étude sur les déterminants biologiques, psychologiques et du travail de l'épuisement professionnel

Cette thèse de doctorat s’intéresse à mieux comprendre, d’une part, ce qui influence la sécrétion de cortisol salivaire, et d’autre part, ce qui influence l’épuisement professionnel. Plusieurs objectifs en découlent. D’abord, elle vise à mieux cerner la contribution des conditions de l’organisation du travail (utilisation des compétences, autorité décisionnelle, demandes psychologiques, demandes physiques, horaire de travail irrégulier, nombre d’heures travaillées, soutien social des collègues, soutien social des superviseurs, insécurité d’emploi) sur la sécrétion de cortisol salivaire, ainsi que le rôle modérateur de certains traits de personnalité (extraversion, agréabilité, névrosisme, conscience, ouverture d’esprit, estime de soi, centre de contrôle) sur la relation entre les conditions de l’organisation du travail et la sécrétion de cortisol salivaire. Par ailleurs, cette thèse vise à établir la contribution des conditions de l’organisation du travail sur l’épuisement professionnel, ainsi que le rôle modérateur des traits de personnalité sur la relation entre les conditions de l’organisation du travail et l’épuisement professionnel. Finalement, cette thèse vise à vérifier si la sécrétion de cortisol salivaire joue un rôle médiateur sur la relation entre les conditions de l’organisation du travail et l’épuisement professionnel, ainsi qu’à identifier les effets de médiation modérés par les traits de personnalité sur la relation entre les conditions de l’organisation du travail et la sécrétion de cortisol salivaire. Ces objectifs sont inspirés de nombreuses limites observées dans la littérature, principalement l’intégration de déterminants à la fois biologiques, psychologiques et du travail dans la compréhension de l’épuisement professionnel. La thèse propose un modèle conceptuel qui tente de savoir comment ces différents stresseurs entraînent une dérégulation de la sécrétion de cortisol dans la salive des travailleurs. Ensuite, ce modèle conceptuel vise à voir si cette dérégulation s’associe à l’épuisement professionnel. Finalement, ce modèle conceptuel cherche à expliquer comment la personnalité peut influencer la manière dont ces variables sont reliées entre elles, c’est-à-dire de voir si la personnalité joue un rôle modérateur. Ce modèle découle de quatre théories particulières, notamment la perspective biologique de Selye (1936). Les travaux de Selye s’orientent sur l’étude de la réaction physiologique d’un organisme soumis à un stresseur. Dans ces circonstances, l’organisme est en perpétuel effort de maintien de son équilibre (homéostasie) et ne tolère que très peu de modifications à cet équilibre. En cas de modifications excessives, une réponse de stress est activée afin d’assurer l’adaptation en maintenant l’équilibre de base de l’organisme. Ensuite, le modèle conceptuel s’appuie sur le modèle de Lazarus et Folkman (1984) qui postule que la réponse de stress dépend plutôt de l’évaluation que font les individus de la situation stressante, et également sur le modèle de Pearlin (1999) qui postule que les individus exposés aux mêmes stresseurs ne sont pas nécessairement affectés de la même manière. Finalement, le modèle conceptuel de cette thèse s’appuie sur le modèle de Marchand (2004) qui postule que les réactions dépendent du décodage que font les acteurs des contraintes et ressources qui les affectent. Diverses hypothèses émergent de cette conceptualisation théorique. La première est que les conditions de l’organisation du travail contribuent directement aux variations de la sécrétion de cortisol salivaire. La deuxième est que les conditions de l’organisation du travail contribuent directement à l’épuisement professionnel. La troisième est que la sécrétion de cortisol salivaire médiatise la relation entre les conditions de l’organisation du travail et l’épuisement professionnel. La quatrième est que la relation entre les conditions de l’organisation du travail et la sécrétion de cortisol salivaire est modérée par les traits de personnalité. La cinquième est que la relation entre les conditions de l’organisation du travail, la sécrétion de cortisol salivaire et l’épuisement professionnel est modérée par les traits de personnalité. Des modèles de régression multiniveaux et des analyses de cheminement de causalité ont été effectués sur un échantillon de travailleurs canadiens provenant de l’étude SALVEO. Les résultats obtenus sont présentés sous forme de trois articles, soumis pour publication, lesquels constituent les chapitres 4 à 6 de cette thèse. Dans l’ensemble, le modèle intégrateur biopsychosocial proposé dans le cadre de cette thèse de doctorat permet de mieux saisir la complexité de l’épuisement professionnel qui trouve une explication biologique, organisationnelle et individuelle. Ce constat permet d’offrir une compréhension élargie et multiniveaux et assure l’avancement des connaissances sur une problématique préoccupante pour les organisations, la société ainsi que pour les travailleurs. Effectivement, la prise en compte des traits de personnalité et de la sécrétion du cortisol salivaire dans l’étude de l’épuisement professionnel assure une analyse intégrée et plus objective. Cette thèse conclue sur les implications de ces résultats pour la recherche, et sur les retombées qui en découlent pour les milieux de travail.

The role of glucocorticoids in naturally fasting grey seal (Halichoerus grypus) pups: dexamethasone stimulates mass loss and protein utilisation, but not departure from the colony

Seals must manage their energy reserves carefully while they fast on land to ensure that they go to sea with sufficient fuel to sustain them until they find food. Glucocorticoids (GCs) have been implicated in the control of fuel metabolism and termination of fasting in pinnipeds. Here we tested the hypothesis that dexamethasone, an artificial GC, increases fat and protein catabolism, and induces departure from the breeding colony in wild, fasting grey seal pups. A single intramuscular dose of dexamethasone completely suppressed cortisol production for 24–72 h, demonstrating activation of GC receptors. In experiment 1, we compared the effects of a single dose of dexamethasone or saline administered 10 days after weaning on fasting mass and body composition changes, cortisol, blood urea nitrogen (BUN) and glucose levels, and timing of departure from the colony. In experiment 2, we investigated the effects of dexamethasone on short-term (5 days) changes in mass loss, body composition and BUN levels. In experiment 1, dexamethasone induced a short-lived increase in mass loss, but there was no difference in timing of departure between dexamethasone- and saline-treated pups (N=10). In experiment 2, dexamethasone increased protein and water loss and prevented a decrease in BUN levels (N=11). Our data suggest changes in cortisol contribute to regulation of protein catabolism in fasting seal pups, irrespective of the sex of the animal, but do not terminate fasting. By affecting the rate of protein depletion, lasting changes in cortisol levels could influence the amount of time seal pups have to find food, and thus may have important consequences for their survival.

Hormonal changes related to paternal and alloparental care in common marmosets (Callithrix jacchus)

The physiological mechanisms of parental and alloparental care in cooperatively breeding nonhuman primate species such as the common marmoset (Callithrix jacchus) are poorly known. In this study, we examined prolactin and cortisol plasma levels of fathers and older offspring of both sexes, with and without previous experience in infant carrying, around parturition and during infant carrying. Blood samples were collected from fathers and older offspring and prolactin and cortisol were measured by RIA and EIA, respectively. Prolactin levels of both caretakers were not influenced by infant’s birth, previous experience or proximity to parturition. However, prolactin levels increased in both caretakers while in physical contact with infants and also with the number of infants being carried in older offspring. These findings suggest that increased prolactin seems to be mainly due to physical effort rather than a physiological trigger of paternal and alloparental care in common marmosets. Cortisol levels were higher for experienced fathers shortly before parturition which could act to reinforce affiliative bonds between breeding males and females at this time or in the ability of males to detect the proximity of the parturition or both

Avaliação da fidedignidade dos ensaios de esteróides fecais realizados no Laboratório de Medidas Hormonais do Departamento de Fisiologia da UFRN

NASCIMENTO, H. G. ; FERNANDES, L. C. ; SOUSA, M. B. C. . Avaliação da fidedignidade dos ensaios de esteróides fecais realizados no Laboratório de Medidas Hormonais do Departamento de Fisiologia da UFRN. Publica , v. 2, p. 39-48, 2006.

Congenital adrenal hyperplasia: focus on the molecular basis of 21-hydroxylase deficiency

Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder caused by defects in one of several steroidogenic enzymes involved in the synthesis of cortisol from cholesterol in the adrenal glands. More than 90% of cases are caused by 21-hydroxylase deficiency, and the severity of the resulting clinical symptoms varies according to the level of 21-hydroxylase activity. 21-Hydroxylase deficiency is usually caused by mutations in the CYP21A2 gene, which is located on the RCCX module, a chromosomal region highly prone to genetic recombination events that can result in a wide variety of complex rearrangements, such as gene duplications, gross deletions and gene conversions of variable extensions. Molecular genotyping of CYP21A2 and the RCCX module has proved useful for a more accurate diagnosis of the disease, and prenatal diagnosis. This article summarises the clinical features of 21-hydroxylase deficiency, explains current understanding of the disease at the molecular level, and highlights recent developments, particularly in diagnosis.

Fórmula CUN-BAE y factores bioquímicos como marcadores predictivos de obesidad y enfermedad cardiovascular en pacientes pre y post gastrectomía vertical

Introducción: El Índice de Masa Corporal (IMC) es uno de los parámetros más utilizados en cirugía bariátrica. Sin embargo, no discrimina el peso asociado a adiposidad. La fórmula CUN-BAE es una ecuación que permite calcular el Porcentaje de Grasa Corporal (PGC) o adiposidad, basándose en valores fáciles de disponer (edad, sexo e IMC). Con esta nueva clasificación muchos de los sujetos considerados con normopeso o sobrepeso (IMC ≤ 30 kg/m²) en realidad tienen un PGC alto y presentan comorbilidades asociadas a la obesidad. El objetivo de este estudio es evaluar PGC cuantificado mediante fórmula CUN-BAE como marcador predictivo de riesgo cardiovascular en pacientes obesos mórbidos, antes y después de ser sometidos a Gastrectomía Vertical (GV). Material y métodos: Realizamos un estudio observacional retrospectivo de mujeres intervenidas de GV entre 2007 y 2012 en el Hospital General Universitario de Elche, calculando el PGC mediante la fórmula CUN-BAE de forma preoperatoria y 12 meses tras la intervención. Se correlacionaron estos valores con diferentes parámetros metabólicos y de riesgo cardiovascular. Resultados: Se estudiaron 50 mujeres. Preoperatoriamente, el IMC medio de 50,4 ± 7,4 kg/m² y PGC del 54,8 ± 3%. Al año de la intervención, el IMC medio era de 27,7 ± 2,6 y el PGC 39,4 ± 3,7%. La PGC se correlacionó significativamente con 3 factores bioquímicos asociados con mayor riesgo cardiovascular (cortisol, vitamina D y cociente TG/HDL). Conclusión: la adiposidad, según la fórmula CUN-BAE, y el análisis de factores bioquímicos predictivos de obesidad, de forma conjunta suponen herramientas útiles para valorar el riesgo de enfermedad cardiovascular, después de GV.

Cambios fisiológicos y bioquímicos en cirugía laparoscópica vs convencional de vías biliares. Hospital Vicente Corral Moscoso Cuenca 2000

Con un diseño cuasiexperimental se realizó un estudio clínico en el hopital Vicente Corral de Cuenca que incluyó 80 pacientes de ambos sexos asignados a dos grupos: 1.- grupo COLELAP formado por cuarenta pacientes a los que se realizó colecistectomía laparoscópica y 2.- grupo CONVENC formado por 40 pacientes a los que se realizó colecistectomía abierta. El procedimiento fue similar para ambos grupos. En los dos grupos se midieron a.- los niveles de cortisol prequirúrgico y posquirúrgico mediante radioinmunoanálisis [Coat-A cortisol r], b.- El dolor antes y después de la cirugía mediante una escala visual y c.- La estadía hospitalaria y las complicaciones. No hubieron diferencias estadísticamente significativas en cuanto a edad, género, procedencia, nivel de instrucción, dolor preoperatro y valoraciones sanguíneas de laboratorio. Los valores de cortisol del grupo COLELAP fueron inferiores a los del grupo CONVENC tanto en el preoperatorio 9.40 más menos 4.81 vs. 20.11 más menos 8.87 [p = 0.001] como en el postoperatorio 12.19 más menos 4.12 vs. 22.1 más menos 7.31 [p=0.0001], sin embargo en el grupo COLELAP el aumento promedio [2.8 mcg/dL vs 1.99 mcg/dL fue mayor. El dolor preoperatorio evaluado mediante una escala análoga visual fue igual en ambos grupos [p=0.22] pero en el postoperatorio fue menor en el grupo COLELAP [p=0.012]. El tiempo quirúrgico promedio fue mayor para el grupo CONVENC [82.25 más menos 31.66 min vs 63.5 más menos 31.23 min] [p=0.0005]. El 90 por ciento de los pacientes del grupo fue de 3.1 más menos días y para el grupo CONVENC de 4.8 más menos 0.87 días. La diferencia fue altamente significativa [p=0.00001]. En conclusión laparoscópica muestra significativas ventajas frente a la colecistectomía abierta; a.- Minimiza el trauma quirúrgico, b.- produce menor dolor postoperatorio y c.- disminuye la estadía hospitalaria

The possible identification and introduction of metallothionein in Persian Sturgeon (Acipenser persicus)

Due to anthropogenic activities, toxic metals still represent a threat for various marine organisms. Metallothionein (MT) and cadmium concentration in gills, liver, and kidney tissues and cadmium partitioning in soluble (cytosol) and insoluble fractions of mentioned tissues of Persian sturgeon (Acipenser persicus) were determined following exposure to sub-lethal levels of waterborne cadmium (Cd) (50, 400 and 1000 μg L-1) after 1, 2, 4 and 14 days. The increases of MT from background levels in comparison to controls were 4.6-, 3-, and 2.8-fold for kidney, liver, and gills, respectively after 14 days. The matallothionein concentration in liver was in the range of 56.89-168.44 μgL-1 and for kidney and gills, 39.78-189.30 and 28.15-91.20 μgL-1, respectively. The results showed that MT level change in the kidney is time and concentration dependent. Also, cortisol measurement revealed elevation at the day 1 of exposure and that followed by MT increase in the liver. Cd concentrations in the cytosol of experimental tissues were measured and the results indicated that Cd levels in the cytosol of liver, kidney, and gills increased 240.71-, 32.05-, and 40.16-fold, respectively 14 days after exposure to 1000 μgL-1 Cd. The accumulation of Cd in cytosol of tissues is in the order of liver > gills > kidney. Spearman correlation coefficients showed the MT content in kidney is correlated with Cd concentration, the value of which is more than in liver and gills. Thus, kidney can be considered as a tissue indicator in Acipenser persicus for waterborne Cd contamination. Also, tissue metal accumulations (gills, liver, kidney and muscle) in Persian sturgeon (Acipenser persicus) were compared following exposure to sublethal levels of waterborne Cd (50, 400 and 1000 μg L-1) after periods of 1, 2, 4 and 14 days. Meanwhile, the trends of Cd concentration increase in different tissues during the exposure periods and concentrations were modelled as equations. The obtained results indicate that at the end of 4 and 14 days of exposure, total tissue cadmium concentration followed the pattern: liver> gill> kidney> muscle. Calculation of bioconcentration factor (BCF) after 14 days exposure showed that at low and high concentrations, highest BCFs were found in kidney and liver, respectively. According to the results, the accumulation capacity of muscle was the lowest at all exposure concentrations. The hematological parameters including osmolarity, total protein, cortisol and glucose of plasma were measured, too. Total protein of plasma was in the range of 416.90-1068.10 mg dl-1 plasma.Total protein decreased not significantly (P≥0.05) after exposure to Cd. Cortisol increased after 1 day exposure that followed by significant (P≤0.05) elevation of glucose. The range of cortisol was very vast and it was determined between 0.03 to 16.21 ng mL-1. The content of plasma osmolarity was in the range of 282.33-294.20 mOsmol L-1.Osmolarity of treated fish plasma showed no significant decrease (P≥0.05). Total protein in gills, liver, and kidney showed that at high concentrations of metal, protein content decreased significantly (P≤0.05) in the liver after 4 and 14 days exposure. Thus, total protein of liver and glucose of plasma can be used as general biomarkers of exposure to Cd. Also, the metallothionein and cadmium were measured in gills, kidney and liver of 8 wild Persian sturgeon caught in coast of Guilan Province. According to the results, the concentration of metallothionein was in the range of 45.87-154.66 microgram per liter with the maximum and minimum concentrations in liver and gills, respectively. The trend of cadmium concentration in cytosol of tissues was: liver> kidney> gills. The results of Spearman correlation test showed that there was a significant positive correlation between metallothionein and cadmium in cytosol of liver (r2= 0.850, p≤ 0.01). In the kidney, the correlation between cadmium and metallothionein was significantly positive (r2= 0.731, p≥ 0.05). But there was not such significant correlation in the gills (p≥ 0.05).