Ghrelin and PYY(3-36) in gastrectomized and vagotomized patients: relations with appetite, energy intake and resting energy expenditure

Background/Objectives: Reduced food intake, appetite loss and alteration of ghrelin and PYY(3-36) secretion have been suggested to have a function in the loss of body weight commonly observed after gastrectomy. The objective of this study was to investigate the circulating concentrations of ghrelin and PYY(3-36) and their relationships with food intake, appetite and resting energy expenditure (REE) after gastrectomy plus vagotomy. Subjects/Methods: Seven patients with total gastrectomy (TG), 14 with partial gastrectomy (PG) and 10 healthy controls were studied. Habitual food intake and REE was assessed; fasting and postprandial plasma total ghrelin, PYY(3-36) concentrations and appetite ratings were determined after ingestion of a liquid test meal. Results: Differently from PG and controls, fasting ghrelin correlated with REE, and a higher energy intake was observed in the TG group. Fasting plasma ghrelin concentrations were lower in TG compared with controls, and no ghrelin response to the meal was observed in either PG or TG. Fasting plasma PYY(3-36) concentrations were not different among the groups. There was an early and exaggerated postprandial rise in PYY(3-36) levels in both PG and TG groups, but not in controls. No effect of ghrelin or PYY(3-36) concentrations was observed on hunger, prospective consumption or fullness ratings. Conclusions: Total ghrelin and PYY(3-36) do not seem to be involved with appetite or energy intake regulation after gastrectomy plus vagotomy. Ghrelin secreted by sources other than stomach is likely to have a function in the long-term regulation of body weight after TG. European Journal of Clinical Nutrition (2010) 64, 845-852; doi: 10.1038/ejcn.2010.88; published online 19 May 2010

Desacyl-ghrelin does not influence insulin sensitivity

Acyl-ghrelin has been reported to increase food intake and adiposity and it is the best studied of the orexigenic gastrointestinal hormones. On the other hand, desacyl-ghrelin – DAG (the unacylated form of the hormone) has been reported as a potential player on carbohydrate metabolism. However, the potential impact of DAG on glucose homeostasis remains uncertain. In this study we aim to assess the association between DAG and insulin sensitivity.

Bases neurobiológicas del efecto de grelina sobre ansiedad, memoria e ingesta. Neurobiological mechanisms of ghrelin effect on anxiety, memory and food intake.

El objetivo de este proyecto es investigar el sustrato neurobiológico que subyace a los efectos centrales de grelina (Gr) en estructuras extrahipotalámicas tales como núcleo dorsal del rafe (NDR), hipocampo(Hi) y amígdala(Am) donde hemos demostrado que el péptido incrementa la memoria e ingesta, Los mecanismos neurales, neurotrasmisores(nt), segundos mensajeros, etc., involucrados en estos procesos fisiológicos, inducidos por el péptido, necesitan aun ser esclarecidos. Hemos demostrado que grelina incrementa la retención de la memoria cuando es inyectado en Hi, NDR y Am. También incrementa la ingesta al ser administrado en Hi y NDR pero no así en Am. En Hi los efectos de Gr sobre la memoria se correlacionan con incremento en los niveles tisulares de óxido nítrico (NO) y con la disponibilidad del nt 5-HT. En lo que a electrofisiología se refiere hemos demostrado que Gr disminuye el umbral para generar potenciación a largo plazo (LTP). A fin de aportar nuevas evidencias que contribuyan a esclarecer los efectos del péptido sobre memoria e ingesta utilizaremos estudios conductuales, determinaciones bioquímicas y determinaciones electrofisiológicas. En lo que a ingesta se refiere intentaremos esclarecer el papel de los núcleos central y basolateral de la Am en aspectos hedónicos de la ingesta inducida por Gr En esta etapa, más específicamente nos proponemos:1) Determinar si los efectos de grelina sobre ingesta y memoria demostrados en hipocampo y NDR después de la su administración se correlacionan con modificaciones en la liberación de serotonina utilizando cortes de hipocampo precargados con 5HT tritiada en presencia y ausencia del péptido.2) Evaluar si el incremento de óxido nítrico inducido por grelina en hipocampo se correlaciona con cambios en la expresión de nNOS, utilizando Western-blot y la importancia de NOS/NO en la acción de grelina repitiendo los experimentos previo tratamiento de las ratas con inhibidores de NOS. 3)Estudiar la participación del nt glutamato en los efectos hipocampales de Gr sobre la memoria. Analizando a) si grelina modifica la liberación del nt a partir de sinaptosomas aislados de hipocampo de ratas pretratadas con Gr.b) la participación de los receptores NMDA y GABAa en los efectos de grelina previo bloqueo farmacológico del mencionado receptor y el test step down.c) la participación de los receptores NMDA y GABAa en los efectos de grelina utilizando electrofisiología y Western Blot. 4) Estudiar el efecto de la administración de Gr en Amigdala Central y Basolateral sobre aspectos hedónicos de la ingesta utilizando diferentes paradigmas conductuales en animales. Estudiaremos:a) si Gr modifica el consumo de alimento de diferente palatabilidad en animales y si afecta el componente motivacional de la conducta de ingesta paradigma de "runway".

Gastric supply manipulation to modulate ghrelin production and enhance vascularization to the cardia: proof of the concept in a porcine model.

Introduction. Selective embolization of the left-gastric artery (LGA) reduces levels of ghrelin and achieves significant short-term weight loss. However, embolization of the LGA would prevent the performance of bariatric procedures because the high-risk leakage area (gastroesophageal junction [GEJ]) would be devascularized. Aim. To assess an alternative vascular approach to the modulation of ghrelin levels and generate a blood flow manipulation, consequently increasing the vascular supply to the GEJ. Materials and methods. A total of 6 pigs underwent a laparoscopic clipping of the left gastroepiploic artery. Preoperative and postoperative CT angiographies were performed. Ghrelin levels were assessed perioperatively and then once per week for 3 weeks. Reactive oxygen species (ROS; expressed as ROS/mg of dry weight [DW]), mitochondria respiratory rate, and capillary lactates were assessed before and 1 hour after clipping (T0 and T1) and after 3 weeks of survival (T2), on seromuscular biopsies. A celiac trunk angiography was performed at 3 weeks. Results. Mean (±standard deviation) ghrelin levels were significantly reduced 1 hour after clipping (1902 ± 307.8 pg/mL vs 1084 ± 680.0; P = .04) and at 3 weeks (954.5 ± 473.2 pg/mL; P = .01). Mean ROS levels were statistically significantly decreased at the cardia at T2 when compared with T0 (0.018 ± 0.006 mg/DW vs 0.02957 ± 0.0096 mg/DW; P = .01) and T1 (0.0376 ± 0.008mg/DW; P = .007). Capillary lactates were significantly decreased after 3 weeks, and the mitochondria respiratory rate remained constant over time at the cardia and pylorus, showing significant regional differences. Conclusions. Manipulation of the gastric flow targeting the gastroepiploic arcade induces ghrelin reduction. An endovascular approach is currently under evaluation.

Preserving Electronic Theses through the MetaArchive network

In the recent years most libraries have focused on mass digitization programs and keeping electronic born documents, showing and organizing them in a repository. While those repositories have evolved to a much more manageable systems focusing on the user expectations and introducing web 2.0 tools, digital preservation is still in the to-do list of most of them. There is quite a lot of studies focused on preservation and some complex models exist, unfortunately, very few practical systems are running and its quite difficult for a library to get involved in a solution already tested by others. The CBUC (Consortium of University Catalan Libraries) runs TDX, an ETD repository now keeping more than 10.000 full text thesis from any of the 12 university members. After 10 years running TDX a solid preservation system was needed to ensure every thesis would be kept as it was regardless what happens to the repository. The perfect solution was found in the MetaArchive cooperative, this is the effort of many insitutions to keep a copy of each other content through a newtwork using the LOCKSS software as a mechanism to keep track of any change. The presentation will shortly introduce what TDX and MetaArchive is but will, in a practical way, show how the LOCKSS network for presrervation works. Finally a summary of the benefits of the overall experience will be shown.

A growth hormone-releasing peptide that binds scavenger receptor CD36 and ghrelin receptor up-regulates sterol transporters and cholesterol efflux in macrophages through a peroxisome proliferator-activated receptor gamma-dependent pathway.

Macrophages play a central role in the pathogenesis of atherosclerosis by accumulating cholesterol through increased uptake of oxidized low-density lipoproteins by scavenger receptor CD36, leading to foam cell formation. Here we demonstrate the ability of hexarelin, a GH-releasing peptide, to enhance the expression of ATP-binding cassette A1 and G1 transporters and cholesterol efflux in macrophages. These effects were associated with a transcriptional activation of nuclear receptor peroxisome proliferator-activated receptor (PPAR)gamma in response to binding of hexarelin to CD36 and GH secretagogue-receptor 1a, the receptor for ghrelin. The hormone binding domain was not required to mediate PPARgamma activation by hexarelin, and phosphorylation of PPARgamma was increased in THP-1 macrophages treated with hexarelin, suggesting that the response to hexarelin may involve PPARgamma activation function-1 activity. However, the activation of PPARgamma by hexarelin did not lead to an increase in CD36 expression, as opposed to liver X receptor (LXR)alpha, suggesting a differential regulation of PPARgamma-targeted genes in response to hexarelin. Chromatin immunoprecipitation assays showed that, in contrast to a PPARgamma agonist, the occupancy of the CD36 promoter by PPARgamma was not increased in THP-1 macrophages treated with hexarelin, whereas the LXRalpha promoter was strongly occupied by PPARgamma in the same conditions. Treatment of apolipoprotein E-null mice maintained on a lipid-rich diet with hexarelin resulted in a significant reduction in atherosclerotic lesions, concomitant with an enhanced expression of PPARgamma and LXRalpha target genes in peritoneal macrophages. The response was strongly impaired in PPARgamma(+/-) macrophages, indicating that PPARgamma was required to mediate the effect of hexarelin. These findings provide a novel mechanism by which the beneficial regulation of PPARgamma and cholesterol metabolism in macrophages could be regulated by CD36 and ghrelin receptor downstream effects.

Gut Microbiota Composition in Male Rat Models under Different Nutritional Status and Physical Activity and Its Association with Serum Leptin and Ghrelin Levels.

BACKGROUND Several evidences indicate that gut microbiota is involved in the control of host energy metabolism. OBJECTIVE To evaluate the differences in the composition of gut microbiota in rat models under different nutritional status and physical activity and to identify their associations with serum leptin and ghrelin levels. METHODS IN A CASE CONTROL STUDY, FORTY MALE RATS WERE RANDOMLY ASSIGNED TO ONE OF THESE FOUR EXPERIMENTAL GROUPS: ABA group with food restriction and free access to exercise; control ABA group with food restriction and no access to exercise; exercise group with free access to exercise and feed ad libitum and ad libitum group without access to exercise and feed ad libitum. The fecal bacteria composition was investigated by PCR-denaturing gradient gel electrophoresis and real-time qPCR. RESULTS In restricted eaters, we have found a significant increase in the number of Proteobacteria, Bacteroides, Clostridium, Enterococcus, Prevotella and M. smithii and a significant decrease in the quantities of Actinobacteria, Firmicutes, Bacteroidetes, B. coccoides-E. rectale group, Lactobacillus and Bifidobacterium with respect to unrestricted eaters. Moreover, a significant increase in the number of Lactobacillus, Bifidobacterium and B. coccoides-E. rectale group was observed in exercise group with respect to the rest of groups. We also found a significant positive correlation between the quantity of Bifidobacterium and Lactobacillus and serum leptin levels, and a significant and negative correlation among the number of Clostridium, Bacteroides and Prevotella and serum leptin levels in all experimental groups. Furthermore, serum ghrelin levels were negatively correlated with the quantity of Bifidobacterium, Lactobacillus and B. coccoides-Eubacterium rectale group and positively correlated with the number of Bacteroides and Prevotella. CONCLUSIONS Nutritional status and physical activity alter gut microbiota composition affecting the diversity and similarity. This study highlights the associations between gut microbiota and appetite-regulating hormones that may be important in terms of satiety and host metabolism.

Astressin B, a nonselective corticotropin-releasing hormone receptor antagonist, prevents the inhibitory effect of ghrelin on luteinizing hormone pulse frequency in the ovariectomized rhesus monkey.

Administration of ghrelin, a key peptide in the regulation of energy homeostasis, has been shown to decrease LH pulse frequency while concomitantly elevating cortisol levels. Because increased endogenous CRH release in stress is associated with an inhibition of reproductive function, we have tested here whether the pulsatile LH decrease after ghrelin may reflect an activated hypothalamic-pituitary-adrenal axis and be prevented by a CRH antagonist. After a 3-h baseline LH pulse frequency monitoring, five adult ovariectomized rhesus monkeys received a 5-h saline (protocol 1) or ghrelin (100-microg bolus followed by 100 microg/h, protocol 2) infusion. In protocols 3 and 4, animals were given astressin B, a nonspecific CRH receptor antagonist (0.45 mg/kg im) 90 min before ghrelin or saline infusion. Blood samples were taken every 15 min for LH measurements, whereas cortisol and GH were measured every 45 min. Mean LH pulse frequency during the 5-h ghrelin infusion was significantly lower than in all other treatments (P < 0.05) and when compared with the baseline period (P < 0.05). Pretreatment with astressin B prevented the decrease. Ghrelin stimulated cortisol and GH secretion, whereas astressin B pretreatment prevented the cortisol, but not the GH, release. Our data indicate that CRH release mediates the inhibitory effect of ghrelin on LH pulse frequency and suggest that the inhibitory impact of an insufficient energy balance on reproductive function may in part be mediated by the hypothalamic-pituitary-adrenal axis.

Ghrelin-induced orexigenic effect in rats depends on the metabolic status and is counteracted by peripheral CB1 receptor antagonism.

Ghrelin is an endogenous regulator of energy homeostasis synthesized by the stomach to stimulate appetite and positive energy balance. Similarly, the endocannabinoid system is part of our internal machinery controlling food intake and energy expenditure. Both peripheral and central mechanisms regulate CB1-mediated control of food intake and a functional relationship between hypothalamic ghrelin and cannabinoid CB1 receptor has been proposed. First of all, we investigated brain ghrelin actions on food intake in rats with different metabolic status (negative or equilibrate energy balance). Secondly, we tested a sub-anxiogenic ultra-low dose of the CB1 antagonist SR141716A (Rimonabant) and the peripheral-acting CB1 antagonist LH-21 on ghrelin orexigenic actions. We found that: 1) central administration of ghrelin promotes food intake in free feeding animals but not in 24 h food-deprived or chronically food-restricted animals; 2) an ultra-low dose of SR141716A (a subthreshold dose 75 folds lower than the EC50 for induction of anxiety) completely counteracts the orexigenic actions of central ghrelin in free feeding animals; 3) the peripheral-restricted CB1 antagonist LH-21 blocks ghrelin-induced hyperphagia in free feeding animals. Our study highlights the importance of the animaĺs metabolic status for the effectiveness of ghrelin in promoting feeding, and suggests that the peripheral endocannabinoid system may interact with ghrelińs signal in the control of food intake under equilibrate energy balance conditions.

Scientific production on workplace bullying/harassment in dissertations and theses in the Brazilian scenario

OBJECTIVE To analyze scientific production about workplace bullying and harassment in dissertations and theses in Brazil, with emphasis on the year of publication; educational institution; area of knowledge; professional and academic background of the authors; keywords used; and concept map organization. METHOD Bibliometric study with a quantitative approach with a sample consisting of 57 papers, 5 theses and 52 dissertations, published between 2002 and 2012. RESULTS It was found that 2012 was the year with the highest number of publications in this topic area. The region that stood out was the Southeast. The institution with the highest number of publications was the Federal University of Santa Catarina. There was a predominance of dissertations and most publications were produced by researchers focused on a multidisciplinary perspective. CONCLUSION Expanding the views regarding bullying in order to disseminate scientific production was proposed, promoting further advancement of debates and raising pertinent questions.

Towards storage and access of electronic theses: A proposal of its organisation for the Consortium of Catalan Libraries

Els objectius d'aquest informe són realitzar un estudi de la tècnica en la digitalització, l'emmagatzematge i l'accés a les tesis doctorals electròniques, per tal de fer una proposta d’organització al Consorci de Biblioteques Universitàries de Catalunya (CBUC). Actualment, tot i que existeixen diverses iniciatives a Europa, és als EUA on la digitalització de tesis doctorals s’ha desenvolupat més amb la creació de la Networked Digital Library for Theses and Dissertation (NDLTD), i ha estat qui ha definit els estàndards en aquest camp. En el següent informe es planteja i es recomana al CBUC l’adhesió institucional a l’NDLTD per poder gaudir de la seva experiència.