GLP-1 and GIP Levels in Patients With Hyperthyroidism: The Effect of Antithyroid Treatment.

PubMed

Cira, Duygu Kalkan; Sari, Ramazan; Ozdem, Sebahat; Yilmaz, Nusret; Bozkurt, Selen

2017-08-01

Incretin hormones (glucagon-like peptide-1 [GLP-1] and gastric inhibitory polypeptide [GIP]) may play a role in the development of glucose intolerance and hyperglycemia in patients with hyperthyroidism. We aimed to assess both incretin levels and treatment-induced changes in incretin levels in those with hyperthyroidism. A total of 24 subjects (12 with hyperthyroidism and 12 healthy) were enrolled in the study. Oral glucose tolerance test was performed and serum glucose, insulin GLP1, and GIP levels were evaluated at 0 (baseline), 30, 60, 90, and 120 minutes using ELISA. Measurements were repeated after euthyroidism was reached in subjects with hyperthyroidism. The baseline glucose level was higher in those with hyperthyroidism compared with controls ( P = 0.03). GLP-1 and GIP responses to oral glucose load did not differ significantly between those with hyperthyroidism and controls. Peak GLP-1 and GIP levels were reached in both groups at 60 and 90 minutes, respectively. Areas under the curve (AUCs) for GLP1 and GIP were similar in those with hyperthyroidism and controls. Although GLP-1 and GIP levels did not change before and after antithyroid treatment in subjects with hyperthyroidism, time to peak GLP-1 and GIP levels were reached at 30 minutes after euthyroid state was achieved. Reversal of hyperthyroid to euthyroid status did not induce significant changes in AUCs for incretins. The findings of the present study suggest that the total incretin response to oral glucose load is preserved in patients with hypertyhroidism, but peak incretin responses may change after achieving euthyroid state.

Internalization and desensitization of the human glucose-dependent-insulinotropic receptor is affected by N-terminal acetylation of the agonist.

PubMed

Ismail, Sadek; Dubois-Vedrenne, Ingrid; Laval, Marie; Tikhonova, Irina G; D'Angelo, Romina; Sanchez, Claire; Clerc, Pascal; Gherardi, Marie-Julie; Gigoux, Véronique; Magnan, Remi; Fourmy, Daniel

2015-10-15

How incretins regulate presence of their receptors at the cell surface and their activity is of paramount importance for the development of therapeutic strategies targeting these receptors. We have studied internalization of the human Glucose-Insulinotropic Polypeptide receptor (GIPR). GIP stimulated rapid robust internalization of the GIPR, the major part being directed to lysosomes. GIPR internalization involved mainly clathrin-coated pits, AP-2 and dynamin. However, neither GIPR C-terminal region nor β-arrestin1/2 was required. Finally, N-acetyl-GIP recognized as a dipeptidyl-IV resistant analogue, fully stimulated cAMP production with a ∼15-fold lower potency than GIP and weakly stimulated GIPR internalization and desensitization of cAMP response. Furthermore, docking N-acetyl-GIP in the binding site of modeled GIPR showed slighter interactions with residues of helices 6 and 7 of GIPR compared to GIP. Therefore, incomplete or partial activity of N-acetyl-GIP on signaling involved in GIPR desensitization and internalization contributes to the enhanced incretin activity of this peptide. Copyright © 2015. Published by Elsevier Ireland Ltd.

Molecular Cloning and Characterization of Glucanase Inhibitor Proteins

PubMed Central

Rose, Jocelyn K. C.; Ham, Kyung-Sik; Darvill, Alan G.; Albersheim, Peter

2002-01-01

A characteristic plant response to microbial attack is the production of endo-β-1,3-glucanases, which are thought to play an important role in plant defense, either directly, through the degradation of β-1,3/1,6-glucans in the pathogen cell wall, or indirectly, by releasing oligosaccharide elicitors that induce additional plant defenses. We report the sequencing and characterization of a class of proteins, termed glucanase inhibitor proteins (GIPs), that are secreted by the oomycete Phytophthora sojae, a pathogen of soybean, and that specifically inhibit the endoglucanase activity of their plant host. GIPs are homologous with the trypsin class of Ser proteases but are proteolytically nonfunctional because one or more residues of the essential catalytic triad is absent. However, specific structural features are conserved that are characteristic of protein–protein interactions, suggesting a mechanism of action that has not been described previously in plant pathogen studies. We also report the identification of two soybean endoglucanases: EGaseA, which acts as a high-affinity ligand for GIP1; and EGaseB, with which GIP1 does not show any association. In vitro, GIP1 inhibits the EGaseA-mediated release of elicitor-active glucan oligosaccharides from P. sojae cell walls. Furthermore, GIPs and soybean endoglucanases interact in vivo during pathogenesis in soybean roots. GIPs represent a novel counterdefensive weapon used by plant pathogens to suppress a plant defense response and potentially function as important pathogenicity determinants. PMID:12084830

Fecal Gluten Peptides Reveal Limitations of Serological Tests and Food Questionnaires for Monitoring Gluten-Free Diet in Celiac Disease Patients.

PubMed

Comino, Isabel; Fernández-Bañares, Fernando; Esteve, María; Ortigosa, Luís; Castillejo, Gemma; Fambuena, Blanca; Ribes-Koninckx, Carmen; Sierra, Carlos; Rodríguez-Herrera, Alfonso; Salazar, José Carlos; Caunedo, Ángel; Marugán-Miguelsanz, J M; Garrote, José Antonio; Vivas, Santiago; Lo Iacono, Oreste; Nuñez, Alejandro; Vaquero, Luis; Vegas, Ana María; Crespo, Laura; Fernández-Salazar, Luis; Arranz, Eduardo; Jiménez-García, Victoria Alejandra; Antonio Montes-Cano, Marco; Espín, Beatriz; Galera, Ana; Valverde, Justo; Girón, Francisco José; Bolonio, Miguel; Millán, Antonio; Cerezo, Francesc Martínez; Guajardo, César; Alberto, José Ramón; Rosinach, Mercé; Segura, Verónica; León, Francisco; Marinich, Jorge; Muñoz-Suano, Alba; Romero-Gómez, Manuel; Cebolla, Ángel; Sousa, Carolina

2016-10-01

Treatment for celiac disease (CD) is a lifelong strict gluten-free diet (GFD). Patients should be followed-up with dietary interviews and serology as CD markers to ensure adherence to the diet. However, none of these methods offer an accurate measure of dietary compliance. Our aim was to evaluate the measurement of gluten immunogenic peptides (GIP) in stools as a marker of GFD adherence in CD patients and compare it with traditional methods of GFD monitoring. We performed a prospective, nonrandomized, multicenter study including 188 CD patients on GFD and 84 healthy controls. Subjects were given a dietary questionnaire and fecal GIP quantified by enzyme-linked immunosorbent assay (ELISA). Serological anti-tissue transglutaminase (anti-tTG) IgA and anti-deamidated gliadin peptide (anti-DGP) IgA antibodies were measured simultaneously. Of the 188 celiac patients, 56 (29.8%) had detectable GIP levels in stools. There was significant association between age and GIP in stools that revealed increasing dietary transgressions with advancing age (39.2% in subjects ≥13 years old) and with gender in certain age groups (60% in men ≥13 years old). No association was found between fecal GIP and dietary questionnaire or anti-tTG antibodies. However, association was detected between GIP and anti-DGP antibodies, although 46 of the 53 GIP stool-positive patients were negative for anti-DGP. Detection of gluten peptides in stools reveals limitations of traditional methods for monitoring GFD in celiac patients. The GIP ELISA enables direct and quantitative assessment of gluten exposure early after ingestion and could aid in the diagnosis and clinical management of nonresponsive CD and refractory CD. Trial registration number NCT02711397.

Effect of caloric restriction with or without n-3 polyunsaturated fatty acids on insulin sensitivity in obese subjects: A randomized placebo controlled trial.

PubMed

Razny, Urszula; Kiec-Wilk, Beata; Polus, Anna; Goralska, Joanna; Malczewska-Malec, Malgorzata; Wnek, Dominika; Zdzienicka, Anna; Gruca, Anna; Childs, Caroline E; Kapusta, Maria; Slowinska-Solnica, Krystyna; Calder, Philip C; Dembinska-Kiec, Aldona

2015-12-01

Caloric restriction and n-3 polyunsaturated fatty acid (PUFA) supplementation protect from some of the metabolic complications. The aim of this study was to assess the influence of a low calorie diet with or without n-3 PUFA supplementation on glucose dependent insulinotropic polypeptide (GIP) output and insulin sensitivity markers in obese subjects. Obese, non-diabetic subjects (BMI 30-40 kg/m(2)) and aged 25-65 yr. were put on low calorie diet (1200-1500 kcal/day) supplemented with either 1.8 g/day n-3 PUFA (DHA/EPA, 5:1) (n = 24) or placebo capsules (n = 24) for three months in a randomized placebo controlled trial. Insulin resistance markers and GIP levels were analysed from samples obtained at fasting and during an oral glucose tolerance test (OGTT). Caloric restriction with n-3 PUFA led to a decrease of insulin resistance index (HOMA-IR) and a significant reduction of insulin output as well as decreased GIP secretion during the OGTT. These effects were not seen with caloric restriction alone. Changes in GIP output were inversely associated with changes in red blood cell EPA content whereas fasting GIP level positively correlated with HOMA-IR index. Blood triglyceride level was lowered by caloric restriction with a greater effect when n-3 PUFA were included and correlated positively with fasting GIP level. Three months of caloric restriction with DHA + EPA supplementation exerts beneficial effects on insulin resistance, GIP and triglycerides. Combining caloric restriction and n-3 PUFA improves insulin sensitivity, which may be related to a decrease of GIP levels.

Fecal Gluten Peptides Reveal Limitations of Serological Tests and Food Questionnaires for Monitoring Gluten-Free Diet in Celiac Disease Patients

PubMed Central

Comino, Isabel; Fernández-Bañares, Fernando; Esteve, María; Ortigosa, Luís; Castillejo, Gemma; Fambuena, Blanca; Ribes-Koninckx, Carmen; Sierra, Carlos; Rodríguez-Herrera, Alfonso; Salazar, José Carlos; Caunedo, Ángel; Marugán-Miguelsanz, J M; Garrote, José Antonio; Vivas, Santiago; lo Iacono, Oreste; Nuñez, Alejandro; Vaquero, Luis; Vegas, Ana María; Crespo, Laura; Fernández-Salazar, Luis; Arranz, Eduardo; Jiménez-García, Victoria Alejandra; Antonio Montes-Cano, Marco; Espín, Beatriz; Galera, Ana; Valverde, Justo; Girón, Francisco José; Bolonio, Miguel; Millán, Antonio; Cerezo, Francesc Martínez; Guajardo, César; Alberto, José Ramón; Rosinach, Mercé; Segura, Verónica; León, Francisco; Marinich, Jorge; Muñoz-Suano, Alba; Romero-Gómez, Manuel; Cebolla, Ángel; Sousa, Carolina

2016-01-01

Objectives: Treatment for celiac disease (CD) is a lifelong strict gluten-free diet (GFD). Patients should be followed-up with dietary interviews and serology as CD markers to ensure adherence to the diet. However, none of these methods offer an accurate measure of dietary compliance. Our aim was to evaluate the measurement of gluten immunogenic peptides (GIP) in stools as a marker of GFD adherence in CD patients and compare it with traditional methods of GFD monitoring. Methods: We performed a prospective, nonrandomized, multicenter study including 188 CD patients on GFD and 84 healthy controls. Subjects were given a dietary questionnaire and fecal GIP quantified by enzyme-linked immunosorbent assay (ELISA). Serological anti-tissue transglutaminase (anti-tTG) IgA and anti-deamidated gliadin peptide (anti-DGP) IgA antibodies were measured simultaneously. Results: Of the 188 celiac patients, 56 (29.8%) had detectable GIP levels in stools. There was significant association between age and GIP in stools that revealed increasing dietary transgressions with advancing age (39.2% in subjects ≥13 years old) and with gender in certain age groups (60% in men ≥13 years old). No association was found between fecal GIP and dietary questionnaire or anti-tTG antibodies. However, association was detected between GIP and anti-DGP antibodies, although 46 of the 53 GIP stool-positive patients were negative for anti-DGP. Conclusions: Detection of gluten peptides in stools reveals limitations of traditional methods for monitoring GFD in celiac patients. The GIP ELISA enables direct and quantitative assessment of gluten exposure early after ingestion and could aid in the diagnosis and clinical management of nonresponsive CD and refractory CD. Trial registration number NCT02711397. PMID:27644734

Human and porcine immunoreactive gastric inhibitory polypeptides (IR-GIP) are not identical.

PubMed

Bacarese-Hamilton, A J; Adrian, T E; Bloom, S R

1984-03-12

Immunoreactive gastric inhibitory polypeptide (IR-GIP) from human and porcine intestine was quantified by radioimmunoassay and the molecular forms characterised by gel permeation and reverse-phase high pressure liquid chromatography (HPLC). Gel filtration revealed two major immunoreactive peaks corresponding to the previously described 5-kDa and 8-kDa molecular forms, which appeared similar in both species. Isocratic reverse-phase HPLC revealed that the major immunoreactive GIP peak (5-kDa) in the human tissue eluted earlier than the corresponding porcine molecular form, indicating the latter to be less hydrophobic. These findings suggest significant species differences between human and porcine GIP.

The effect of unabsorbable carbohydrate on gut hormones. Modification of post-prandial GIP secretion by guar.

PubMed

Morgan, L M; Goulder, T J; Tsiolakis, D; Marks, V; Alberti, K G

1979-08-01

Five healthy volunteers and 6 diabetics were given a mixed test meal on two occasions--once with and once without 10 g guar flour. Addition of guar caused a 47% decrease in maximum post-prandial GIP levels, a 48% decrease in blood glucose and a 48% decrease in plasma insulin in normal subjects. In diabetics, addition of guar caused a 30% reduction in maximum post-prandial GIP and 58% decrease in blood glucose. Four normal and 6 diabetic subjects were given a predominantly carbohydrate meal, again with and without 10 g guar. Addition of guar caused a 78% decrease in blood glucose and a 59% decrease in plasma insulin in normal subjects. In diabetics addition of guar caused a 71% decrease in maximum post-prandial plasma GIP and a 68% decrease in blood glucose. Lowering of post-prandial blood glucose, plasma insulin and GIP levels by guar was statistically significant in every case. Addition of guar to the predominantly carbohydrate meal caused a decrease in total plasma GLI in both normal and diabetic subjects but reached statistical significance only in the normal subjects. There was a highly significant correlation (r = 0.83; p less than 0.0005) between peak post-prandial insulin levels in normal subjects and the corresponding plasma GIP concentration. The reduction of GIP or GLI secretion may, therefore, be partly responsible for the smaller rise in plasma insulin observed in normal volunteers when guar is added to meals.

Insulinotropic properties of synthetic human gastric inhibitory polypeptide in man: interactions with glucose, phenylalanine, and cholecystokinin-8.

PubMed

Nauck, M; Schmidt, W E; Ebert, R; Strietzel, J; Cantor, P; Hoffmann, G; Creutzfeldt, W

1989-09-01

The quantitative contribution of glucose-dependent insulinotropic polypeptide [gastric inhibitory polypeptide (GIP)] to the incretin effect after oral glucose (augmentation of insulin secretion over the degree that is explained by the glycemic rise) is not known. Therefore, hyperglycemic clamp experiments (8 mmol/L, corresponding to postprandial glucose concentrations) were performed in healthy volunteers, and synthetic human GIP was infused for 60 min at a rate (approximately 1.3 pmol/kg.min) that results in plasma GIP concentrations similar to those occurring after oral glucose loads of 75 g. The MCR for exogenous GIP was approximately 6 mL/kg.min; the decay after ceasing infusion was exponential with a t1/2 of about 18 min, and the resulting volume of distribution was about 140 mL/kg. At euglycemic (basal) plasma glucose concentrations (5.0 mmol/L) similar values were found. Insulin secretion was stimulated by hyperglycemia alone, but was greatly (2.3-fold based on C-peptide) potentiated by GIP infusions (P less than or equal to 0.001 for integrated incremental values). When integrated incremental responses over 120 min of GIP, immunoreactive insulin, and immunoreactive C-peptide were compared after oral glucose and during GIP infusions, no significant differences were found. Peak glucose concentrations after oral glucose (7.6 +/- 0.6 mmol/L) were similar to mean plasma glucose values during clamp experiments (8.2 +/- 0.1 mmol/L; P = 0.124). However, mean glucose concentrations after oral glucose were lower (6.0 +/- 0.3 mmol/L; P = 0.0004). Additional infusion of sulfated cholecystokinin-8 (25 pmol/kg.h) or the amino acid phenylalanine (1.7 mumol/kg.min) did not further stimulate insulin secretion and had no influence on the pharmacokinetics of exogenous GIP. It is concluded that human synthetic GIP is insulinotropic in man and that this activity may well explain a substantial part of the incretin effect after oral glucose. There is no interaction with cholecystokinin or phenylalanine in concentrations found after mixed meals.

A selective glucose sensor based on direct oxidation on a bimetal catalyst with a molecular imprinted polymer.

PubMed

Cho, Seong Je; Noh, Hui-Bog; Won, Mi-Sook; Cho, Chul-Ho; Kim, Kwang Bok; Shim, Yoon-Bo

2018-01-15

A selective nonenzymatic glucose sensor was developed based on the direct oxidation of glucose on hierarchical CuCo bimetal-coated with a glucose-imprinted polymer (GIP). Glucose was introduced into the GIP composed of Nafion and polyurethane along with aminophenyl boronic acid (APBA), which was formed on the bimetal electrode formed on a screen-printed electrode. The extraction of glucose from the GIP allowed for the selective permeation of glucose into the bimetal electrode surface for oxidation. The GIP-coated bimetal sensor probe was characterized using electrochemical and surface analytical methods. The GIP layer coated on the NaOH pre-treated bimetal electrode exhibited a dynamic range between 1.0µM and 25.0mM with a detection limit of 0.65±0.10µM in phosphate buffer solution (pH 7.4). The anodic responses of uric acid, acetaminophen, dopamine, ascorbic acid, L-cysteine, and other saccharides (monosaccharides: galactose, mannose, fructose, and xylose; disaccharides: sucrose, lactose, and maltose) were not detected using the GIP-coated bimetal sensor. The reliability of the sensor was evaluated by the determination of glucose in artificial and whole blood samples. Copyright © 2017 Elsevier B.V. All rights reserved.

Short-term administration of the GLP-1 analog liraglutide decreases circulating leptin and increases GIP levels and these changes are associated with alterations in CNS responses to food cues: A randomized, placebo-controlled, crossover study

PubMed Central

Farr, Olivia M.; Tsoukas, Michael A.; Triantafyllou, Georgios; Dincer, Fadime; Filippaios, Andreas; Ko, Byung-Joon; Mantzoros, Christos S.

2016-01-01

Background GLP-1 agonists, including liraglutide, have emerged as effective therapies for type 2 diabetes (DM) and obesity. Here, we attempted to delineate how liraglutide, at doses approved for DM, may impact circulating hormones influencing energy homeostasis in diabetics. Basic Procedures Using a randomized, placebo-controlled, double-blind, cross-over trial of 20 patients with type 2 diabetes, we examined the effects of liraglutide as compared to placebo on fasting levels of circulating hormones important to energy homeostasis, including leptin, ghrelin, PYY, and GIP. After 17 days (0.6 mg for 7 days, 1.2 mg for 7 days and 1.8 mg for 3 days) of treatment, we also studied changes in fMRI responses to food cues. Main Findings By design, to avoid any confounding by weight changes, subjects were studied for 17 days, i.e. before body weight changed. Participants on liraglutide had significantly increased GLP-1 levels (p<0.001), decreased percent change in leptin levels (p<0.01) and increased GIP levels (p<0.03) in comparison to placebo treated subjects. Whole brain regressions of functional activity in response to food cues reveal that increased GIP levels were associated with deactivation of the attention- and reward-related insula. Decreases in leptin levels were associated with activations in the reward-related midbrain, precuneus, and dorsolateral prefrontal cortex (DLPFC), and sensorimotor-related motor cortex and with deactivations in the attention-related parietal cortex and the cognitive control-related thalamus and pre-SMA. Principal Conclusions We demonstrate herein short-term changes to circulating levels of GIP and leptin in response to GLP-1 agonist liraglutide therapy. These findings suggest that liraglutide may alter the circulating levels of hormones important in energy homeostasis that, in turn, influence CNS perception of food cues. This could possibly lead to compensatory changes in energy homeostasis that would over time limit the efficacy of liraglutide to decrease body weight. These novel findings, which, pointing to the potential advantages of combination therapies, may have therapeutic implications, will need to be confirmed by larger and longer-term trials. PMID:27282865

Gastric inhibitory polypeptide-dependent cortisol hypersecretion--a new cause of Cushing's syndrome.

PubMed

Lacroix, A; Bolté, E; Tremblay, J; Dupré, J; Poitras, P; Fournier, H; Garon, J; Garrel, D; Bayard, F; Taillefer, R

1992-10-01

Corticotropin-independent nodular adrenal hyperplasia is a rare cause of Cushing's syndrome, and the factors responsible for the adrenal hyperplasia are not known. We studied a 48-year-old woman with Cushing's syndrome, nodular adrenal hyperplasia, and undetectable plasma corticotropin concentrations in whom food stimulated cortisol secretion. Cortisol secretion had an inverse diurnal rhythm in this patient, with low-to-normal fasting plasma cortisol concentrations and elevated postprandial cortisol concentrations that could not be suppressed with dexamethasone. The cortisol concentrations increased in response to oral glucose (4-fold increase) and a lipid-rich meal (4.8-fold increase) or a protein-rich meal (2.6-fold increase), but not intravenous glucose. The infusion of somatostatin blunted the plasma cortisol response to oral glucose. Intravenous infusion of gastric inhibitory polypeptide (GIP) for one hour increased the plasma cortisol concentration in the patient but not in four normal subjects. Fasting plasma GIP concentrations in the patient were similar to those in the normal subjects; feeding the patient test meals induced increases in plasma GIP concentrations that paralleled those in plasma cortisol concentrations. Cell suspensions of adrenal tissue from the patient produced more cortisol when stimulated by GIP than when stimulated by corticotropin. In contrast, adrenal cells from normal adults and fetuses or patients with cortisol-producting or aldosterone-producing adenomas responded to corticotropin but not to GIP. Nodular adrenal hyperplasia and Cushing's syndrome may be food-dependent as a result of abnormal responsiveness of adrenal cells to physiologic secretion of GIP. "Illicit" (ectopic) expression of GIP receptors on adrenal cells presumably underlies this disorder.

Hospice Agencies’ Hospital Contract Status and Differing Levels of Hospice Care

PubMed Central

Chung, Kyusuk; Richards, Nicole; Burke, Sloane C.

2014-01-01

In response to a 2011 finding that approximately 27% of Medicare-certified hospices do not provide a single day of general inpatient (GIP) level of care, the authors explored the extent to which hospices have contracts with hospitals for GIP. Using the 2007 National Home and Hospice Care Survey (NHHCS), we estimated that 1,119 agencies (32%) had no contract with any hospitals in 2007 and half of those with no contract did not have a contract with a skilled nursing facility (SNF) either. As a result, these hospices were unable to provide GIP patient referrals for those in need of inpatient care for acute pain and symptom management. More importantly, not having a contract with a hospital was just one of the factors influencing GIP provision. In the multivariate logistic model, after controlling for contract status with a hospital and other hospice characteristics, agencies in the second quartile of hospice patient census (12 to 29 vs. 73 or more, Adjusted OR=14.10; 95% CI: 4.26–46.62) were independently related to providing only routine home care. These hospices are more likely to rely solely on scatter beds for GIP provision. Given that a significant portion of hospices do not have a contract with a hospital, policy makers need to understand barriers to contracts with a hospital/SNF for GIP and consider a hospice’s contract status as one of the standards for hospice certification. In addition, further research is necessary to understand why hospices that do have a contract with a hospital do not make GIP referral. PMID:24576832

Hospice agencies' hospital contract status and differing levels of hospice care.

PubMed

Chung, Kyusuk; Richards, Nicole; Burke, Sloane

2015-05-01

In response to a 2011 finding that approximately 27% of Medicare-certified hospices do not provide a single day of general inpatient care (GIP), the authors explored the extent to which hospices have contracts with hospitals for GIP. Using the 2007 National Home and Hospice Care Survey, we estimated that 1119 (32%) agencies had no contract with any hospitals in 2007 and half of those with no contract did not have a contract with a skilled nursing facility (SNF) either. As a result, these hospices were unable to provide GIP referrals for those in need of inpatient care for acute pain and symptom management. More importantly, not having a contract with a hospital was just one of the factors influencing GIP provision. In the multivariate logistic model, after controlling for contract status with a hospital and other hospice characteristics, agencies in the second quartile of hospice patient census (12-29 vs 73 or more, adjusted odds ratio = 14.10; 95% confidence interval 4.26-46.62) were independently related to providing only routine home care. These hospices are more likely to rely solely on scatter beds for GIP provision. Given that a significant portion of hospices do not have a contract with a hospital, policy makers need to understand barriers to contracts with a hospital/SNF for GIP and consider a hospice's contract status as one of the standards for hospice certification. In addition, further research is necessary to understand why hospices that do have a contract with a hospital do not make GIP referral. © The Author(s) 2014.

Basic and Meal Stimulated Plasma GIP Levels are Higher in Lean PCOS Women with FAI over 5.

PubMed

Milewicz, T; Migacz, K; Kiałka, M; Rogatko, I; Kowalczuk, A; Spalkowska, M; Mrozińska, S; Czajkowska, Z; Sztefko, K

2016-02-01

Glucose dependent insulinotropic peptide (GIP) belongs to the incretins which are responsible for 70% of the insulin release after oral glucose intake. Its impaired secretion was noted in several conditions involving insulin resistance, including polycystic ovary syndrome (PCOS), known as the state with increased testosterone level. This paper considers a possible relationship between the free androgen index (FAI) and basal as well as meal stimulated level of GIP in lean women affected by PCOS. To our knowledge, no previous study has evaluated the matter so far. cross-sectional study 50 age-matched lean women (BMI=20.76±1.83) were enrolled to the study and divided into 2 groups. Patients with phenotype with FAI<5 were classified as group 1, PCOS patients with FAI>5 formed group 2. All subjects underwent standard meal test. Serum GIP concentration was determined both at fasting and at 60 min of the test. Calculations were carried out using Statistica 10. Mann-Whitney test indicated a statistically significant difference in medians values of GIP plasma levels between groups on fasting (36.4 pg/ml vs. 59.6 pg/ml; p=0.0007) and at 60 min after meal test (50.1 pg/ml vs. 72.5 pg/ml; p=0.006). Spearman test indicated significant positive correlation between FAI and GIP levels at 0' and 60' in total study population (0':R=0.37;p=0.008; 60':R=0.28; p=0.049). Excess androgen activity might be a factor contributing to alter secretion of incretins in lean PCOS women. However it could not be ruled out that it is also possible that increased GIP levels might induce hyperandrogenemia in PCOS. An increased GIP levels may induce hyperinsulinemia and play an additive to insulin resistance role in progression to diabetes mellitus type 2 (DMT2). © Georg Thieme Verlag KG Stuttgart · New York.

Difference in protective effects of GIP and GLP-1 on endothelial cells according to cyclic adenosine monophosphate response.

PubMed

Lim, Dong-Mee; Park, Keun-Young; Hwang, Won-Min; Kim, Ju-Young; Kim, Byung-Joon

2017-05-01

Receptors for glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) are present in vascular endothelial cells. Previous studies investigating euglycemic status have demonstrated that GIP is directly involved in the physiology of blood vessels by controlling the blood flow rate of portal veins and that GLP-1 has a protective effect on blood vessels by acting on endothelial cells. However, to the best of our knowledge, the effects of GIP and GLP-1 on endothelial cells in patients with hyperglycemia remain unknown. Therefore, the present study investigated whether the effect of the incretin hormones GLP-1 and GIP differed with regards to the reversal of endothelial cell dysfunction caused by hyperglycemia. The production of nitric oxide (NO) was measured using the Griess reagent system kit and the expression of cyclic adenosine monophosphate (cAMP) in the cell was measured at a wavelength of 405 nm with the ELISA reader using the cyclic AMP EIA kit. Exposure of human umbilical vein endothelial cells (HUVEC) to a high glucose concentration decreased NO and endothelial nitric oxide synthase (eNOS) levels but increased inducible NOS (iNOS) levels. However, when HUVECs were pretreated with GLP-1, a reduction of iNOS expression was observed and the expression of eNOS and NO were increased, as opposed to pretreatment with GIP. The results differed according to the response of cAMP, the second messenger of incretin hormones: The GIP pretreatment group did not exhibit an increase in cAMP levels while the GLP-1 pretreatment group did. The results of the present study provide evidence that GLP-1, but not GIP, has a protective effect on endothelial function associated with cardiovascular disease, as it is associated with increased eNOS expression and the levels of NO. This effect may be due to an increase in the cAMP concentration during hyperglycemic events.

The glucose-dependent insulinotropic polypeptide and glucose-stimulated insulin response to exercise training and diet in obesity.

PubMed

Kelly, Karen R; Brooks, Latina M; Solomon, Thomas P J; Kashyap, Sangeeta R; O'Leary, Valerie B; Kirwan, John P

2009-06-01

Aging and obesity are characterized by decreased beta-cell sensitivity and defects in the potentiation of nutrient-stimulated insulin secretion by GIP. Exercise and diet are known to improve glucose metabolism and the pancreatic insulin response to glucose, and this effect may be mediated through the incretin effect of GIP. The purpose of this study was to assess the effects of a 12-wk exercise training intervention (5 days/wk, 60 min/day, 75% Vo(2 max)) combined with a eucaloric (EX, n = 10) or hypocaloric (EX-HYPO, pre: 1,945 +/- 190, post: 1,269 +/- 70, kcal/day; n = 9) diet on the GIP response to glucose in older (66.8 +/- 1.5 yr), obese (34.4 +/- 1.7 kg/m(2)) adults with impaired glucose tolerance. In addition to GIP, plasma PYY(3-36), insulin, and glucose responses were measured during a 3-h, 75-g oral glucose tolerance test. Both interventions led to a significant improvement in Vo(2 max) (P < 0.05). Weight loss (kg) was significant in both groups but was greater after EX-HYPO (-8.3 +/- 1.1 vs. -2.8 +/- 0.5, P = 0.002). The glucose-stimulated insulin response was reduced after EX-HYPO (P = 0.02), as was the glucose-stimulated GIP response (P < 0.05). Furthermore, after the intervention, changes in insulin (DeltaI(0-30)/DeltaG(0-30)) and GIP (Delta(0-30)) secretion were correlated (r = 0.69, P = 0.05). The PYY(3-36) (Delta(0-30)) response to glucose was increased after both interventions (P < 0.05). We conclude that 1) a combination of caloric restriction and exercise reduces the GIP response to ingested glucose, 2) GIP may mediate the attenuated glucose-stimulated insulin response after exercise/diet interventions, and 3) the increased PYY(3-36) response represents an improved capacity to regulate satiety and potentially body weight in older, obese, insulin-resistant adults.

Effects of gastric inhibitory polypeptide, glucagon-like peptide-1 and glucagon-like peptide-1 receptor agonists on Bone Cell Metabolism.

PubMed

Hansen, Morten S S; Tencerova, Michaela; Frølich, Jacob; Kassem, Moustapha; Frost, Morten

2018-01-01

The relationship between gut and skeleton is increasingly recognized as part of the integrated physiology of the whole organism. The incretin hormones gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are secreted from the intestine in response to nutrient intake and exhibit several physiological functions including regulation of islet hormone secretion and glucose levels. A number of GLP-1 receptor agonists (GLP-1RAs) are currently used in treatment of type 2 diabetes and obesity. However, GIP and GLP-1 cognate receptors are widely expressed suggesting that incretin hormones mediate effects beyond control of glucose homeostasis, and reports on associations between incretin hormones and bone metabolism have emerged. The aim of this MiniReview was to provide an overview of current knowledge regarding the in vivo and in vitro effects of GIP and GLP-1 on bone metabolism. We identified a total of 30 pre-clinical and clinical investigations of the effects of GIP, GLP-1 and GLP-1RAs on bone turnover markers, bone mineral density (BMD), bone microarchitecture and fracture risk. Studies conducted in cell cultures and rodents demonstrated that GIP and GLP-1 play a role in regulating skeletal homeostasis, with pre-clinical data suggesting that GIP inhibits bone resorption whereas GLP-1 may promote bone formation and enhance bone material properties. These effects are not corroborated by clinical studies. While there is evidence of effects of GIP and GLP-1 on bone metabolism in pre-clinical investigations, clinical trials are needed to clarify whether similar effects are present and clinically relevant in humans. © 2017 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Glucose-dependent insulinotropic peptide stimulates thymidine incorporation in endothelial cells: role of endothelin-1

NASA Technical Reports Server (NTRS)

Ding, Ke-Hong; Zhong, Qing; Isales, Carlos M.; Iscules, C. M. (Principal Investigator)

2003-01-01

We have previously characterized the receptor for glucose-dependent insulinotropic polypeptide (GIPR) in vascular endothelial cells (EC). Different EC types were found to contain distinct GIPR splice variants. To determine whether activation of the GIPR splice variants resulted in different cellular responses, we examined GIP effects on human umbilical vein endothelial cells (HUVEC), which contain two GIPR splice variants, and compared them with a spontaneously transformed human umbilical vein EC line, ECV 304, which contains four GIPR splice variants. GIP dose-dependently stimulated HUVEC and ECV 304 proliferation as measured by [3H]thymidine incorporation. GIP increased endothelin-1 (ET-1) secretion from HUVEC but not from ECV 304. Use of the endothelin B receptor blocker BQ-788 resulted in an inhibition of [3H]thymidine incorporation in HUVEC but not in ECV 304. These findings suggest that, although GIP increases [3H]thymidine incorporation in both HUVEC and ECV 304, this proliferative response is mediated by ET-1 only in HUVEC. These differences in cellular response to GIP may be related to differences in activation of GIPR splice variants.

The glucose-dependent insulinotropic polypeptide and glucose-stimulated insulin response to exercise training and diet in obesity

PubMed Central

Kelly, Karen R.; Brooks, Latina M.; Solomon, Thomas P. J.; Kashyap, Sangeeta R.; O'Leary, Valerie B.; Kirwan, John P.

2009-01-01

Aging and obesity are characterized by decreased β-cell sensitivity and defects in the potentiation of nutrient-stimulated insulin secretion by GIP. Exercise and diet are known to improve glucose metabolism and the pancreatic insulin response to glucose, and this effect may be mediated through the incretin effect of GIP. The purpose of this study was to assess the effects of a 12-wk exercise training intervention (5 days/wk, 60 min/day, 75% V̇o2 max) combined with a eucaloric (EX, n = 10) or hypocaloric (EX-HYPO, pre: 1,945 ± 190, post: 1,269 ± 70, kcal/day; n = 9) diet on the GIP response to glucose in older (66.8 ± 1.5 yr), obese (34.4 ± 1.7 kg/m2) adults with impaired glucose tolerance. In addition to GIP, plasma PYY3–36, insulin, and glucose responses were measured during a 3-h, 75-g oral glucose tolerance test. Both interventions led to a significant improvement in V̇o2 max (P < 0.05). Weight loss (kg) was significant in both groups but was greater after EX-HYPO (−8.3 ± 1.1 vs. −2.8 ± 0.5, P = 0.002). The glucose-stimulated insulin response was reduced after EX-HYPO (P = 0.02), as was the glucose-stimulated GIP response (P < 0.05). Furthermore, after the intervention, changes in insulin (ΔI0–30/ΔG0–30) and GIP (Δ0–30) secretion were correlated (r = 0.69, P = 0.05). The PYY3–36 (Δ0–30) response to glucose was increased after both interventions (P < 0.05). We conclude that 1) a combination of caloric restriction and exercise reduces the GIP response to ingested glucose, 2) GIP may mediate the attenuated glucose-stimulated insulin response after exercise/diet interventions, and 3) the increased PYY3–36 response represents an improved capacity to regulate satiety and potentially body weight in older, obese, insulin-resistant adults. PMID:19351807

Analysis of the putative regulatory region of the gastric inhibitory polypeptide receptor gene in food-dependent Cushing's syndrome.

PubMed

Antonini, S R; N'Diaye, N; Baldacchino, V; Hamet, P; Tremblay, J; Lacroix, A

2004-07-01

Gastric inhibitory polypeptide (GIP)-dependent Cushing's syndrome (CS) results from the ectopic expression of non-mutated GIP receptor (hGIPR) in the adrenal cortex. We evaluated whether mutations or polymorphisms in the regulatory region of the GIPR gene could lead to this aberrant expression. We studied 9.0kb upstream and 1.3kb downstream of the GIPR gene putative promoter (pProm) by sequencing leukocyte DNA from controls and from adrenal tissues of GIP- and non-GIP-dependent CS patients. The putative proximal promoter region (800 bp) and the first exon and intron of the hGIPR gene were sequenced on adrenal DNA from nine GIP-dependent CS, as well as on leukocyte DNA of nine normal controls. Three variations found in this region were found in all patients and controls; at position -4/-5, an insertion of a T was seen in four out of nine patients and in five out of nine controls. Transient transfection studies conducted in rat GC and mouse Y1 cells showed that the TT allele confers loss of 40% in the promoter activity. The analysis of the 8-kb distal pProm region revealed eight distal single nucleotide polymorphisms (SNPs) without probable association with the disease, since frequencies in patients and controls were very similar. In conclusion, mutations or SNPs in the regulatory region of the GIPR gene are unlikely to underlie GIP-dependent CS. Copyright 2004 Elsevier Ltd.

Effect of Roux-en-Y gastric bypass on the distribution and hormone expression of small-intestinal enteroendocrine cells in obese patients with type 2 diabetes.

PubMed

Rhee, Nicolai A; Wahlgren, Camilla D; Pedersen, Jens; Mortensen, Brynjulf; Langholz, Ebbe; Wandall, Erik P; Friis, Steffen U; Vilmann, Peter; Paulsen, Sarah J; Kristiansen, Viggo B; Jelsing, Jacob; Dalbøge, Louise S; Poulsen, Steen S; Holst, Jens J; Vilsbøll, Tina; Knop, Filip K

2015-10-01

We studied the impact of Roux-en-Y gastric bypass (RYGB) on the density and hormonal gene expression of small-intestinal enteroendocrine cells in obese patients with type 2 diabetes. Twelve patients with diabetes and 11 age- and BMI-matched controls underwent RYGB followed by enteroscopy ~10 months later. Mucosal biopsies taken during surgery and enteroscopy were immunohistochemically stained for glucagon-like peptide-1 (GLP-1), peptide YY (PYY), cholecystokinin (CCK), glucose-dependent insulinotropic polypeptide (GIP) and prohormone convertase 2 (PC2) and the expression of GCG (encoding preproglucagon), PYY, CCK, GIP, GHRL (encoding ghrelin), SCT (encoding secretin), NTS (encoding neurotensin) and NR1H4 (encoding farnesoid X receptor) was evaluated. The density of cells immunoreactive for GLP-1, CCK and GIP increased in patients after RYGB and the density of those immunoreactive for GLP-1, PYY, CCK and PC2 increased in controls. In both groups, GHRL, SCT and GIP mRNA was reduced after RYGB while PYY, CCK, NTS and NR1H4 gene expression was unaltered. GCG mRNA was upregulated in both groups. Numerous alterations in the distribution of enteroendocrine cells and their expression of hormonal genes are seen after RYGB and include increased density of GLP-1-, PYY-, CCK-, GIP- and PC2-positive cells, reduced gene expression of GHRL, SCT and GIP and increased expression of GCG.

Fructose stimulates GLP-1 but not GIP secretion in mice, rats, and humans

PubMed Central

Kuhre, Rune E.; Gribble, Fiona M.; Hartmann, Bolette; Reimann, Frank; Windeløv, Johanne A.; Rehfeld, Jens F.

2014-01-01

Nutrients often stimulate gut hormone secretion, but the effects of fructose are incompletely understood. We studied the effects of fructose on a number of gut hormones with particular focus on glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). In healthy humans, fructose intake caused a rise in blood glucose and plasma insulin and GLP-1, albeit to a lower degree than isocaloric glucose. Cholecystokinin secretion was stimulated similarly by both carbohydrates, but neither peptide YY3–36 nor glucagon secretion was affected by either treatment. Remarkably, while glucose potently stimulated GIP release, fructose was without effect. Similar patterns were found in the mouse and rat, with both fructose and glucose stimulating GLP-1 secretion, whereas only glucose caused GIP secretion. In GLUTag cells, a murine cell line used as model for L cells, fructose was metabolized and stimulated GLP-1 secretion dose-dependently (EC50 = 0.155 mM) by ATP-sensitive potassium channel closure and cell depolarization. Because fructose elicits GLP-1 secretion without simultaneous release of glucagonotropic GIP, the pathways underlying fructose-stimulated GLP-1 release might be useful targets for type 2 diabetes mellitus and obesity drug development. PMID:24525020

Glucose-Dependent Insulinotropic Polypeptide Ameliorates Mild Traumatic Brain Injury-Induced Cognitive and Sensorimotor Deficits and Neuroinflammation in Rats

PubMed Central

Yu, Yu-Wen; Hsieh, Tsung-Hsun; Chen, Kai-Yun; Wu, John Chung-Che; Hoffer, Barry J.; Greig, Nigel H.; Li, Yazhou; Lai, Jing-Huei; Chang, Cheng-Fu; Lin, Jia-Wei; Chen, Yu-Hsin

2016-01-01

Abstract Mild traumatic brain injury (mTBI) is a major public health issue, representing 75–90% of all cases of TBI. In clinical settings, mTBI, which is defined as a Glascow Coma Scale (GCS) score of 13–15, can lead to various physical, cognitive, emotional, and psychological-related symptoms. To date, there are no pharmaceutical-based therapies to manage the development of the pathological deficits associated with mTBI. In this study, the neurotrophic and neuroprotective properties of glucose-dependent insulinotropic polypeptide (GIP), an incretin similar to glucagon-like peptide-1 (GLP-1), was investigated after its steady-state subcutaneous administration, focusing on behavior after mTBI in an in vivo animal model. The mTBI rat model was generated by a mild controlled cortical impact (mCCI) and used to evaluate the therapeutic potential of GIP. We used the Morris water maze and novel object recognition tests, which are tasks for spatial and recognition memory, respectively, to identify the putative therapeutic effects of GIP on cognitive function. Further, beam walking and the adhesive removal tests were used to evaluate locomotor activity and somatosensory functions in rats with and without GIP administration after mCCI lesion. Lastly, we used immunohistochemical (IHC) staining and Western blot analyses to evaluate the inflammatory markers, glial fibrillary acidic protein (GFAP), amyloid-β precursor protein (APP), and bone marrow tyrosine kinase gene in chromosome X (BMX) in animals with mTBI. GIP was well tolerated and ameliorated mTBI-induced memory impairments, poor balance, and sensorimotor deficits after initiation in the post-injury period. In addition, GIP mitigated mTBI-induced neuroinflammatory changes on GFAP, APP, and BMX protein levels. These findings suggest GIP has significant benefits in managing mTBI-related symptoms and represents a novel strategy for mTBI treatment. PMID:26972789

Glucose-Dependent Insulinotropic Polypeptide Ameliorates Mild Traumatic Brain Injury-Induced Cognitive and Sensorimotor Deficits and Neuroinflammation in Rats.

PubMed

Yu, Yu-Wen; Hsieh, Tsung-Hsun; Chen, Kai-Yun; Wu, John Chung-Che; Hoffer, Barry J; Greig, Nigel H; Li, Yazhou; Lai, Jing-Huei; Chang, Cheng-Fu; Lin, Jia-Wei; Chen, Yu-Hsin; Yang, Liang-Yo; Chiang, Yung-Hsiao

2016-11-15

Mild traumatic brain injury (mTBI) is a major public health issue, representing 75-90% of all cases of TBI. In clinical settings, mTBI, which is defined as a Glascow Coma Scale (GCS) score of 13-15, can lead to various physical, cognitive, emotional, and psychological-related symptoms. To date, there are no pharmaceutical-based therapies to manage the development of the pathological deficits associated with mTBI. In this study, the neurotrophic and neuroprotective properties of glucose-dependent insulinotropic polypeptide (GIP), an incretin similar to glucagon-like peptide-1 (GLP-1), was investigated after its steady-state subcutaneous administration, focusing on behavior after mTBI in an in vivo animal model. The mTBI rat model was generated by a mild controlled cortical impact (mCCI) and used to evaluate the therapeutic potential of GIP. We used the Morris water maze and novel object recognition tests, which are tasks for spatial and recognition memory, respectively, to identify the putative therapeutic effects of GIP on cognitive function. Further, beam walking and the adhesive removal tests were used to evaluate locomotor activity and somatosensory functions in rats with and without GIP administration after mCCI lesion. Lastly, we used immunohistochemical (IHC) staining and Western blot analyses to evaluate the inflammatory markers, glial fibrillary acidic protein (GFAP), amyloid-β precursor protein (APP), and bone marrow tyrosine kinase gene in chromosome X (BMX) in animals with mTBI. GIP was well tolerated and ameliorated mTBI-induced memory impairments, poor balance, and sensorimotor deficits after initiation in the post-injury period. In addition, GIP mitigated mTBI-induced neuroinflammatory changes on GFAP, APP, and BMX protein levels. These findings suggest GIP has significant benefits in managing mTBI-related symptoms and represents a novel strategy for mTBI treatment.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grosso, Marcos; Kalstein, Adrian; Parisi, Gustavo

The native state of a protein consists of an equilibrium of conformational states on an energy landscape rather than existing as a single static state. The co-existence of conformers with different ligand-affinities in a dynamical equilibrium is the basis for the conformational selection model for ligand binding. In this context, the development of theoretical methods that allow us to analyze not only the structural changes but also changes in the fluctuation patterns between conformers will contribute to elucidate the differential properties acquired upon ligand binding. Molecular dynamics simulations can provide the required information to explore these features. Its use inmore » combination with subsequent essential dynamics analysis allows separating large concerted conformational rearrangements from irrelevant fluctuations. We present a novel procedure to define the size and composition of essential dynamics subspaces associated with ligand-bound and ligand-free conformations. These definitions allow us to compare essential dynamics subspaces between different conformers. Our procedure attempts to emphasize the main similarities and differences between the different essential dynamics in an unbiased way. Essential dynamics subspaces associated to conformational transitions can also be analyzed. As a test case, we study the glutaminase interacting protein (GIP), composed of a single PDZ domain. Both GIP ligand-free state and glutaminase L peptide-bound states are analyzed. Our findings concerning the relative changes in the flexibility pattern upon binding are in good agreement with experimental Nuclear Magnetic Resonance data.« less

Adrenal GIPR expression and chromosome 19q13 microduplications in GIP-dependent Cushing's syndrome.

PubMed

Lecoq, Anne-Lise; Stratakis, Constantine A; Viengchareun, Say; Chaligné, Ronan; Tosca, Lucie; Deméocq, Vianney; Hage, Mirella; Berthon, Annabel; Faucz, Fabio R; Hanna, Patrick; Boyer, Hadrien-Gaël; Servant, Nicolas; Salenave, Sylvie; Tachdjian, Gérard; Adam, Clovis; Benhamo, Vanessa; Clauser, Eric; Guiochon-Mantel, Anne; Young, Jacques; Lombès, Marc; Bourdeau, Isabelle; Maiter, Dominique; Tabarin, Antoine; Bertherat, Jérôme; Lefebvre, Hervé; de Herder, Wouter; Louiset, Estelle; Lacroix, André; Chanson, Philippe; Bouligand, Jérôme; Kamenický, Peter

2017-09-21

GIP-dependent Cushing's syndrome is caused by ectopic expression of glucose-dependent insulinotropic polypeptide receptor (GIPR) in cortisol-producing adrenal adenomas or in bilateral macronodular adrenal hyperplasias. Molecular mechanisms leading to ectopic GIPR expression in adrenal tissue are not known. Here we performed molecular analyses on adrenocortical adenomas and bilateral macronodular adrenal hyperplasias obtained from 14 patients with GIP-dependent adrenal Cushing's syndrome and one patient with GIP-dependent aldosteronism. GIPR expression in all adenoma and hyperplasia samples occurred through transcriptional activation of a single allele of the GIPR gene. While no abnormality was detected in proximal GIPR promoter methylation, we identified somatic duplications in chromosome region 19q13.32 containing the GIPR locus in the adrenocortical lesions derived from 3 patients. In 2 adenoma samples, the duplicated 19q13.32 region was rearranged with other chromosome regions, whereas a single tissue sample with hyperplasia had a 19q duplication only. We demonstrated that juxtaposition with cis-acting regulatory sequences such as glucocorticoid response elements in the newly identified genomic environment drives abnormal expression of the translocated GIPR allele in adenoma cells. Altogether, our results provide insight into the molecular pathogenesis of GIP-dependent Cushing's syndrome, occurring through monoallelic transcriptional activation of GIPR driven in some adrenal lesions by structural variations.

Detection of gluten immunogenic peptides in the urine of patients with coeliac disease reveals transgressions in the gluten-free diet and incomplete mucosal healing

PubMed Central

Moreno, María de Lourdes; Cebolla, Ángel; Muñoz-Suano, Alba; Carrillo-Carrion, Carolina; Comino, Isabel; Pizarro, Ángeles; León, Francisco; Rodríguez-Herrera, Alfonso; Sousa, Carolina

2017-01-01

Objective Gluten-free diet (GFD) is the only management for coeliac disease (CD). Available methods to assess GFD compliance are insufficiently sensitive to detect occasional dietary transgressions that may cause gut mucosal damage. We aimed to develop a method to determine gluten intake and monitor GFD compliance in patients with CD and to evaluate its correlation with mucosal damage. Design Urine samples of 76 healthy subjects and 58 patients with CD subjected to different gluten dietary conditions were collected. A lateral flow test (LFT) with the highly sensitive and specific G12 monoclonal antibody for the most dominant gluten immunogenic peptides (GIP) and a LFT reader were used to quantify GIP in solid-phase extracted urines. Results GIP were detectable in concentrated urines from healthy individuals previously subjected to GFD as early as 4–6 h after single gluten intake, and remained detectable for 1–2 days. The urine assay revealed infringement of the GFD in about 50% of the patients. Analysis of duodenal biopsies revealed that most of patients with CD (89%) with no villous atrophy had no detectable GIP in urine, while all patients with quantifiable GIP in urine showed incomplete intestinal mucosa recovery. Conclusion GIP are detected in urine after gluten consumption, enabling a new and non-invasive method to monitor GFD compliance and transgressions. The method was sensitive, specific and simple enough to be convenient for clinical monitoring of patients with CD as well as for basic and clinical research applications including drug development. Trial registration number NCT02344758. PMID:26608460

Detection of gluten immunogenic peptides in the urine of patients with coeliac disease reveals transgressions in the gluten-free diet and incomplete mucosal healing.

PubMed

Moreno, María de Lourdes; Cebolla, Ángel; Muñoz-Suano, Alba; Carrillo-Carrion, Carolina; Comino, Isabel; Pizarro, Ángeles; León, Francisco; Rodríguez-Herrera, Alfonso; Sousa, Carolina

2017-02-01

Gluten-free diet (GFD) is the only management for coeliac disease (CD). Available methods to assess GFD compliance are insufficiently sensitive to detect occasional dietary transgressions that may cause gut mucosal damage. We aimed to develop a method to determine gluten intake and monitor GFD compliance in patients with CD and to evaluate its correlation with mucosal damage. Urine samples of 76 healthy subjects and 58 patients with CD subjected to different gluten dietary conditions were collected. A lateral flow test (LFT) with the highly sensitive and specific G12 monoclonal antibody for the most dominant gluten immunogenic peptides (GIP) and a LFT reader were used to quantify GIP in solid-phase extracted urines. GIP were detectable in concentrated urines from healthy individuals previously subjected to GFD as early as 4-6 h after single gluten intake, and remained detectable for 1-2 days. The urine assay revealed infringement of the GFD in about 50% of the patients. Analysis of duodenal biopsies revealed that most of patients with CD (89%) with no villous atrophy had no detectable GIP in urine, while all patients with quantifiable GIP in urine showed incomplete intestinal mucosa recovery. GIP are detected in urine after gluten consumption, enabling a new and non-invasive method to monitor GFD compliance and transgressions. The method was sensitive, specific and simple enough to be convenient for clinical monitoring of patients with CD as well as for basic and clinical research applications including drug development. NCT02344758. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Direct effects of glucose, insulin, GLP-1, and GIP on bulbospinal neurons in the rostral ventrolateral medulla in neonatal wistar rats.

PubMed

Oshima, Naoki; Onimaru, Hiroshi; Matsubara, Hidehito; Uchida, Takahiro; Watanabe, Atsushi; Imakiire, Toshihiko; Nishida, Yasuhiro; Kumagai, Hiroo

2017-03-06

Although patients with diabetes mellitus (DM) often exhibit hypertension, the mechanisms responsible for this correlation are not well known. We hypothesized that the bulbospinal neurons in the rostral ventrolateral medulla (RVLM) are affected by the levels of glucose, insulin, or incretins (glucagon like peptide-1 [GLP-1] or glucose-dependent insulinotropic peptide [GIP]) in patients with DM. To investigate whether RVLM neurons are activated by glucose, insulin, GLP-1, or GIP, we examined changes in the membrane potentials of bulbospinal RVLM neurons using whole-cell patch-clamp technique during superfusion with various levels of glucose or these hormones in neonatal Wistar rats. A brainstem-spinal cord preparation was used for the experiments. A low level of glucose stimulated bulbospinal RVLM neurons. During insulin superfusion, almost all the RVLM neurons were depolarized, while during GLP-1 or GIP superfusion, almost all the RVLM neurons were hyperpolarized. Next, histological examinations were performed to examine transporters for glucose and receptors for insulin, GLP-1, and GIP on RVLM neurons. Low-level glucose-depolarized RVLM neurons exhibited the presence of glucose transporter 3 (GLUT3). Meanwhile, insulin-depolarized, GLP-1-hyperpolarized, and GIP-hyperpolarized RVLM neurons showed each of the respective specific receptor. These results indicate that a low level of glucose stimulates bulbospinal RVLM neurons via specific transporters on these neurons, inducing hypertension. Furthermore, an increase in insulin or a reduction in incretins may also activate the sympathetic nervous system and induce hypertension by activating RVLM neurons via their own receptors. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

The effect of guar gum on carbohydrate-, fat- and protein-stimulated gut hormone secretion: modification of postprandial gastric inhibitory polypeptide and gastrin responses.

PubMed

Morgan, L M; Tredger, J A; Madden, A; Kwasowski, P; Marks, V

1985-05-01

The effect of incorporating guar gum into predominantly single-component meals of carbohydrate, fat or protein on liquid gastric emptying and on the secretion of gastric inhibitory polypeptide (GIP), gastrin and motilin, was studied in healthy human volunteers. Volunteers were given either 80 ml Hycal (carbohydrate meal), 150 g cooked lean minced beef (protein meal) or 200 ml double cream (fat meal) either with or without 5 or 6 g guar gum. Liquid gastric emptying was monitored in the fat and protein meals by taking 1.5 g paracetamol, consumed in water, with the meals and monitoring its appearance in circulation. Postprandial insulin and GIP levels were both significantly reduced by addition of guar gum to the carbohydrate meal. Postprandial GIP secretion was also reduced by addition of guar gum to the protein meal, but protein-stimulated gastrin secretion was enhanced by guar gum. There was a significant negative correlation between peak circulating gastrin levels and the corresponding GIP levels. Postprandial GIP secretion and plasma motilin levels were unaffected by addition of guar gum to the fat meal. 5 and 10 g guar gum/l solutions in water possessed buffering capacities between pH 2.75 and 5.5. Guar gum at 5 g/l caused no detectable change in liquid gastric-emptying time. The observed augmentation of gastrin secretion by guar gum following a protein meal could be due either to the buffering capacity of guar gum or to the attenuation of GIP secretion. It is possible that the chronic use of guar gum could be associated with changes in gastric acid secretion.

What do we know about the secretion and degradation of incretin hormones?

PubMed

Deacon, Carolyn F

2005-06-15

The incretin hormones, glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1) are secreted from endocrine cells located in the intestinal mucosa, and act to enhance meal-induced insulin secretion. GIP and GLP-1 concentrations in the plasma rise rapidly after food ingestion, and the presence of unabsorbed nutrients in the intestinal lumen is a strong stimulus for their secretion. Nutrients can stimulate release of both hormones by direct contact with the K-cell (GIP) and L-cell (GLP-1), and this may be the most important signal. However, nutrients also stimulate GLP-1 and GIP secretion indirectly via other mechanisms. Incretin hormone secretion can be modulated neurally, with cholinergic muscarinic, beta-adrenergic and peptidergic (gastrin-releasing peptide, GRP) fibres generally having positive effects, while secretion is restrained by alpha-adrenergic and somatostatinergic fibres. Hormonal factors may also influence incretin hormone secretion. Somatostatin exerts a local inhibitory effect on the activity of both K- and L-cells via a paracrine mechanism, while, in rodents at least, GIP from the proximal intestine has a stimulatory effect on GLP-1 secretion, possibly mediated via a neural loop involving GRP. Once they have been released, both GLP-1 and GIP are subject to rapid degradation. The ubiquitous enzyme, dipeptidyl peptidase IV (DPP IV) cleaves N-terminally, removing a dipeptide and thereby inactivating both peptides, because the N-terminus is crucial for receptor binding. Subsequently, the peptides may be degraded by other enzymes and extracted in an organ-specific manner. The intact peptides are inactivated during passage across the hepatic bed and further metabolised by the peripheral tissues, while the kidney is important for the final elimination of the metabolites.

[Interpreting change scores of the Behavioural Rating Scale for Geriatric Inpatients (GIP)].

PubMed

Diesfeldt, H F A

2013-09-01

The Behavioural Rating Scale for Geriatric Inpatients (GIP) consists of fourteen, Rasch modelled subscales, each measuring different aspects of behavioural, cognitive and affective disturbances in elderly patients. Four additional measures are derived from the GIP: care dependency, apathy, cognition and affect. The objective of the study was to determine the reproducibility of the 18 measures. A convenience sample of 56 patients in psychogeriatric day care was assessed twice by the same observer (a professional caregiver). The median time interval between rating occasions was 45 days (interquartile range 34-58 days). Reproducibility was determined by calculating intraclass correlation coefficients (ICC agreement) for test-retest reliability. The minimal detectable difference (MDD) was calculated based on the standard error of measurement (SEM agreement). Test-retest reliability expressed by the ICCs varied from 0.57 (incoherent behaviour) to 0.93 (anxious behaviour). Standard errors of measurement varied from 0.28 (anxious behaviour) to 1.63 (care dependency). The results show how the GIP can be applied when interpreting individual change in psychogeriatric day care participants.

Fructose intervention for 12 weeks does not impair glycemic control or incretin hormone responses during oral glucose or mixed meal tests in obese men.

PubMed

Matikainen, N; Söderlund, S; Björnson, E; Bogl, L H; Pietiläinen, K H; Hakkarainen, A; Lundbom, N; Eliasson, B; Räsänen, S M; Rivellese, A; Patti, L; Prinster, A; Riccardi, G; Després, J-P; Alméras, N; Holst, J J; Deacon, C F; Borén, J; Taskinen, M-R

2017-06-01

Incretin hormones glucagon-like peptide (GLP)-1 and glucose-dependent insulinotropic polypeptide (GIP) are affected early on in the pathogenesis of metabolic syndrome and type 2 diabetes. Epidemiologic studies consistently link high fructose consumption to insulin resistance but whether fructose consumption impairs the incretin response remains unknown. As many as 66 obese (BMI 26-40 kg/m 2 ) male subjects consumed fructose-sweetened beverages containing 75 g fructose/day for 12 weeks while continuing their usual lifestyle. Glucose, insulin, GLP-1 and GIP were measured during oral glucose tolerance test (OGTT) and triglycerides (TG), GLP-1, GIP and PYY during a mixed meal test before and after fructose intervention. Fructose intervention did not worsen glucose and insulin responses during OGTT, and GLP-1 and GIP responses during OGTT and fat-rich meal were unchanged. Postprandial TG response increased significantly, p = 0.004, and we observed small but significant increases in weight and liver fat content, but not in visceral or subcutaneous fat depots. However, even the subgroups who gained weight or liver fat during fructose intervention did not worsen their glucose, insulin, GLP-1 or PYY responses. A minor increase in GIP response during OGTT occurred in subjects who gained liver fat (p = 0.049). In obese males with features of metabolic syndrome, 12 weeks fructose intervention 75 g/day did not change glucose, insulin, GLP-1 or GIP responses during OGTT or GLP-1, GIP or PYY responses during a mixed meal. Therefore, fructose intake, even accompanied with mild weight gain, increases in liver fat and worsening of postprandial TG profile, does not impair glucose tolerance or gut incretin response to oral glucose or mixed meal challenge. Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

Pancreatic cancer-derived exosomes suppress the production of GIP and GLP-1 from STC-1 cells in vitro by down-regulating the PCSK1/3.

PubMed

Zhang, Yuefeng; Huang, Shifei; Li, Pengping; Chen, Qing; Li, Yongzhou; Zhou, Yizhao; Wang, Lantian; Kang, Muxing; Zhang, Bo; Yang, Bin; Wu, Yulian

2018-05-22

One hallmark of pancreatic cancer (PC) is the high prevalence of pancreatic cancer-associated diabetes mellitus (PC-DM), but the mechanisms remain to be elucidated. Patients with PC who are diagnosed with new-onset diabetes/prediabetes have recently been shown to display significantly lower levels of glucose-dependent insulinotropic peptide (GIP) secreted mainly by enteroendocrine cells. We hypothesized that PC-derived exosomes are responsible for the decreased levels of incretins in patients with PC-DM. In this study, exosomes were successfully isolated from PANC-1, MIA PaCa-2 and SW620 cells and characterized. Only the exosomes from MIA PaCa-2 cells (Exo-Mia) reduce the production of GIP and glucagon-like peptide-1 (GLP-1) from STC-1 cells in vitro in a concentration- and time-dependent manner. Moreover, Exo-Mia increased the levels of the Gip and proglucagon mRNAs and decreased the expression of proprotein convertase subtilisin/kexin type 1/3 (PCSK1/3), which is responsible for the post-translational processing of Gip and proglucagon. Furthermore, differentially expressed exosomal miRNAs (miR-6796-3p, miR-6763-5p, miR-4750-3p and miR-197-3p) were identified and considered to be responsible for the inhibitory effects on GIP and GLP-1 production. To further determine the approach of cancer-derived exosomes reaching enteroendocrine cells, we analyzed the uptake and distribution of exosomes in animal model. It was observed that exosomes infused into the intestinal cavity were more easily internalized by the intestinal epithelium than exosomes injected into blood. In conclusion, pancreatic cancer-derived exosomes (Exo-Mia) suppress the synthesis of GIP and GLP-1 from STC-1 cells in vitro by down-regulating the PCSK1/3. Moreover, it may be the pancreatic juice that transport cancer-derived exosomes to target cells (K and L cells) in the gut. Copyright © 2018 Elsevier B.V. All rights reserved.

The GIP receptor displays higher basal activity than the GLP-1 receptor but does not recruit GRK2 or arrestin3 effectively.

PubMed

Al-Sabah, Suleiman; Al-Fulaij, Munya; Shaaban, Ghina; Ahmed, Hanadi A; Mann, Rosalind J; Donnelly, Dan; Bünemann, Moritz; Krasel, Cornelius

2014-01-01

Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are important regulators of insulin secretion, and their functional loss is an early characteristic of type 2 diabetes mellitus (T2DM). Pharmacological levels of GLP-1, but not GIP, can overcome this loss. GLP-1 and GIP exert their insulinotropic effects through their respective receptors expressed on pancreatic β-cells. Both the GLP-1 receptor (GLP-1R) and the GIP receptor (GIPR) are members of the secretin family of G protein-coupled receptors (GPCRs) and couple positively to adenylate cyclase. We compared the signalling properties of these two receptors to gain further insight into why GLP-1, but not GIP, remains insulinotropic in T2DM patients. GLP-1R and GIPR were transiently expressed in HEK-293 cells, and basal and ligand-induced cAMP production were investigated using a cAMP-responsive luciferase reporter gene assay. Arrestin3 (Arr3) recruitment to the two receptors was investigated using enzyme fragment complementation, confocal microscopy and fluorescence resonance energy transfer (FRET). GIPR displayed significantly higher (P<0.05) ligand-independent activity than GLP-1R. Arr3 displayed a robust translocation to agonist-stimulated GLP-1R but not to GIPR. These observations were confirmed in FRET experiments, in which GLP-1 stimulated the recruitment of both GPCR kinase 2 (GRK2) and Arr3 to GLP-1R. These interactions were not reversed upon agonist washout. In contrast, GIP did not stimulate recruitment of either GRK2 or Arr3 to its receptor. Interestingly, arrestin remained at the plasma membrane even after prolonged (30 min) stimulation with GLP-1. Although the GLP-1R/arrestin interaction could not be reversed by agonist washout, GLP-1R and arrestin did not co-internalise, suggesting that GLP-1R is a class A receptor with regard to arrestin binding. GIPR displays higher basal activity than GLP-1R but does not effectively recruit GRK2 or Arr3.

Adrenal GIPR expression and chromosome 19q13 microduplications in GIP-dependent Cushing’s syndrome

PubMed Central

Lecoq, Anne-Lise; Stratakis, Constantine A.; Viengchareun, Say; Chaligné, Ronan; Tosca, Lucie; Hage, Mirella; Berthon, Annabel; Faucz, Fabio R.; Hanna, Patrick; Boyer, Hadrien-Gaël; Servant, Nicolas; Salenave, Sylvie; Tachdjian, Gérard; Adam, Clovis; Benhamo, Vanessa; Clauser, Eric; Guiochon-Mantel, Anne; Young, Jacques; Lombès, Marc; Bourdeau, Isabelle; Maiter, Dominique; Tabarin, Antoine; Bertherat, Jérôme; Lefebvre, Hervé; Louiset, Estelle; Lacroix, André; Bouligand, Jérôme; Kamenický, Peter

2017-01-01

GIP-dependent Cushing’s syndrome is caused by ectopic expression of glucose-dependent insulinotropic polypeptide receptor (GIPR) in cortisol-producing adrenal adenomas or in bilateral macronodular adrenal hyperplasias. Molecular mechanisms leading to ectopic GIPR expression in adrenal tissue are not known. Here we performed molecular analyses on adrenocortical adenomas and bilateral macronodular adrenal hyperplasias obtained from 14 patients with GIP-dependent adrenal Cushing’s syndrome and one patient with GIP-dependent aldosteronism. GIPR expression in all adenoma and hyperplasia samples occurred through transcriptional activation of a single allele of the GIPR gene. While no abnormality was detected in proximal GIPR promoter methylation, we identified somatic duplications in chromosome region 19q13.32 containing the GIPR locus in the adrenocortical lesions derived from 3 patients. In 2 adenoma samples, the duplicated 19q13.32 region was rearranged with other chromosome regions, whereas a single tissue sample with hyperplasia had a 19q duplication only. We demonstrated that juxtaposition with cis-acting regulatory sequences such as glucocorticoid response elements in the newly identified genomic environment drives abnormal expression of the translocated GIPR allele in adenoma cells. Altogether, our results provide insight into the molecular pathogenesis of GIP-dependent Cushing’s syndrome, occurring through monoallelic transcriptional activation of GIPR driven in some adrenal lesions by structural variations. PMID:28931750

A Design for an Integrated Lunar Geophysics Instrument Package (L-GIP)

NASA Astrophysics Data System (ADS)

Neal, C. R.

2007-12-01

The development of the Lunar Geophysics Instrument Package (L-GIP) is international collaborative investigation to record geophysical measurements on the surface of the Moon over several years (>6) and transmit the data back to Earth either directly, or via a surface or orbital relay asset. The L-GIP will include a seismometer, a heat flow probe, and a magnetometer. Each instrument that forms the L-GIP is relatively mature and was/is a payload on past, current or future planetary missions. However, the modifications to these (for integrating into one deployable unit), along with the required architecture, are needed. Significant trade studies include how to operate in an adverse thermal regime (transition between lunar night/day), long-lived power supply options, networking of different L-GIPs, defining the best design of heat flow probe to achieve the sciences goals (i.e., designs from Apollo, Lunar-A penetrator, and Rosetta missions), inclusion (or not) of a solar wind detector for the magnetic studies, and deployment strategies. The L-GIP instruments have been chosen because their individual data sets will address several unanswered scientific questions regarding the lunar interior and lunar evolution, as well as provide valuable data for exploration. The as yet unanswered science questions include: What is the composition and size of the lunar core? What is the internal structure of the whole Moon? What is the global thermal budget of the Moon and how has this impacted its evolution? Did the early Moon have a dynamo and if so, when did it start and when did it stop? Unanswered exploration questions include: What is the nature of ground movement in response to the large (body wave magnitude 5 or greater) Moonquakes that are known to occur? Do meteoroid impacts fall more in one area than another on the Moon? A global network of L-GIP instruments strategically placed around the Moon and operational for 6+ years will go a long way to answering such questions. The fundamental importance of the L-GIP is that the dataset from one instrument will enhance the datasets from the others. This is vital because using combined data types together in cooperative inversion approaches can be effective in limiting the number of acceptable interpretations. For example, magnetic data can provide good constraints on near-surface density, especially if combined with gravity data (a higher resolution data set of which will become available with the Japanese SELENE mission). The seismic models tend to resolve horizontal layers well, while magnetic approaches resolve lateral variations or vertical interfaces in subsurface magnetic susceptibility (and density if gravity data again are available). Heat flow data can provide additional lateral and sometimes (coarse) vertical property constraints, but also provide key model constraints for seismic (velocity) and density models. So, by combining these instruments in the L-GIP the datasets thus generated will dramatically lessen ambi¬guities in our understanding of the lunar interior.

Giant-cell interstitial pneumonia in a gas station worker.

PubMed

Lee, S M; Moon, C H; Oh, Y B; Kim, H Y; Ahn, Y; Ko, E J; Joo, J E

1998-10-01

Giant-cell interstitial Pneumonia (GIP) is a very uncommon respiratory disease. The majority of cases of GIP are caused by exposure to cobalt, tungsten and other hard metals. In this report, we describe GIP in a patient who worked in gas station and dealt in propane gas vessels. He presented with clinical features of chronic interstitial lung disease and underwent an open lung biopsy that showed DIP-like reaction with large numbers of intra-alveolar macrophages and numerous large, multinucleated histiocytes which were admixed with the macrophages. Analysis of lung tissue for hard metals was done. Cobalt was the main component of detected hard metals. Corticosteroid therapy was started and he recovered fully.

On the analysis and comparison of conformer-specific essential dynamics upon ligand binding to a protein.

PubMed

Grosso, Marcos; Kalstein, Adrian; Parisi, Gustavo; Roitberg, Adrian E; Fernandez-Alberti, Sebastian

2015-06-28

The native state of a protein consists of an equilibrium of conformational states on an energy landscape rather than existing as a single static state. The co-existence of conformers with different ligand-affinities in a dynamical equilibrium is the basis for the conformational selection model for ligand binding. In this context, the development of theoretical methods that allow us to analyze not only the structural changes but also changes in the fluctuation patterns between conformers will contribute to elucidate the differential properties acquired upon ligand binding. Molecular dynamics simulations can provide the required information to explore these features. Its use in combination with subsequent essential dynamics analysis allows separating large concerted conformational rearrangements from irrelevant fluctuations. We present a novel procedure to define the size and composition of essential dynamics subspaces associated with ligand-bound and ligand-free conformations. These definitions allow us to compare essential dynamics subspaces between different conformers. Our procedure attempts to emphasize the main similarities and differences between the different essential dynamics in an unbiased way. Essential dynamics subspaces associated to conformational transitions can also be analyzed. As a test case, we study the glutaminase interacting protein (GIP), composed of a single PDZ domain. Both GIP ligand-free state and glutaminase L peptide-bound states are analyzed. Our findings concerning the relative changes in the flexibility pattern upon binding are in good agreement with experimental Nuclear Magnetic Resonance data.

On the analysis and comparison of conformer-specific essential dynamics upon ligand binding to a protein

NASA Astrophysics Data System (ADS)

Grosso, Marcos; Kalstein, Adrian; Parisi, Gustavo; Roitberg, Adrian E.; Fernandez-Alberti, Sebastian

2015-06-01

The native state of a protein consists of an equilibrium of conformational states on an energy landscape rather than existing as a single static state. The co-existence of conformers with different ligand-affinities in a dynamical equilibrium is the basis for the conformational selection model for ligand binding. In this context, the development of theoretical methods that allow us to analyze not only the structural changes but also changes in the fluctuation patterns between conformers will contribute to elucidate the differential properties acquired upon ligand binding. Molecular dynamics simulations can provide the required information to explore these features. Its use in combination with subsequent essential dynamics analysis allows separating large concerted conformational rearrangements from irrelevant fluctuations. We present a novel procedure to define the size and composition of essential dynamics subspaces associated with ligand-bound and ligand-free conformations. These definitions allow us to compare essential dynamics subspaces between different conformers. Our procedure attempts to emphasize the main similarities and differences between the different essential dynamics in an unbiased way. Essential dynamics subspaces associated to conformational transitions can also be analyzed. As a test case, we study the glutaminase interacting protein (GIP), composed of a single PDZ domain. Both GIP ligand-free state and glutaminase L peptide-bound states are analyzed. Our findings concerning the relative changes in the flexibility pattern upon binding are in good agreement with experimental Nuclear Magnetic Resonance data.

Appetite, Glycemia, and Entero-Insular Hormone Responses Differ Between Oral, Gastric-Remnant, and Duodenal Administration of a Mixed-Meal Test After Roux-en-Y Gastric Bypass.

PubMed

Gero, Daniel; Steinert, Robert E; Hosa, Hanna; Cummings, David E; Bueter, Marco

2018-06-01

To examine the effect of different feeding routes on appetite and metabolic responses after Roux-en-Y gastric bypass (RYGB). A standard liquid meal was administered either orally, into the gastric remnant, or intraduodenally 6 months after RYGB. Changes in plasma glucose, insulin, glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), peptide YY (PYY), and appetite were measured pre- and postprandially. Postprandial GLP-1 and PYY responses were similar, whereas glucose, insulin, and GIP levels differed markedly after oral versus intraduodenal feeding. Intraduodenal feeding prompted an intermediate appetite response (i.e., between oral and intragastric). For postprandial glucose, insulin, and GIP levels, the intraduodenal route was more similar to the intragastric than the oral route. Intragastric administration did not evoke changes in appetite, glucose, or insulin; however, it slightly increased GLP-1 and PYY and moderately increased GIP. Appetite and metabolic responses after RYGB depend on the route by which nutrients enter the gastrointestinal tract. © 2018 by the American Diabetes Association.

Evaluation of the NanoCHIP® Gastrointestinal Panel (GIP) Test for Simultaneous Detection of Parasitic and Bacterial Enteric Pathogens in Fecal Specimens

PubMed Central

Ken Dror, Shifra; Pavlotzky, Elsa; Barak, Mira

2016-01-01

Infectious gastroenteritis is a global health problem associated with high morbidity and mortality rates. Rapid and accurate diagnosis is crucial to allow appropriate and timely treatment. Current laboratory stool testing has a long turnaround time (TAT) and demands highly qualified personnel and multiple techniques. The need for high throughput and the number of possible enteric pathogens compels the implementation of a molecular approach which uses multiplex technology, without compromising performance requirements. In this work we evaluated the feasibility of the NanoCHIP® Gastrointestinal Panel (GIP) (Savyon Diagnostics, Ashdod, IL), a molecular microarray-based screening test, to be used in the routine workflow of our laboratory, a big outpatient microbiology laboratory. The NanoCHIP® GIP test provides simultaneous detection of nine major enteric bacteria and parasites: Campylobacter spp., Salmonella spp., Shigella spp., Giardia sp., Cryptosporidium spp., Entamoeba histolytica, Entamoeba dispar, Dientamoeba fragilis, and Blastocystis spp. The required high-throughput was obtained by the NanoCHIP® detection system together with the MagNA Pure 96 DNA purification system (Roche Diagnostics Ltd., Switzerland). This combined system has demonstrated a higher sensitivity and detection yield compared to the conventional methods in both, retrospective and prospective samples. The identification of multiple parasites and bacteria in a single test also enabled increased efficiency of detecting mixed infections, as well as reduced hands-on time and work load. In conclusion, the combination of these two automated systems is a proper response to the laboratory needs in terms of improving laboratory workflow, turn-around-time, minimizing human errors and can be efficiently integrated in the routine work of the laboratory. PMID:27447173

Effects of different sweet preloads on incretin hormone secretion, gastric emptying, and postprandial glycemia in healthy humans.

PubMed

Wu, Tongzhi; Zhao, Beiyi R; Bound, Michelle J; Checklin, Helen L; Bellon, Max; Little, Tanya J; Young, Richard L; Jones, Karen L; Horowitz, Michael; Rayner, Christopher K

2012-01-01

Macronutrient "preloads" can stimulate glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), slow gastric emptying, and reduce postprandial glycemic excursions. After sweet preloads, these effects may be signaled by sodium-glucose cotransporter-1 (SGLT1), sweet taste receptors, or both. We determined the effects of 4 sweet preloads on GIP and GLP-1 release, gastric emptying, and postprandial glycemia. Ten healthy subjects were studied on 4 separate occasions each. A preload drink containing 40 g glucose, 40 g tagatose/isomalt mixture (TIM), 40 g 3-O-methylglucose (3OMG; a nonmetabolized substrate of SGLT1), or 60 mg sucralose was consumed 15 min before a (13)C-octanoic acid-labeled mashed potato meal. Blood glucose, plasma total GLP-1 and GIP, serum insulin, and gastric emptying were determined. Both glucose and 3OMG stimulated GLP-1 and GIP release in advance of the meal (each P < 0.05), whereas TIM and sucralose did not. The overall postprandial GLP-1 response was greater after glucose, 3OMG, and TIM than after sucralose (P < 0.05), albeit later after TIM than the other preloads. The blood glucose and insulin responses in the first 30 min after the meal were greatest after glucose (each P < 0.05). Gastric emptying was slower after both 3OMG and TIM than after sucralose (each P < 0.05). In healthy humans, SGLT1 substrates stimulate GLP-1 and GIP and slow gastric emptying, regardless of whether they are metabolized, whereas the artificial sweetener sucralose does not. Poorly absorbed sweet tastants (TIM), which probably expose a greater length of gut to nutrients, result in delayed GLP-1 secretion but not in delayed GIP release. These observations have the potential to optimize the use of preloads for glycemic control. This trial was registered at www.actr.org.au as ACTRN12611000775910.

Role of Peptide YY3-36 and Glucose-Dependent Insulinotropic Polypeptide in Anorexia Induction by Trichothecences T-2 Toxin, HT-2 Toxin, Diacetoxyscirpenol, and Neosolaniol.

PubMed

Zhang, Jie; Jia, Hui; Wang, Qingqing; Zhang, Yajie; Wu, Wenda; Zhang, Haibin

2017-09-01

Trichothecences, secondary metabolites produced by Fusarium, are serious health risks to humans and animals worldwide. Although type A trichothecence-induced food refusal has been observed, the mechanism underlying the anorexia caused by these compounds is not fully understood. In this study, we hypothesized that anorexia induced by type A trichothecenes, including T-2 toxin (T-2), HT-2 toxin (HT-2), diacetoxyscirpenol (DAS), and neosolaniol (NEO), in mice corresponds to the changes in the gut satiety hormones peptide YY3-36 (PYY3-36) and glucose-dependent insulinotropic polypeptide (GIP) in plasma. A well-characterized mouse food refusal model was used in this assay. Oral exposure to or intraperitoneal (ip) injection of 1 mg/kg bw T-2, HT-2, DAS, or NEO resulted in dramatically decreased food intake, and PYY3-36 and GIP concentrations were elevated accordingly. Specifically, the PYY3-36 and GIP concentrations peaked at 2 h following oral exposure to these 4 toxins individually, although the durations were not identical. After ip administration of T-2 or HT-2, PYY3-36 significantly increased within 6 h. However, no significant difference was found in the DAS and NEO groups. The GIP levels peaked within 2, 2, 0.5, and 0.5 h, respectively, and remained increased up to 6, 6, 2, and 6 h, respectively, following T-2, HT-2, DAS, or NEO ip exposure. The increase in GIP was greater than that of PYY3-36 after exposure to the 4 toxins using 2 administration routes. Together, these findings suggest that PYY3-36 and GIP play a role in T-2-, HT-2-, DAS-, and NEO-induced anorexia. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Third Exposure to a Reduced Carbohydrate Meal Lowers Evening Postprandial Insulin and GIP Responses and HOMA-IR Estimate of Insulin Resistance.

PubMed

Lin, Po-Ju; Borer, Katarina T

2016-01-01

Postprandial hyperinsulinemia, hyperglycemia, and insulin resistance increase the risk of type 2 diabetes (T2D) and cardiovascular disease mortality. Postprandial hyperinsulinemia and hyperglycemia also occur in metabolically healthy subjects consuming high-carbohydrate diets particularly after evening meals and when carbohydrate loads follow acute exercise. We hypothesized the involvement of dietary carbohydrate load, especially when timed after exercise, and mediation by the glucose-dependent insulinotropic peptide (GIP) in this phenomenon, as this incretin promotes insulin secretion after carbohydrate intake in insulin-sensitive, but not in insulin-resistant states. Four groups of eight metabolically healthy weight-matched postmenopausal women were provided with three isocaloric meals (a pre-trial meal and two meals during the trial day) containing either 30% or 60% carbohydrate, with and without two-hours of moderate-intensity exercise before the last two meals. Plasma glucose, insulin, glucagon, GIP, glucagon-like peptide 1 (GLP-1), free fatty acids (FFAs), and D-3-hydroxybutyrate concentrations were measured during 4-h postprandial periods and 3-h exercise periods, and their areas under the curve (AUCs) were analyzed by mixed-model ANOVA, and insulin resistance during fasting and meal tolerance tests within each diet was estimated using homeostasis-model assessment (HOMA-IR). The third low-carbohydrate meal, but not the high-carbohydrate meal, reduced: (1) evening insulin AUC by 39% without exercise and by 31% after exercise; (2) GIP AUC by 48% without exercise and by 45% after exercise, and (3) evening insulin resistance by 37% without exercise and by 24% after exercise. Pre-meal exercise did not alter insulin-, GIP- and HOMA-IR- lowering effects of low-carbohydrate diet, but exacerbated evening hyperglycemia. Evening postprandial insulin and GIP responses and insulin resistance declined by over 30% after three meals that limited daily carbohydrate intake to 30% compared to no such changes after three 60%-carbohydrate meals, an effect that was independent of pre-meal exercise. The parallel timing and magnitude of postprandial insulin and GIP changes suggest their dependence on a delayed intestinal adaptation to a low-carbohydrate diet. Pre-meal exercise exacerbated glucose intolerance with both diets most likely due to impairment of insulin signaling by pre-meal elevation of FFAs.

A new stable GIP-Oxyntomodulin hybrid peptide improved bone strength both at the organ and tissue levels in genetically-inherited type 2 diabetes mellitus.

PubMed

Mansur, Sity Aishah; Mieczkowska, Aleksandra; Flatt, Peter R; Bouvard, Beatrice; Chappard, Daniel; Irwin, Nigel; Mabilleau, Guillaume

2016-06-01

Obesity and type 2 diabetes mellitus (T2DM) progress worldwide with detrimental effects on several physiological systems including bone tissue mainly by affecting bone quality. Several gut hormones analogues have been proven potent in ameliorating bone quality. In the present study, we used the leptin receptor-deficient db/db mice as a model of obesity and severe T2DM to assess the extent of bone quality alterations at the organ and tissue levels. We also examined the beneficial effects of gut hormone therapy in this model by using a new triple agonist ([d-Ala(2)]GIP-Oxm) active at the GIP, GLP-1 and glucagon receptors. As expected, db/db mice presented with dramatic alterations of bone strength at the organ level associated with deterioration of trabecular and cortical microarchitectures and an augmentation in osteoclast numbers. At the tissue level, these animals presented also with alterations of bone strength (reduced hardness, indentation modulus and dissipated energy) with modifications of tissue mineral distribution, collagen glycation and collagen maturity. The use of [d-Ala(2)]GIP-Oxm considerably improved bone strength at the organ level with modest effects on trabecular microarchitecture. At the tissue level, [d-Ala(2)]GIP-Oxm ameliorated bone strength reductions with positive effects on collagen glycation and collagen maturity. This study provides support for including gut hormone analogues as possible new therapeutic strategies for improving bone quality in bone complications associated to T2DM. Copyright © 2016 Elsevier Inc. All rights reserved.

Architecture, Design and Implementation of RC64, a Many-Core High-Performance DSP for Space Applications

NASA Astrophysics Data System (ADS)

Ginosar, Ran; Aviely, Peleg; Liran, Tuvia; Alon, Dov; Dobkin, Reuven; Goldberg, Michael

2013-08-01

RC64, a novel 64-core many-core signal processing chip targets DSP performance of 12.8 GIPS, 100 GOPS and 12.8 single precision GFLOS while dissipating only 3 Watts. RC64 employs advanced DSP cores, a multi-bank shared memory and a hardware scheduler, supports DDR2 memory and communicates over five proprietary 6.4 Gbps channels. The programming model employs sequential fine-grain tasks and a separate task map to define task dependencies. RC64 is implemented as a 200 MHz ASIC on Tower 130nm CMOS technology, assembled in hermetically sealed ceramic QFP package and qualified to the highest space standards.

The effect of nopal (Opuntia ficus indica) on postprandial blood glucose, incretins, and antioxidant activity in Mexican patients with type 2 diabetes after consumption of two different composition breakfasts.

PubMed

López-Romero, Patricia; Pichardo-Ontiveros, Edgar; Avila-Nava, Azalia; Vázquez-Manjarrez, Natalia; Tovar, Armando R; Pedraza-Chaverri, José; Torres, Nimbe

2014-11-01

Nopal is a plant used in traditional Mexican medicine to treat diabetes. However, there is insufficient scientific evidence to demonstrate whether nopal can regulate postprandial glucose. The purpose for conducting this study was to evaluate the glycemic index, insulinemic index, glucose-dependent insulinotropic peptide (GIP) index, and the glucagon-like peptide 1 (GLP-1) index, and the effect of nopal on patients with type 2 diabetes after consumption of a high-carbohydrate breakfast (HCB) or high-soy-protein breakfast (HSPB) on the postprandial response of glucose, insulin, GIP, GLP-1, and antioxidant activity. In study 1, the glycemic index, insulinemic index, GIP index, and GLP-1 index were calculated for seven healthy participants who consumed 50 g of available carbohydrates from glucose or dehydrated nopal. In study 2, 14 patients with type 2 diabetes consumed nopal in HCB or HSPB with or without 300 g steamed nopal. The glycemic index of nopal was 32.5±4, insulinemic index was 36.1±6, GIP index was 6.5±3.0, and GLP-1 index was 25.9±18. For those patients with type 2 diabetes who consumed the HCB+nopal, there was significantly lower area under the curve for glucose (287±30) than for those who consumed the HCB only (443±49), and lower incremental area under the curve for insulin (5,952±833 vs 7,313±1,090), and those patients with type 2 diabetes who consumed the HSPB avoided postprandial blood glucose peaks. Consumption of the HSPB+nopal significantly reduced the postprandial peaks of GIP concentration at 30 and 45 minutes and increased the antioxidant activity after 2 hours measured by the 2,2-diphenyl-1-picrilhidracyl method. These findings suggest that nopal could reduce postprandial blood glucose, serum insulin, and plasma GIP peaks, as well as increase antioxidant activity in healthy people and patients with type 2 diabetes. Copyright © 2014 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

Impact of incretin on early-phase insulin secretion and glucose excursion.

PubMed

Shen, Jie; Chen, Zhi; Chen, Chaofeng; Zhu, Xiao; Han, Yajuan

2013-10-01

This study investigated the impact of incretin on early-phase insulin secretion and glucose excursion. The normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and type 2 diabetes mellitus (T2DM) groups included 16, 8, and 19 subjects, respectively. Subjects underwent continuous glucose monitoring for 3 days, followed by an oral glucose tolerance test. Plasma glucose, insulin, glucagon, total glucose-dependent insulinotropic polypeptide (GIP), and glucagon-like peptide-l (GLP-1) levels were measured at 30-min increments for 2 h after glucose intake. Differences with P < 0.05 were considered statistically significant. The area under the curve (AUC) of total GIP (120-min GIP-AUC) of the T2DM group was significantly lower than those of the NGT and IGT groups. The 120-min GLP-1-AUC of the NGT group was significantly larger than those of the T2DM and IGT groups. The early-phase insulin secretion index (ΔI30/ΔG30) of the T2DM group was significantly lower than those of the NGT and IGT groups. Mean amplitudes of glycemic excursions (MAGEs) went in the order of NGT < IGT < T2DM (P < 0.01, IGT vs. NGT; P < 0.001, T2DM vs. IGT). The 120-min GIP-AUC was negatively correlated with MAGE (r = -0.464), but uncorrelated with ΔI30/ΔG30. The 120-min GLP-1-AUC was positively correlated with ΔI30/ΔG30 (r = 0.580), but negatively correlated with MAGE (r = -0.606). Incretin may ameliorate glucose excursions, and GLP-1 may exert them by promoting early-phase insulin secretion. No correlation was observed between GIP secretion and early-phase insulin secretion.

Effects of short-term therapy with glibenclamide and repaglinide on incretin hormones and oxidative damage associated with postprandial hyperglycaemia in people with type 2 diabetes mellitus.

PubMed

Stephens, J W; Bodvarsdottir, T B; Wareham, K; Prior, S L; Bracken, R M; Lowe, G D; Rumley, A; Dunseath, G; Luzio, S; Deacon, C F; Holst, J J; Bain, S C

2011-11-01

To examine the effects of glibenclamide and repaglinide on glucose stimulated insulin release, incretins, oxidative stress and cell adhesion molecules in patients with type 2 diabetes suboptimally treated with metformin. A randomized clinical trial was performed recruiting 27 subjects (HbA(1c) between 7.5 and 10.5%) free from cardiovascular and renal disease. Glucose, insulin, C-peptide, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), total antioxidant status, F(2)-isoprostane, interleukin-6 and cell adhesion molecules were measured during an oral glucose load at baseline and after eight weeks of treatment. The areas under the curve were analysed at 45, 60 and 120 min (AUC(45), AUC(60), AUC(120)). Significant improvements in glucose were observed with repaglinide (HBA(1c): -1.5%, fasting glucose: -2.8 mmol/L, 2-h glucose: -3.7 mmol/L, AUC(120): -18.9%) and glibenclamide (-1.0%, -2.2 mmol/L, -2.5 mmol/L, -17.5%). Repaglinide was also associated with an increase in the AUC(60) and AUC(120) for insulin (+56%, +61%) and C-peptide (+41%, +36%). GLP-1, GIP, IL-6, ICAM-1 and E-selectin levels did not change in either group. No association was observed between GLP-1, GIP-1 and plasma markers of oxidative stress. Repaglinide is associated with improved postprandial glycaemic control via insulin and C-peptide release. We observed no direct effects of glibenclamide or repaglinide on plasma levels of GLP-1 or GIP. We observed no associations of GLP-1 and GIP with plasma markers of oxidative stress. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Add-on therapy with anagliptin in Japanese patients with type-2 diabetes mellitus treated with metformin and miglitol can maintain higher concentrations of biologically active GLP-1/total GIP and a lower concentration of leptin.

PubMed

Osonoi, Takeshi; Saito, Miyoko; Hariya, Natsuyo; Goto, Moritaka; Mochizuki, Kazuki

2016-12-01

Metformin, α-glucosidase inhibitors (α-GIs), and dipeptidyl peptidase 4 inhibitors (DPP-4Is) reduce hyperglycemia without excessive insulin secretion, and enhance postprandial plasma concentration of glucagon-like peptide-1 (GLP-1) in type-2 diabetes mellitus (T2DM) patients. We assessed add-on therapeutic effects of DPP-4I anagliptin in Japanese T2DM patients treated with metformin, an α-GI miglitol, or both drugs on postprandial responses of GLP-1 and glucose-dependent insulinotropic polypeptide (GIP), and on plasma concentration of the appetite-suppressing hormone leptin. Forty-two Japanese T2DM patients with inadequately controlled disease (HbA1c: 6.5%-8.0%) treated with metformin (n=14), miglitol (n=14) or a combination of the two drugs (n=14) received additional treatment with anagliptin (100mg, p.o., b.i.d.) for 52 weeks. We assessed glycemic control, postprandial responses of GLP-1 and glucose-dependent insulinotropic polypeptide (GIP), and on plasma concentration of leptin in those patients. Add-on therapy with anagliptin for 52 weeks improved glycemic control and increased the area under the curve of biologically active GLP-1 concentration without altering obesity indicators. Total GIP concentration at 52 weeks was reduced by add-on therapy in groups treated with miglitol compared with those treated with metformin. Add-on therapy reduced leptin concentrations. Add-on therapy with anagliptin in Japanese T2DM patients treated with metformin and miglitol for 52 weeks improved glycemic control and enhanced postprandial concentrations of active GLP-1/total GIP, and reduce the leptin concentration. Copyright © 2016 Elsevier Inc. All rights reserved.

A novel GLP-1/GIP/Gcg triagonist reduces cognitive deficits and pathology in the 3xTg mouse model of Alzheimer's disease.

PubMed

Li, Tian; Jiao, Juan-Juan; Hölscher, Christian; Wu, Mei-Na; Zhang, Jun; Tong, Jia-Qing; Dong, Xue-Fan; Qu, Xue-Song; Cao, Yue; Cai, Hong-Yan; Su, Qiang; Qi, Jin-Shun

2018-05-01

Type 2 diabetes mellitus (T2DM) is an important risk factor for Alzheimer's disease (AD). Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) have been identified to be effective in T2DM treatment and neuroprotection. In this study, we further explored the effects of a novel unimolecular GLP-1/GIP/Gcg triagonist on the cognitive behavior and cerebral pathology in the 7-month-old triple transgenic mouse model of AD (3xTg-AD), and investigated its possible electrophysiological and molecular mechanisms. After chronic administration of the GLP-1/GIP/Gcg triagonist (10 nmol/kg bodyweight, once daily, i.p.) for 30 days, open field, Y maze and Morris water maze tests were performed, followed by in vivo electrophysiological recording, immunofluorescence and Western blotting experiments. We found that the chronic treatment with the triagonist could improve long-term spatial memory of 3xTg-AD mice in Morris water maze, as well as the working memory in Y maze task. The triagonist also alleviated the suppression of long-term potentiation (LTP) in the CA1 region of hippocampus. In addition, the triagonist significantly reduced hippocampal pathological damages, including amyloid-β (Aβ) and phosphorylated tau aggregates, and upregulated the expression levels of S133 p-CREB, T286 p-CAMKII and S9 p-GSK3β in the hippocampus of the 3xTg-AD mice. These results demonstrate for the first time that the novel GLP-1/GIP/Gcg triagonist is efficacious in ameliorating cognitive deficits and pathological damages of 3xTg-AD mice, suggesting that the triagonist might be potentially beneficial in the treatment of AD. © 2018 Wiley Periodicals, Inc.

Glucose-dependent insulinotropic polypeptide-producing K cells in dexamethasone-treated rats.

PubMed

Koko, V; Glisic, R; Todorovic, V; Drndarevic, N; Mitrovic, O

2008-12-01

Some studies indicate that diabetes mellitus exerts an influence on the gastrointestinal tract and its diffuse neuroendocrine system (DNES) in regard to cellular density and neuroendocrine content. Since there is no data about relationship between experimentally induced non-insulin-dependent (type 2) diabetes mellitus (NIDDM) on the gut K cells, the aim of our study was to investigate immunohistochemical, stereological and ultrastructural changes of rat K cells after 12 days of dexamethasone treatment. Twenty male Wistar rats aged 30 days were given daily intraperitoneally 2 mg kg(-1) dexamethasone (group DEX, 10 rats) or saline (group C, 10 rats) for 12 days. Tissue specimens were obtained from each antrum with corpus and different parts of the small (SI) and large intestine (LI) of all animals. Immunohistochemistry was carried out using antisera against the GIP and insulin. Transmission electron microscopy was also used. Although, according to the literature data, rat K cells are present in the duodenum and jejunum and, to a lesser extent, in the ileum, in the present study we observed that those cells were abundant also in all parts of the LI. We observed generally that GIP-producing K cells were augmented in all parts of SI and decreased in the LI of DEX rats. Insulin immunoreactivity (ir) coexpressed with GIP-ir in K cells and was stronger in the SI of DEX rats as compared with C rats. We also found by electron microscopy that small intestinal K cells have features not only of GIP-secreted but also of insulin-secreted cells. We concluded that dexamethasone treatment caused proliferation of K cells in the rat SI, and simultaneously transformation of GIP-producing K cells to insulin-synthesizing cells.

Prebiotic Fibre Supplementation In Combination With Metformin Modifies Appetite, Energy Metabolism, And Gut Satiety Hormones In Obese Rats

NASA Astrophysics Data System (ADS)

Pyra, Kim Alicia

The prebiotic fibre, oligofructose (OFS), reduces energy intake and improves glycemic control in rodents and man. Metformin (MT) is a commonly used insulin-sensitizing agent that may limit weight gain in individuals with type 2 diabetes. Our objective was to determine if using OFS as an adjunct to MT therapy (AD) modifies satiety hormone production and metabolism in obese rats. Independently, OFS and MT decreased energy intake, body fat, hepatic triglyceride content, plasma leptin and glucose-dependent insulinotropic peptide (GIP) levels. OFS and AD but not MT rats showed superior glycemic control during an oral glucose tolerance test (OGTT) compared to C. Area under the curve for GIP was lowest in ADThe prebiotic fibre, oligofructose (OFS), reduces energy intake and improves glycemic control in rodents and man. Metformin (MT) is a commonly used insulin-sensitizing agent that may limit weight gain in individuals with type 2 diabetes. Our objective was to determine if using OFS as an adjunct to MT therapy (AD) modifies satiety hormone production and metabolism in obese rats. Independently, OFS and MT decreased energy intake, body fat, hepatic triglyceride content, plasma leptin and glucose-dependent insulinotropic peptide (GIP) levels. OFS and AD but not MT rats showed superior glycemic control during an oral glucose tolerance test (OGTT) compared to C. Area under the curve for GIP was lowest in AD

Glycemic, insulinemic and incretin responses after oral trehalose ingestion in healthy subjects.

PubMed

Yoshizane, Chiyo; Mizote, Akiko; Yamada, Mika; Arai, Norie; Arai, Shigeyuki; Maruta, Kazuhiko; Mitsuzumi, Hitoshi; Ariyasu, Toshio; Ushio, Shimpei; Fukuda, Shigeharu

2017-02-06

Trehalose is hydrolyzed by a specific intestinal brush-border disaccharidase (trehalase) into two glucose molecules. In animal studies, trehalose has been shown to prevent adipocyte hypertrophy and mitigate insulin resistance in mice fed a high-fat diet. Recently, we found that trehalose improved glucose tolerance in human subjects. However, the underlying metabolic responses after trehalose ingestion in humans are not well understood. Therefore, we examined the glycemic, insulinemic and incretin responses after trehalose ingestion in healthy Japanese volunteers. In a crossover study, 20 fasted healthy volunteers consumed 25 g trehalose or glucose in 100 mL water. Blood samples were taken frequently over the following 3 h, and blood glucose, insulin, active gastric inhibitory polypeptide (GIP) and active glucagon-like peptide-1 (GLP-1) levels were measured. Trehalose ingestion did not evoke rapid increases in blood glucose levels, and had a lower stimulatory potency of insulin and active GIP secretion compared with glucose ingestion. Conversely, active GLP-1 showed higher levels from 45 to 180 min after trehalose ingestion as compared with glucose ingestion. Specifically, active GIP secretion, which induces fat accumulation, was markedly lower after trehalose ingestion. Our findings indicate that trehalose may be a useful saccharide for good health because of properties that do not stimulate rapid increases in blood glucose and excessive secretion of insulin and GIP promoting fat accumulation.

Postmeal increment in intact glucagon-like peptide 1 level, but not intact glucose-dependent insulinotropic polypeptide levels, is inversely associated with metabolic syndrome in patients with type 2 diabetes.

PubMed

Yoo, Soyeon; Yang, Eun-Jin; Lee, Sang Ah; Koh, Gwanpyo

2018-02-01

Metabolic syndrome increases the risk of cardiovascular disease. Recently glucagon-like peptide 1 (GLP-1) agonists proved to be effective in preventing cardiovascular disease (CVD) in patients with type 2 diabetes. We investigated the association of blood incretin levels with metabolic syndrome in patients with type 2 diabetes. This is a cross-sectional study involving 334 people with type 2 diabetes. Intact GLP-1 (iGLP-1) and intact glucose-dependent insulinotropic polypeptide (iGIP) levels were measured in a fasted state and 30 min after ingestion of a standard mixed meal. Metabolic syndrome was diagnosed based on the criteria of the International Diabetes Federation. Two hundred twenty-five (69%) of the subjects have metabolic syndrome. The fasting iGLP-1 level was no different between groups. Thirty-min postprandial iGLP-1 was non-significantly lower in the subjects who had metabolic syndrome. Incremental iGLP-1 (ΔiGLP-1, the difference between 30-min postmeal and fasting iGLP-1 levels) was significantly lower in those with metabolic syndrome. There were no significant differences in fasting iGIP, postprandial iGIP, and ΔiGIP between groups. The ΔiGLP-1, but not ΔiGIP levels decreased significantly as the number of metabolic syndrome components increased. In hierarchical logistic regression analysis, the ΔiGLP-1 level was found to be a significant contributor to metabolic syndrome even after adjusting for other covariates. Taken together, the iGLP-1 increment in the 30 min after meal ingestion is inversely associated with metabolic syndrome in patients with type 2 diabetes. This suggests that postmeal iGLP-1 increment could be useful in assessing cardiovascular risk in type 2 diabetes.

Identification of Metabolic Modifiers That Underlie Phenotypic Variations in Energy-Balance Regulation

PubMed Central

Chang, Chia Lin; Cai, James J.; Cheng, Po Jen; Chueh, Ho Yen; Hsu, Sheau Yu Teddy

2011-01-01

OBJECTIVE Although recent studies have shown that human genomes contain hundreds of loci that exhibit signatures of positive selection, variants that are associated with adaptation in energy-balance regulation remain elusive. We reasoned that the difficulty in identifying such variants could be due to heterogeneity in selection pressure and that an integrative approach that incorporated experiment-based evidence and population genetics-based statistical judgments would be needed to reveal important metabolic modifiers in humans. RESEARCH DESIGN AND METHODS To identify common metabolic modifiers that underlie phenotypic variation in diabetes-associated or obesity-associated traits in humans, or both, we screened 207 candidate loci for regulatory single nucleotide polymorphisms (SNPs) that exhibited evidence of gene–environmental interactions. RESULTS Three SNPs (rs3895874, rs3848460, and rs937301) at the 5′ gene region of human GIP were identified as prime metabolic-modifier candidates at the enteroinsular axis. Functional studies have shown that GIP promoter reporters carrying derived alleles of these three SNPs (haplotype GIP−1920A) have significantly lower transcriptional activities than those with ancestral alleles at corresponding positions (haplotype GIP−1920G). Consistently, studies of pregnant women who have undergone a screening test for gestational diabetes have shown that patients with a homozygous GIP−1920A/A genotype have significantly lower serum concentrations of glucose-dependent insulinotropic polypeptide (GIP) than those carrying an ancestral GIP−1920G haplotype. After controlling for a GIPR variation, we showed that serum glucose concentrations of patients carrying GIP−1920A/A homozygotes are significantly higher than that of those carrying an ancestral GIP−1920G haplotype (odds ratio 3.53). CONCLUSIONS Our proof-of-concept study indicates that common regulatory GIP variants impart a difference in GIP and glucose metabolism. The study also provides a rare example that identified the common variant-common phenotypic variation pattern based on evidence of moderate gene–environmental interactions. PMID:21300845

High-Fat Diet During Mouse Pregnancy and Lactation Targets GIP-Regulated Metabolic Pathways in Adult Male Offspring.

PubMed

Kruse, Michael; Keyhani-Nejad, Farnaz; Isken, Frank; Nitz, Barbara; Kretschmer, Anja; Reischl, Eva; de las Heras Gala, Tonia; Osterhoff, Martin A; Grallert, Harald; Pfeiffer, Andreas F H

2016-03-01

Maternal obesity is a worldwide problem associated with increased risk of metabolic diseases in the offspring. Genetic deletion of the gastric inhibitory polypeptide (GIP) receptor (GIPR) prevents high-fat diet (HFD)-induced obesity in mice due to specific changes in energy and fat cell metabolism. We investigated whether GIP-associated pathways may be targeted by fetal programming and mimicked the situation by exposing pregnant mice to control or HFD during pregnancy (intrauterine [IU]) and lactation (L). Male wild-type (WT) and Gipr(-/-) offspring received control chow until 25 weeks of age followed by 20 weeks of HFD. Gipr(-/-) offspring of mice exposed to HFD during IU/L became insulin resistant and obese and exhibited increased adipose tissue inflammation and decreased peripheral tissue substrate utilization after being reintroduced to HFD, similar to WT mice on regular chow during IU/L. They showed decreased hypothalamic insulin sensitivity compared with Gipr(-/-) mice on control diet during IU/L. DNA methylation analysis revealed increased methylation of CpG dinucleotides and differential transcription factor binding of promoter regions of genes involved in lipid oxidation in the muscle of Gipr(-/-) offspring on HFD during IU/L, which were inversely correlated with gene expression levels. Our data identify GIP-regulated metabolic pathways that are targeted by fetal programming. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Actions of incretin metabolites on locomotor activity, cognitive function and in vivo hippocampal synaptic plasticity in high fat fed mice.

PubMed

Porter, David; Faivre, Emilie; Flatt, Peter R; Hölscher, Christian; Gault, Victor A

2012-05-01

The incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) improve markers of cognitive function in obesity-diabetes, however, both are rapidly degraded to their major metabolites, GLP-1(9-36)amide and GIP(3-42), respectively. Therefore, the present study investigated effects of GLP-1(9-36)amide and GIP(3-42) on locomotor activity, cognitive function and hippocampal synaptic plasticity in mice with diet-induced obesity and insulin resistance. High-fat fed Swiss TO mice treated with GLP-1(9-36)amide, GIP(3-42) or exendin(9-39)amide (twice-daily for 60 days) did not exhibit any changes in bodyweight, non-fasting plasma glucose and plasma insulin concentrations or glucose tolerance compared with high-fat saline controls. Similarly, locomotor and feeding activity, O(2) consumption, CO(2) production, respiratory exchange ratio and energy expenditure were not altered by chronic treatment with incretin metabolites. Administration of the truncated metabolites did not alter general behavior in an open field test or learning and memory ability as recorded during an object recognition test. High-fat mice exhibited a significant impairment in hippocampal long-term potentiation (LTP) which was not affected by treatment with incretin metabolites. These data indicate that incretin metabolites do not influence locomotor activity, cognitive function and hippocampal synaptic plasticity when administered at pharmacological doses to mice fed a high-fat diet. Copyright © 2012 Elsevier Inc. All rights reserved.

A novel dual GLP-1 and GIP incretin receptor agonist is neuroprotective in a mouse model of Parkinson's disease by reducing chronic inflammation in the brain.

PubMed

Cao, Lijun; Li, Dongfang; Feng, Peng; Li, Lin; Xue, Guo-Fang; Li, Guanglai; Hölscher, Christian

2016-04-13

The incretins glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are growth factors. GLP-1 mimetics are on the market as treatments for type 2 diabetes. Both GLP-1 and GIP mimetics have shown neuroprotective properties in previous studies. In addition, the GLP-1 mimetic exendin-4 has shown protective effects in a clinical trial in Parkinson's disease (PD) patients. Novel GLP-1/GIP dual-agonist peptides have been developed to treat diabetes. Here, we report the neuroprotective effects of a novel dual agonist (DA-JC1) in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. MPTP was injected once daily (20 mg/kg intraperitoneally) for 7 days and the dual agonist was coinjected once daily (50 nmol/kg intraperitoneally). We found that the drug reduced most of the MPTP-induced motor impairments in the rotarod, open-field locomotion, and muscle strength test. The number of tyrosine hydroxylase-positive neurons in the substantia nigra and striatum was reduced by MPTP and increased by DA-JC1. Synapse numbers (synaptophysin expression) were reduced in the substantia nigra and the striatum by MPTP and DA-JC1 reversed this effect. The activation of a chronic inflammation response by MPTP was considerably reduced by the dual agonist (DA) (astroglia and microglia activation). Therefore, dual agonists show promise as a novel treatment of PD.

Comparing olive oil and C4-dietary oil, a prodrug for the GPR119 agonist, 2-oleoyl glycerol, less energy intake of the latter is needed to stimulate incretin hormone secretion in overweight subjects with type 2 diabetes.

PubMed

Mandøe, Mette Johannsen; Hansen, Katrine Bagge; Windeløv, Johanne Agerlin; Knop, Filip Krag; Rehfeld, Jens Frederik; Rosenkilde, Mette Marie; Holst, Jens Juul; Hansen, Harald Severin

2018-01-12

After digestion, dietary triacylglycerol stimulates incretin release in humans, mainly through generation of 2-monoacylglycerol, an agonist for the intestinal G protein-coupled receptor 119 (GPR119). Enhanced incretin release may have beneficial metabolic effects. However, dietary fat may promote weight gain and should therefore be restricted in obesity. We designed C4-dietary oil (1,3-di-butyryl-2-oleoyl glycerol) as a 2-oleoyl glycerol (2-OG)-generating fat type, which would stimulate incretin release to the same extent while providing less calories than equimolar amounts of common triglycerides, e.g., olive oil. We studied the effect over 180 min of (a) 19 g olive oil plus 200 g carrot, (b) 10.7 g C4 dietary oil plus 200 g carrot and (c) 200 g carrot, respectively, on plasma responses of gut and pancreatic hormones in 13 overweight patients with type 2 diabetes (T2D). Theoretically, both oil meals result in formation of 7.7 g 2-OG during digestion. Both olive oil and C4-dietary oil resulted in greater postprandial (P ≤ 0.01) glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) responses (incremental area under curve (iAUC)): iAUC GLP-1 : 645 ± 194 and 702 ± 97 pM × min; iAUC GIP : 4,338 ± 764 and 2,894 ± 601 pM × min) compared to the carrot meal (iAUC GLP-1 : 7 ± 103 pM × min; iAUC GIP : 266 ± 234 pM × min). iAUC for GLP-1 and GIP were similar for C4-dietary oil and olive oil, although olive oil resulted in a higher peak value for GIP than C4-dietary oil. C4-dietary oil enhanced secretion of GLP-1 and GIP to almost the same extent as olive oil, in spite of liberation of both 2-OG and oleic acid, which also may stimulate incretin secretion, from olive oil. Thus, C4-dietary oil is more effective as incretin releaser than olive oil per unit of energy and may be useful for dietary intervention.

Characterization of beta cell and incretin function in patients with MODY1 (HNF4A MODY) and MODY3 (HNF1A MODY) in a Swedish patient collection.

PubMed

Ekholm, E; Shaat, N; Holst, J J

2012-10-01

The aim of this study was to evaluate the beta cell and incretin function in patients with HNF4A and HNF1A MODY during a test meal. Clinical characteristics and biochemical data (glucose, proinsulin, insulin, C-peptide, GLP-1 and GIP) during a test meal were compared between MODY patients from eight different families. BMI-matched T2D and healthy subjects were used as two separate control groups. The early phase of insulin secretion was attenuated in HNF4A, HNF1A MODY and T2D (AUC0-30 controls: 558.2 ± 101.2, HNF4A MODY: 93.8 ± 57.0, HNF1A MODY: 170.2 ± 64.5, T2D: 211.2 ± 65.3, P < 0.01). Markedly reduced levels of proinsulin were found in HNF4A MODY compared to T2D and that tended to be so also in HNF1A MODY (HNF4A MODY: 3.7 ± 1.2, HNF1A MODY: 8.3 ± 3.8 vs. T2D: 26.6 ± 14.3). Patients with HNF4A MODY had similar total GLP-1 and GIP responses as controls (GLP-1 AUC: (control: 823.9 ± 703.8, T2D: 556.4 ± 698.2, HNF4A MODY: 1,257.0 ± 999.3, HNF1A MODY: 697.1 ± 818.4) but with a different secretion pattern. The AUC insulin during the test meal was strongly correlated with the GIP secretion (Correlation coefficient 1.0, P < 0.001). No such correlation was seen for insulin and GLP-1. Patients with HNF4A and HNF1A MODY showed an attenuated early phase of insulin secretion similar to T2Ds. AUC insulin during the test meal was strongly correlated with GIP secretion, whereas no such correlation was seen for insulin and GLP-1. Thus, GIP may be a more important factor for insulin secretion than GLP-1 in MODY patients.

Effect of the artificial sweetener, sucralose, on gastric emptying and incretin hormone release in healthy subjects.

PubMed

Ma, Jing; Bellon, Max; Wishart, Judith M; Young, Richard; Blackshaw, L Ashley; Jones, Karen L; Horowitz, Michael; Rayner, Christopher K

2009-04-01

The incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), play an important role in glucose homeostasis in both health and diabetes. In mice, sucralose, an artificial sweetener, stimulates GLP-1 release via sweet taste receptors on enteroendocrine cells. We studied blood glucose, plasma levels of insulin, GLP-1, and GIP, and gastric emptying (by a breath test) in 7 healthy humans after intragastric infusions of 1) 50 g sucrose in water to a total volume of 500 ml (approximately 290 mosmol/l), 2) 80 mg sucralose in 500 ml normal saline (approximately 300 mosmol/l, 0.4 mM sucralose), 3) 800 mg sucralose in 500 ml normal saline (approximately 300 mosmol/l, 4 mM sucralose), and 4) 500 ml normal saline (approximately 300 mosmol/l), all labeled with 150 mg 13C-acetate. Blood glucose increased only in response to sucrose (P<0.05). GLP-1, GIP, and insulin also increased after sucrose (P=0.0001) but not after either load of sucralose or saline. Gastric emptying of sucrose was slower than that of saline (t50: 87.4+/-4.1 min vs. 74.7+/-3.2 min, P<0.005), whereas there were no differences in t50 between sucralose 0.4 mM (73.7+/-3.1 min) or 4 mM (76.7+/-3.1 min) and saline. We conclude that sucralose, delivered by intragastric infusion, does not stimulate insulin, GLP-1, or GIP release or slow gastric emptying in healthy humans.

A Novel C2H2 Transcription Factor that Regulates gliA Expression Interdependently with GliZ in Aspergillus fumigatus

PubMed Central

Schoberle, Taylor J.; Nguyen-Coleman, C. Kim; Herold, Jennifer; Yang, Ally; Weirauch, Matt; Hughes, Timothy R.; McMurray, John S.; May, Gregory S.

2014-01-01

Secondary metabolites are produced by numerous organisms and can either be beneficial, benign, or harmful to humans. Genes involved in the synthesis and transport of these secondary metabolites are frequently found in gene clusters, which are often coordinately regulated, being almost exclusively dependent on transcription factors that are located within the clusters themselves. Gliotoxin, which is produced by a variety of Aspergillus species, Trichoderma species, and Penicillium species, exhibits immunosuppressive properties and has therefore been the subject of research for many laboratories. There have been a few proteins shown to regulate the gliotoxin cluster, most notably GliZ, a Zn2Cys6 binuclear finger transcription factor that lies within the cluster, and LaeA, a putative methyltransferase that globally regulates secondary metabolism clusters within numerous fungal species. Using a high-copy inducer screen in A. fumigatus, our lab has identified a novel C2H2 transcription factor, which plays an important role in regulating the gliotoxin biosynthetic cluster. This transcription factor, named GipA, induces gliotoxin production when present in extra copies. Furthermore, loss of gipA reduces gliotoxin production significantly. Through protein binding microarray and mutagenesis, we have identified a DNA binding site recognized by GipA that is in extremely close proximity to a potential GliZ DNA binding site in the 5′ untranslated region of gliA, which encodes an efflux pump within the gliotoxin cluster. Not surprisingly, GliZ and GipA appear to work in an interdependent fashion to positively control gliA expression. PMID:24784729

Effect of the artificial sweetener, sucralose, on gastric emptying and incretin hormone release in healthy subjects

PubMed Central

Ma, Jing; Bellon, Max; Wishart, Judith M.; Young, Richard; Blackshaw, L. Ashley; Jones, Karen L.; Horowitz, Michael; Rayner, Christopher K.

2009-01-01

The incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), play an important role in glucose homeostasis in both health and diabetes. In mice, sucralose, an artificial sweetener, stimulates GLP-1 release via sweet taste receptors on enteroendocrine cells. We studied blood glucose, plasma levels of insulin, GLP-1, and GIP, and gastric emptying (by a breath test) in 7 healthy humans after intragastric infusions of 1) 50 g sucrose in water to a total volume of 500 ml (∼290 mosmol/l), 2) 80 mg sucralose in 500 ml normal saline (∼300 mosmol/l, 0.4 mM sucralose), 3) 800 mg sucralose in 500 ml normal saline (∼300 mosmol/l, 4 mM sucralose), and 4) 500 ml normal saline (∼300 mosmol/l), all labeled with 150 mg 13C-acetate. Blood glucose increased only in response to sucrose (P < 0.05). GLP-1, GIP, and insulin also increased after sucrose (P = 0.0001) but not after either load of sucralose or saline. Gastric emptying of sucrose was slower than that of saline (t50: 87.4 ± 4.1 min vs. 74.7 ± 3.2 min, P < 0.005), whereas there were no differences in t50 between sucralose 0.4 mM (73.7 ± 3.1 min) or 4 mM (76.7 ± 3.1 min) and saline. We conclude that sucralose, delivered by intragastric infusion, does not stimulate insulin, GLP-1, or GIP release or slow gastric emptying in healthy humans. PMID:19221011

Comparison of effects of ingested medium- and long-chain triglyceride on gallbladder volume and release of cholecystokinin and other gut peptides.

PubMed

Isaacs, P E; Ladas, S; Forgacs, I C; Dowling, R H; Ellam, S V; Adrian, T E; Bloom, S R

1987-05-01

In a double-blind, crossover study of the effect of ingested medium-chain triglyceride (MCT) and long-chain triglyceride (LCT) in six normal subjects, the gallbladder did not contract after ingestion of MCT but instead had significantly increased in volume at 2 hr after the meal. Plasma cholecystokinin (CCK) increased after the MCT meal, but gastrin, motilin, pancreatic polypeptide (PP), and GIP were unaffected. The long-chain triglyceride meal evoked a brisk and sustained gallbladder contraction, higher levels of CCK, and a significant increase in plasma PP and GIP levels.

The Impact of Bariatric Surgery on Type 2 Diabetes Mellitus and the Management of Hypoglycemic Events

PubMed Central

Kassem, Mahmoud Attia Mohamed; Durda, Michael Andrew; Stoicea, Nicoleta; Cavus, Omer; Sahin, Levent; Rogers, Barbara

2017-01-01

Recent studies discussed the benefit of bariatric surgery on obese patients diagnosed with type 2 diabetes mellitus (T2DM). Several factors play an essential role in predicting the impact of bariatric surgery on T2DM, such as ABCD score (age, BMI, C-peptide, and duration of the disease), HbA1c, and fasting blood glucose, incretins [glucagon-like peptide-1 (GLP-1) and gastric inhibitory peptide (GIP)]. DiaRem score known to include factors such as age, HbA1c, medication, and insulin usage used to predict the remission of T2DM, but it has some limitations. An extensive literature search was conducted on PubMed and Google Scholar using keywords such as gastric bypass, T2DM, bariatric surgery, GLP-1, GIP, and post bariatric hypoglycemia. Restrictive-malabsorptive procedures are most effective in treating T2DM patients based on changes induced in appetite through regulation of gastrointestinal hormones, with decreased hunger and increased satiation. We provide a review of bariatric surgery influence on T2DM and management of post-intervention hypoglycemic events. Post-bariatric surgery hypoglycemia is a serious complication especially when patients develop life-threatening neuroglycopenia with loss of consciousness and seizure. The avoidance of this adverse event may be achieved by strict dietary modification including a restriction on carbohydrates as well as foods with high glycemic index. Further research will provide more information on post-bariatric surgery hyperinsulinemic hypoglycemia pathophysiology and management. PMID:28298900

One-step endosonography-guided drainage of a pancreatic pseudocyst: a new technique of stent delivery through the echo endoscope.

PubMed

Vilmann, P; Hancke, S; Pless, T; Schell-Hincke, J D; Henriksen, F W

1998-10-01

We report here the first case of a one-step endosonography(EUS)-guided pseudocyst drainage. A prototype large channel curved array echo endoscope (Pentax FG-38 UX) and a prototype delivery system for placement of an endoprosthesis was used for the procedure. The delivery system (GIP MedicinTechnik GmbH/Medi-Globe Corporation) consists of a handle part with a piston, a metal ring sheath, a plastic catheter with a diathermy needle and a double pigtail endoprosthesis (8.5 Fr). When mounted on the endoscope the endoprosthesis can be advanced out of the distal end of the endoscope. The introduction of the stent as well as the stent release can be monitored entirely by ultrasound. The procedure was tested in a 76-year-old woman with a pseudocyst measuring 60 mm in diameter located in the tail of the pancreas. The procedure was well tolerated by the patient, and there were no procedural complications. The advantage of a large channel echo endoscope and our new prototype delivery system is that the endoprosthesis can be inserted in to a pancreatic cyst guided exclusively by EUS without exchange of endoscopes, catheters or guide wires. Further studies are warranted.

GIP Contributions to the Regulation of Centromere at the Interface Between the Nuclear Envelope and the Nucleoplasm.

PubMed

Chabouté, Marie-Edith; Berr, Alexandre

2016-01-01

Centromeres are known as specific chromatin domains without which eukaryotic cells cannot divide properly during mitosis. Despite the considerable efforts to understand the centromere/kinetochore assembly during mitosis, until recently, comparatively few studies have dealt with the regulation of centromere during interphase. Here, we briefly review and discuss past and recent advances about the architecture of centromeres and their regulation during the cell cycle. Furthermore, we highlight and discuss new findings and hypotheses regarding the specific regulation of centromeres in both plant and animal nuclei, especially with GIP proteins at the interface between the nuclear envelope and the nucleoplasm.

Pancreatic polypeptide, glucagon and insulin secretion from the isolated perfused canine pancreas.

PubMed

Adrian, T E; Bloom, S R; Hermansen, K; Iversen, J

1978-06-01

The release of pancreatic polypeptide (PP) by gut hormones, acetyl choline and adrenaline was investigated in an isolated perfused pancreas preparation. PP was potently released by 1 nmol/1 caerulein (186 +/- 12%, p is less than 0.001) and gastric inhibitory peptide (GIP) (211 +/- 31%, p is less than 0.005) as well as by 1 mumol/1 acetyl choline (1097 +/- 59%, p is less than 0.001). A significant two-fold release of PP was also evoked by 1 nmol/1 vasoactive intestinal peptide (VIP) (129 +/- 38%, p is less than 0.02 and gastrin (108 +/- 25% p is less than 0.01). Insulin release, induced by high glucose concentration was enhanced by both GIP (210 +/- 38%, p is less than (0.01) and VIP (48 +/- 5%, p is less than 0.001). In addition GIP enhanced the release of glucagon by 179 +/- 18% (p is less 0.001) at 1.4 mmol/1 glucose and by 127 +/- 24% (p is less than 0.005) at 8.3 mmol/1 glucose. Thus no simple inter-relationship appears to exist between the control of the three circulating islet hormones.

Responses of python gastrointestinal regulatory peptides to feeding

PubMed Central

Secor, Stephen M.; Fehsenfeld, Drew; Diamond, Jared; Adrian, Thomas E.

2001-01-01

In the Burmese python (Python molurus), the rapid up-regulation of gastrointestinal (GI) function and morphology after feeding, and subsequent down-regulation on completing digestion, are expected to be mediated by GI hormones and neuropeptides. Hence, we examined postfeeding changes in plasma and tissue concentrations of 11 GI hormones and neuropeptides in the python. Circulating levels of cholecystokinin (CCK), glucose-dependent insulinotropic peptide (GIP), glucagon, and neurotensin increase by respective factors of 25-, 6-, 6-, and 3.3-fold within 24 h after feeding. In digesting pythons, the regulatory peptides neurotensin, somatostatin, motilin, and vasoactive intestinal peptide occur largely in the stomach, GIP and glucagon in the pancreas, and CCK and substance P in the small intestine. Tissue concentrations of CCK, GIP, and neurotensin decline with feeding. Tissue distributions and molecular forms (as determined by gel-permeation chromatography) of many python GI peptides are similar or identical to those of their mammalian counterparts. The postfeeding release of GI peptides from tissues, and their concurrent rise in plasma concentrations, suggests that they play a role in regulating python-digestive responses. These large postfeeding responses, and similarities of peptide structure with mammals, make pythons an attractive model for studying GI peptides. PMID:11707600

The incretin effect in healthy individuals and those with type 2 diabetes: physiology, pathophysiology, and response to therapeutic interventions.

PubMed

Nauck, Michael A; Meier, Juris J

2016-06-01

The incretin effect describes the phenomenon whereby oral glucose elicits higher insulin secretory responses than does intravenous glucose, despite inducing similar levels of glycaemia, in healthy individuals. This effect, which is uniformly defective in patients with type 2 diabetes, is mediated by the gut-derived incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). The importance of the incretin effect for the maintenance of glucose homoeostasis is clearly established, and incretin-based therapies are among the most promising new therapies for type 2 diabetes. However, despite the effectiveness of these therapies in many patients, the idea that they restore the incretin effect is a common misconception. In type 2 diabetes, the endocrine pancreas remains responsive to GLP-1 but is no longer responsive to GIP, which is the most likely reason for a reduced or absent incretin effect. Incretin-based drugs, including GLP-1 receptor agonists and dipeptidyl peptidase 4 (DPP-4) inhibitors, stimulate GLP-1 receptors and thus augment insulin secretion in response to both oral and intravenous glucose stimulation, thereby abolishing any potential difference in the responses to these stimuli. These drugs therefore do not restore the defective incretin effect in patients. By contrast, some bariatric surgical procedures enhance GLP-1 responses and also restore the incretin effect in obese individuals with type 2 diabetes. Thus, not all biological actions elicited by the stimulation of GLP-1 receptors lead to quantitative changes to the incretin effect. Copyright © 2016 Elsevier Ltd. All rights reserved.

Decaffeinated coffee improves insulin sensitivity in healthy men.

PubMed

Reis, Caio E G; Paiva, Cicília L R Dos S; Amato, Angélica A; Lofrano-Porto, Adriana; Wassell, Sara; Bluck, Leslie J C; Dórea, José G; da Costa, Teresa H M

2018-05-01

Epidemiological studies have found coffee consumption is associated with a lower risk for type 2 diabetes mellitus, but the underlying mechanisms remain unclear. Thus, the aim of this randomised, cross-over single-blind study was to investigate the effects of regular coffee, regular coffee with sugar and decaffeinated coffee consumption on glucose metabolism and incretin hormones. Seventeen healthy men participated in five trials each, during which they consumed coffee (decaffeinated, regular (containing caffeine) or regular with sugar) or water (with or without sugar). After 1 h of each intervention, they received an oral glucose tolerance test with one intravenous dose of [1-13C]glucose. The Oral Dose Intravenous Label Experiment was applied and glucose and insulin levels were interpreted using a stable isotope two-compartment minimal model. A mixed-model procedure (PROC MIXED), with subject as random effect and time as repeated measure, was used to compare the effects of the beverages on glucose metabolism and incretin parameters (glucose-dependent insulinotropic peptide (GIP)) and glucagon-like peptide-1 (GLP-1)). Insulin sensitivity was higher with decaffeinated coffee than with water (P<0·05). Regular coffee with sugar did not significantly affect glucose, insulin, C-peptide and incretin hormones, compared with water with sugar. Glucose, insulin, C-peptide, GLP-1 and GIP levels were not statistically different after regular and decaffeinated coffee compared with water. Our findings demonstrated that the consumption of decaffeinated coffee improves insulin sensitivity without changing incretin hormones levels. There was no short-term adverse effect on glucose homoeostasis, after an oral glucose challenge, attributable to the consumption of regular coffee with sugar.

Benefits and challenges of a QSP approach through case study: Evaluation of a hypothetical GLP-1/GIP dual agonist therapy.

PubMed

Rieger, Theodore R; Musante, Cynthia J

2016-10-30

Quantitative Systems Pharmacology (QSP) is an emerging science with increasing application to pharmaceutical research and development paradigms. Through case study we provide an overview of the benefits and challenges of applying QSP approaches to inform program decisions in the early stages of drug discovery and development. Specifically, we describe the use of a type 2 diabetes systems model to inform a No-Go decision prior to lead development for a potential GLP-1/GIP dual agonist program, enabling prioritization of exploratory programs with higher probability of clinical success. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Glucometabolic hormones and cardiovascular risk markers in antipsychotic-treated patients.

PubMed

Ebdrup, Bjørn H; Knop, Filip K; Madsen, Anna; Mortensen, Henrik B; Søgaard, Birgitte; Holst, Jens J; Szecsi, Pal B; Lublin, Henrik

2014-09-01

Treatment with antipsychotic drugs is widely associated with metabolic side effects such as weight gain and disturbed glucose metabolism, but the pathophysiologic mechanisms are unclear. Fifty nondiabetic (fasting plasma glucose ≤ 7.0 mmol/L), antipsychotic-treated male patients (ICD-10 diagnosis code F20, F21, F22, F25, F28, or F60; mean ± SD age = 33.0 ± 6.7 years; body mass index [BMI; kg/m²] = 26.0 ± 4.7; waist circumference = 95.9 ± 13.3 cm; glycated hemoglobin A1c [HbA1c] = 5.7% ± 0.3%) and 93 age- and waist circumference-matched healthy male controls (age = 33 ± 7.3 years; BMI = 26.1 ± 3.9; waist circumference = 94.6 ± 11.9 cm; HbA1c = 5.7% ± 0.3%) participated in this cross-sectional study. Blood was sampled in the fasting state and 90 minutes after ingestion of a standardized liquid meal (2,268 kJ). The primary outcomes were glucometabolic hormones and cardiovascular risk markers. Data were collected between March 2008 and February 2010. Compared to healthy controls, patients were characterized by elevated fasting levels of proinsulin, C-peptide, and glucose-dependent insulinotropic polypeptide (GIP) (P < .05) and higher postprandial levels of insulin, proinsulin, C-peptide, and GIP (P ≤ .02). Also, patients exhibited elevated plasma levels of C-reactive protein and signs of dyslipidemia. Fasting plasma levels of insulin, glucagon, glucagon-like peptide-1 (GLP-1), ghrelin, leptin, adiponectin, tumor necrosis factor-α, plasminogen activator inhibitor-1, and interleukin-6 and postprandial levels of glucagon, GLP-1, ghrelin, leptin, and adiponectin did not differ between groups. Presenting with an insulin resistant-like pattern, including beta cell hypersecretion and elevated GIP levels, nondiabetic antipsychotic-treated patients display emerging signs of dysmetabolism and a compromised cardiovascular risk profile. The appetite-regulating hormones GLP-1 and ghrelin appear not to be influenced by antipsychotic treatment. Our findings provide new clinical insight into the pathophysiology associated with metabolic side effects of antipsychotic treatment and put emphasis on the importance of implementing metabolic screening into psychiatric practice. ClinicalTrials.gov identifier NCT00627757. © Copyright 2014 Physicians Postgraduate Press, Inc.

The incretin effect and secretion in obese and lean women with polycystic ovary syndrome: a pilot study.

PubMed

Pontikis, Charalambos; Yavropoulou, Maria P; Toulis, Konstantinos A; Kotsa, Kalliopi; Kazakos, Kyriakos; Papazisi, Aleka; Gotzamani-Psarakou, Anna; Yovos, John G

2011-06-01

Insulin resistance is considered to play an important role in the pathogenesis of polycystic ovary syndrome (PCOS) and in the progression to type 2 diabetes. Recent reports concentrate on a possible relationship between incretin secretion and beta-cell function in PCOS. The aim of the present study is to investigate the incretin effect in obese and lean women with PCOS. Twenty women with PCOS and ten age-matched healthy women were recruited in the study. The oral glucose tolerance test (OGTT) and isoglycemic test were carried out on each participant after an overnight fast at 2-weeks interval. Plasma levels of insulin, glucose, C-peptide, glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1) were assayed. Obese women with PCOS demonstrated lower GIP concentrations (area under the curve [AUC]) in response to OGTT compared to the control group. The incretin effect was found significantly augmented in the obese women with PCOS compared to controls. This finding remained robust in the subgroup analysis including only body mass index (BMI)-matched healthy women. Increased insulinotropic effect could counteract the blunted GIP response to OGTT in obese women with PCOS. It is suggested that the pathology of PCOS may also include impaired activity of the enteroinsular axis.

A novel GIP analogue, ZP4165, enhances glucagon-like peptide-1-induced body weight loss and improves glycaemic control in rodents.

PubMed

Nørregaard, Pia K; Deryabina, Maria A; Tofteng Shelton, Pernille; Fog, Jacob U; Daugaard, Jens R; Eriksson, Per-Olof; Larsen, Lone F; Jessen, Lene

2018-01-01

To investigate the effects of the novel glucose-dependent insulinotropic polypeptide (GIP) analogue, ZP4165, on body weight and glycaemic control in rodents, and to investigate if ZP4165 modulates the anti-obesity and anti-hyperglycaemic effects of a glucagon-like peptide-1 (GLP-1) agonist (liraglutide). The acute insulinotropic effect of ZP4165 was investigated in rats during an oral glucose tolerance test. The long-term effects of ZP4165 on body weight and glycaemic control, either alone or in combination with liraglutide, were assessed in diet-induced obese mice and diabetic db/db mice. ZP4165 showed insulinotropic action in rats. The GIP analogue did not alter the body weight of obese mice but enhanced GLP-1-induced weight loss. In diabetic mice, 4 weeks' dosing with ZP4165 reduced glycated haemoglobin levels vs vehicle by an extent similar to the GLP-1 agonist. ZP4165 potentiated the anti-obesity effect of a GLP-1 agonist in obese mice and improved glycaemic control in diabetic mice. These studies support further investigation of dual-incretin therapy as a more effective treatment option than mono GLP-1 medication for type 2 diabetes mellitus and obesity. © 2017 John Wiley & Sons Ltd.

Older Subjects with β-cell Dysfunction have an Accentuated Incretin Release.

PubMed

Garduno-Garcia, José de Jesús; Gastaldelli, Amalia; DeFronzo, Ralph A; Lertwattanarak, Raweewan; Holst, Jens J; Musi, Nicolas

2018-04-16

Insulin secretion declines with age and this contributes to the increased risk of developing impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM) in older subjects. Insulin secretion is regulated by the incretin hormones glucagon-like peptide (GLP) 1 and glucose-dependent insulinotropic peptide (GIP). Here we tested the hypotheses that incretin release is reduced in older subjects, and that this decline is associated with β-cell dysfunction. 40 young (25±3 y) and 53 older (74±7 y) lean non-diabetic subjects underwent a 2 h oral glucose tolerance test (OGTT). Based on the OGTT, subjects were divided in 3 groups: young normal glucose tolerant (Y-NGT, n=40), older with NGT (O-NGT, n=32), and older with IGT (O-IGT, n=21). Plasma insulin, C-peptide, GLP-1, and GIP concentrations were measured every 15-30 min. We quantitated insulin sensitivity (Matsuda index) and insulin secretory rate (ISR) by deconvolution of C-peptide with the calculation of β-cell glucose sensitivity. Matsuda index, early phase ISR (0-30min) and parameters of β-cell function were reduced in O-IGT vs. Y-NGT, but not in O-NGT. GLP-1 concentrations were elevated in both older groups [GLP-1_AUC0-120 was 2.8±0.1 in Y-NGT, 3.8±0.5 in O-NGT, and 3.7±0.4 nmol/l∙120 min in O-IGT (P<0.05)] while GIP secretion was elevated in O-NGT vs. Y-NGT [GIP_AUC0-120 was 4.7±0.3 in Y-NGT, 6.0±0.4 in O-NGT, and 4.8±0.3 nmol/l∙120 min in O-IGT (P<0.05)]. Aging is associated with an exaggerated GLP-1 secretory response. However, this was not sufficient to increase insulin first phase release in O-IGT and overcome insulin resistance.

Early Serum Gut Hormone Concentrations Associated with Time to Full Enteral Feedings in Preterm Infants.

PubMed

Shanahan, Kristen H; Yu, Xinting; Miller, Laura G; Freedman, Steven D; Martin, Camilia R

2018-04-03

The primary objective of this study was to evaluate early postnatal serum gut hormone concentrations in preterm infants as predictors of time to full enteral feedings. The secondary objective was to identify infant characteristics and nutritional factors that modulate serum gut hormone concentrations and time to full enteral feedings. Sixty-four preterm infants less than 30 weeks of gestation were included in this retrospective cohort study. Serum gut hormone concentrations at postnatal days 0 and 7 were measured using enzyme-linked immunosorbent assays. Linear regression and mediation analyses were performed. Median (IQR) serum concentrations of glucose-dependent insulinotropic peptide (GIP) and peptide YY (PYY) on postnatal day 7 were 31.3 pg/mL (18.2, 52.3) and 1181.7 pg/mL (859.0, 1650.2), respectively. GIP and PYY concentrations on day 7 were associated with days to full enteral feedings after adjustment for confounders (β = -1.1, p = 0.03; and β = -0.002, p = 0.02, respectively). Nutritional intake was correlated with serum concentrations of GIP and PYY on postnatal day 7 and time to full enteral feedings. Mediation analysis revealed that the effect of serum gut hormone concentrations on time to full enteral feedings was not fully explained by nutritional intake. Intrauterine growth restriction (IUGR), mechanical ventilation on postnatal day 7, and patent ductus arteriosus (PDA) treated with indomethacin were associated with longer time to full enteral feedings. Serum concentrations of GIP and PYY on postnatal 7 are independently associated with time to full enteral feedings. The link between serum gut hormone concentrations and time to full enteral feedings is not fully mediated by nutritional factors, suggesting an independent mechanism underlying the influence of gut hormones on feeding tolerance and time to full enteral feedings.

Postprandial plasma incretin hormones in exercise-trained versus untrained subjects.

PubMed

Weiss, Edward P; Royer, Nathaniel K; Fisher, Jonathan S; Holloszy, John O; Fontana, Luigi

2014-06-01

After food ingestion, the incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), are secreted by the intestines into circulation where they act on the pancreas to promote insulin secretion. We evaluated the hypothesis that low postprandial plasma insulin levels in lean exercise-trained individuals are associated with low concentrations of incretin hormones. A cross-sectional study was performed to compare postprandial incretin hormone levels in lean endurance exercise-trained individuals (EX; n = 14, ≥40 yr) and age- and sex-matched, nonobese, sedentary control subjects (CON, n = 14). The main outcome measures were GLP-1, GIP, insulin, and glucose incremental areas under the curve (AUC) as measured in plasma samples collected during a 2-h,75-g oral glucose tolerance test (OGTT). The EX group had lower body fat percentage (14.6% ± 1.1% vs 23.3% ± 1.7%, P = 0.0002) and higher maximal oxygen uptake (53 ± 2 vs 34 ± 2, P < 0.0001) than CON. Glucose AUC did not differ between groups (P = 0.20). Insulin AUC was lower in EX (2.5 ± 0.5 vs 4.2 ± 1.2 μU·mL·1000 min, P = 0.02). No differences were observed between groups (EX and CON, respectively) for GLP-1 AUC (3.5 ± 0.7 vs 4.1 ± 1.1 pmol·min·100 L, P = 0.61) or GIP AUC (19.2 ± 1.4 vs 18.0 ± 1.4 pg·min·1000 mL; P = 0.56). In CON, insulin AUC was correlated with AUC for GLP-1 (r = 0.53, P = 0.05) and GIP (r = 0.71, P = 0.004), but no such correlations were observed in EX (both P ≥ 0.67). Low postprandial insulin levels in lean exercise-trained individuals are not attributable to lower incretin hormone concentrations. However, exercise may decrease the dependency of postprandial insulin levels on incretin hormones.

A novel dual GLP-1 and GIP receptor agonist is neuroprotective in the MPTP mouse model of Parkinson's disease by increasing expression of BNDF.

PubMed

Ji, Chenhui; Xue, Guo-Fang; Lijun, Cao; Feng, Peng; Li, Dongfang; Li, Lin; Li, Guanglai; Hölscher, Christian

2016-03-01

The incretins glucagon-like peptide 1 (GLP-1) and glucose dependent insulinotropic polypeptide (GIP) are growth factors with neuroprotective properties. GLP-1 mimetics are on the market as treatments for type 2 diabetes and are well tolerated. Both GLP-1 and GIP mimetics have shown neuroprotective properties in animal models of Parkinson's and Alzheimer's disease. In addition, the GLP-1 mimetic exendin-4 has shown protective effects in a clinical trial in Parkinson's disease (PD) patients. Novel GLP-1/GIP dual-agonist peptides have been developed and are tested in diabetic patients. Here we demonstrate the neuroprotective effects of a novel dual agonist (DA-JC1) in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. MPTP was injected once-daily (20 mg/kg i.p.) for 7 days, and the dual agonist was injected 30 min later i.p. (50 nmol/kg bw). The PI3k inhibitor LY294002 (0.6 mg/kg i.v.) was co-injected in one group. DA-JC1 reduced or reversed most of the MPTP induced motor impairments in the rotarod and in a muscle strength test. The number of tyrosine hydroxylase (TH) positive neurons in the substantia nigra (SN) was reduced by MPTP and increased by DA-JC1. The ratio of anti-inflammatory Bcl-2 to pro-inflammatory BAX as well as the activation of the growth factor kinase Akt was reduced by MPTP and reversed by DA-JC1. The PI3k inhibitor had only limited effect on the DA-JC1 drug effect. Importantly, levels of the neuroprotective brain derived neurotropic factor (BDNF) were reduced by MPTP and enhanced by DA-JC1. The results demonstrate that DA-JC1 shows promise as a novel treatment for PD. Copyright © 2016. Published by Elsevier B.V.

A novel GLP-1/GIP dual agonist is more effective than liraglutide in reducing inflammation and enhancing GDNF release in the MPTP mouse model of Parkinson's disease.

PubMed

Yuan, Ziyue; Li, Dongfang; Feng, Peng; Xue, Guofang; Ji, Chenhui; Li, Guanglai; Hölscher, Christian

2017-10-05

Type 2 diabetes mellitus (T2DM) is one of the risk factors for Parkinson's disease (PD). Insulin desensitisation has been observed in the brains of patients, which may promote neurodegeneration. Incretins are a family of growth factors that can re-sensitise insulin signalling. We have previously shown that mimetics of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) have neuroprotective effects in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropypridine (MPTP) mouse model of PD. Recently, dual GLP-1/GIP receptor agonists have been developed. We therefore tested the novel dual agonist DA3-CH in comparison with the best GLP-1 analogue currently on the market, liraglutide (both drugs 25nmol/kg ip once-daily for 7 days) in the MPTP mouse model of PD (25mg/kg ip once-daily for 7 days). In the Rotarod and grip strength assessment, DA3-CH was superior to liraglutide in reversing the MPTP-induced motor impairment. Dopamine synthesis as indicated by levels of tyrosine hydroxylase was much reduced by MPTP in the substantia nigra and striatum, and DA3-CH reversed this while liragutide only partially reversed this. The chronic inflammation response as shown in increased levels of activated microglia and astrocytes was reduced by both drugs. Importantly, expression levels of the neuroprotective growth factor Glial Derived Neurotrophic Factor (GDNF) was much enhanced by both DA3-CH and liragutide. The results demonstrate that the combination of GLP-1 and GIP receptor activation is superior to single GLP-1 receptor activation alone. Therefore, new dual agonists may be a promising treatment for PD. The GLP-1 receptor agonist exendin-4 has already shown disease modifying effects in clinical trials in PD patients. Copyright © 2017 Elsevier B.V. All rights reserved.

Effect of dietary macronutrients on postprandial incretin hormone release and satiety in obese and normal-weight women.

PubMed

Wikarek, Tomasz; Chudek, Jerzy; Owczarek, Aleksander; Olszanecka-Glinianowicz, Magdalena

2014-01-28

The aim of the present study was to assess the effect of dietary macronutrients on postprandial incretin responses and satiety and hunger sensation in obese and normal-weight women. A total of eleven obese and nine normal-weight women were recruited for the assessment of plasma concentrations of glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and insulin and the sensation of satiety and hunger using a visual analogue scale before and during a 6 h period after administration of three different macronutrient test meals. The AUCtotal GLP-1 and AUCtotal GIP values were decreased in obese women after the consumption of a fatty meal and all the test meals, respectively. However, the AUCtotal insulin value after a carbohydrate meal was greater in the obese group. The AUCtotal satiety value was decreased only after the intake of the protein meal in obese women when compared with normal-weight women. After the consumption of the fatty meal, a significant positive correlation between maximum satiety sensation and the AUCtotal GLP-1 value in the obese group and that between minimum hunger sensation and the AUCtotal GLP-1 value in the normal-weight group were observed. In conclusion, the findings of the present study suggest that: (1) satiety sensation after consumption of carbohydrate and protein meals in the obese group is related to the postprandial insulin response, while after consumption of a fatty meal, it is related to the postprandial GLP-1 release; (2) the postprandial GIP response does not influence the sensation of satiety and hunger; (3) the reduced GLP-1 release after the intake of a fatty meal in obese individuals may explain impaired satiety sensation; (4) the impaired postprandial GIP response is not related to the consumption of macronutrients and may be the early indicator of incretin axis dysfunction in obese women.

Incretin and islet hormone responses to meals of increasing size in healthy subjects.

PubMed

Alsalim, Wathik; Omar, Bilal; Pacini, Giovanni; Bizzotto, Roberto; Mari, Andrea; Ahrén, Bo

2015-02-01

Postprandial glucose homeostasis is regulated through the secretion of glucagon-like peptide 1 (GLP-1) through the stimulation of insulin secretion and inhibition of glucagon secretion. However, how these processes dynamically adapt to demands created by caloric challenges achieved during daily life is not known. The objective of the study was to explore the adaptation of incretin and islet hormones after mixed meals of increasing size in healthy subjects. Twenty-four healthy lean subjects ingested a standard breakfast after an overnight fast followed, after 4 hours, by a lunch of a different size (511, 743, and 1034 kcal) but with identical nutrient composition together with 1.5 g paracetamol. Glucose, insulin, C-peptide, glucagon, intact GLP-1, and glucose-dependent insulinotropic polypeptide (GIP) and paracetamol were measured after the meals. Area under the 180-minute curve (AUC) for insulin, C-peptide, glucagon, GLP-1, and GIP and model-derived β-cell function and paracetamol appearance were calculated. Glucose profiles were similar after the two larger meals, whereas after the smaller meal, there was a postpeak reduction below baseline to a nadir of 3.8 ± 0.1 mmol/L after 75 minutes (P < .001). The AUC for GLP-1, GIP, insulin, and C-peptide were significantly higher by increasing the caloric load as was β-cell sensitivity to glucose. In contrast, the AUC glucagon was the same for all three meals, although there was an increase in glucagon after the postpeak glucose reduction in the smaller meal. The 0- to 20-minute paracetamol appearance was increased by increasing meal size. Mixed lunch meals of increasing size elicit a caloric-dependent insulin response due to increased β-cell secretion achieved by increased GIP and GLP-1 levels. The adaptation at larger meals results in identical glucose excursions, whereas after a lower caloric lunch, the insulin response is high, resulting in a postpeak suppression of glucose below baseline.

Receptors and effects of gut hormones in three osteoblastic cell lines.

PubMed

Pacheco-Pantoja, Elda L; Ranganath, Lakshminarayan R; Gallagher, James A; Wilson, Peter J M; Fraser, William D

2011-07-29

In recent years the interest on the relationship of gut hormones to bone processes has increased and represents one of the most interesting aspects in skeletal research. The proportion of bone mass to soft tissue is a relationship that seems to be controlled by delicate and subtle regulations that imply "cross-talks" between the nutrient intake and tissues like fat. Thus, recognition of the mechanisms that integrate a gastrointestinal-fat-bone axis and its application to several aspects of human health is vital for improving treatments related to bone diseases. This work analysed the effects of gut hormones in cell cultures of three osteoblastic cell lines which represent different stages in osteoblastic development. Also, this is the first time that there is a report on the direct effects of glucagon-like peptide 2, and obestatin on osteoblast-like cells. mRNA expression levels of five gut hormone receptors (glucose-dependent insulinotropic peptide [GIP], glucagon-like peptide 1 [GLP-1], glucagon-like peptide 2 [GLP-2], ghrelin [GHR] and obestatin [OB]) were analysed in three osteoblastic cell lines (Saos-2, TE-85 and MG-63) showing different stages of osteoblast development using reverse transcription and real time polymerase chain reaction. The responses to the gut peptides were studied using assays for cell viability, and biochemical bone markers: alkaline phosphatase (ALP), procollagen type 1 amino-terminal propeptides (P1NP), and osteocalcin production. The gut hormone receptor mRNA displayed the highest levels for GIP in Saos-2 and the lowest levels in MG-63, whereas GHR and GPR39 (the putative obestatin receptor) expression was higher in TE-85 and MG-63 and lower in Saos-2. GLP-1 and GLP-2 were expressed only in MG-63 and TE-85. Treatment of gut hormones to cell lines showed differential responses: higher levels in cell viability in Saos-2 after GIP, in TE-85 and MG-63 after GLP-1, GLP-2, ghrelin and obestatin. ALP showed higher levels in Saos-2 after GIP, GHR and OB and in TE-85 after GHR. P1NP showed higher levels after GIP and OB in Saos-2. Decreased levels of P1NP were observed in TE-85 and MG-63 after GLP-1, GLP-2 and OB. MG-63 showed opposite responses in osteocalcin levels after GLP-2. These results suggest that osteoblast activity modulation varies according to different development stage under different nutrition related-peptides.

Chronic Consumption of Sweeteners and Its Effect on Glycaemia, Cytokines, Hormones, and Lymphocytes of GALT in CD1 Mice

PubMed Central

Ramírez-Durán, Ninfa

2018-01-01

Background The consumption of sweeteners has increased in recent years, being used to control body weight and blood glucose. However, they can cause increased appetite, modification of immune function, and secretion of hormones in the GALT. Objective To assess the effect of chronic sweetener consumption on glycaemia, cytokines, hormones, and GALT lymphocytes in CD1 mice. Material and Methods 72 CD1 mice divided into 3 groups were used: (a) baseline, (b) middle, and (c) final. Groups (b) and (c) were divided into 4 subgroups: (i) Control, (ii) Sucrose, (iii) Sucralose, and (iv) Stevia. The following were determined: body weight, hormones (GIP, insulin, and leptin), lymphocytes CD3+T cells and CD19+B cells, IgA+ plasma cells, and cytokines (IL-4, IL-5, IFN-γ, and TNF-α). Results Sucralose reduces secretion of GIP and glycaemia but does not modify insulin concentration, increases body weight, and reduces food intake. Stevia increases the secretion of GIP, insulin, leptin, body weight, and glycaemia but keeps food consumption normal. Sucralose and Stevia showed a higher percentage of CD3+T cells, CD19+B cells, and IgA+ plasma cells in Peyer's patches, but only Stevia in lamina propria. Conclusion Sweeteners modulate the hormonal response of cytokines and the proliferation of lymphocytes in the intestinal mucosa. PMID:29854725

The Acute Effects of Simple Sugar Ingestion on Appetite, Gut-Derived Hormone Response, and Metabolic Markers in Men

PubMed Central

Yau, Adora M. W.; McLaughlin, John; Gilmore, William; Maughan, Ronald J.; Evans, Gethin H.

2017-01-01

This pilot study aimed to investigate the effect of simple sugar ingestion, in amounts typical of common ingestion, on appetite and the gut-derived hormone response. Seven healthy men ingested water (W) and equicaloric solutions containing 39.6 g glucose monohydrate (G), 36 g fructose (F), 36 g sucrose (S), and 19.8 g glucose monohydrate + 18 g fructose (C), in a randomised order. Serum concentrations of ghrelin, glucose dependent insulinotropic polypeptide (GIP), glucagon like peptide-1 (GLP-1), insulin, lactate, triglycerides, non-esterified fatty acids (NEFA), and d-3 hydroxybutyrate, were measured for 60 min. Appetite was measured using visual analogue scales (VAS). The ingestion of F and S resulted in a lower GIP incremental area under the curve (iAUC) compared to the ingestion of G (p < 0.05). No differences in the iAUC for GLP-1 or ghrelin were present between the trials, nor for insulin between the sugars. No differences in appetite ratings or hepatic metabolism measures were found, except for lactate, which was greater following the ingestion of F, S, and C, when compared to W and G (p < 0.05). The acute ingestion of typical amounts of fructose, in a variety of forms, results in marked differences in circulating GIP and lactate concentration, but no differences in appetite ratings, triglyceride concentration, indicative lipolysis, or NEFA metabolism, when compared to glucose. PMID:28216550

The effect of meal frequency in a reduced-energy regimen on the gastrointestinal and appetite hormones in patients with type 2 diabetes: A randomised crossover study

PubMed Central

Belinova, Lenka; Kahleova, Hana; Oliyarnyk, Olena; Kazdova, Ludmila; Hill, Martin; Pelikanova, Terezie

2017-01-01

Background Appetite and gastrointestinal hormones (GIHs) participate in energy homeostasis, feeding behavior and regulation of body weight. We demonstrated previously the superior effect of a hypocaloric diet regimen with lower meal frequency (B2) on body weight, hepatic fat content, insulin sensitivity and feelings of hunger compared to the same diet divided into six smaller meals a day (A6). Studies with isoenergetic diet regimens indicate that lower meal frequency should also have an effect on fasting and postprandial responses of GIHs. The aim of this secondary analysis was to explore the effect of two hypocaloric diet regimens on fasting levels of appetite and GIHs and on their postprandial responses after a standard meal. It was hypothesized that lower meal frequency in a reduced-energy regimen leading to greater body weight reduction and reduced hunger would be associated with decreased plasma concentrations of GIHs: gastric inhibitory peptide (GIP), glucagon-like peptide-1(GLP-1), peptide YY(PYY), pancreatic polypeptide (PP) and leptin and increased plasma concentration of ghrelin. The postprandial response of satiety hormones (GLP-1, PYY and PP) and postprandial suppression of ghrelin will be improved. Methods In a randomized crossover study, 54 patients suffering from type 2 diabetes (T2D) underwent both regimens. The concentrations of GLP-1, GIP, PP, PYY, amylin, leptin and ghrelin were determined using multiplex immunoanalyses. Results Fasting leptin and GIP decreased in response to both regimens with no difference between the treatments (p = 0.37 and p = 0.83, respectively). Fasting ghrelin decreased in A6 and increased in B2 (with difference between regimens p = 0.023). Fasting PP increased in B2with no significant difference between regimens (p = 0.17). Neither GLP-1 nor PYY did change in either regimen. The decrease in body weight correlated negatively with changes in fasting ghrelin (r = -0.4, p<0.043) and the postprandial reduction of ghrelin correlated positively with its fasting level (r = 0.9, p<0.001). The postprandial responses of GIHs and appetite hormones were similar after both diet regimens. Conclusions Both hypocaloric diet regimens reduced fasting leptin and GIP and postprandial response of GIP comparably. The postprandial responses of GIHs and appetite hormones were similar after both diet regimens. Eating only breakfast and lunch increased fasting plasma ghrelin more than the same caloric restriction split into six meals. The changes in fasting ghrelin correlated negatively with the decrease in body weight. These results suggest that for type 2 diabetic patients on a hypocaloric diet, eating larger breakfast and lunch may be more efficient than six smaller meals during the day. PMID:28369078

Gas in Place Resource Assessment for Concentrated Hydrate Deposits in the Kumano Forearc Basin, Offshore Japan, from NanTroSEIZE and 3D Seismic Data

NASA Astrophysics Data System (ADS)

Taladay, K.; Boston, B.

2015-12-01

Natural gas hydrates (NGHs) are crystalline inclusion compounds that form within the pore spaces of marine sediments along continental margins worldwide. It has been proposed that these NGH deposits are the largest dynamic reservoir of organic carbon on this planet, yet global estimates for the amount of gas in place (GIP) range across several orders of magnitude. Thus there is a tremendous need for climate scientists and countries seeking energy security to better constrain the amount of GIP locked up in NGHs through the development of rigorous exploration strategies and standardized reservoir characterization methods. This research utilizes NanTroSEIZE drilling data from International Ocean Drilling Program (IODP) Sites C0002 and C0009 to constrain 3D seismic interpretations of the gas hydrate petroleum system in the Kumano Forearc Basin. We investigate the gas source, fluid migration mechanisms and pathways, and the 3D distribution of prospective HCZs. There is empirical and interpretive evidence that deeply sourced fluids charge concentrated NGH deposits just above the base of gas hydrate stability (BGHS) appearing in the seismic data as continuous bottoms simulating reflections (BSRs). These HCZs cover an area of 11 by 18 km, range in thickness between 10 - 80 m with an average thickness of 40 m, and are analogous to the confirmed HCZs at Daini Atsumi Knoll in the eastern Nankai Trough where the first offshore NGH production trial was conducted in 2013. For consistency, we calculated a volumetric GIP estimate using the same method employed by Japan Oil, Gas and Metals National Corporation (JOGMEC) to estimate GIP in the eastern Nankai Trough. Double BSRs are also common throughout the basin, and BGHS modeling along with drilling indicators for gas hydrates beneath the primary BSRs provides compelling evidence that the double BSRs reflect a BGHS for structure-II methane-ethane hydrates beneath a structure-I methane hydrate phase boundary. Additional drilling data would be needed to confirm the validity of this assessment, but the implications are that stacked NGH deposits could be common and unaccounted for in NGH reserve estimates.

Degradation and Stabilization of Peptide Hormones in Human Blood Specimens

PubMed Central

Yi, Jizu; Warunek, David; Craft, David

2015-01-01

Plasma hormone peptides, including GLP-1, GIP, Glucagon, and OXM, possess multiple physiological roles and potential therapeutic and diagnostic utility as biomarkers in the research of metabolic disorders. These peptides are subject to proteolytic degradation causing preanalytical variations. Stabilization for accurate quantitation of these active peptides in ex vivo blood specimens is essential for drug and biomarker development. We investigated the protease-driven instability of these peptides in conventional serum, plasma, anticoagulated whole blood, as well as whole blood and plasma stabilized with protease inhibitors. The peptide was monitored by both time-course Matrix-Assisted Laser Desorption Ionization Time-to-Flight Mass Spectrometry (MALDI –TOF MS) and Ab-based assay (ELISA or RIA). MS enabled the identification of proteolytic fragments. In non-stabilized blood samples, the results clearly indicated that dipeptidyl peptidase-IV (DPP-IV) removed the N-terminal two amino acid residues from GLP-1, GIP and OXM(1-37) and not-yet identified peptidase(s) cleave(s) the full-length OXM(1-37) and its fragments. DPP-IV also continued to remove two additional N-terminal residues of processed OXM(3–37) to yield OXM(5–37). Importantly, both DPP-IV and other peptidase(s) activities were inhibited efficiently by the protease inhibitors included in the BD P800* tube. There was preservation of GLP-1, GIP, OXM and glucagon in the P800 plasma samples with half-lives > 96, 96, 72, and 45 hours at room temperature (RT), respectively. In the BD P700* plasma samples, the stabilization of GLP-1 was also achieved with half-life > 96 hours at RT. The stabilization of these variable peptides increased their utility in drug and/or biomarker development. While stability results of GLP-1 obtained with Ab-based assay were consistent with those obtained by MS analysis, the Ab-based results of GIP, Glucagon, and OXM did not reflect the time-dependent degradations revealed by MS analysis. Therefore, we recommended characterizing the degradation of the peptide using the MS-based method when investigating the stability of a specific peptide. PMID:26222180

[Nicorandil improves cognitive dysfunction in mice with streptozotocin-induced diabetes].

PubMed

Yan, Wen-Hui; Zhang, Chun-Xi; Xing, Tong; Gong, Xue; Yang, Yu-Xuan; Li, Yi-Nuo; Liu, Xuan; Ayijiang, Jiamaliding; Yu, Ye; Zhang, Meng; Chen, Li-Na

2018-04-20

To observe the protective effects of potassium channel opener nicorandil against cognitive dysfunction in mice with streptozotocin (STZ)-induced diabetes. C57BL/6J mouse models of type 1 diabetes mellitus (T1DM) were established by intraperitoneal injection of STZ and received daily treatment with intragastric administration of nicorandil or saline (model group) for 4 consecutive weeks, with normal C57BL/6J mice serving as control. Fasting blood glucose level was recorded every week and Morris water maze was used to evaluate the cognitive behavior of the mice in the 4th week. At the end of the experiment, the mice were sacrificed to observe the ultrastructural changes in the hippocampus and pancreas under transmission electron microscopy; the contents of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) in the hippocampus and SOD activity and MDA level in the brain tissue were determined. Compared with the control group, the model group showed significantly increased fasting blood glucose (P<0.001), significantly prolonged escape latency (P<0.05) and increased swimming distance (P<0.01) with ultrastructural damage of pancreatic β cells and in the hippocampus; GIP and GLP-1 contents in the hippocampus (P<0.01) and SOD activity in the brain were significantly decreased (P<0.05) and MDA content was significantly increased in the model group (P<0.05). Compared with the model group, nicorandil treatment did not cause significant changes in fasting blood glucose, but significantly reduced the swimming distance (P<0.05); nicorandil did not improve the ultrastructural changes in pancreatic β cells but obviously improved the ultrastructures of hippocampal neurons and synapses. Nicorandil also significantly increased the contents of GIP and GLP-1 in the hippocampus (P<0.05), enhanced SOD activity (P<0.05) and decreased MDA level (P<0.01) in the brain tissue. Nicorandil improves cognitive dysfunction in mice with STZ-induced diabetes by increasing GIP and GLP-1 contents in the hippocampus and promoting antioxidation to relieve hippocampal injury.

LX4211 increases serum glucagon-like peptide 1 and peptide YY levels by reducing sodium/glucose cotransporter 1 (SGLT1)-mediated absorption of intestinal glucose.

PubMed

Powell, David R; Smith, Melinda; Greer, Jennifer; Harris, Angela; Zhao, Sharon; DaCosta, Christopher; Mseeh, Faika; Shadoan, Melanie K; Sands, Arthur; Zambrowicz, Brian; Ding, Zhi-Ming

2013-05-01

LX4211 [(2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(methylthio)tetrahydro-2H-pyran-3,4,5-triol], a dual sodium/glucose cotransporter 1 (SGLT1) and SGLT2 inhibitor, is thought to decrease both renal glucose reabsorption by inhibiting SGLT2 and intestinal glucose absorption by inhibiting SGLT1. In clinical trials in patients with type 2 diabetes mellitus (T2DM), LX4211 treatment improved glycemic control while increasing circulating levels of glucagon-like peptide 1 (GLP-1) and peptide YY (PYY). To better understand how LX4211 increases GLP-1 and PYY levels, we challenged SGLT1 knockout (-/-) mice, SGLT2-/- mice, and LX4211-treated mice with oral glucose. LX4211-treated mice and SGLT1-/- mice had increased levels of plasma GLP-1, plasma PYY, and intestinal glucose during the 6 hours after a glucose-containing meal, as reflected by area under the curve (AUC) values, whereas SGLT2-/- mice showed no response. LX4211-treated mice and SGLT1-/- mice also had increased GLP-1 AUC values, decreased glucose-dependent insulinotropic polypeptide (GIP) AUC values, and decreased blood glucose excursions during the 6 hours after a challenge with oral glucose alone. However, GLP-1 and GIP levels were not increased in LX4211-treated mice and were decreased in SGLT1-/- mice, 5 minutes after oral glucose, consistent with studies linking decreased intestinal SGLT1 activity with reduced GLP-1 and GIP levels 5 minutes after oral glucose. These data suggest that LX4211 reduces intestinal glucose absorption by inhibiting SGLT1, resulting in net increases in GLP-1 and PYY release and decreases in GIP release and blood glucose excursions. The ability to inhibit both intestinal SGLT1 and renal SGLT2 provides LX4211 with a novel dual mechanism of action for improving glycemic control in patients with T2DM.

Sitagliptin decreases ventricular arrhythmias by attenuated glucose-dependent insulinotropic polypeptide (GIP)-dependent resistin signalling in infarcted rats.

PubMed

Lee, Tsung-Ming; Chen, Wei-Ting; Chang, Nen-Chung

2016-01-25

Myocardial infarction (MI) was associated with insulin resistance, in which resistin acts as a critical mediator. We aimed to determine whether sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, can attenuate arrhythmias by regulating resistin-dependent nerve growth factor (NGF) expression in postinfarcted rats. Normoglycaemic male Wistar rats after ligating coronary artery were randomized to either vehicle or sitagliptin for 4 weeks starting 24 h after operation. Post-infarction was associated with increased myocardial noradrenaline [norepinephrine (NE)] levels and sympathetic hyperinnervation. Compared with vehicle, sympathetic innervation was blunted after administering sitagliptin, as assessed by immunofluorescent analysis of tyrosine hydroxylase, growth-associated factor 43 and neurofilament and western blotting and real-time quantitative RT-PCR of NGF. Arrhythmic scores in the sitagliptin-treated infarcted rats were significantly lower than those in vehicle. Furthermore, sitagliptin was associated with reduced resistin expression and increased Akt activity. Ex vivo studies showed that glucose-dependent insulinotropic polypeptide (GIP) infusion, but not glucagon-like peptide-1 (GLP-1), produced similar reduction in resistin levels to sitagliptin in postinfarcted rats. Furthermore, the attenuated effects of sitagliptin on NGF levels can be reversed by wortmannin (a phosphatidylinositol 3-kinase antagonist) and exogenous resistin infusion. Sitagliptin protects ventricular arrhythmias by attenuating sympathetic innervation in the non-diabetic infarcted rats. Sitagliptin attenuated resistin expression via the GIP-dependent pathway, which inhibited sympathetic innervation through a signalling pathway involving phosphatidylinositol 3-kinase (PI3K) and Akt protein. © 2016 Authors.

Incretin response to a standard test meal in a rat model of sleeve gastrectomy with diet-induced obesity.

PubMed

Al-Sabah, Suleiman; Alasfar, Fahad; Al-Khaledi, Ghanim; Dinesh, Reshma; Al-Saleh, Mervat; Abul, Habib

2014-01-01

Currently, the most effective treatment for obesity is bariatric surgery. Gastroduodenal bypass surgery produces sustained weight loss and improves glycemic control and insulin sensitivity. Previous studies have shown that sleeve gastrectomy (SG) produces similar results and implicate changes in incretin hormone release in these effects. Male Sprague-Dawley rats were divided into four groups; lean control (lean), diet-induced obesity (DIO), DIO animals that had undergone SG (SG), and DIO animals that had undergone a sham operation (sham). After a 2-week recovery period, the incretin response to a standard test meal was measured. Blood sampling was performed in free-moving rats at various time points using chronic vascular access to the right jugular vein. There was a significant increase in the bodyweight of DIO animals fed a high-fat/high-sugar diet compared with the lean animals, which was reversed by SG. DIO caused an impairment of the GLP-1 response to a standard test meal, but not the GIP response. SG resulted in a dramatic increase in the GLP-1 response to a standard test meal but had no effect on the GIP response. A rapid rise in blood sugar was observed in the SG group following a standard test meal that was followed by reactive hypoglycemia. SG dramatically increases the GLP-1 response to a standard test meal but has no effect on GIP in a rat model of DIO.

Generation and characterization of induced pluripotent stem cells from guinea pig fetal fibroblasts.

PubMed

Wu, Yuehong; Li, Ouyang; He, Chengwen; Li, Yong; Li, Min; Liu, Xiaoming Liu; Wang, Yujiong; He, Yulong

2017-06-01

Induced pluripotent stem cells (iPS) represent an important tool to develop disease‑modeling assays, drug testing assays and cell‑based replacement therapies. The application of iPS in these fields requires the development of suitable animal models. Of the suitable species, guinea pigs are particularly important and offer significant advantages. Successful iPS generation has been accomplished in a number of species; however, it has not been reported in the guinea pig. The present study successfully generated iPS from guinea pigs (giPS) using single polycistronic virus transduction with mouse octamer‑binding transcription factor 4 (Oct4), sex determining region Y‑box 2 (Sox2), Kruppel‑like factor 4 and c‑Myc. The giPS cell lines were cultured in media containing leukemia inhibitory factor and guinea pig fibroblast cells were used as feeder cells. These cultures were expanded under feeder‑free culture conditions using ESGRO Complete Plus Clonal Grade medium containing 15% fetal bovine serum on gelatin‑coated dishes. The resultant cells had a normal karyotype, exhibited alkaline phosphatase activity and expressed the pluripotency markers Oct4, Sox2 and Nanog. The cells differentiated in vivo to form teratomas that contained all three germ layers of the tissue cells. The generation of giPS may facilitate future studies investigating the mechanisms underlying innate immunity, particularly for tuberculosis. These experiments provide proof of principle that iPS technology may be adapted to use the guinea pig as a model of human diseases.

Gastric inhibitory peptide, serotonin, and glucagon are unexpected chloride secretagogues in the rectal gland of the skate (Leucoraja erinacea).

PubMed

Kelley, Catherine A; Decker, Sarah E; Silva, Patricio; Forrest, John N

2014-05-01

Since the discovery of the rectal gland of the dogfish shark 50 years ago, experiments with this tissue have greatly aided our understanding of secondary active chloride secretion and the secretagogues responsible for this function. In contrast, very little is known about the rectal gland of skates. In the present experiments, we performed the first studies in the perfused rectal gland of the little skate (Leucoraja erinacea), an organ weighing less than one-tenth of the shark rectal gland. Our results indicate that the skate gland can be studied by modified perfusion techniques and in primary culture monolayers, and that secretion is blocked by the inhibitors of membrane proteins required for secondary active chloride secretion. Our major finding is that three G protein-coupled receptor agonists, the incretin gastric inhibitory polypeptide (GIP), also known as glucose-dependent insulinotropic peptide, as well as glucagon and serotonin, are unexpected potent chloride secretagogues in the skate but not the shark. Glucagon stimulated chloride secretion to a mean value of 1,661 ± 587 μeq·h(-1)·g(-1) and serotonin stimulated to 2,893 ± 699 μeq·h(-1)·g(-1). GIP stimulated chloride secretion to 3,733 ± 679 μeq·h(-1)·g(-1) and significantly increased tissue cAMP content compared with basal conditions. This is the first report of GIP functioning as a chloride secretagogue in any species or tissue.

Gastric inhibitory peptide, serotonin, and glucagon are unexpected chloride secretagogues in the rectal gland of the skate (Leucoraja erinacea)

PubMed Central

Kelley, Catherine A.; Decker, Sarah E.; Silva, Patricio

2014-01-01

Since the discovery of the rectal gland of the dogfish shark 50 years ago, experiments with this tissue have greatly aided our understanding of secondary active chloride secretion and the secretagogues responsible for this function. In contrast, very little is known about the rectal gland of skates. In the present experiments, we performed the first studies in the perfused rectal gland of the little skate (Leucoraja erinacea), an organ weighing less than one-tenth of the shark rectal gland. Our results indicate that the skate gland can be studied by modified perfusion techniques and in primary culture monolayers, and that secretion is blocked by the inhibitors of membrane proteins required for secondary active chloride secretion. Our major finding is that three G protein-coupled receptor agonists, the incretin gastric inhibitory polypeptide (GIP), also known as glucose-dependent insulinotropic peptide, as well as glucagon and serotonin, are unexpected potent chloride secretagogues in the skate but not the shark. Glucagon stimulated chloride secretion to a mean value of 1,661 ± 587 μeq·h−1·g−1 and serotonin stimulated to 2,893 ± 699 μeq·h−1·g−1. GIP stimulated chloride secretion to 3,733 ± 679 μeq·h−1·g−1 and significantly increased tissue cAMP content compared with basal conditions. This is the first report of GIP functioning as a chloride secretagogue in any species or tissue. PMID:24553297

Generation and characterization of induced pluripotent stem cells from guinea pig fetal fibroblasts

PubMed Central

Wu, Yuehong; Li, Ouyang; He, Chengwen; Li, Yong; Li, Min; Liu, Xiaoming; Wang, Yujiong; He, Yulong

2017-01-01

Induced pluripotent stem cells (iPS) represent an important tool to develop disease-modeling assays, drug testing assays and cell-based replacement therapies. The application of iPS in these fields requires the development of suitable animal models. Of the suitable species, guinea pigs are particularly important and offer significant advantages. Successful iPS generation has been accomplished in a number of species; however, it has not been reported in the guinea pig. The present study successfully generated iPS from guinea pigs (giPS) using single polycistronic virus transduction with mouse octamer-binding transcription factor 4 (Oct4), sex determining region Y-box 2 (Sox2), Kruppel-like factor 4 and c-Myc. The giPS cell lines were cultured in media containing leukemia inhibitory factor and guinea pig fibroblast cells were used as feeder cells. These cultures were expanded under feeder-free culture conditions using ESGRO Complete Plus Clonal Grade medium containing 15% fetal bovine serum on gelatin-coated dishes. The resultant cells had a normal karyotype, exhibited alkaline phosphatase activity and expressed the pluripotency markers Oct4, Sox2 and Nanog. The cells differentiated in vivo to form teratomas that contained all three germ layers of the tissue cells. The generation of giPS may facilitate future studies investigating the mechanisms underlying innate immunity, particularly for tuberculosis. These experiments provide proof of principle that iPS technology may be adapted to use the guinea pig as a model of human diseases. PMID:28393187

Improved health-relevant functionality in dark germinated Mucuna pruriens sprouts by elicitation with peptide and phytochemical elicitors.

PubMed

Randhir, Reena; Kwon, Young-In; Shetty, Kalidas

2009-10-01

The health-relevant functionality of Mucuna pruriens was improved by priming the seeds with elicitors of the pentose phosphate pathway (PPP) such as fish protein hydrolysates (FPHs), lactoferrin (LF) and oregano extract (OE) followed by dark germination. FPH elicited the highest phenolic content of 19 mg/g FW on day 1, which was 38% higher than control sprouts. OE enhanced Parkinson's disease-relevant L-DOPA content by 33% on day 1 compared to control sprouts. Anti-diabetes-relevant alpha-amylase inhibition percent (AIP) and alpha-glucosidase inhibition percent (GIP) were high in the cotyledons and decreased following elicitation and sprouting. For potential anti-diabetic applications, low AIP and high GIP with moderate L-DOPA content on day 4 of dark germination could be optimal. Improved L-DOPA concentrations in a soluble phenolic and antioxidant-rich M. pruriens background on day 1 sprouts have potential for Parkinson's disease management.

Sequential Gaussian co-simulation of rate decline parameters of longwall gob gas ventholes.

PubMed

Karacan, C Özgen; Olea, Ricardo A

2013-04-01

Gob gas ventholes (GGVs) are used to control methane inflows into a longwall mining operation by capturing the gas within the overlying fractured strata before it enters the work environment. Using geostatistical co-simulation techniques, this paper maps the parameters of their rate decline behaviors across the study area, a longwall mine in the Northern Appalachian basin. Geostatistical gas-in-place (GIP) simulations were performed, using data from 64 exploration boreholes, and GIP data were mapped within the fractured zone of the study area. In addition, methane flowrates monitored from 10 GGVs were analyzed using decline curve analyses (DCA) techniques to determine parameters of decline rates. Surface elevation showed the most influence on methane production from GGVs and thus was used to investigate its relation with DCA parameters using correlation techniques on normal-scored data. Geostatistical analysis was pursued using sequential Gaussian co-simulation with surface elevation as the secondary variable and with DCA parameters as the primary variables. The primary DCA variables were effective percentage decline rate, rate at production start, rate at the beginning of forecast period, and production end duration. Co-simulation results were presented to visualize decline parameters at an area-wide scale. Wells located at lower elevations, i.e., at the bottom of valleys, tend to perform better in terms of their rate declines compared to those at higher elevations. These results were used to calculate drainage radii of GGVs using GIP realizations. The calculated drainage radii are close to ones predicted by pressure transient tests.

Expression of PCSK1 (PC1/3), PCSK2 (PC2) and PCSK3 (furin) in mouse small intestine.

PubMed

Gagnon, Jeffrey; Mayne, Janice; Mbikay, Majambu; Woulfe, John; Chrétien, Michel

2009-01-08

The family of serine proteases known as the proprotein convertases subtilisin/kexin type (PCSK) is responsible for the cleavage and maturation of many precursor hormones. Over its three successive regions, the duodenum, the jejunum and the ileum, the small intestine (SI) expresses over 40 peptide hormones necessary for normal intestinal physiology. Most of these hormones derive from proteolytic cleavage of their cognate inactive polypeptide precursors. Members of the PCSK family of proteases have been implicated in this process, although details of enzyme-substrate interactions are largely lacking. As a first step towards elucidating these interactions, we have analyzed by immunohistochemistry the regional distribution of PCSK1, PCSK2 and PCSK3 in mouse SI as well as their cellular co-localization with substance P (SP), cholecystokinin (CCK), glucose-dependent insulinotropic polypeptide (GIP) and somatostatin (SS), 4 peptide hormones known to result from PCSK-mediated processing. Results indicate that PCSK1 is found in all three regions of the SI while PCSK2 and PCSK3 are primarily expressed in the upper two, the duodenum and the jejunum. In these proximal regions, PCSK1 was detectable in 100% of SP-positive (+) cells, 85% of CCK+ cells and 50% of GIP+ cells; PCSK2 was detectable in 40% of SS+ cells and 35% of SP+ cells; PCSK3 was detectable in 75% of GIP+ cells and 60% of SP+ cells. These histological data suggest that the 3 PCSKs may play differential and overlapping roles in prohormone processing in the three regions of the SI.

Increased Incretin But Not Insulin Response after Oral versus Intravenous Branched Chain Amino Acids.

PubMed

Gojda, Jan; Straková, Radka; Plíhalová, Andrea; Tůma, Petr; Potočková, Jana; Polák, Jan; Anděl, Michal

2017-01-01

Branched chain amino acids (BCAAs) are known to exert an insulinotropic effect. Whether this effect is mediated by incretins (glucagon like peptide 1 [GLP-1] or glucose-dependent insulinotropic peptide [GIP]) is not known. The aim of this study was to show whether an equivalent dose of BCAA elicits a greater insulin and incretin response when administered orally than intravenously (IV). Eighteen healthy, male subjects participated in 3 tests: IV application of BCAA solution, oral ingestion of BCAA and placebo in an equivalent dose (30.7 ± 1.1 g). Glucose, insulin, C-peptide, glucagon, GLP-1, GIP, valine, leucine and isoleucine concentrations were measured. Rise in serum BCAA was achieved in both BCAA tests, with incremental areas under the curve (iAUC) being 2.1 times greater for IV BCAA compared with those of the oral BCAA test (p < 0.0001). Oral and IV BCAA induced comparable insulin response greater than placebo (240 min insulin iAUC: oral 3,411 ± 577 vs. IV 2,361 ± 384 vs. placebo 961.2 ± 175 pmol/L, p = 0.0006). Oral BCAA induced higher GLP-1 (p < 0.0001) and GIP response (p < 0.0001) compared with the IV or placebo. Glucose levels declined significantly (p < 0.001) in the same pattern during both BCAA tests with no change in the placebo group. An equivalent dose of BCAA elicited a comparable insulin and greater incretin response when administered orally and not when administered through IV. We conclude that insulinotropic effects of BCAA are partially incretin dependent. © 2017 S. Karger AG, Basel.

Obesity and the gastrointestinal tract: you are what you eat.

PubMed

Wolfe, M Michael; Boylan, Michael O

2014-01-01

Obesity represents a complex multifactorial syndrome that develops from interactions among genetic and environmental factors and is a leading cause of illness and death. The prevalence of obesity in the United States has increased dramatically since 1975. Although often ignored, the gastrointestinal tract, and the gastrointestinal regulatory peptides in particular, constitutes an ideal starting point for defining and investigating obesity as it represents the route by which all nutrients are ingested, processed, and absorbed. Another important factor to consider when evaluating the etiology of obesity is the capacity for all animals to store nutrients. Insulin is the most potent anabolic hormone, and it appears to have evolved from the need to maximize energy efficiency, obviating the requirement to continuously forage for food. Organisms expressing this important peptide possessed a distinct survival advantage and flourished. During the course of evolution, insulin biosynthesis translocated from the intestine to pancreatic islets, which necessitated a messenger from the intestine to complete the "enteroinsular axis." The eventual development of glucose-dependent insulinotropic polypeptide (GIP) and other incretins fulfilled this requirement. GIP appears to offer an additional survival benefit by not only stimulating intestinal glucose transport and maximally releasing insulin to facilitate nutrient storage but also by its insulin-mimetic properties, including enhanced uptake of glucose by adipocytes. This physiological redundancy offered by insulin and GIP ensured the survival of organisms during times when food was scarce. As food is no longer scarce, at least in the West, this survival advantage appears to have contributed to the current obesity epidemic.

The Effects of a Hypocaloric Diet on Diet-Induced Thermogenesis and Blood Hormone Response in Healthy Male Adults: A Pilot Study.

PubMed

Ishii, Shunsuke; Osaki, Noriko; Shimotoyodome, Akira

2016-01-01

Calorie restriction is a common strategy for weight loss and management. Consumption of food and nutrients stimulates diet-induced thermogenesis (DIT), as well as pancreatic and gastrointestinal hormone secretion that may regulate energy metabolism. Yet, little is known about the impact of hypocaloric diets on energy metabolism-related parameters. In this study, we assessed the effects of hypocaloric diets on hormonal variance in relation to DIT in healthy adults. Ten healthy male adults were enrolled in a randomized crossover study comprising three meal trials. Each subject was given a meal of 200 (extremely hypocaloric), 400 (moderately hypocaloric), or 800 kcal (normocaloric). Postprandial blood variables and energy expenditure were measured for 4 h (after the 200- and 400-kcal meals) or 6 h (after the 800-kcal meal). DIT and postprandial changes in blood pancreatic peptide and ghrelin were significantly smaller after the extremely or moderately hypocaloric diet than after the normocaloric diet but were similar between the hypocaloric diets. Postprandial blood insulin, amylin, glucose-dependent insulinotropic polypeptide (GIP), and glucagon-like peptide type-1 (GLP-1) increased in a calorie-dependent manner. Thermogenic efficiency (DIT per energy intake) was negatively correlated with the maximum blood level (Cmax) (p=0.01) and incremental area under the curve (p=0.01) of the blood GIP response. Calorie restriction thus leads to hormonal responses and lower DIT in healthy adults. Extreme calorie restriction, however, led to greater thermogenic efficiency compared with moderate calorie restriction. The postprandial GIP response may be a good predictor of postprandial thermogenic efficiency.

Impact of short-term high-fat feeding on glucose and insulin metabolism in young healthy men.

PubMed

Brøns, Charlotte; Jensen, Christine B; Storgaard, Heidi; Hiscock, Natalie J; White, Andrew; Appel, Julie S; Jacobsen, Stine; Nilsson, Emma; Larsen, Claus M; Astrup, Arne; Quistorff, Bjørn; Vaag, Allan

2009-05-15

A high-fat, high-calorie diet is associated with obesity and type 2 diabetes. However, the relative contribution of metabolic defects to the development of hyperglycaemia and type 2 diabetes is controversial. Accumulation of excess fat in muscle and adipose tissue in insulin resistance and type 2 diabetes may be linked with defective mitochondrial oxidative phosphorylation. The aim of the current study was to investigate acute effects of short-term fat overfeeding on glucose and insulin metabolism in young men. We studied the effects of 5 days' high-fat (60% energy) overfeeding (+50%) versus a control diet on hepatic and peripheral insulin action by a hyperinsulinaemic euglycaemic clamp, muscle mitochondrial function by (31)P magnetic resonance spectroscopy, and gene expression by qrt-PCR and microarray in 26 young men. Hepatic glucose production and fasting glucose levels increased significantly in response to overfeeding. However, peripheral insulin action, muscle mitochondrial function, and general and specific oxidative phosphorylation gene expression were unaffected by high-fat feeding. Insulin secretion increased appropriately to compensate for hepatic, and not for peripheral, insulin resistance. High-fat feeding increased fasting levels of plasma adiponectin, leptin and gastric inhibitory peptide (GIP). High-fat overfeeding increases fasting glucose levels due to increased hepatic glucose production. The increased insulin secretion may compensate for hepatic insulin resistance possibly mediated by elevated GIP secretion. Increased insulin secretion precedes the development of peripheral insulin resistance, mitochondrial dysfunction and obesity in response to overfeeding, suggesting a role for insulin per se as well GIP, in the development of peripheral insulin resistance and obesity.

Sequential Gaussian co-simulation of rate decline parameters of longwall gob gas ventholes

USGS Publications Warehouse

Karacan, C. Özgen; Olea, Ricardo A.

2013-01-01

Gob gas ventholes (GGVs) are used to control methane inflows into a longwall mining operation by capturing the gas within the overlying fractured strata before it enters the work environment. Using geostatistical co-simulation techniques, this paper maps the parameters of their rate decline behaviors across the study area, a longwall mine in the Northern Appalachian basin. Geostatistical gas-in-place (GIP) simulations were performed, using data from 64 exploration boreholes, and GIP data were mapped within the fractured zone of the study area. In addition, methane flowrates monitored from 10 GGVs were analyzed using decline curve analyses (DCA) techniques to determine parameters of decline rates. Surface elevation showed the most influence on methane production from GGVs and thus was used to investigate its relation with DCA parameters using correlation techniques on normal-scored data. Geostatistical analysis was pursued using sequential Gaussian co-simulation with surface elevation as the secondary variable and with DCA parameters as the primary variables. The primary DCA variables were effective percentage decline rate, rate at production start, rate at the beginning of forecast period, and production end duration. Co-simulation results were presented to visualize decline parameters at an area-wide scale. Wells located at lower elevations, i.e., at the bottom of valleys, tend to perform better in terms of their rate declines compared to those at higher elevations. These results were used to calculate drainage radii of GGVs using GIP realizations. The calculated drainage radii are close to ones predicted by pressure transient tests.

Sequential Gaussian co-simulation of rate decline parameters of longwall gob gas ventholes

PubMed Central

Karacan, C.Özgen; Olea, Ricardo A.

2015-01-01

Gob gas ventholes (GGVs) are used to control methane inflows into a longwall mining operation by capturing the gas within the overlying fractured strata before it enters the work environment. Using geostatistical co-simulation techniques, this paper maps the parameters of their rate decline behaviors across the study area, a longwall mine in the Northern Appalachian basin. Geostatistical gas-in-place (GIP) simulations were performed, using data from 64 exploration boreholes, and GIP data were mapped within the fractured zone of the study area. In addition, methane flowrates monitored from 10 GGVs were analyzed using decline curve analyses (DCA) techniques to determine parameters of decline rates. Surface elevation showed the most influence on methane production from GGVs and thus was used to investigate its relation with DCA parameters using correlation techniques on normal-scored data. Geostatistical analysis was pursued using sequential Gaussian co-simulation with surface elevation as the secondary variable and with DCA parameters as the primary variables. The primary DCA variables were effective percentage decline rate, rate at production start, rate at the beginning of forecast period, and production end duration. Co-simulation results were presented to visualize decline parameters at an area-wide scale. Wells located at lower elevations, i.e., at the bottom of valleys, tend to perform better in terms of their rate declines compared to those at higher elevations. These results were used to calculate drainage radii of GGVs using GIP realizations. The calculated drainage radii are close to ones predicted by pressure transient tests. PMID:26190930

The 2-monoacylglycerol moiety of dietary fat appears to be responsible for the fat-induced release of GLP-1 in humans.

PubMed

Mandøe, Mette J; Hansen, Katrine B; Hartmann, Bolette; Rehfeld, Jens F; Holst, Jens J; Hansen, Harald S

2015-09-01

Dietary triglycerides can, after digestion, stimulate the intestinal release of incretin hormones through activation of G protein-coupled receptor (GPR) 119 by 2-monoacylglycerol and by the activation of fatty acid receptors for long- and short-chain fatty acids. Medium-chain fatty acids do not stimulate the release of intestinal hormones. To dissect the mechanism of fat-induced glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) release in humans, we compared the effects of tributyrin (containing short-chain fatty acids; i.e., butyric acid), olive oil [containing long-chain fatty acids; e.g., oleic acid plus 2-oleoyl glycerol (2-OG)], and 1,3-dioctanoyl-2-oleoyl glycerol (C8-dietary oil), which is digested to form medium-chain fatty acids : i.e., octanoic acid : and 2-OG. In a randomized, single-blinded crossover study, 12 healthy white men [mean age: 24 y; BMI (in kg/m(2)): 22] were given the following 4 meals on 4 different days: 200 g carrots + 6.53 g tributyrin, 200 g carrots + 13.15 g C8-dietary oil, 200 g carrots + 19 g olive oil, or 200 g carrots. All of the lipids totaled 0.0216 mol. Main outcome measures were incremental areas under the curve for total GLP-1, GIP, and cholecystokinin (CCK) in plasma. C8-dietary oil and olive oil showed the same GLP-1 response [583 ± 101 and 538 ± 71 (pmol/L) × 120 min; P = 0.733], whereas the GIP response was higher for olive oil than for C8-dietary oil [3293 ± 404 and 1674 ± 270 (pmol/L) × 120 min; P = 0.002]. Tributyrin and carrots alone resulted in no increase in any of the measured hormones. Peptide YY (PYY) and neurotensin responses resembled those of GLP-1. Only olive oil stimulated CCK release. Under our study conditions, 2-OG and GPR119 activation can fully explain the olive oil-induced secretion of GLP-1, PYY, and neurotensin. In contrast, both oleic acid and 2-OG contributed to the GIP response. Dietary butyrate did not stimulate gut hormone secretion. Olive oil-derived oleic acid seems to be fully responsible for olive oil-induced CCK secretion. This trial was registered at clinicaltrials.gov as NCT02264951. © 2015 American Society for Nutrition.

Inhibition of dipeptidyl peptidase-4 augments insulin secretion in response to exogenously administered glucagon-like peptide-1, glucose-dependent insulinotropic polypeptide, pituitary adenylate cyclase-activating polypeptide, and gastrin-releasing peptide in mice.

PubMed

Ahrén, Bo; Hughes, Thomas E

2005-04-01

Inhibition of dipeptidyl peptidase-4 (DPP-4) is currently being explored as a new approach to the treatment of type 2 diabetes. This concept has emerged from the powerful and rapid action of the enzyme to inactivate glucagon-like peptide-1 (GLP-1). However, other bioactive peptides with potential influence of islet function are also substrates of DPP-4. Whether this inactivation may add to the beneficial effects of DPP-4 inhibition is not known. In this study, we explored whether DPP-4 inhibition by valine-pyrrolidide (val-pyr; 100 micromol/kg administered through gastric gavage at t = -30 min) affects the insulin and glucose responses to iv glucose (1 g/kg) together with GLP-1 (10 nmol/kg), glucose-dependent insulinotropic polypeptide (GIP; 10 nmol/kg), pituitary adenylate cyclase-activating polypeptide 38 (PACAP38; 1.3 nmol/kg), or gastrin-releasing peptide (GRP; 20 nmol/kg) given at t = 0 in anesthetized C57BL/6J mice. It was found that the acute (1-5 min) insulin response to GLP-1 was augmented by val-pyr by 80% (4.2 +/- 0.4 vs. 7.6 +/- 0.8 nmol/liter), that to GIP by 40% (2.7 +/- 0.3 vs. 3.8 +/- 0.4 nmol/liter), that to PACAP38 by 75% (4.6 +/- 0.5 vs. 8.1 +/- 0.6 nmol/liter), and that to GRP by 25% (1.8 +/- 0.2 vs. 2.3 +/- 0.3 nmol/liter; all P < 0.05 or less). This was associated with enhanced glucose elimination rate after GLP-1 [glucose elimination constant (K(G)) 2.1 +/- 0.2 vs. 3.1 +/- 0.3%/min] and PACAP38 (2.1 +/- 0.3 vs. 3.2 +/- 0.3%/min; both P < 0.01), but not after GIP or GRP. The augmented insulin response to GRP by val-pyr was prevented by the GLP-1 receptor antagonist, exendin(3) (9-39), raising the possibility that GRP effects may occur secondary to stimulation of GLP-1 secretion. We conclude that DPP-4 inhibition augments the insulin response not only to GLP-1 but also to GIP, PACAP38, and GRP.

The regulation of K- and L-cell activity by GLUT2 and the calcium-sensing receptor CasR in rat small intestine

PubMed Central

Mace, Oliver J; Schindler, Marcus; Patel, Sonal

2012-01-01

Intestinal enteroendocrine cells (IECs) secrete gut peptides in response to both nutrients and non-nutrients. Glucose and amino acids both stimulate gut peptide secretion. Our hypothesis was that the facilitative glucose transporter, GLUT2, could act as a glucose sensor and the calcium-sensing receptor, CasR, could detect amino acids in the intestine to modify gut peptide secretion. We used isolated loops of rat small intestine to study the secretion of gluco-insulinotropic peptide (GIP), glucagon-like peptide-1 (GLP-1) and peptide tyrosine tyrosine (PYY) secretion stimulated by luminal perfusion of nutrients or bile acid. Inhibition of the sodium-dependent glucose cotransporter 1 (SGLT1) with phloridzin partially inhibited GIP, GLP-1 and PYY secretion by 45%, suggesting another glucose sensor might be involved in modulating peptide secretion. The response was completely abolished in the presence of the GLUT2 inhibitors phloretin or cytochalasin B. Given that GLUT2 modified gut peptide secretion stimulated by glucose, we investigated whether it was involved in the secretion of gut peptide by other gut peptide secretagogues. Phloretin completely abolished gut peptide secretion stimulated by artificial sweetener (sucralose), dipeptide (glycylsarcosine), lipid (oleoylethanolamine), short chain fatty acid (propionate) and major rat bile acid (taurocholate) indicating a fundamental position for GLUT2 in the gut peptide secretory mechanism. We investigated how GLUT2 was able to influence gut peptide secretion mediated by a diverse range of stimulators and discovered that GLUT2 affected membrane depolarisation through the closure of K+ATP-sensitive channels. In the absence of SGLT1 activity (or presence of phloridzin), the secretion of GIP, GLP-1 and PYY was sensitive to K+ATP-sensitive channel modulators tolbutamide and diazoxide. l-Amino acids phenylalanine (Phe), tryptophan (Trp), asparagine (Asn), arginine (Arg) and glutamine (Gln) also stimulated GIP, GLP-1 and PYY secretion, which was completely abolished when extracellular Ca2+ was absent. The gut peptide response stimulated by the amino acids was also blocked by the CasR inhibitor Calhex 231 and augmented by the CasR agonist NPS-R568. GLUT2 and CasR regulate K- and L-cell activity in response to nutrient and non-nutrient stimuli. PMID:22495587

Elemental analysis of occupational and environmental lung diseases by electron probe microanalyzer with wavelength dispersive spectrometer.

PubMed

Takada, Toshinori; Moriyama, Hiroshi; Suzuki, Eiichi

2014-01-01

Occupational and environmental lung diseases are a group of pulmonary disorders caused by inhalation of harmful particles, mists, vapors or gases. Mineralogical analysis is not generally required in the diagnosis of most cases of these diseases. Apart from minerals that are encountered rarely or only in specific occupations, small quantities of mineral dusts are present in the healthy lung. As such when mineralogical analysis is required, quantitative or semi-quantitative methods must be employed. An electron probe microanalyzer with wavelength dispersive spectrometer (EPMA-WDS) enables analysis of human lung tissue for deposits of elements by both qualitative and semi-quantitative methods. Since 1993, we have analyzed 162 cases of suspected occupational and environmental lung diseases using an EPMA-WDS. Our institute has been accepting online requests for elemental analysis of lung tissue samples by EPMA-WDS since January 2011. Hard metal lung disease is an occupational interstitial lung disease that primarily affects workers exposed to the dust of tungsten carbide. The characteristic pathological findings of the disease are giant cell interstitial pneumonia (GIP) with centrilobular fibrosis, surrounded by mild alveolitis with giant cells within the alveolar space. EPMA-WDS analysis of biopsied lung tissue from patients with GIP has demonstrated that tungsten and/or cobalt is distributed in the giant cells and centrilobular fibrosing lesion in GIP. Pneumoconiosis, caused by amorphous silica, and acute interstitial pneumonia, associated with the giant tsunami, were also elementally analyzed by EPMA-WDS. The results suggest that commonly found elements, such as silicon, aluminum, and iron, may cause occupational and environmental lung diseases. Copyright © 2013 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

Comprehensive Evaluation of Repowering Systems for Utilizing Waste Heat from Small Scale Garbage Incineration Plants

NASA Astrophysics Data System (ADS)

Pak, Pyong Sik

This paper evaluates two proposed repowering systems together with a conventional repowering system. A power generation system utilizing waste heat produced by a garbage incineration plant (GIP), which treats 45 t/d of garbage, was taken as an objective power generation system to be repowered. As the conventional repowering system (Sys-C), a gas turbine system with waste heat boiler was adopted. In the proposed system 1 (Sys-P1), temperature of the low temperature steam generated at the GIP is raised in the gas combustor by burning fuel, and used to drive a gas turbine generator. Hence, required power for compressing the air becomes remarkably small and expected to be high efficient compared with Sys-C. In the proposed system 2 (Sys-P2), the low temperature steam generated at the GIP is superheated by using regenerative burner and used to drive a steam turbine generator, and hence making steam condition optimal becomes easy. Various basic characteristics of the three repowering systems were estimated through computer simulation, such as repowering efficiency, energy saving characteristics, and amount of CO2 reduction. It was shown that Sys-P1 and Sys-P2 were both superior to the conventional repowering system Sys-C in the all characteristics, and Sys-P1 to Sys-P2 in repowering efficiency, and that Sys-P2 to Sys-P1 in energy saving characteristics and CO2 reduction effect. It has also been estimated that all the repowering systems are economically feasible, and that the proposed systems Sys-P1 and Sys-P2 are both superior to the Sys-C in the three economical indices of unit cost of power, annual gross profit and depreciation year.

Plasma endocannabinoid levels in lean, overweight and obese humans: relationships with intestinal permeability markers, inflammation and incretin secretion.

PubMed

Little, Tanya J; Cvijanovic, Nada; DiPatrizio, Nicholas V; Argueta, Donovan A; Rayner, Christopher K; Feinle-Bisset, Christine; Young, Richard L

2018-02-13

Intestinal production of endocannabinoid and oleoylethanolamide (OEA) is impaired in high-fat diet/obese rodents, leading to reduced satiety. Such diets also alter the intestinal microbiome in association with enhanced intestinal permeability and inflammation, however little is known of these effects in humans. This study aimed to: (i) evaluate effects of lipid on plasma anandamide (AEA), 2-arachidonyl-sn-glycerol (2-AG) and OEA in humans, and (ii) examine relationships with intestinal permeability, inflammation markers and incretin hormone secretion. 20 lean, 18 overweight and 19 obese participants underwent intraduodenal Intralipid® infusion (2 kcal/min) with collection of endoscopic duodenal biopsies and blood. Plasma AEA, 2-AG, and OEA (HPLC/tandem mass spectrometry), tumour necrosis factor-α (TNF-α), glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) (multiplex), and duodenal expression of occludin, zona-occludin-1 (ZO-1), intestinal-alkaline-phosphatase (IAP), and toll-like receptor-4 (TLR4) (RT-PCR), were assessed. Fasting plasma AEA was increased in obese, compared with lean and overweight (P<0.05), with no effect of BMI group or ID lipid infusion on plasma 2-AG or OEA. Duodenal expression of IAP and ZO-1 was reduced in obese, compared with lean (P<0.05), and these levels related negatively to plasma AEA (P<0.05). The iAUC for AEA was positively related to iAUC GIP (r=0.384, P=0.005). Obese individuals have increased plasma AEA and decreased duodenal expression of ZO-1 and IAP, in comparison to lean and overweight. The relationships between plasma AEA with duodenal ZO-1 and IAP, and GIP, suggest that altered endocannabinoid signalling may contribute to changes in intestinal permeability, inflammation and incretin release in human obesity.

Pitfalls in gastrointestinal permeability measurement in ICU patients with multiple organ failure using differential sugar absorption.

PubMed

Oudemans-van Straaten, Heleen M; van der Voort, Peter J; Hoek, Frans J; Bosman, Rob J; van der Spoel, Johan I; Zandstra, Durk F

2002-02-01

To assess whether gastrointestinal permeability (GIP) at intensive care unit (ICU) admission, measured by differential sugar absorption, is related to severity of disease and multiple organ failure (MOF). Post hoc, to analyse the relation between the urinary sugar recovery and renal function. Prospective observational cohort study. Eighteen-bed general ICU of a teaching hospital. Sixty-four ventilated patients admitted with MOF. GIP was assessed within 24 h using cellobiose (C), sucrose (S) and mannitol (M) absorption. Severity of disease: APACHE II and III, SAPS II and MPM II systems. Organ failure: SOFA, MODS and Goris score. The median urinary recovery of C was 0.147% (range 0.004-2.145%), of S 0.249% (0.001-3.656%) and of M 10.7% (0.6-270%). In 16 patients, M recovery was over 100% of the oral dose. They received red blood cell transfusion (RBC). In the non-transfused, the median cellobiose/mannitol (CM) ratio was 0.015 (0.0004-0.550). CM ratio was not related to severity of disease and inversely related to the SOFA score ( r=-0.30, p=0.04). Post hoc regression analysis showed that recoveries of C, S and M were positively related to urinary volume. Recoveries of C and S, but not of M, were positively related to creatinine clearance. The CM ratio corrected for diuresis, but was inversely related to creatinine clearance. Differential C, S and M absorption testing is unreliable after RBC transfusion, since bank blood contains mannitol. The excretion of C and S, but not of M, is limited by renal dysfunction. Differential sugar absorption is not reliable to test GIP in MOF patients, since non-permeability related factors act as confounders.

Bright light therapy and melatonin in motor restless behaviour in dementia: a placebo-controlled study.

PubMed

Haffmans, P M; Sival, R C; Lucius, S A; Cats, Q; van Gelder, L

2001-01-01

The purpose of this study was to evaluate the effects of bright light therapy combined with melatonin on motor restless behaviour in dementia. Double-blind, placebo-controlled, cross-over trial consisting of four periods. One week wash-out was followed by a 2-week period of light therapy in combination with placebo or melatonin. The second wash-out period of 1 week was followed by 2 weeks of treatment (cross-over). Twenty-four bed medium-stay psychogeriatric ward at a Dutch psychiatric teaching hospital. Ten patients, who met the criteria for dementia (DSM-IV) and motor restless behaviour (subscale 10 of the GIP), were included. Informed consent was obtained by proxy. All subjects were exposed during 2x5 consecutive days for 30 minutes to 10,000 lux bright light and randomly administered 2.5 mg melatonin or placebo at 22.00 h. Clinical Global Impression (CGI), Dutch version of the geriatric behavioural observation scale (GIP), Social Dysfunction and Aggression Scale (SDAS) were assessed after each wash-out and treatment period. Outcome criteria were CGI, assessing motor restless behaviour, the SDAS, measuring extrovert aggression and the GIP, assessing social, psychomotor and emotional behaviour. Six demented inpatients completed the trial. Positive effects were found for the treatment combined with placebo. Patients were less restless and more co-operative. The condition with melatonin showed no additional positive effects, additionally, patients became more aggressive and showed the same or more disturbed behaviour. Bright light therapy has a positive effect on motor restless behaviour. Light therapy in combination with melatonin has no positive effects. The results might be explained by a possible overshoot of chronobiological synchronisation or the timing of the melatonin intake. Copyright 2001 John Wiley & Sons, Ltd.

Effects of 1 and 3 g cinnamon on gastric emptying, satiety, and postprandial blood glucose, insulin, glucose-dependent insulinotropic polypeptide, glucagon-like peptide 1, and ghrelin concentrations in healthy subjects.

PubMed

Hlebowicz, Joanna; Hlebowicz, Anna; Lindstedt, Sandra; Björgell, Ola; Höglund, Peter; Holst, Jens J; Darwiche, Gassan; Almér, Lars-Olof

2009-03-01

A previous study of healthy subjects showed that intake of 6 g cinnamon with rice pudding reduced postprandial blood glucose and the gastric emptying rate (GER) without affecting satiety. The objective was to study the effect of 1 and 3 g cinnamon on GER, postprandial blood glucose, plasma concentrations of insulin and incretin hormones [glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1)], the ghrelin response, and satiety in healthy subjects. GER was measured by using real-time ultrasonography after ingestion of rice pudding with and without 1 or 3 g cinnamon. Fifteen healthy subjects were assessed in a crossover trial. The addition of 1 or 3 g cinnamon had no significant effect on GER, satiety, glucose, GIP, or the ghrelin response. The insulin response at 60 min and the area under the curve (AUC) at 120 min were significantly lower after ingestion of rice pudding with 3 g cinnamon (P = 0.05 and P = 0.036, respectively, after Bonferroni correction). The change in GLP-1 response (DeltaAUC) and the change in the maximum concentration (DeltaC(max)) were both significantly higher after ingestion of rice pudding with 3 g cinnamon (P = 0.0082 and P = 0.0138, respectively, after Bonferroni correction). Ingestion of 3 g cinnamon reduced postprandial serum insulin and increased GLP-1 concentrations without significantly affecting blood glucose, GIP, the ghrelin concentration, satiety, or GER in healthy subjects. The results indicate a relation between the amount of cinnamon consumed and the decrease in insulin concentration.

Closing the theory to practice gap for newly qualified doctors: evaluation of a peer-delivered practical skills training course for newly qualified doctors in preparation for clinical practice.

PubMed

Beane, A; Padeniya, A; De Silva, A P; Stephens, T; De Alwis, S; Mahipala, P G; Sigera, P C; Munasinghe, S; Weeratunga, P; Ranasinghe, D; Deshani, E M; Weerasinghe, T; Thilakasiri, K; Jayasinghe, Kas; Dondorp, A M; Haniffa, R

2017-10-01

The Good Intern Programme (GIP) in Sri Lanka has been implemented to bridge the 'theory to practice gap' of doctors preparing for their internship. This paper evaluates the impact of a 2-day peer-delivered Acute Care Skills Training (ACST) course as part of the GIP. The ACST course was developed by an interprofessional faculty, including newly graduated doctors awaiting internship (pre-intern), focusing on the recognition and management of common medical and surgical emergencies. Course delivery was entirely by pre-intern doctors to their peers. Knowledge was evaluated by a pre- and post-course multiple choice test. Participants' confidence (post-course) and 12 acute care skills (pre- and post-course) were assessed using Likert scale-based questions. A subset of participants provided feedback on the peer learning experience. Seventeen courses were delivered by a faculty consisting of eight peer trainers over 4 months, training 320 participants. The mean (SD) multiple choice questionnaire score was 71.03 (13.19) pre-course compared with 77.98 (7.7) post-course (p<0.05). Increased overall confidence in managing ward emergencies was reported by 97.2% (n=283) of respondents. Participants rated their post-course skills to be significantly higher (p<0.05) than pre-course in all 12 assessed skills. Extended feedback on the peer learning experience was overwhelmingly positive and 96.5% would recommend the course to a colleague. A peer-delivered ACST course was extremely well received and can improve newly qualified medical graduates' knowledge, skills and confidence in managing medical and surgical emergencies. This peer-based model may have utility beyond pre-interns and beyond Sri Lanka. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

The entero-insular axis: implications for human metabolism.

PubMed

Ranganath, Lakshminarayan R

2008-01-01

Incretins such as glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) are intestinal hormones that are released in response to ingestion of nutrients, especially carbohydrate. They have a number of important biological effects, which include release of insulin, inhibition of glucagon and somatostatin, maintenance of beta-cell mass, delay of gastric emptying, and inhibition of feeding. These properties allow them to be potentially suitable agents for the treatment of type 2 diabetes (T2D). Incretin receptors are also present in other parts of the body including the brain, where their effects are beginning to be understood and their relevance to disorders of nutrition and ageing are being explored. There is currently a pandemic of obesity and diabetes, and existing treatments are largely inadequate in regard to efficacy as well as their ability to tackle important factors in the pathogenesis of T2D. There is increasing evidence that current treatments do not address the issue of progressive beta-cell failure in T2D. As obesity is the engine that is driving the epidemic of diabetes, it is disappointing that most treatments that succeed in lowering plasma glucose are also associated with weight gain. It is now well established that intensively treated T2D has a better outcome than standard treatment. Consequently, achieving better control of diabetes with lower HbA1c is the goal of optimal treatment. Despite the use of usual therapeutic agents in T2D, often in high doses and as combinations, such as metformin, sulphonylurea, alpha-glycosidase inhibitors, thiazolidinediones and a number of animal and human insulin preparations, optimal control of glycaemia is not achieved. The use of incretins as therapeutic agents offers a new approach to the treatment of T2D. Incretin metabolism is abnormal in T2D, evidenced by a decreased incretin effect, reduction in nutrient-mediated secretion of GIP and GLP-1 in T2D, and resistance to GIP. GLP-1, on the other hand, when administered intravenously in T2D is able to increase insulin secretion and improve glucose homeostasis. As GLP-1 has a very short half-life, due to rapid degradation by the enzyme dipeptidyl peptidase IV (DPPIV), analogues of GIP and GLP-1 that are resistant to the action of DPPIV have been developed and clinical trials have shown their effectiveness. Another novel agent, naturally resistant to DPPIV that is given by subcutaneous injection is a synthetic peptide called exenatide, has recently been approved for treatment of T2D in the USA. Efforts are underway to develop agents that can be given orally and include a DPPIV inhibitor that has been licensed for the treatment of T2D in the USA, and several other agents are undergoing clinical trials. Strategies to augment the biological actions of GIP and/or GLP-1 in T2D are expected to minimise weight gain, reduce hypoglycaemic episodes and prevent progressive beta-cell failure by increasing beta-cell mass. The optimal agent(s) that may mimic and replace the endogenous incretin effect is not fully known and awaits the outcome of clinical trials that are still ongoing. The potential therapeutic role in non-diabetic states, including obesity and neurodegenerative disease, is intriguing and depends upon results from ongoing research.

Effect of proximal versus distal 50% enterectomy on nutritional parameters in rats preconditioned with a high-fat diet or regular chow.

PubMed

Yanala, Ujwal R; Reidelberger, Roger D; Thompson, Jon S; Shostrom, Valerie K; Carlson, Mark A

2015-11-27

Obesity may protect against the nutritional consequences of short bowel syndrome. We hypothesized that rats preconditioned with an obesogenic diet would have better outcomes after surgical induction of short bowel syndrome compared to rats on regular chow. Rats were fed a high-fat diet or regular rat chow for six months, and then underwent 50% proximal, 50% distal, or sham enterectomy. Food intake, weight, and body composition were monitored before and for 4 weeks after surgery. The high-fat diet consistently produced obesity (>25% body fat). All procedures induced weight loss, but there was no discernable difference between resection vs. sham resection. Rats on the high-fat diet had a greater post-resection loss of body fat compared to rats on chow (36 vs. 26 g, respectively). There was a nonsignificant trend of less lean mass loss in the former compared to the latter rats (16 vs. 33 g, respectively). Enterectomy moderated serum ghrelin, GIP, PPY, insulin, and leptin. Intestinal adaptation was not different between obese vs. non-obese rats. Rats preconditioned with the high-fat diet may have had better retention of lean body mass after a surgical procedure compared to rats on chow. The effect of 50% enterectomy was less than expected.

76 FR 54507 - Proposed Generic Communication; Draft NRC Generic Letter 2011-XX: Seismic Risk Evaluations for...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-01

... design estimates. Analyses performed under the Generic Issue program (GIP) indicated the need to evaluate... Examination of External Events (IPEEE) for Severe Accident Vulnerabilities,'' (ADAMS Accession No. ML031150485) to request that each licensee identify and report to the NRC all plant- specific vulnerabilities to...

Controlled Synthesis and Understanding of Growth Mechanism – Parameters for Atmospheric Pressure Hydrothermal Synthesis of Ultrathin Secondary ZnO Nanowires

DOE PAGES

Jiao, Mingzhi; Nguyen, Duc; Nguyen, Van; ...

2015-11-10

We measured luminescence and scintillation in ZnO single crystals by photoluminescence and X-ray-induced luminescence (XRIL). XRIL allowed a direct comparison to be made between the near-band emission (NBE) and trap emissions providing insight into the carrier recombination efficiency in the ZnO crystals. In the origin of green emission, the dominant trap emission in ZnO, was investigated by gamma-induced positron spectroscopy (GIPS) - a unique defect spectroscopy method that enables positron lifetime measurements to be made for a sample without contributions from positron annihilation in the source materials or the surroundings. Moreover, the measurements showed the absence of positron traps inmore » the crystals and yielded a bulk positron lifetime value that is in complete agreement with the predicted theoretical value = thereby confirming the advantage of the GIPS method. By combining scintillation measurements with XRIL, the fast scintillation in ZnO crystals was found to be strongly correlated with the ratio between the defect luminescence and NBE.« less

The Role of Incretins in Glucose Homeostasis and Diabetes Treatment

PubMed Central

Kim, Wook; Egan, Josephine M.

2009-01-01

Incretins are gut hormones that are secreted from enteroendocrine cells into the blood within minutes after eating. One of their many physiological roles is to regulate the amount of insulin that is secreted after eating. In this manner, as well as others to be described in this review, their final common raison d’être is to aid in disposal of the products of digestion. There are two incretins, known as glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1), that share many common actions in the pancreas but have distinct actions outside of the pancreas. Both incretins are rapidly deactivated by an enzyme called dipeptidyl peptidase 4 (DPP4). A lack of secretion of incretins or an increase in their clearance are not pathogenic factors in diabetes. However, in type 2 diabetes (T2DM), GIP no longer modulates glucose-dependent insulin secretion, even at supraphysiological (pharmacological) plasma levels, and therefore GIP incompetence is detrimental to β-cell function, especially after eating. GLP-1, on the other hand, is still insulinotropic in T2DM, and this has led to the development of compounds that activate the GLP-1 receptor with a view to improving insulin secretion. Since 2005, two new classes of drugs based on incretin action have been approved for lowering blood glucose levels in T2DM: an incretin mimetic (exenatide, which is a potent long-acting agonist of the GLP-1 receptor) and an incretin enhancer (sitagliptin, which is a DPP4 inhibitor). Exenatide is injected subcutaneously twice daily and its use leads to lower blood glucose and higher insulin levels, especially in the fed state. There is glucose-dependency to its insulin secretory capacity, making it unlikely to cause low blood sugars (hypoglycemia). DPP4 inhibitors are orally active and they increase endogenous blood levels of active incretins, thus leading to prolonged incretin action. The elevated levels of GLP-1 are thought to be the mechanism underlying their blood glucose-lowering effects. PMID:19074620

Acute peripheral administration of synthetic human GLP-1 (7-36 amide) decreases circulating IL-6 in obese patients with type 2 diabetes mellitus: a potential role for GLP-1 in modulation of the diabetic pro-inflammatory state?

PubMed

Daousi, Christina; Pinkney, Jonathan H; Cleator, Jacqueline; Wilding, John P; Ranganath, L R

2013-05-10

To explore the effects of acute administration of GLP-1 and GIP on circulating levels of key adipocyte-derived hormones and gut-brain peptides with established roles in energy and appetite regulation, modulation of insulin sensitivity and inflammation. Six obese male patients with diet-treated type 2 diabetes (T2DM) and 6 healthy lean subjects were studied. The protocol included 4 experiments for each participant that were carried out in randomised order and comprised: GLP-1 infusion at a rate of 1 pmol/kg/min for 4h, GIP at a rate of 2 pmol/kg/min, GLP-1+GIP and placebo infusion. Plasma leptin, adiponectin, IL-6, insulin, ghrelin and obestatin were measured at baseline, 15, 60, 120, 180 and 240 min following the start of infusion. Patients with T2DM had higher baseline IL-6 compared with healthy [day of placebo infusion: T2DM IL-6 mean (SEM) 1.3 (0.3) pg/ml vs 0.3 (0.1)pg/ml, p=0.003]. GLP-1 infusion in T2DM was associated with a significant reduction in circulating IL-6 [baseline IL-6 1.2 pg/ml vs IL-6=0.7 at 120 min, p=0.0001; vs IL-6=0.8 at 180 min, p=0.001]. There was no significant change in leptin, adiponectin, ghrelin or obestatin compared to baseline on all 4 experimental days in both groups. Short-term infusion of supraphysiological concentrations of GLP-1 in T2DM results in suppression of IL-6, a key inflammatory mediator strongly linked to development of obesity and T2DM-related insulin resistance. It remains to be confirmed whether GLP-1-based diabetes therapies can impact favourably on cardiovascular outcomes. Copyright © 2013 Elsevier B.V. All rights reserved.

Integration of vertical and in-seam horizontal well production analyses with stochastic geostatistical algorithms to estimate pre-mining methane drainage efficiency from coal seams: Blue Creek seam, Alabama

PubMed Central

Karacan, C. Özgen

2015-01-01

Coal seam degasification and its efficiency are directly related to the safety of coal mining. Degasification activities in the Black Warrior basin started in the early 1980s by using vertical boreholes. Although the Blue Creek seam, which is part of the Mary Lee coal group, has been the main seam of interest for coal mining, vertical wellbores have also been completed in the Pratt, Mary Lee, and Black Creek coal groups of the Upper Pottsville formation to degasify multiple seams. Currently, the Blue Creek seam is further degasified 2–3 years in advance of mining using in-seam horizontal boreholes to ensure safe mining. The studied location in this work is located between Tuscaloosa and Jefferson counties in Alabama and was degasified using 81 vertical boreholes, some of which are still active. When the current long mine expanded its operation into this area in 2009, horizontal boreholes were also drilled in advance of mining for further degasification of only the Blue Creek seam to ensure a safe and a productive operation. This paper presents an integrated study and a methodology to combine history matching results from vertical boreholes with production modeling of horizontal boreholes using geostatistical simulation to evaluate spatial effectiveness of in-seam boreholes in reducing gas-in-place (GIP). Results in this study showed that in-seam wells' boreholes had an estimated effective drainage area of 2050 acres with cumulative production of 604 MMscf methane during ~2 years of operation. With horizontal borehole production, GIP in the Blue Creek seam decreased from an average of 1.52 MMscf to 1.23 MMscf per acre. It was also shown that effective gas flow capacity, which was independently modeled using vertical borehole data, affected horizontal borehole production. GIP and effective gas flow capacity of coal seam gas were also used to predict remaining gas potential for the Blue Creek seam. PMID:26435557

Integration of vertical and in-seam horizontal well production analyses with stochastic geostatistical algorithms to estimate pre-mining methane drainage efficiency from coal seams: Blue Creek seam, Alabama.

PubMed

Karacan, C Özgen

2013-07-30

Coal seam degasification and its efficiency are directly related to the safety of coal mining. Degasification activities in the Black Warrior basin started in the early 1980s by using vertical boreholes. Although the Blue Creek seam, which is part of the Mary Lee coal group, has been the main seam of interest for coal mining, vertical wellbores have also been completed in the Pratt, Mary Lee, and Black Creek coal groups of the Upper Pottsville formation to degasify multiple seams. Currently, the Blue Creek seam is further degasified 2-3 years in advance of mining using in-seam horizontal boreholes to ensure safe mining. The studied location in this work is located between Tuscaloosa and Jefferson counties in Alabama and was degasified using 81 vertical boreholes, some of which are still active. When the current long mine expanded its operation into this area in 2009, horizontal boreholes were also drilled in advance of mining for further degasification of only the Blue Creek seam to ensure a safe and a productive operation. This paper presents an integrated study and a methodology to combine history matching results from vertical boreholes with production modeling of horizontal boreholes using geostatistical simulation to evaluate spatial effectiveness of in-seam boreholes in reducing gas-in-place (GIP). Results in this study showed that in-seam wells' boreholes had an estimated effective drainage area of 2050 acres with cumulative production of 604 MMscf methane during ~2 years of operation. With horizontal borehole production, GIP in the Blue Creek seam decreased from an average of 1.52 MMscf to 1.23 MMscf per acre. It was also shown that effective gas flow capacity, which was independently modeled using vertical borehole data, affected horizontal borehole production. GIP and effective gas flow capacity of coal seam gas were also used to predict remaining gas potential for the Blue Creek seam.

Use of CRISPR/Cas9-engineered INS-1 pancreatic β cells to define the pharmacology of dual GIPR/GLP-1R agonists.

PubMed

Naylor, Jacqueline; Suckow, Arthur T; Seth, Asha; Baker, David J; Sermadiras, Isabelle; Ravn, Peter; Howes, Rob; Li, Jianliang; Snaith, Mike R; Coghlan, Matthew P; Hornigold, David C

2016-09-15

Dual-agonist molecules combining glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) activity represent an exciting therapeutic strategy for diabetes treatment. Although challenging due to shared downstream signalling pathways, determining the relative activity of dual agonists at each receptor is essential when developing potential novel therapeutics. The challenge is exacerbated in physiologically relevant cell systems expressing both receptors. To this end, either GIP receptors (GIPR) or GLP-1 receptors (GLP-1R) were ablated via RNA-guided clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 endonucleases in the INS-1 pancreatic β-cell line. Multiple clonal cell lines harbouring gene disruptions for each receptor were isolated and assayed for receptor activity to identify functional knockouts (KOs). cAMP production in response to GIPR or GLP-1R activation was abolished and GIP- or GLP-1-induced potentiation of glucose-stimulated insulin secretion (GSIS) was attenuated in the cognate KO cell lines. The contributions of individual receptors derived from cAMP and GSIS assays were confirmed in vivo using GLP-1R KO mice in combination with a monoclonal antibody antagonist of GIPR. We have successfully applied CRISPR/Cas9-engineered cell lines to determining selectivity and relative potency contributions of dual-agonist molecules targeting receptors with overlapping native expression profiles and downstream signalling pathways. Specifically, we have characterised molecules as biased towards GIPR or GLP-1R, or with relatively balanced potency in a physiologically relevant β-cell system. This demonstrates the broad utility of CRISPR/Cas9 when applied to native expression systems for the development of drugs that target multiple receptors, particularly where the balance of receptor activity is critical. © 2016 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

Resistant starch intake at breakfast affects postprandial responses in type 2 diabetics and enhances the glucose-dependent insulinotropic polypeptide--insulin relationship following a second meal.

PubMed

MacNeil, Stacey; Rebry, Rachel M; Tetlow, Ian J; Emes, Michael J; McKeown, Bruce; Graham, Terry E

2013-12-01

Resistant starch (RS) consumption can modulate postprandial metabolic responses, but its effects on carbohydrate (CHO) handling in type 2 diabetics (T2D) are unclear. It was hypothesized that a bagel high in RS would improve glucose and insulin homeostasis following the 1st meal, regardless of the amount of available CHO, and that in association with incretins, the effects would carry over to a 2nd meal. Using a randomized crossover design, 12 T2D ingested four different bagel treatments (their 1st meal) determined by available CHO and the weight or amount of bagel consumed: treatment A, without RS (50 g of available CHO); treatment B, with RS (same total CHO as in A); treatment C, with RS (same available CHO as in A); and treatment D, with the same RS as in B and available CHO as in A and C. A standard 2nd meal was ingested 3 h later. Following the first meal, B elicited a lower glucose incremental area under the curve (iAUC) than C (P < 0.05), D (P < 0.05), and A (trend; P = 0.07), lower insulin iAUC than A (P < 0.05) and C (P < 0.05), and lower glucose-dependent insulinotropic polypeptide (GIP) iAUC than A (P < 0.05). There was a positive correlation (P < 0.05) between GIP and insulin iAUCs after the 2nd meal, and C had a 3 times greater slope than the other treatments (r = 0.91, P < 0.001), yet lacked a significant concomitant improvement in glucose disposal. These results show that for the 1st meal, RS was effective when it replaced a portion of the available CHO, while ingesting more RS influenced the GIP-insulin axis following the 2nd meal.

Ghrelin, Amylin, Gastric Inhibitory Peptide and Cognition in Middle-Aged HIV-Infected and Uninfected Women: The Women’s Interagency HIV Study

PubMed Central

McFarlane, Samy I; Mielke, Michelle M; Uglialoro, Anthony; Keating, Sheila M; Holman, Susan; Minkoff, Howard; Crystal, Howard A; Gustafson, Deborah R

2017-01-01

Objective To explore the gut-brain axis by examining gut hormone levels and cognitive test scores in women with (HIV+) and without (HIV−) HIV infection. Design/methods Participants included 356 women (248 HIV+, 108 at risk HIV−) in the Brooklyn Women’s Interagency HIV Study (WIHS) with measured levels of ghrelin, amylin and gastric inhibitory peptide (GIP), also known as glucose-dependent insulinotropic polypeptide. Cross-sectional analyses using linear regression models estimated the relationship between gut hormones and Trails A, Trails B, Stroop interference time, Stroop word recall, Stroop color naming and reading, and Symbol Digit Modalities Test (SDMT) with consideration for age, HIV infection status, Wide Range Achievement Test score (WRAT), CD4 count, insulin resistance, drug use, and race/ethnicity. Results Among women at mid-life with chronic (at least 10 years) HIV infection or among those at risk, ghrelin, amylin and GIP were differentially related to cognitive test performance by cognitive domain. Better performance on cognitive tests was generally associated with higher ghrelin, amylin and GIP levels. However, the strength of association varied, as did significance level by HIV status. Conclusion Previous analyses in WIHS participants have suggested that higher BMI, waist, and WHR are associated with better cognitive function among women at mid-life with HIV infection. This study indicates that higher gut hormone levels are also associated with better cognition. Gut hormones may provide additional mechanistic insights regarding the association between obesity and Type 2 diabetes and cognition in middle-aged HIV+ and at risk HIV− women. In addition, measuring these hormones longitudinally would add to the understanding of mechanisms of actions of these hormones and their use as potential clinical tools for early identification and intervention on cognitive decline in this vulnerable population. PMID:28690913

Patients With Long-QT Syndrome Caused by Impaired hERG-Encoded Kv11.1 Potassium Channel Have Exaggerated Endocrine Pancreatic and Incretin Function Associated With Reactive Hypoglycemia

PubMed Central

Hyltén-Cavallius, Louise; Iepsen, Eva W.; Wewer Albrechtsen, Nicolai J.; Svendstrup, Mathilde; Lubberding, Anniek F.; Hartmann, Bolette; Jespersen, Thomas; Linneberg, Allan; Christiansen, Michael; Vestergaard, Henrik; Pedersen, Oluf; Holst, Jens J.; Kanters, Jørgen K.

2017-01-01

Background: Loss-of-function mutations in hERG (encoding the Kv11.1 voltage-gated potassium channel) cause long-QT syndrome type 2 (LQT2) because of prolonged cardiac repolarization. However, Kv11.1 is also present in pancreatic α and β cells and intestinal L and K cells, secreting glucagon, insulin, and the incretins glucagon-like peptide-1 (GLP-1) and GIP (glucose-dependent insulinotropic polypeptide), respectively. These hormones are crucial for glucose regulation, and long-QT syndrome may cause disturbed glucose regulation. We measured secretion of these hormones and cardiac repolarization in response to glucose ingestion in LQT2 patients with functional mutations in hERG and matched healthy participants, testing the hypothesis that LQT2 patients have increased incretin and β-cell function and decreased α-cell function, and thus lower glucose levels. Methods: Eleven patients with LQT2 and 22 sex-, age-, and body mass index–matched control participants underwent a 6-hour 75-g oral glucose tolerance test with ECG recording and blood sampling for measurements of glucose, insulin, C-peptide, glucagon, GLP-1, and GIP. Results: In comparison with matched control participants, LQT2 patients had 56% to 78% increased serum insulin, serum C-peptide, plasma GLP-1, and plasma GIP responses (P=0.03–0.001) and decreased plasma glucose levels after glucose ingestion (P=0.02) with more symptoms of hypoglycemia (P=0.04). Sixty-three percent of LQT2 patients developed hypoglycemic plasma glucose levels (<70 mg/dL) versus 36% control participants (P=0.16), and 18% patients developed serious hypoglycemia (<50 mg/dL) versus none of the controls. LQT2 patients had defective glucagon responses to low glucose, P=0.008. β-Cell function (Insulin Secretion Sensitivity Index-2) was 2-fold higher in LQT2 patients than in controls (4398 [95% confidence interval, 2259–8562] versus 2156 [1961–3201], P=0.03). Pharmacological Kv11.1 blockade (dofetilide) in rats had similar effect, and small interfering RNA inhibition of hERG in β and L cells increased insulin and GLP-1 secretion up to 50%. Glucose ingestion caused cardiac repolarization disturbances with increased QTc intervals in both patients and controls, but with a 122% greater increase in QTcF interval in LQT2 patients (P=0.004). Conclusions: Besides a prolonged cardiac repolarization phase, LQT2 patients display increased GLP-1, GIP, and insulin secretion and defective glucagon secretion, causing decreased plasma glucose and thus increased risk of hypoglycemia. Furthermore, glucose ingestion increased QT interval and aggravated the cardiac repolarization disturbances in LQT2 patients. Clinical Trial Registration: URL: http://clinicaltrials.gov. Unique identifier: NCT02775513. PMID:28235848

Accelerating Smith-Waterman Algorithm for Biological Database Search on CUDA-Compatible GPUs

NASA Astrophysics Data System (ADS)

Munekawa, Yuma; Ino, Fumihiko; Hagihara, Kenichi

This paper presents a fast method capable of accelerating the Smith-Waterman algorithm for biological database search on a cluster of graphics processing units (GPUs). Our method is implemented using compute unified device architecture (CUDA), which is available on the nVIDIA GPU. As compared with previous methods, our method has four major contributions. (1) The method efficiently uses on-chip shared memory to reduce the data amount being transferred between off-chip video memory and processing elements in the GPU. (2) It also reduces the number of data fetches by applying a data reuse technique to query and database sequences. (3) A pipelined method is also implemented to overlap GPU execution with database access. (4) Finally, a master/worker paradigm is employed to accelerate hundreds of database searches on a cluster system. In experiments, the peak performance on a GeForce GTX 280 card reaches 8.32 giga cell updates per second (GCUPS). We also find that our method reduces the amount of data fetches to 1/140, achieving approximately three times higher performance than a previous CUDA-based method. Our 32-node cluster version is approximately 28 times faster than a single GPU version. Furthermore, the effective performance reaches 75.6 giga instructions per second (GIPS) using 32 GeForce 8800 GTX cards.

Linagliptin: farmacology, efficacy and safety in type 2 diabetes treatment

PubMed Central

2013-01-01

Type 2 diabetes mellitus (T2DM) has a high prevalence and incidence around the world. The complex pathophysiology mechanism is among the barriers for diabetes treatment. Type 2 diabetes patients have dysfunction in incretin hormones (as glucagon-like peptide-1 or GLP-1, and glucose-dependent insulinotropic polypeptide or GIP). By inhibiting the dipeptidyl peptidase-4 (DPP-4) enzyme, it is possible to slow the inactivation of GLP-1 and GIP, promoting blood glucose level reduction in a glucose-dependent manner. Linagliptin is a highly specific and potent inhibitor of DPP-4 that is currently indicated for the treatment of type 2 diabetes. Clinical studies with linagliptin demonstrated efficacy in reducing glycated hemoglobin (HbA1c) levels in type 2 diabetes patients, while maintaining a placebo-like safety and tolerability profile. Linagliptin has an interesting pharmacokinetic profile in terms of its predominantly non-renal elimination and the main implication of this characteristic is that no dose adjustment is necessary in patients with renal disease. Also, no dose adjustment is required in patients with hepatic insufficiency, as well in elderly or obese patients. This article will review the pharmacokinetic profile, efficacy data and safety aspects of linagliptin in type 2 diabetes patients. PMID:23697612

The effects of incretins on energy homeostasis: physiology and implications for the treatment of type 2 diabetes mellitus and obesity.

PubMed

Karras, Spyridon; Goulis, Dimitrios G; Mintziori, Gesthimani; Katsiki, Niki; Tzotzas, Themistoklis

2012-11-01

Energy homeostasis in mammalians is a teleological process regulated by the interplay between caloric intake and energy expenditure. Incretins are a significant component of the complex homeostatic network regulating the metabolic state in humans. This narrative review will focus on the basic concepts regarding incretins physiology and their regulatory feedback mechanisms affecting energy homeostasis. In this context, glucagon-like peptide 1 (GLP-1) promotes satiety and weight loss through centrally and peripherally mediated pathways. On the other hand, gastric inhibitory peptide (GIP) is implicated in energy storage by its actions on adipose tissue. Understanding this biological model requires a holistic approach, since it is dually manifested by promoting weight reduction, in the case of GLP-1, or favoring lipid accumulation, in the case of GIP. The complete spectrum of incretin actions related to energy homeostasis is yet to be fully elucidated. Currently, new drugs based on incretin physiology are available for treatment of type 2 diabetes mellitus, whereas the implication of similar drugs in the treatment of obesity is under investigation. These agents exert several beneficial effects that minimize cardiovascular risk.

Medicinal Chemistry and Applications of Incretins and DPP-4 Inhibitors in the Treatment of Type 2 Diabetes Mellitus

PubMed Central

Lotfy, Mohamed; Singh, Jaipaul; Kalász, Huba; Tekes, Kornelia; Adeghate, Ernest

2011-01-01

Diabetes mellitus (DM) is a major metabolic disorder currently affecting over 200 million people worldwide. Approximately 90% of all diabetic patients suffer from Type 2 diabetes mellitus (T2DM). The world's economy coughs out billions of dollars annually to diagnose, treat and manage patients with diabetes. It has been shown that the naturally occurring gut hormones incretins, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) can preserve the morphology and function of pancreatic beta cell. In addition, GIP and GLP-1 act on insulin receptors to facilitate insulin-receptor binding, resulting in optimal glucose metabolism. This review examines the medicinal chemistry and roles of incretins, specifically, GLP-1 and drugs which can mimic its actions and prevent its enzymatic degradation. The review discussed GLP-1 agonists such as exenatide, liraglutide, taspoglutide and albiglutide. The paper also identified and reviewed a number of inhibitors, which can block dipeptidyl peptidase 4 (DPP-4), the enzyme responsible for the rapid degradation of GLP-1. These DPP-4 inhibitors include sitagliptin, saxagliptin, vildagliptin and many others which are still in the experimental phase. PMID:21966329

Effect of partially depolymerized guar gum on acute metabolic variables in patients with non-insulin-dependent diabetes.

PubMed

Gatenby, S J; Ellis, P R; Morgan, L M; Judd, P A

1996-04-01

Fourteen patients with non-insulin-dependent diabetes (NIDDM) attended the study centre on 4 mornings separated by at least 3 days, to receive in random order 75 g carbohydrate breakfast meals of control or guar breads with jam and butter. Guar gum flours of low, medium, and high molecular weight (MW) were incorporated into wheat bread rolls to provide 7.6 g guar per meal. Venous blood samples were taken via an indwelling cannula in a forearm vein at fasting and at eight postprandial times and then analysed for blood glucose, plasma insulin, C-peptide, and gastric inhibitory polypeptide (GIP). Guar gum bread significantly reduced the postprandial rise in blood glucose, plasma insulin, and, except for bread containing low MW guar gum, plasma GIP levels compared to the control. Thus, the partial depolymerization of guar gum does not diminish its physiological activity. No reductions in postprandial plasma C-peptide levels were seen after any of the guar bread meals. This suggests that guar gum attenuates the insulin concentration in peripheral venous blood in patients with NIDDM by increasing the hepatic extraction of insulin.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Scott, G.; Daugomah, J.; Devane, J.

Urbanization of coastal regions has resulted in the increased discharge of polycyclic aromatic hydrocarbons trace metals and habitat changes/modifications in adjacent upland areas which may affect grass shrimp populations. A study was conducted comparing larval abundance and adult grass shrimp biomass, abundance, size structure and sex ratios in an urbanized estuary, Murrells Inlet with pristine North Inlet, a NOAA national estuarine research reserve and sanctuary site. A total of 60 sites were sampled during the peak of grass shrimp abundance and compared in terms of spatial distributions and other relevant ancillary information. Factors such as sediment contaminant levels, physico-chemical parametersmore » and land-use habitat modification were statistically compared using a Geographical Information Processing (GIP) techniques and appropriate spatial statistical methods. GIP results indicated similar levels of larval abundance in both estuaries and identified specific nursery ground regions in both estuaries. Adult grass shrimp abundances were greatly reduced in urban areas and grass shrimp desert regions were identified. These areas were correlated with regions having high levels of chemical contaminants and greatest physical disturbances. The mortality rate between larval and adult stages was much higher in urban areas suggesting that urbanization had a profound impact on grass shrimp.« less

The Impact of Ownership on Hospice Service Use, 2005–2011

PubMed Central

Stevenson, David G.; Grabowski, David C.; Keating, Nancy L.; Huskamp, Haiden A.

2016-01-01

Background/Objectives For-profit agencies comprise the majority of all United States hospice agencies, prompting concerns about aggressive enrollment practices and deficient care. Using detailed administrative data from 2005–2011, we sought to assess differences in patient populations and service use by hospice ownership, chain status, and agency size. Design/Participants Retrospective cohort study of 5,405,526 Medicare beneficiaries age 65+ enrolled in hospice during 2005–2011. Hospice use by ownership category (for-profit non-chain and chain, not-for-profit non-chain and chain, government) and agency size (0–50 patients, 51–200, 201–400, 401+). Mean length-of-use, stays ≤3 days, stays ending with live discharge, and decedents receiving no general inpatient care (GIP) or continuous home care (CHC) level hospice in the last 7 days of life. Results After adjusting for patient and geographic differences, for-profit non-chain and chain agencies had longer mean lengths-of-use (84.5 and 91.2 days, respectively) than other agency types (66.3–72.5 days); higher rates of live discharge (21.0% and 20.2% versus 14.6%–15.9%); and lower proportions of stays of ≤3 days (13.9% and 14.7% versus 16.6%–17.5%) (all p-values<0.001). The proportion of decedents not receiving GIP/CHC level care before death was highest among for-profit chains (75.9%) and lowest among not-for-profit non-chains (63.2%). Across ownership categories, smaller agencies had longer mean lengths-of-use, higher live discharge rates, lower rates of stays ≤3 days, and higher rates of patients receiving no GIP/CHC level care. Considerable variation in patient traits and unadjusted service use existed among the nation’s largest chains. Conclusion Although for-profit and not-for-profit hospice agencies differ along key dimensions, our results convey substantial heterogeneity within these categories, highlighting the need to consider factors such as agency size and chain affiliation in understanding variations in Medicare beneficiaries’ hospice care. PMID:27131344

Characterization of glucagon-like peptide-1 receptor-binding determinants.

PubMed

Xiao, Q; Jeng, W; Wheeler, M B

2000-12-01

Glucagon-like peptide 1 (GLP-1) is a potent insulinotropic hormone currently under study as a therapeutic agent for type 2 diabetes. Since an understanding of the molecular mechanisms leading to high-affinity receptor (R) binding and activation may facilitate the development of more potent GLP-1R agonists, we have localized specific regions of GLP-1R required for binding. The purified N-terminal fragment (hereafter referred to as NT) of the GLP-1R produced in either insect (Sf9) or mammalian (COS-7) cells was shown to bind GLP-1. The physical interaction of NT with GLP-1 was first demonstrated by cross-linking ((125)I-GLP-1/NT complex band at approximately 28 kDa) and secondly by attachment to Ni(2+)-NTA beads. The GLP-1R NT protein attached to beads bound GLP-1, but with lower affinity (inhibitory concentration (IC(50)): 4.5 x 10(-7) M) than wild-type (WT) GLP-1R (IC(50): 5.2 x 10(-9)M). The low affinity of GLP-1R NT suggested that other receptor domains may contribute to GLP-1 binding. This was supported by studies using chimeric glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptors. GIP(1-151)/GLP-1R, but not GIP(1-222)/GLP-1R, exhibited specific GLP-1 binding and GLP-1-induced cAMP production, suggesting that the region encompassing transmembrane (TM) domain 1 through to TM3 was required for binding. Since it was hypothesized that certain charged or polar amino acids in this region might be involved in binding, these residues (TM2-TM3) were analyzed by substitution mutagenesis. Five mutants (K197A, D198A, K202A, D215A, R227A) displayed remarkably reduced binding affinity. These studies indicate that the NT domain of the GLP-1R is able to bind GLP-1, but charged residues concentrated at the distal TM2/extracellular loop-1 (EC1) interface (K197, D198, K202) and in EC1 (D215 and R227) probably contribute to the binding determinants of the GLP-1R.

Screening Smokes

DTIC Science & Technology

1942-03-15

It should be capable of being readily dispersed . 6. It would be desirable to use a material which reacts with the atmosphere to edd weight. (White...experimental unit handling 15 gip.m. at 5000 lbs. (equivalent in liquid volume dispersed to well over 1000 small Tweedales) has a theoretical...of real promise. "> - 9 - Solid Smokes It has bt»an suggested that various a*mnd8ntly-avallable solid materials might be dispersed as

ZnO Luminescence and scintillation studied via photoexcitation, X-ray excitation, and gamma-induced positron spectroscopy.

PubMed

Ji, J; Colosimo, A M; Anwand, W; Boatner, L A; Wagner, A; Stepanov, P S; Trinh, T T; Liedke, M O; Krause-Rehberg, R; Cowan, T E; Selim, F A

2016-08-23

The luminescence and scintillation properties of ZnO single crystals were studied by photoluminescence and X-ray-induced luminescence (XRIL) techniques. XRIL allowed a direct comparison to be made between the near-band emission (NBE) and trap emissions providing insight into the carrier recombination efficiency in the ZnO crystals. It also provided bulk luminescence measurements that were not affected by surface states. The origin of a green emission, the dominant trap emission in ZnO, was then investigated by gamma-induced positron spectroscopy (GIPS) - a unique defect spectroscopy method that enables positron lifetime measurements to be made for a sample without contributions from positron annihilation in the source materials. The measurements showed a single positron decay curve with a 175 ps lifetime component that was attributed to Zn vacancies passivated by hydrogen. Both oxygen vacancies and hydrogen-decorated Zn vacancies were suggested to contribute to the green emission. By combining scintillation measurements with XRIL, the fast scintillation in ZnO crystals was found to be strongly correlated with the ratio between the defect luminescence and NBE. This study reports the first application of GIPS to semiconductors, and it reveals the great benefits of the XRIL technique for the study of emission and scintillation properties of materials.

ZnO Luminescence and scintillation studied via photoexcitation, X-ray excitation, and gamma-induced positron spectroscopy

NASA Astrophysics Data System (ADS)

Ji, J.; Colosimo, A. M.; Anwand, W.; Boatner, L. A.; Wagner, A.; Stepanov, P. S.; Trinh, T. T.; Liedke, M. O.; Krause-Rehberg, R.; Cowan, T. E.; Selim, F. A.

2016-08-01

The luminescence and scintillation properties of ZnO single crystals were studied by photoluminescence and X-ray-induced luminescence (XRIL) techniques. XRIL allowed a direct comparison to be made between the near-band emission (NBE) and trap emissions providing insight into the carrier recombination efficiency in the ZnO crystals. It also provided bulk luminescence measurements that were not affected by surface states. The origin of a green emission, the dominant trap emission in ZnO, was then investigated by gamma-induced positron spectroscopy (GIPS) - a unique defect spectroscopy method that enables positron lifetime measurements to be made for a sample without contributions from positron annihilation in the source materials. The measurements showed a single positron decay curve with a 175 ps lifetime component that was attributed to Zn vacancies passivated by hydrogen. Both oxygen vacancies and hydrogen-decorated Zn vacancies were suggested to contribute to the green emission. By combining scintillation measurements with XRIL, the fast scintillation in ZnO crystals was found to be strongly correlated with the ratio between the defect luminescence and NBE. This study reports the first application of GIPS to semiconductors, and it reveals the great benefits of the XRIL technique for the study of emission and scintillation properties of materials.

ZnO Luminescence and scintillation studied via photoexcitation, X-ray excitation, and gamma-induced positron spectroscopy

PubMed Central

Ji, J.; Colosimo, A. M.; Anwand, W.; Boatner, L. A.; Wagner, A.; Stepanov, P. S.; Trinh, T. T.; Liedke, M. O.; Krause-Rehberg, R.; Cowan, T. E.; Selim, F. A.

2016-01-01

The luminescence and scintillation properties of ZnO single crystals were studied by photoluminescence and X-ray-induced luminescence (XRIL) techniques. XRIL allowed a direct comparison to be made between the near-band emission (NBE) and trap emissions providing insight into the carrier recombination efficiency in the ZnO crystals. It also provided bulk luminescence measurements that were not affected by surface states. The origin of a green emission, the dominant trap emission in ZnO, was then investigated by gamma-induced positron spectroscopy (GIPS) - a unique defect spectroscopy method that enables positron lifetime measurements to be made for a sample without contributions from positron annihilation in the source materials. The measurements showed a single positron decay curve with a 175 ps lifetime component that was attributed to Zn vacancies passivated by hydrogen. Both oxygen vacancies and hydrogen-decorated Zn vacancies were suggested to contribute to the green emission. By combining scintillation measurements with XRIL, the fast scintillation in ZnO crystals was found to be strongly correlated with the ratio between the defect luminescence and NBE. This study reports the first application of GIPS to semiconductors, and it reveals the great benefits of the XRIL technique for the study of emission and scintillation properties of materials. PMID:27550235

Choosing between GLP-1 Receptor Agonists and DPP-4 Inhibitors: A Pharmacological Perspective

PubMed Central

Brown, Dominique Xavier; Evans, Marc

2012-01-01

In recent years the incretin therapies have provided a new treatment option for patients with type 2 diabetes mellitus (T2DM). The incretin therapies focus on the increasing levels of the two incretin hormones, glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). This results in increased glucose dependent insulin synthesis and release. GLP-1 receptor agonists such as liraglutide and exenatide exert an intrinsic biological effect on GLP-1 receptors directly stimulating the release of insulin from pancreatic beta cells. DPP-4 inhibitors such as sitagliptin and linagliptin prevent the inactivation of endogenous GLP-1 and GIP through competitive inhibition of the DPP-4 enzyme. Both incretin therapies have good safety and tolerability profiles and interact minimally with a number of medications commonly prescribed in T2DM. This paper focuses on the pharmacological basis by which the incretin therapies function and how this knowledge can inform and benefit clinical decisions. Each individual incretin agent has benefits and pitfalls relating to aspects such as glycaemic and nonglycaemic efficacy, safety and tolerability, ease of administration, and cost. Overall, a personalized medicine approach has been found to be favourable, tailoring the incretin agent to benefit and suit patient's needs such as renal impairment (RI) or hepatic impairment (HI). PMID:23125920

Fibroblast Activation Protein-Alpha, a Serine protease that Facilitates Metastasis by Modification of Diverse Microenvironments

DTIC Science & Technology

2009-10-01

pyrrolidine (LAF-237, vildagliptin ). Both boroPro compounds are effective against FAP at nanomolar concentrations; however, micromolar LAF-237 is...dependent insulinotropic polypeptide (GIP) that are substrates for DPPIV. NVP LAF-237 or vildagliptin is one of the DPPIV inhibitors approved for type 2...peptide truncation by Tumor growth is promoted by catalytically-inactive FAP 24 Vildagliptin ((2S)-{[(3-hydroxyadamantan-1-yl)amino]acetyl

Intelligent Advanced Communications IP Telephony Feasibility for the U.S. Navy: Phase 2

DTIC Science & Technology

2009-03-31

PDAs) and smart phones. In addition, it considers how solutions integrate on-premise enterprise functions with the functions of mobile operators...and Control System GIG Global Information Grid GigE Gigabit Ethernet GIPS Global IP Solutions Inc. GMSK Gaussian Minimum Shift Keying GPHY Gigabit...Feasibility for the U.S. Navy – Phase 2 UAC User Agent Client UART Universal Asynchronous Receiver/Transmitter UAS User Agent Server UCR

Incretin hormone receptors are required for normal beta cell development and function in female mice.

PubMed

Omar, Bilal; Ahlkvist, Linda; Yamada, Yuchiro; Seino, Yutaka; Ahrén, Bo

2016-05-01

The incretin hormones, glucose dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1), potentiate insulin secretion and are responsible for the majority of insulin secretion that occurs after a meal. They may also, however, have a fundamental role in pancreatic beta cell development and function, independently of their role in potentiating insulin secretion after a meal. This has led to observations that a loss of GIP or GLP-1 action affects normal beta cell function, however each one of the incretin hormones may compensate when the action of the other is lost and therefore the overall impact of the incretin hormones on beta cell function is not known. We therefore utilized a mouse line deficient in both the GLP-1 and GIP receptor genes, the double incretin receptor knockout (DIRKO), to determine the consequences of a lifelong, complete lack of incretin hormone action on beta cell function, in vivo, in intact animals. We found that DIRKO mice displayed impaired glucose tolerance and insulin secretion in response to both oral glucose and mixed meal tolerance tests compared to wild-type mice. Assessment of beta cell function using the hyperglycemic clamp technique revealed an 80% decrease in first phase insulin response in DIRKO mice, but a normal second phase insulin secretion. A similar decline was seen when wild-type mice were given acute intravenous injection of glucose together with the GLP-1 receptor antagonist Ex9-39. Ex vivo assessments of the pancreas revealed significantly fewer islets in the pancreata of DIRKO mice despite no differences in total pancreatic mass. Insulin secretion from isolated islets of DIRKO mice was impaired to a similar extent to that seen during the hyperglycemic clamp. Insulin secretion in wild-type islets was impaired by acute treatment with Ex9-39 to a similar extent as the in vivo intravenous glucose tolerance tests. In conclusion, a loss of the action of both incretin hormones results in direct impairment of beta cell function both in vivo and in vitro in a process that appears to be independent of the intestinally secreted incretin hormones. We therefore conclude that the incretin hormones together significantly impact both beta-cell function and beta-cell development. Copyright © 2016. Published by Elsevier Inc.

Active phytochemicals of Pueraria tuberosa for DPP-IV inhibition: in silico and experimental approach.

PubMed

Srivastava, Shivani; Shree, Priya; Tripathi, Yamini Bhusan

2017-01-01

We had earlier reported that the extract of Pueraria tuberosa significantly inhibits DPP-IV enzyme, resulting in glucose tolerance response in rats. In this study, we have explored the active phytochemicals responsible for this potential. The results have been validated in both fasting and postprandial states in the plasma of normal rats and also in fasting blood and intestinal homogenates of diabetic models. Pueraria tuberosa water extract (PTWE) was administered to normal Charles Foster rats for 35 days and to diabetic model (65 mg/kg bw) for 10 days. After treatments, oral glucose tolerance test (OGTT) and insulin was done for 90 min, and the changes in the levels of GLP-1, GIP, and DPP-IV activities were monitored in fasting and postprandial states. In the case of the diabetic model, DPP-IV activity was measured in intestinal homogenate and basal insulin in plasma. The components of PTWE were analyzed via HPLC-MS based on their chemical formula, molecular mass, and retention time. Using the molecular docking study, we have selected the top five components having strong binding energy with DPP-IV. The increase in secretion of GLP-1 and GIP was significantly higher in the postprandial state when compared to fasting condition. GLP-1 plasma concentration increased by 5.8 and 2.9 folds and GIP increased by 8.7 and 2.4 folds in PTWE and control rats, respectively. In contrast, the postprandial decrease in DPP-IV specific activities was recorded at 2.3 and 1.4 folds. The response in OGTT and insulin was also consistent with these changes. In comparison to diabetic controls, PTWE-administered rats showed decreased DPP-IV activity in the intestine, leading to enhanced basal insulin concentration. Through molecular docking, we found Puerarone and Robinin to be the most potential phytochemicals of PTWE for DPP-IV inhibition. Binding energy (kcal/mol) and dissociation constant (pM) of Robinin with DPP-IV protein were found to be 7.543 and 2,957,383.75, respectively. For Puerarone, it was 7.376 and 3,920,309, respectively. Thus, this study provides the novel active components that contribute to the DPP-IV inhibitory property of PTWE.

The effect of α- or β-casein addition to waxy maize starch on postprandial levels of glucose, insulin, and incretin hormones in pigs as a model for humans

PubMed Central

Kett, Anthony P.; Bruen, Christine M.; O'Halloran, Fiona; Chaurin, Valérie; Lawlor, Peadar G.; O'Mahony, James A.; Giblin, Linda; Fenelon, Mark A.

2012-01-01

Background Starch is a main source of glucose and energy in the human diet. The extent to which it is digested in the gastrointestinal tract plays a major role in variations in postprandial blood glucose levels. Interactions with other biopolymers, such as dairy proteins, during processing can influence both the duration and extent of this postprandial surge. Objective To evaluate the effect of the addition of bovine α- or β-casein to waxy maize starch on changes in postprandial blood glucose, insulin, and incretin hormones [glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1)] in 30 kg pigs used as an animal model for humans. Design Gelatinised starch, starch gelatinised with α-casein, and starch gelatinised with β-casein were orally administered to trained pigs (n = 8) at a level of 60 g of available carbohydrate. Pre- and postprandial glucose measurements were taken every 15 min for the first hour and every 30 min thereafter up to 180 min. Insulin, GIP, and GLP-1 levels were measured in plasma samples up to 90 min postprandial. Results Starch gelatinised with α-casein had a significantly (p < 0.05) lower peak viscosity on pasting and resulted in significantly lower glucose release at 15, 30, and 90 min postprandial compared to starch gelatinised with β-casein. During the first 45-min postprandial, the area under the glucose curve (AUC) for starch gelatinised with α-casein was significantly (p < 0.05) lower than that for starch gelatinised with β-casein. There was also a significant (p < 0.05) difference at T30 in GIP levels in response to the control compared to starch gelatinised with α- or β-casein. Significant (p < 0.05) increases in several free amino acid concentrations were observed on ingestion of either α- or β-casein gelatinised with starch at 30 and 90 min postprandial compared to starch alone. In addition, plasma levels of six individual amino acids were increased on ingestion of starch gelatinised with α-casein compared to ingestion of starch gelatinised with β-casein. Conclusion The presence of casein fractions (α- or β-casein) in gelatinised waxy maize starch affects swelling characteristics, viscosity, and subsequent in vivo digestion as determined by glucose levels in blood postprandial. PMID:22509144

Glucagon-related peptides in the mouse retina and the effects of deprivation of form vision.

PubMed

Mathis, Ute; Schaeffel, Frank

2007-02-01

In chickens, retinal glucagon amacrine cells play an important role in emmetropization, since they express the transcription factor ZENK (also known as NGFI-A, zif268, tis8, cef5, Krox24) in correlation with the sign of imposed image defocus. Pharmacological studies have shown that glucagon can act as a stop signal for axial eye growth, making it a promising target for pharmacological intervention of myopia. Unfortunately, in mammalian retina, glucagon itself has not yet been detected by immunohistochemical staining. To learn more about its possible role in emmetropization in mammals, we studied the expression of different members of the glucagon hormone family in mouse retina, and whether their abundance is regulated by visual experience. Black wildtype C57BL/6 mice, raised under a 12/12 h light/dark cycle, were studied at postnatal ages between P29 and P40. Frosted hemispherical thin plastic shells (diffusers) were placed in front of the right eyes to impose visual conditions that are known to induce myopia. The left eyes remained uncovered and served as controls. Transversal retinal cryostat sections were single- or double-labeled by indirect immunofluorescence for early growth response protein 1 (Egr-1, the mammalian ortholog of ZENK), glucagon, glucagon-like peptide-2 (GLP-2), glucose-dependent insulinotropic polypeptide (GIP), peptide histidine isoleucine (PHI), growth hormone-releasing hormone (GHRH), pituitary adenylate cyclase-activating polypeptide (PACAP), secretin, and vasoactive intestinal polypeptide (VIP). In total, retinas of 45 mice were studied, 28 treated with diffusers, and 17 serving as controls. Glucagon itself was not detected in mouse retina. VIP, PHI, PACAP and GIP were localized. VIP was co-localized with PHI and Egr-1, which itself was strongly regulated by retinal illumination. Diffusers, applied for various durations (1, 2, 6, and 24 h) had no effect on the expression of VIP, PHI, PACAP, and GIP, at least at the protein level. Similarly, even if the analysis was confined to cells that also expressed Egr-1, no difference was found between VIP expression in eyes with diffusers and in eyes with normal vision. Several members of the glucagon super family are expressed in mouse retina (although not glucagon itself), but their expression pattern does not seem to be regulated by visual experience.

The Effect of Short-Term Dietary Fructose Supplementation on Gastric Emptying Rate and Gastrointestinal Hormone Responses in Healthy Men.

PubMed

Yau, Adora M W; McLaughlin, John; Maughan, Ronald J; Gilmore, William; Evans, Gethin H

2017-03-10

This study aimed to examine gastric emptying rate and gastrointestinal hormone responses to fructose and glucose ingestion following 3 days of dietary fructose supplementation. Using the 13 C-breath test method, gastric emptying rates of equicaloric fructose and glucose solutions were measured in 10 healthy men with prior fructose supplementation (fructose supplement, FS; glucose supplement, GS) and without prior fructose supplementation (fructose control, FC; glucose control, GC). In addition, circulating concentrations of acylated ghrelin (GHR), glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and insulin were determined, as well as leptin, lactate, and triglycerides. Increased dietary fructose ingestion resulted in accelerated gastric emptying rate of a fructose solution but not a glucose solution. No differences in GIP, GLP-1, or insulin incremental area under curve (iAUC) were found between control and supplement trials for either fructose or glucose ingestion. However, a trend for lower ghrelin iAUC was observed for FS compared to FC. In addition, a trend of lower GHR concentration was observed at 45 min for FS compared to FC and GHR concentration for GS was greater than GC at 10 min. The accelerated gastric emptying rate of fructose following short-term supplementation with fructose may be partially explained by subtle changes in delayed postprandial ghrelin suppression.

[The role of single nucleotide polymorphisms in GIPR gene in the changes of secretion in hormones and adipokines in patients with obesity with type 2 diabetes].

PubMed

Skuratovskaia, D A; Vulf, M A; Kirienkova, E V; Mironyuk, N I; Zatolokin, P A; Litvinova, L S

2018-03-01

The relationship between the rs2302382, rs8111428 and Glu354Gln (rs1800437) polymorphisms in GIPR (glucosedependent insulinotropic polypeptide receptor) gene and plasma levels of mediators involved in the regulation of carbohydrate metabolism in obese patients with type 2 diabetes (before and after a test breakfast) was investigated. The contribution of polymorphic variants of rs2302382, rs8111428 in GIPR gene in the predisposition to type 2 diabetes in individuals belonging to the Slavic population of Russia was found. Polymorphisms rs2302382 and rs8111428 in the GIPR gene were characterized by the nonequilibrium cohesion. The decrease in the level of expression of the GIPR gene in adipose tissue of the small intestine mesentery in the carriers of the CC genotype rs2302382 and AA rs8111428 was associated with the increase in the plasma leptin level, whereas during normal expression, the plasma content of insulin, and GIP (in persons with the genotype of the polymorphism rs2302382 and AG polymorphism rs8111428), resistin and ghrelin (in individuals with the genotype of the polymorphism rs2302382) increased. We propose the stimulating effect of GIP on the secretion of resistin, leptin and ghrelin, with an increase in insulin production in obese patients with type 2 diabetes.

The Effect of Short-Term Dietary Fructose Supplementation on Gastric Emptying Rate and Gastrointestinal Hormone Responses in Healthy Men

PubMed Central

Yau, Adora M. W.; McLaughlin, John; Maughan, Ronald J.; Gilmore, William; Evans, Gethin H.

2017-01-01

This study aimed to examine gastric emptying rate and gastrointestinal hormone responses to fructose and glucose ingestion following 3 days of dietary fructose supplementation. Using the 13C-breath test method, gastric emptying rates of equicaloric fructose and glucose solutions were measured in 10 healthy men with prior fructose supplementation (fructose supplement, FS; glucose supplement, GS) and without prior fructose supplementation (fructose control, FC; glucose control, GC). In addition, circulating concentrations of acylated ghrelin (GHR), glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and insulin were determined, as well as leptin, lactate, and triglycerides. Increased dietary fructose ingestion resulted in accelerated gastric emptying rate of a fructose solution but not a glucose solution. No differences in GIP, GLP-1, or insulin incremental area under curve (iAUC) were found between control and supplement trials for either fructose or glucose ingestion. However, a trend for lower ghrelin iAUC was observed for FS compared to FC. In addition, a trend of lower GHR concentration was observed at 45 min for FS compared to FC and GHR concentration for GS was greater than GC at 10 min. The accelerated gastric emptying rate of fructose following short-term supplementation with fructose may be partially explained by subtle changes in delayed postprandial ghrelin suppression. PMID:28287413

Thioamide Substitution Selectively Modulates Proteolysis and Receptor Activity of Therapeutic Peptide Hormones.

PubMed

Chen, Xing; Mietlicki-Baase, Elizabeth G; Barrett, Taylor M; McGrath, Lauren E; Koch-Laskowski, Kieran; Ferrie, John J; Hayes, Matthew R; Petersson, E James

2017-11-22

Peptide hormones are attractive as injectable therapeutics and imaging agents, but they often require extensive modification by mutagenesis and/or chemical synthesis to prevent rapid in vivo degradation. Alternatively, the single-atom, O-to-S modification of peptide backbone thioamidation has the potential to selectively perturb interactions with proteases while preserving interactions with other proteins, such as target receptors. Here, we use the validated diabetes therapeutic, glucagon-like peptide-1 (GLP-1), and the target of clinical investigation, gastric inhibitory polypeptide (GIP), as proof-of-principle peptides to demonstrate the value of thioamide substitution. In GLP-1 and GIP, a single thioamide near the scissile bond renders these peptides up to 750-fold more stable than the corresponding oxopeptides toward cleavage by dipeptidyl peptidase 4, the principal regulator of their in vivo stability. These stabilized analogues are nearly equipotent with their parent peptide in cyclic AMP activation assays, but the GLP-1 thiopeptides have much lower β-arrestin potency, making them novel agonists with altered signaling bias. Initial tests show that a thioamide GLP-1 analogue is biologically active in rats, with an in vivo potency for glycemic control surpassing that of native GLP-1. Taken together, these experiments demonstrate the potential for thioamides to modulate specific protein interactions to increase proteolytic stability or tune activation of different signaling pathways.

34 CFR 300.150 - SEA implementation of procedural safeguards.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 34 Education 2 2012-07-01 2012-07-01 false SEA implementation of procedural safeguards. 300.150... EDUCATION OF CHILDREN WITH DISABILITIES State Eligibility Sea Responsibility for General Supervision and Implementation of Procedural Safeguards § 300.150 SEA implementation of procedural safeguards. The SEA (and any...

34 CFR 300.150 - SEA implementation of procedural safeguards.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 34 Education 2 2013-07-01 2013-07-01 false SEA implementation of procedural safeguards. 300.150... EDUCATION OF CHILDREN WITH DISABILITIES State Eligibility Sea Responsibility for General Supervision and Implementation of Procedural Safeguards § 300.150 SEA implementation of procedural safeguards. The SEA (and any...

34 CFR 300.150 - SEA implementation of procedural safeguards.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 34 Education 2 2014-07-01 2013-07-01 true SEA implementation of procedural safeguards. 300.150... EDUCATION OF CHILDREN WITH DISABILITIES State Eligibility Sea Responsibility for General Supervision and Implementation of Procedural Safeguards § 300.150 SEA implementation of procedural safeguards. The SEA (and any...

34 CFR 300.150 - SEA implementation of procedural safeguards.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 34 Education 2 2011-07-01 2010-07-01 true SEA implementation of procedural safeguards. 300.150... EDUCATION OF CHILDREN WITH DISABILITIES State Eligibility Sea Responsibility for General Supervision and Implementation of Procedural Safeguards § 300.150 SEA implementation of procedural safeguards. The SEA (and any...

34 CFR 300.150 - SEA implementation of procedural safeguards.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 34 Education 2 2010-07-01 2010-07-01 false SEA implementation of procedural safeguards. 300.150... EDUCATION OF CHILDREN WITH DISABILITIES State Eligibility Sea Responsibility for General Supervision and Implementation of Procedural Safeguards § 300.150 SEA implementation of procedural safeguards. The SEA (and any...

Anthocyanin profiles and biological properties of caneberry (Rubus spp.) press residues.

PubMed

Šaponjac, Vesna Tumbas; Gironés-Vilaplana, Amadeo; Djilas, Sonja; Mena, Pedro; Cetković, Gordana; Moreno, Diego A; Canadanović-Brunet, Jasna; Vulić, Jelena; Stajčić, Slađana; Krunić, Milica

2014-09-01

The global interest in natural food colours shows increasing attention towards new product development to replace synthetic colourants, because of the strengthening of legislative rules and consumer awareness of synthetic additives and chemicals in food. This study was designed to evaluate anthocyanin content and biological activities of press residues from four caneberries: two raspberry (Rubus idaeus, cv. 'Meeker' (RM) and 'Willamette' (RW)) and two blackberry (Rubus fruticosus, cv. 'Thornfree' (BT) and 'Čačanska bestrna' (BC)) cultivars. Analysis by high-performance liquid chromatography-diode array detection-electrospray ionization-tandem mass spectrometry identified cyanidin glycosides in all press residues, cyanidin 3-glucoside being prevalent in BC (1360.6 mg kg(-1)) and BT (1397.7 mg kg(-1)), and cyanidin 3-sophoroside in RM (349.2 mg kg(-1) ) and RW (581.0 mg kg(-1)). Antioxidant capacity (AC), evaluated by ABTS (2,2'-azino-bis(3-ethyl benzothiazoline-6-sulfonic acid) assay, reducing power (RP) and α-glucosidase inhibitory potential (α-GIP) was higher in blackberry press residues. Total anthocyanin content was in good correlation with AC (r = 0.953; P < 0.05), RP (r = 0.993, P < 0.01) and α-GIP (r = 0.852, P < 0.15). This study has revealed the potential for valorization of juice production byproducts for further industrial use as a rich source of bioactive compounds and natural colourants (mainly anthocyanins). Also, they can provide health-promoting effects beyond their general organoleptic acceptance in food product development. © 2014 Society of Chemical Industry.

[Performance of entero-insular axis in an athletic population: diet and exercise influence].

PubMed

Rodriguez, Carmen; Quezada-Feijoo, Maribel; Toro, Carmen; Barón-Esquivias, Gonzalo; Segura, Eduardo; Mangas, Alipio; Toro, Rocio

2015-05-01

The relationship between physical exercise and appetite regulation can lead to improved competitive performance of athletes. Mediators of the entero-insular axis generate neurohumoral signals that influence on the appetite regulation and energy homeostasis. Determine the influence of diet and prolonged exercise on intestinal peptide, ghrelin, resistin, leptin, and incretins (GLP-1 and GIP) in an athlete population. It is a prospective intervention study, conducted from October 2012 to March 2013. 32 healthy semiprofessional rugby players, aged 13-39 years were included. Anthropometric measurements and blood samples were taken at time 0 and after six months of study. Athletes were randomized to a protein diet (PD) or Mediterranean diet (MD) and plasma levels of intestinal peptide, ghrelin, resistin, leptin, and incretins were calculated. In the PD group, GLP-1 and GIP plasmatic levels showed a significant decrease (p <0.03; p <0.01 respectively). GLP-1 and ghrelin plasmatic concentration demonstrated a significant decrease (p <0.03 respectively) in those who experienced gain of muscle mass (MM). Finally, the athletes related to the PD who showed increased total weight and muscle mass presented significantly decreased GLP-1 concentration (p <0.03 and p<0.002, respectively). GLP-1 plasmatic concentration was decreased, with the PD suggesting to be more beneficial for the athletes in order to avoid hypoglycemia. Furthermore, muscle mass and total weight gain, linked to the PD, could enhance athletic performance in certain sport modalities. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Improving Effect of the Acute Administration of Dietary Fiber-Enriched Cereals on Blood Glucose Levels and Gut Hormone Secretion

PubMed Central

2016-01-01

Dietary fiber improves hyperglycemia in patients with type 2 diabetes through its physicochemical properties and possible modulation of gut hormone secretion, such as glucagon-like peptide 1 (GLP-1). We assessed the effect of dietary fiber-enriched cereal flakes (DC) on postprandial hyperglycemia and gut hormone secretion in patients with type 2 diabetes. Thirteen participants ate isocaloric meals based on either DC or conventional cereal flakes (CC) in a crossover design. DC or CC was provided for dinner, night snack on day 1 and breakfast on day 2, followed by a high-fat lunch. On day 2, the levels of plasma glucose, GLP-1, glucose-dependent insulinotropic polypeptide (GIP), and insulin were measured. Compared to CC, DC intake exhibited a lower post-breakfast 2-hours glucose level (198.5±12.8 vs. 245.9±15.2 mg/dL, P<0.05) and a lower incremental peak of glucose from baseline (101.8±9.1 vs. 140.3±14.3 mg/dL, P<0.001). The incremental area under the curve (iAUC) of glucose after breakfast was lower with DC than with CC (P<0.001). However, there were no differences in the plasma insulin, glucagon, GLP-1, and GIP levels. In conclusion, acute administration of DC attenuates postprandial hyperglycemia without any significant change in the representative glucose-regulating hormones in patients with type 2 diabetes (ClinicalTrials.gov. NCT 01997281). PMID:26839476

Geostatistical modeling of the gas emission zone and its in-place gas content for Pittsburgh-seam mines using sequential Gaussian simulation

USGS Publications Warehouse

Karacan, C.O.; Olea, R.A.; Goodman, G.

2012-01-01

Determination of the size of the gas emission zone, the locations of gas sources within, and especially the amount of gas retained in those zones is one of the most important steps for designing a successful methane control strategy and an efficient ventilation system in longwall coal mining. The formation of the gas emission zone and the potential amount of gas-in-place (GIP) that might be available for migration into a mine are factors of local geology and rock properties that usually show spatial variability in continuity and may also show geometric anisotropy. Geostatistical methods are used here for modeling and prediction of gas amounts and for assessing their associated uncertainty in gas emission zones of longwall mines for methane control.This study used core data obtained from 276 vertical exploration boreholes drilled from the surface to the bottom of the Pittsburgh coal seam in a mining district in the Northern Appalachian basin. After identifying important coal and non-coal layers for the gas emission zone, univariate statistical and semivariogram analyses were conducted for data from different formations to define the distribution and continuity of various attributes. Sequential simulations performed stochastic assessment of these attributes, such as gas content, strata thickness, and strata displacement. These analyses were followed by calculations of gas-in-place and their uncertainties in the Pittsburgh seam caved zone and fractured zone of longwall mines in this mining district. Grid blanking was used to isolate the volume over the actual panels from the entire modeled district and to calculate gas amounts that were directly related to the emissions in longwall mines.Results indicated that gas-in-place in the Pittsburgh seam, in the caved zone and in the fractured zone, as well as displacements in major rock units, showed spatial correlations that could be modeled and estimated using geostatistical methods. This study showed that GIP volumes may change up to 3. MMscf per acre and, in a multi-panel district, may total 9. Bcf of methane within the gas emission zone. Therefore, ventilation and gas capture systems should be designed accordingly. In addition, rock displacements within the gas emission zone are spatially distributed. From an engineering and practical point of view, spatial distributions of GIP and distributions of rock displacements should be correlated with in-mine emissions and gob gas venthole productions. ?? 2011.

Geostatistical modeling of the gas emission zone and its in-place gas content for Pittsburgh-seam mines using sequential Gaussian simulation

PubMed Central

Karacan, C. Özgen; Olea, Ricardo A.; Goodman, Gerrit

2015-01-01

Determination of the size of the gas emission zone, the locations of gas sources within, and especially the amount of gas retained in those zones is one of the most important steps for designing a successful methane control strategy and an efficient ventilation system in longwall coal mining. The formation of the gas emission zone and the potential amount of gas-in-place (GIP) that might be available for migration into a mine are factors of local geology and rock properties that usually show spatial variability in continuity and may also show geometric anisotropy. Geostatistical methods are used here for modeling and prediction of gas amounts and for assessing their associated uncertainty in gas emission zones of longwall mines for methane control. This study used core data obtained from 276 vertical exploration boreholes drilled from the surface to the bottom of the Pittsburgh coal seam in a mining district in the Northern Appalachian basin. After identifying important coal and non-coal layers for the gas emission zone, univariate statistical and semivariogram analyses were conducted for data from different formations to define the distribution and continuity of various attributes. Sequential simulations performed stochastic assessment of these attributes, such as gas content, strata thickness, and strata displacement. These analyses were followed by calculations of gas-in-place and their uncertainties in the Pittsburgh seam caved zone and fractured zone of longwall mines in this mining district. Grid blanking was used to isolate the volume over the actual panels from the entire modeled district and to calculate gas amounts that were directly related to the emissions in longwall mines. Results indicated that gas-in-place in the Pittsburgh seam, in the caved zone and in the fractured zone, as well as displacements in major rock units, showed spatial correlations that could be modeled and estimated using geostatistical methods. This study showed that GIP volumes may change up to 3 MMscf per acre and, in a multi-panel district, may total 9 Bcf of methane within the gas emission zone. Therefore, ventilation and gas capture systems should be designed accordingly. In addition, rock displacements within the gas emission zone are spatially distributed. From an engineering and practical point of view, spatial distributions of GIP and distributions of rock displacements should be correlated with in-mine emissions and gob gas venthole productions. PMID:26435558

Triphenyltin impairs a protein kinase A (PKA)-dependent increase of cytosolic Na{sup +} and Ca{sup 2+} and PKA-independent increase of cytosolic Ca{sup 2+} associated with insulin secretion in hamster pancreatic {beta}-cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miura, Yoshikazu; Matsui, Hisao

2006-11-01

Oral administration of triphenyltin chloride (TPT) (60 mg/kg body weight) inhibits the insulin secretion by decreasing the cytoplasmic Ca{sup 2+} concentration ([Ca{sup 2+}] {sub i}) induced by glucose-dependent insulinotropic polypeptide (GIP) in pancreatic {beta}-cells of the hamster. To test the possibility that the abnormal level of [Ca{sup 2+}] {sub i} induced by TPT administration could be due to a defect in the cAMP-dependent cytoplasmic Na{sup +} concentration ([Na{sup +}] {sub i}) in the {beta}-cells, we investigated the effects of TPT administration on the changes of [Na{sup +}] {sub i} induced by GIP, glucagon-like peptide-1 (GLP-1), or forskolin, an activator ofmore » adenylyl cyclase, and on the changes of [Na{sup +}] {sub i} or [Ca{sup 2+}] {sub i} induced by 6-Bnz-cAMP, an activator of protein kinase A (PKA), and 8-pCPT-2'-O-Me-cAMP, an activator of Epac. The [Na{sup +}] {sub i} and [Ca{sup 2+}] {sub i} were measured in islet cells loaded with sodium-binding benzofuran isophthalate (SBFI) and fura-2, respectively. In the presence of 135 mM Na{sup +}, TPT administration significantly reduced the rise in [Na{sup +}] {sub i} by 10 nM GLP-1, 10 {mu}M forskolin, and 50 {mu}M 6-Bnz-cAMP, but had not effect in a Na{sup +}-free medium. In the presence of 135 mM Na{sup +}, TPT administration also reduced the rise in [Ca{sup 2+}] {sub i} by 8-pCPT-2'-O-Me-cAMP plus10 {mu}M H-89, a inhibitor of PKA, and 6-Bnz-cAMP. Moreover, TPT administration significantly reduced the insulin secretion by 2 mM db-cAMP, GLP-1, GIP, and 8-pCPT-2'-O-Me-cAMP with and without H-89, and that by 6-Bnz-cAMP and forskolin. Our study suggested that TPT has inhibitory effects on the cellular Ca{sup 2+} response due to a reduced Na{sup +} permeability through PKA-dependent mechanisms in hamster islet cells. Also TPT has the reduction of [Ca{sup 2+}] {sub i} related to Na{sup +}-dependent insulin secretion after an activation of Epac.« less

Intragastric administration of leucine or isoleucine lowers the blood glucose response to a mixed-nutrient drink by different mechanisms in healthy, lean volunteers.

PubMed

Ullrich, Sina S; Fitzgerald, Penelope Ce; Schober, Gudrun; Steinert, Robert E; Horowitz, Michael; Feinle-Bisset, Christine

2016-11-01

The branched-chain amino acids leucine and isoleucine lower blood glucose after oral glucose ingestion, and the intraduodenal infusion of leucine decreases energy intake in healthy, lean men. We investigated the effects of the intragastric administration of leucine and isoleucine on the gastric emptying of, and blood glucose responses to, a physiologic mixed-macronutrient drink and subsequent energy intake. In 2 separate studies, 12 healthy, lean subjects received on 3 separate occasions an intragastric infusion of 5 g leucine (leucine-5g) or an intragastric infusion of 10 g leucine (leucine-10g), an intragastric infusion of 5 g isoleucine (isoleucine-5g) or an intragastric infusion of 10 g isoleucine (isoleucine-10g), or a control. Fifteen minutes later, subjects consumed a mixed-nutrient drink (400 kcal, 56 g carbohydrates, 15 g protein, and 12 g fat), and gastric emptying ( 13 C-acetate breath test) and blood glucose, plasma insulin, C-peptide, glucagon, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and cholecystokinin (leucine study only) were measured for 60 min. Immediately afterward, energy intake from a cold, buffet-style meal was assessed. Compared with the control, leucine-10g decreased the blood glucose area under the curve (AUC) (P < 0.05) and tended to reduce peak blood glucose (P = 0.07), whereas effects of leucine-5g were NS. Leucine-10g, but not leucine-5g, increased plasma insulin and C-peptide AUCs (P < 0.01 for both), but neither dose affected glucagon, GLP-1, GIP, cholecystokinin, gastric emptying, or energy intake. Compared with the control, isoleucine-10g reduced the blood glucose AUC and peak blood glucose (P < 0.01), whereas effects of isoleucine-5g were NS. Neither load affected insulin, C-peptide, glucagon, GLP-1, or GIP. Isoleucine-10g, but not isoleucine-5g, slowed gastric emptying (P < 0.05), but gastric emptying was not correlated with the blood glucose AUC. Isoleucine did not affect energy intake. In healthy subjects, both leucine and isoleucine reduced blood glucose in response to a mixed-nutrient drink but did not affect subsequent energy intake. The mechanisms underlying glucose lowering appear to differ; leucine stimulated insulin, whereas isoleucine acted insulin independently. These trials were registered at www.anzctr.org.au as 12613000899741 and 12614000837628. © 2016 American Society for Nutrition.

The Coast Artillery Journal. Volume 85, Number 4, July-August 1942

DTIC Science & Technology

1942-08-01

Panay and T olur rivers and in the mountains. The sap of this tree is so poisonous that its entry into the body of man or animal is fatal. The dalit is a...aroused: that is the famous king cobra of India and Luzon." Passing of the GIP’s The War Department is gradually replacing the Gun- ners’ Instruction...Scie~tists of the United Nations, especially in this country, Britain and India , have found new secrets of the behavior of steel and other metallic

45 CFR 164.308 - Administrative safeguards.

Code of Federal Regulations, 2012 CFR

2012-10-01

...)(i) Standard: Security management process. Implement policies and procedures to prevent, detect... this subpart for the entity. (3)(i) Standard: Workforce security. Implement policies and procedures to...) Standard: Information access management. Implement policies and procedures for authorizing access to...

45 CFR 164.308 - Administrative safeguards.

Code of Federal Regulations, 2011 CFR

2011-10-01

...)(i) Standard: Security management process. Implement policies and procedures to prevent, detect... this subpart for the entity. (3)(i) Standard: Workforce security. Implement policies and procedures to...) Standard: Information access management. Implement policies and procedures for authorizing access to...

78 FR 24347 - Approval and Promulgation of Implementation Plans; Oregon: Open Burning and Enforcement Procedures

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-25

... Promulgation of Implementation Plans; Oregon: Open Burning and Enforcement Procedures AGENCY: Environmental..., 2008 that relate to open burning rules, enforcement procedures, civil penalties, and procedures in.... These revisions relate to open burning rules, enforcement procedures, civil penalties, and procedures in...

The Effect of Laparoscopic Gastric Banding Surgery on Plasma Levels of Appetite-Control, Insulinotropic, and Digestive Hormones

PubMed Central

Shak, Joshua R.; Roper, Jatin; Perez-Perez, Guillermo I.; Tseng, Chi-hong; Francois, Fritz; Gamagaris, Zoi; Patterson, Carlie; Weinshel, Elizabeth; Fielding, George A.; Ren, Christine

2013-01-01

Background We hypothesized that laparoscopic adjustable gastric banding (LAGB) reduces weight and modulates ghrelin production, but largely spares gastrointestinal endocrine function. To examine this hypothesis, we determined plasma concentrations of appetite-control, insulinotropic, and digestive hormones in relation to LAGB. Methods Twenty-four patients undergoing LAGB were prospectively enrolled. Body mass index (BMI) was measured and blood samples obtained at baseline and 6 and 12 months post-surgery. Plasma concentrations of leptin, acylated and total ghrelin, pancreatic polypeptide (PP), insulin, glucose-dependent insulinotropic peptide (GIP), active glucagon-like peptide-1 (GLP-1), gastrin, and pepsinogens I and II were measured using enzyme-linked immunoassays. Results Median percent excess weight loss (%EWL) over 12 months was 45.7% with median BMI decreasing from 43.2 at baseline to 33.8 at 12 months post-surgery (p<0.001). Median leptin levels decreased from 19.7 ng/ml at baseline to 6.9 ng/ml at 12 months post-surgery (p<0.001). In contrast, plasma levels of acylated and total ghrelin, PP, insulin, GIP, GLP-1, gastrin, and pepsinogen I did not change in relation to surgery (p>0.05). Pepsinogen II levels were significantly lower 6 months after LAGB but returned to baseline levels by 12 months. Conclusions LAGB yielded substantial %EWL and a proportional decrease in plasma leptin. Our results support the hypothesis that LAGB works in part by suppressing the rise in ghrelin that normally accompanies weight loss. Unchanged concentrations of insulinotropic and digestive hormones suggest that gastrointestinal endocrine function is largely maintained in the long term. PMID:18408980

Effect of canagliflozin on circulating active GLP-1 levels in patients with type 2 diabetes: a randomized trial.

PubMed

Takebayashi, Kohzo; Hara, Kenji; Terasawa, Tomoko; Naruse, Rika; Suetsugu, Mariko; Tsuchiya, Takafumi; Inukai, Toshihiko

2017-09-30

Canagliflozin has a robust inhibitory effect on sodium glucose transporter (SGLT)-2 and a mild inhibitory effect on SGLT1. The main purpose of this study was to investigate the effect of canagliflozin on circulating active glucagon-like peptide 1 (GLP-1) levels in patients with type 2 diabetes. Patients were randomly divided into a control group (n =15) and a canagliflozin-treated group (n =15). After hospitalization, the canagliflozin-treated group took 100 mg/day canagliflozin for the entire study, and after 3 days both groups took 20 mg/day teneligliptin for an additional 3 days. In a meal test, canagliflozin significantly decreased the area under curve (AUC) (0-120 min) for plasma glucose (PG) after 3 days when compared with that at baseline, and addition of teneligliptin to the canagliflozin-treated group further decreased it. A significant decrease in the AUC (0-120 min) for serum insulin by canagliflozin was obtained, but the addition of teneligliptin elevated the AUC, and thus abolished the significant difference from baseline. A significant increase in the AUC (0-120 min) of plasma active GLP-1 by canagliflozin-treatment compared with that at baseline was observed, and the addition of teneligliptin resulted in a further increase. However, canagliflozin-treatment did not change the AUC (0-120 min) of plasma active glucose-dependent insulinotropic peptide (GIP). In conclusions, canagliflozin-administration before meals decreased PG and serum insulin, and increased plasma active GLP-1 levels in patients with type 2 diabetes. Canagliflozin did not greatly influence plasma active GIP levels.

The effect of laparoscopic gastric banding surgery on plasma levels of appetite-control, insulinotropic, and digestive hormones.

PubMed

Shak, Joshua R; Roper, Jatin; Perez-Perez, Guillermo I; Tseng, Chi-hong; Francois, Fritz; Gamagaris, Zoi; Patterson, Carlie; Weinshel, Elizabeth; Fielding, George A; Ren, Christine; Blaser, Martin J

2008-09-01

We hypothesized that laparoscopic adjustable gastric banding (LAGB) reduces weight and modulates ghrelin production, but largely spares gastrointestinal endocrine function. To examine this hypothesis, we determined plasma concentrations of appetite-control, insulinotropic, and digestive hormones in relation to LAGB. Twenty-four patients undergoing LAGB were prospectively enrolled. Body mass index (BMI) was measured and blood samples obtained at baseline and 6 and 12 months post-surgery. Plasma concentrations of leptin, acylated and total ghrelin, pancreatic polypeptide (PP), insulin, glucose-dependent insulinotropic peptide (GIP), active glucagon-like peptide-1 (GLP-1), gastrin, and pepsinogens I and II were measured using enzyme-linked immunoassays. Median percent excess weight loss (%EWL) over 12 months was 45.7% with median BMI decreasing from 43.2 at baseline to 33.8 at 12 months post-surgery (p < 0.001). Median leptin levels decreased from 19.7 ng/ml at baseline to 6.9 ng/ml at 12 months post-surgery (p < 0.001). In contrast, plasma levels of acylated and total ghrelin, PP, insulin, GIP, GLP-1, gastrin, and pepsinogen I did not change in relation to surgery (p > 0.05). Pepsinogen II levels were significantly lower 6 months after LAGB but returned to baseline levels by 12 months. LAGB yielded substantial %EWL and a proportional decrease in plasma leptin. Our results support the hypothesis that LAGB works in part by suppressing the rise in ghrelin that normally accompanies weight loss. Unchanged concentrations of insulinotropic and digestive hormones suggest that gastrointestinal endocrine function is largely maintained in the long term.

Gastrointestinal and pancreatic hormones in the human fetus and mother at 18-21 weeks of gestation.

PubMed

Adrian, T E; Soltesz, G; MacKenzie, I Z; Bloom, S R; Aynsley-Green, A

1995-01-01

Several gastrointestinal hormones appear to play an important developmental role in the newborn, particularly in preterm neonates. Although the cells producing these peptides develop towards the end of the first trimester, fetal secretion of these regulatory peptides has not hitherto been demonstrated. Using samples collected by fetoscopy at 19-21 weeks of gestation we have measured concentrations of several gastrointestinal and pancreatic hormones. Maternal venous and amniotic fluid hormone concentrations were measured simultaneously. Concentrations of the pancreatic hormones, insulin, glucagon and pancreatic polypeptide (PP) were similar in fetal and maternal blood. Gastrin and motilin were present in the fetal circulation but at about 30% (p < 0.05) and 60% (p < 0.01) of the maternal levels, respectively. In contrast, enteroglucagon concentrations were more than twofold higher in the fetal circulation compared with maternal levels (p < 0.05). Concentrations of gastric inhibitory polypeptide (GIP) in fetal blood were higher than levels in maternal blood but not significantly. Concentrations of GIP (p < 0.001) were higher in the amniotic fluid than the fetal circulation. Gastrin and glucagon levels were similar in amniotic fluid and fetal blood. In contrast, PP and motilin were present in amniotic fluid, but at lower concentrations than in fetal blood. Enteroglucagon was not detectable in amniotic fluid. In conclusion, several alimentary hormones are secreted in the fetus at midterm. Since these peptides have trophic, secretory and motor effects on the gut, it is likely that these regulatory peptides are involved in the functional development of the fetal intestine.

The effect of 8 days of strict bed rest on the incretin effect in healthy volunteers.

PubMed

Nielsen, Signe Tellerup; Harder-Lauridsen, Nina Majlund; Benatti, Fabiana Braga; Wedell-Neergaard, Anne-Sophie; Lyngbæk, Mark Preben; Møller, Kirsten; Pedersen, Bente Klarlund; Krogh-Madsen, Rikke

2016-03-15

Bed rest and physical inactivity are the consequences of hospital admission for many patients. Physical inactivity induces changes in glucose metabolism, but its effect on the incretin effect, which is reduced in, e.g., Type 2 diabetes, is unknown. To investigate how 8 days of strict bed rest affects the incretin effect, 10 healthy nonobese male volunteers underwent 8 days of strict bed rest. Before and after the intervention, all volunteers underwent an oral glucose tolerance test (OGTT) followed by an intravenous glucose infusion (IVGI) on the following day to mimic the blood glucose profile from the OGTT. Blood glucose, serum insulin, serum C-peptide, plasma incretin hormones [glucagon-like peptide (GLP-1) and glucose-dependent insulinotropic peptide (GIP)], and serum glucagon were measured serially during both the OGTT and the IVGI. The incretin effect is calculated as the relative difference between the area under the curve for the insulin response during the OGTT and that of the corresponding IVGI, respectively. Concentrations of glucose, insulin, C-peptide, and GIP measured during the OGTT were higher after the bed rest intervention (all P < 0.05), whereas there was no difference in the levels of GLP-1 and Glucagon. Bed rest led to a mean loss of 2.4 kg of fat-free mass, and induced insulin resistance evaluated by the Matsuda index, but did not affect the incretin effect (P = 0.6). In conclusion, 8 days of bed rest induces insulin resistance, but we did not see evidence of an associated change in the incretin effect. Copyright © 2016 the American Physiological Society.

78 FR 44138 - National Environmental Policy Act; Implementing Procedures; Addition of Categorical Exclusion for...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-23

... Policy Act; Implementing Procedures; Addition of Categorical Exclusion for Real Property Disposal AGENCY... announces the addition of a new Categorical Exclusion (CATEX) for Real Property Disposal under the National... Security NEPA implementing procedures by establishing a new CATEX for real property disposal undertaken by...

14 CFR 1232.104 - Implementation procedures by non-NASA institutions.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 14 Aeronautics and Space 5 2012-01-01 2012-01-01 false Implementation procedures by non-NASA... CARE AND USE OF ANIMALS IN THE CONDUCT OF NASA ACTIVITIES § 1232.104 Implementation procedures by non-NASA institutions. (a) Proposal Information. No animal subjects may be utilized unless a proposal...

14 CFR 1232.104 - Implementation procedures by non-NASA institutions.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 14 Aeronautics and Space 5 2013-01-01 2013-01-01 false Implementation procedures by non-NASA... CARE AND USE OF ANIMALS IN THE CONDUCT OF NASA ACTIVITIES § 1232.104 Implementation procedures by non-NASA institutions. (a) Proposal Information. No animal subjects may be utilized unless a proposal...

14 CFR 1232.104 - Implementation procedures by non-NASA institutions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 5 2011-01-01 2010-01-01 true Implementation procedures by non-NASA... CARE AND USE OF ANIMALS IN THE CONDUCT OF NASA ACTIVITIES § 1232.104 Implementation procedures by non-NASA institutions. (a) Proposal Information. No animal subjects may be utilized unless a proposal...

14 CFR 1232.104 - Implementation procedures by non-NASA institutions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Implementation procedures by non-NASA... CARE AND USE OF ANIMALS IN THE CONDUCT OF NASA ACTIVITIES § 1232.104 Implementation procedures by non-NASA institutions. (a) Proposal Information. No animal subjects may be utilized unless a proposal...

10 CFR 26.127 - Procedures.

Code of Federal Regulations, 2014 CFR

2014-01-01

..., implement, and maintain written standard operating procedures for each assay performed for drug and specimen... facility shall develop, implement, and maintain written standard operating procedures for each test. The...; (2) Preparation of reagents, standards, and controls; (3) Calibration procedures; (4) Derivation of...

10 CFR 26.127 - Procedures.

Code of Federal Regulations, 2012 CFR

2012-01-01

..., implement, and maintain written standard operating procedures for each assay performed for drug and specimen... facility shall develop, implement, and maintain written standard operating procedures for each test. The...; (2) Preparation of reagents, standards, and controls; (3) Calibration procedures; (4) Derivation of...

10 CFR 26.127 - Procedures.

Code of Federal Regulations, 2013 CFR

2013-01-01

..., implement, and maintain written standard operating procedures for each assay performed for drug and specimen... facility shall develop, implement, and maintain written standard operating procedures for each test. The...; (2) Preparation of reagents, standards, and controls; (3) Calibration procedures; (4) Derivation of...

Gut hormones in acute diarrhoea.

PubMed Central

Besterman, H S; Christofides, N D; Welsby, P D; Adrian, T E; Sarson, D L; Bloom, S R

1983-01-01

The gut hormone response to a breakfast meal was studied in 12 subjects hospitalised for an episode of acute diarrhoea (presumed infective) who were otherwise well and in 13 healthy control subjects. Fasting blood glucose concentrations were low but basal insulin concentrations were raised. Basal concentrations of pancreatic polypeptide and both basal and postprandial responses of motilin, enteroglucagon, and vasoactive intestinal polypeptide (VIP) were also significantly greater than controls. No abnormalities in plasma concentrations of gastrin, gastric inhibitory polypeptide (GIP) or pancreatic glucagon were found. The suggested physiological actions of the raised hormones may be relevant to the pathophysiology of diarrhoea. PMID:6345284

Gut hormones in acute diarrhoea.

PubMed

Besterman, H S; Christofides, N D; Welsby, P D; Adrian, T E; Sarson, D L; Bloom, S R

1983-07-01

The gut hormone response to a breakfast meal was studied in 12 subjects hospitalised for an episode of acute diarrhoea (presumed infective) who were otherwise well and in 13 healthy control subjects. Fasting blood glucose concentrations were low but basal insulin concentrations were raised. Basal concentrations of pancreatic polypeptide and both basal and postprandial responses of motilin, enteroglucagon, and vasoactive intestinal polypeptide (VIP) were also significantly greater than controls. No abnormalities in plasma concentrations of gastrin, gastric inhibitory polypeptide (GIP) or pancreatic glucagon were found. The suggested physiological actions of the raised hormones may be relevant to the pathophysiology of diarrhoea.

15 CFR 23.7 - Notice to Department of Commerce organizational units of implementation and procedures.

Code of Federal Regulations, 2010 CFR

2010-01-01

... organizational units of implementation and procedures. 23.7 Section 23.7 Commerce and Foreign Trade Office of the... Department of Commerce organizational units of implementation and procedures. Following are roles and...) Otherwise determine and control the use of missing children materials and information by the Operating Unit...

14 CFR § 1232.105 - Implementation procedures by NASA field installations.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 5 2014-01-01 2014-01-01 false Implementation procedures by NASA field... ADMINISTRATION CARE AND USE OF ANIMALS IN THE CONDUCT OF NASA ACTIVITIES (Eff. until 2-14-14) § 1232.105 Implementation procedures by NASA field installations. (a) Proposal Information. The information required for...

28 CFR Appendix D to Part 61 - Office of Justice Assistance, Research, and Statistics Procedures Relating to the Implementation...

Code of Federal Regulations, 2011 CFR

2011-07-01

..., and Statistics Procedures Relating to the Implementation of the National Environmental Policy Act D... Assistance, Research, and Statistics Procedures Relating to the Implementation of the National Environmental... Statistics (OJARS) assists State and local units of government in strengthening and improving law enforcement...

28 CFR Appendix D to Part 61 - Office of Justice Assistance, Research, and Statistics Procedures Relating to the Implementation...

Code of Federal Regulations, 2010 CFR

2010-07-01

..., and Statistics Procedures Relating to the Implementation of the National Environmental Policy Act D... Assistance, Research, and Statistics Procedures Relating to the Implementation of the National Environmental... Statistics (OJARS) assists State and local units of government in strengthening and improving law enforcement...

49 CFR 218.97 - Good faith challenge procedures.

Code of Federal Regulations, 2011 CFR

2011-10-01

... the railroad's operating rules implementing the requirements of this subpart. (b) General procedures... requirements of this subpart. (1) Each railroad or employer shall adopt and implement written procedures which... fulfill the requirements of this subpart. Each railroad or employer's written procedures shall provide for...

49 CFR 218.97 - Good faith challenge procedures.

Code of Federal Regulations, 2014 CFR

2014-10-01

... the railroad's operating rules implementing the requirements of this subpart. (b) General procedures... requirements of this subpart. (1) Each railroad or employer shall adopt and implement written procedures which... fulfill the requirements of this subpart. Each railroad or employer's written procedures shall provide for...

49 CFR 218.97 - Good faith challenge procedures.

Code of Federal Regulations, 2013 CFR

2013-10-01

... the railroad's operating rules implementing the requirements of this subpart. (b) General procedures... requirements of this subpart. (1) Each railroad or employer shall adopt and implement written procedures which... fulfill the requirements of this subpart. Each railroad or employer's written procedures shall provide for...

49 CFR 218.97 - Good faith challenge procedures.

Code of Federal Regulations, 2010 CFR

2010-10-01

... the railroad's operating rules implementing the requirements of this subpart. (b) General procedures... requirements of this subpart. (1) Each railroad or employer shall adopt and implement written procedures which... fulfill the requirements of this subpart. Each railroad or employer's written procedures shall provide for...

49 CFR 218.97 - Good faith challenge procedures.

Code of Federal Regulations, 2012 CFR

2012-10-01

... the railroad's operating rules implementing the requirements of this subpart. (b) General procedures... requirements of this subpart. (1) Each railroad or employer shall adopt and implement written procedures which... fulfill the requirements of this subpart. Each railroad or employer's written procedures shall provide for...

Improved Equivalent Linearization Implementations Using Nonlinear Stiffness Evaluation

NASA Technical Reports Server (NTRS)

Rizzi, Stephen A.; Muravyov, Alexander A.

2001-01-01

This report documents two new implementations of equivalent linearization for solving geometrically nonlinear random vibration problems of complicated structures. The implementations are given the acronym ELSTEP, for "Equivalent Linearization using a STiffness Evaluation Procedure." Both implementations of ELSTEP are fundamentally the same in that they use a novel nonlinear stiffness evaluation procedure to numerically compute otherwise inaccessible nonlinear stiffness terms from commercial finite element programs. The commercial finite element program MSC/NASTRAN (NASTRAN) was chosen as the core of ELSTEP. The FORTRAN implementation calculates the nonlinear stiffness terms and performs the equivalent linearization analysis outside of NASTRAN. The Direct Matrix Abstraction Program (DMAP) implementation performs these operations within NASTRAN. Both provide nearly identical results. Within each implementation, two error minimization approaches for the equivalent linearization procedure are available - force and strain energy error minimization. Sample results for a simply supported rectangular plate are included to illustrate the analysis procedure.

14 CFR 1232.105 - Implementation procedures by NASA field installations.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 5 2011-01-01 2010-01-01 true Implementation procedures by NASA field... CARE AND USE OF ANIMALS IN THE CONDUCT OF NASA ACTIVITIES § 1232.105 Implementation procedures by NASA... of animal subjects is identical to that described in § 1232.104(a). (b) Proposal Approval by the NASA...

14 CFR 1232.105 - Implementation procedures by NASA field installations.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 14 Aeronautics and Space 5 2012-01-01 2012-01-01 false Implementation procedures by NASA field... CARE AND USE OF ANIMALS IN THE CONDUCT OF NASA ACTIVITIES § 1232.105 Implementation procedures by NASA... of animal subjects is identical to that described in § 1232.104(a). (b) Proposal Approval by the NASA...

14 CFR § 1232.104 - Implementation procedures by non-NASA institutions.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 5 2014-01-01 2014-01-01 false Implementation procedures by non-NASA... ADMINISTRATION CARE AND USE OF ANIMALS IN THE CONDUCT OF NASA ACTIVITIES (Eff. until 2-14-14) § 1232.104 Implementation procedures by non-NASA institutions. (a) Proposal Information. No animal subjects may be utilized...

14 CFR 1232.105 - Implementation procedures by NASA field installations.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Implementation procedures by NASA field... CARE AND USE OF ANIMALS IN THE CONDUCT OF NASA ACTIVITIES § 1232.105 Implementation procedures by NASA... of animal subjects is identical to that described in § 1232.104(a). (b) Proposal Approval by the NASA...

14 CFR 1232.105 - Implementation procedures by NASA field installations.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 14 Aeronautics and Space 5 2013-01-01 2013-01-01 false Implementation procedures by NASA field... CARE AND USE OF ANIMALS IN THE CONDUCT OF NASA ACTIVITIES § 1232.105 Implementation procedures by NASA... of animal subjects is identical to that described in § 1232.104(a). (b) Proposal Approval by the NASA...

22 CFR 911.3 - Procedure.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 22 Foreign Relations 2 2014-04-01 2014-04-01 false Procedure. 911.3 Section 911.3 Foreign Relations FOREIGN SERVICE GRIEVANCE BOARD IMPLEMENTATION DISPUTES § 911.3 Procedure. Implementation disputes shall be handled by the Board in accordance with the procedures set forth in parts 901-910 of this...

22 CFR 911.3 - Procedure.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 22 Foreign Relations 2 2011-04-01 2009-04-01 true Procedure. 911.3 Section 911.3 Foreign Relations FOREIGN SERVICE GRIEVANCE BOARD IMPLEMENTATION DISPUTES § 911.3 Procedure. Implementation disputes shall be handled by the Board in accordance with the procedures set forth in parts 901-910 of this chapter. ...

22 CFR 911.3 - Procedure.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 22 Foreign Relations 2 2013-04-01 2009-04-01 true Procedure. 911.3 Section 911.3 Foreign Relations FOREIGN SERVICE GRIEVANCE BOARD IMPLEMENTATION DISPUTES § 911.3 Procedure. Implementation disputes shall be handled by the Board in accordance with the procedures set forth in parts 901-910 of this chapter. ...

22 CFR 911.3 - Procedure.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 22 Foreign Relations 2 2012-04-01 2009-04-01 true Procedure. 911.3 Section 911.3 Foreign Relations FOREIGN SERVICE GRIEVANCE BOARD IMPLEMENTATION DISPUTES § 911.3 Procedure. Implementation disputes shall be handled by the Board in accordance with the procedures set forth in parts 901-910 of this chapter. ...

22 CFR 911.3 - Procedure.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 22 Foreign Relations 2 2010-04-01 2010-04-01 true Procedure. 911.3 Section 911.3 Foreign Relations FOREIGN SERVICE GRIEVANCE BOARD IMPLEMENTATION DISPUTES § 911.3 Procedure. Implementation disputes shall be handled by the Board in accordance with the procedures set forth in parts 901-910 of this chapter. ...

Clinical Pharmacokinetics and Pharmacodynamics of Saxagliptin, a Dipeptidyl Peptidase-4 Inhibitor.

PubMed

Boulton, David W

2017-01-01

Saxagliptin is an orally active, highly potent, selective and competitive dipeptidyl peptidase (DPP)-4 inhibitor used in the treatment of type 2 diabetes mellitus at doses of 2.5 or 5 mg once daily. DPP-4 is responsible for degrading the intestinally derived hormones glucagon-like peptide (GLP)-1 and glucose-dependent insulinotropic polypeptide (GIP). Inhibition of DPP-4 increases intact plasma GLP-1 and GIP concentrations, augmenting glucose-dependent insulin secretion. Both saxagliptin and its major active metabolite, 5-hydroxy saxagliptin, demonstrate high degrees of selectivity for DPP-4 compared with other DPP enzymes. Saxagliptin is orally absorbed and can be administered with or without food. The half-life of plasma DPP-4 inhibition with saxagliptin 5 mg is ~27 h, which supports a once-daily dosing regimen. Saxagliptin is metabolized by cytochrome P450 (CYP) 3A4/5 and is eliminated by a combination of renal and hepatic clearance. No clinically meaningful differences in saxagliptin or 5-hydroxy saxagliptin pharmacokinetics have been detected in patients with hepatic impairment. No clinically meaningful differences in saxagliptin or 5-hydroxy saxagliptin pharmacokinetics have been detected in patients with mild renal impairment, whereas dose reduction is recommended in patients with moderate or severe renal impairment because of greater systemic exposure [the area under the plasma concentration-time curve (AUC)] to saxagliptin total active moieties. Clinically relevant drug-drug interactions have not been detected; however, limiting the dose to 2.5 mg once daily is recommended in the USA when saxagliptin is coadministered with strong CYP inhibitors, because of increased saxagliptin exposure. In summary, saxagliptin has a predictable pharmacokinetic and pharmacodynamic profile.

High fat diet impairs the function of glucagon-like peptide-1 producing L-cells.

PubMed

Richards, Paul; Pais, Ramona; Habib, Abdella M; Brighton, Cheryl A; Yeo, Giles S H; Reimann, Frank; Gribble, Fiona M

2016-03-01

Glucagon-like peptide-1 (GLP-1) acts as a satiety signal and enhances insulin release. This study examined how GLP-1 production from intestinal L-cells is modified by dietary changes. Transgenic mouse models were utilized in which L-cells could be purified by cell specific expression of a yellow fluorescent protein, Venus. Mice were fed on chow or 60% high fat diet (HFD) for 2 or 16 weeks. L-cells were purified by flow cytometry and analysed by microarray and quantitative RT-PCR. Enteroendocrine cell populations were examined by FACS analysis, and GLP-1 secretion was assessed in primary intestinal cultures. Two weeks HFD reduced the numbers of GLP-1 positive cells in the colon, and of GIP positive cells in the small intestine. Purified small intestinal L-cells showed major shifts in their gene expression profiles. In mice on HFD for 16 weeks, significant reductions were observed in the expression of L-cell specific genes, including those encoding gut hormones (Gip, Cck, Sct, Nts), prohormone processing enzymes (Pcsk1, Cpe), granins (Chgb, Scg2), nutrient sensing machinery (Slc5a1, Slc15a1, Abcc8, Gpr120) and enteroendocrine-specific transcription factors (Etv1, Isl1, Mlxipl, Nkx2.2 and Rfx6). A corresponding reduction in the GLP-1 secretory responsiveness to nutrient stimuli was observed in primary small intestinal cultures. Mice fed on HFD exhibited reduced expression in L-cells of many L-cell specific genes, suggesting an impairment of enteroendocrine cell function. Our results suggest that a western style diet may detrimentally affect the secretion of gut hormones and normal post-prandial signaling, which could impact on insulin secretion and satiety. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Incretin secretion in obese Korean children and adolescents with newly diagnosed type 2 diabetes.

PubMed

Park, So Hyun; Jung, Min Ho; Cho, Won Kyoung; Park, Mi Sun; Suh, Byung Kyu

2016-01-01

The role of incretins in type 2 diabetes is controversial. This study investigated the association between incretin levels in obese Korean children and adolescents newly diagnosed with type 2 diabetes. We performed a 2-hr oral glucose tolerance test (OGTT) in obese children and adolescents with type 2 diabetes and with normal glucose tolerance. Twelve obese children and adolescents with newly diagnosed type 2 diabetes (DM group) and 12 obese age-matched subjects without type 2 diabetes (NDM group) were included. An OGTT was conducted and insulin, C-peptide, glucagon, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) were measured during the OGTT. The mean age of the patients was 13·8 ± 2·0 years, and the mean body mass index (BMI) Z-score was 2·1 ± 0·5. The groups were comparable in age, sex, BMI Z-score and waist:hip ratio. The DM group had significantly lower homeostasis model assessment of β and insulinogenic index values (P < 0·001). The homeostasis model assessment of insulin resistance index was not different between the two groups. Insulin and C-peptide secretions were significantly lower in the DM group than in the NDM group (P < 0·001). Total GLP-1 secretion was significantly higher in the DM group while intact GLP-1 and GIP secretion values were not significantly different between the two groups. Impaired insulin secretion might be important in the pathogenesis of type 2 diabetes in obese Korean children and adolescents, however, which may not be attributed to incretin secretion. © 2015 John Wiley & Sons Ltd.

Isolation and characterization of Salmonella enterica in day-old ducklings in Egypt

PubMed Central

Osman, Kamelia M; Marouf, Sherif H; Zolnikov, Tara R; AlAtfeehy, Nayerah

2014-01-01

Importing day-old ducklings (DOD) unknowingly infected with non-typhoid Salmonella (NTS) may be associated with disease risk. Domestic and international trade may enhance this risk. Salmonella enterica serovars, their virulence genes combinations and antibiotic resistance, garner attention for their potentiality to contribute to the adverse health effects on populations throughout the world. The aim of this study was to estimate the risk of imported versus domestic DOD as potential carriers of NTS. The results confirm the prevalence of salmonellosis in imported ducklings was 18.5% (25/135), whereas only 12% (9/75) of cases were determined in the domestic ducklings. Fourteen serovars (Salmonella enteritidis, Salmonella kisii, Salmonella typhimurium, Salmonella gaillac, Salmonella uno, Salmonella eingedi, Salmonella shubra, Salmonella bardo, Salmonella inganda, Salmonella kentucky, Salmonella stanley, Salmonella virchow, Salmonella haifa, and Salmonella anatum) were isolated from the imported ducklings, whereas only S. enteritidis, S. typhimurium, S. virchow, and S. shubra were isolated from the domestic ducklings. The isolated Salmonella serovars were 100% susceptible to only colistin sulphate and 100% resistant to lincomycin. The 14 Salmonella serovars were screened for 11 virulence genes (invA, avrA, ssaQ, mgtC, siiD, sopB, gipA, sodC1, sopE1, spvC, and bcfC) by PCR. The invA, sopB, and bcfC genes were detected in 100% of the Salmonella serovars; alternatively, the gipA gene was absent in all of the isolated Salmonella serovars. The 11 virulent genes were not detected in either of S. stanley or S. haifa serovars. The results confirm an association between antibiotic resistance and virulence of Salmonella in the DOD. This study confirms the need for a country adherence to strict public health and food safety regimes. PMID:24548159

The impact of food viscosity on eating rate, subjective appetite, glycemic response and gastric emptying rate.

PubMed

Zhu, Yong; Hsu, Walter H; Hollis, James H

2013-01-01

Understanding the impact of rheological properties of food on postprandial appetite and glycemic response helps to design novel functional products. It has been shown that solid foods have a stronger satiating effect than their liquid equivalent. However, whether a subtle change in viscosity of a semi-solid food would have a similar effect on appetite is unknown. Fifteen healthy males participated in the randomized cross-over study. Each participant consumed a 1690 kJ portion of a standard viscosity (SV) and a high viscosity (HV) semi-solid meal with 1000 mg acetaminophen in two separate sessions. At regular intervals during the three hours following the meal, subjective appetite ratings were measured and blood samples collected. The plasma samples were assayed for insulin, glucose-dependent insulinotropic peptide (GIP), glucose and acetaminophen. After three hours, the participants were provided with an ad libitum pasta meal. Compared with the SV meal, HV was consumed at a slower eating rate (P = 0.020), with postprandial hunger and desire to eat being lower (P = 0.019 and P<0.001 respectively) while fullness was higher (P<0.001). In addition, consuming the HV resulted in lower plasma concentration of GIP (P<0.001), higher plasma concentration of glucose (P<0.001) and delayed gastric emptying as revealed by the acetaminophen absorption test (P<0.001). However, there was no effect of food viscosity on insulin or food intake at the subsequent meal. In conclusion, increasing the viscosity of a semi-solid food modulates glycemic response and suppresses postprandial satiety, although the effect may be short-lived. A slower eating rate and a delayed gastric emptying rate can partly explain for the stronger satiating properties of high viscous semi-solid foods.

Effect of Acarbose, Sitagliptin and combination therapy on blood glucose, insulin, and incretin hormone concentrations in experimentally induced postprandial hyperglycemia of healthy cats.

PubMed

Mori, Akihiro; Ueda, Kaori; Lee, Peter; Oda, Hitomi; Ishioka, Katsumi; Arai, Toshiro; Sako, Toshinori

2016-06-01

Acarbose (AC) and Sitagliptin (STGP) are oral hypoglycemic agents currently used either alone or in conjunction with human diabetic (Type 2) patients. AC has been used with diabetic cats, but not STGP thus far. Therefore, the objective of this study was to determine the potential use of AC or STGP alone and in combination for diabetic cats, by observing their effect on short-term post-prandial serum glucose, insulin, and incretin hormone (active glucagon-like peptide-1 (GLP-1) and total glucose dependent insulinotropic polypeptide (GIP)) concentrations in five healthy cats, following ingestion of a meal with maltose. All treatments tended (p<0.10; 5-7.5% reduction) to reduce postprandial glucose area under the curve (AUC), with an accompanying significant reduction (p<0.05, 35-45%) in postprandial insulin AUC as compared to no treatment. Meanwhile, a significant increase (p<0.05) in postprandial active GLP-1 AUC was observed with STGP (100% higher) and combined treatment (130% greater), as compared to either AC or no treatment. Lastly, a significant reduction (p<0.05) in postprandial total GIP AUC was observed with STGP (21% reduction) and combined treatment (7% reduction) as compared to control. Overall, AC, STGP, or combined treatment can significantly induce positive post-prandial changes to insulin and incretin hormone levels of healthy cats. Increasing active GLP-1 and reducing postprandial hyperglycemia appear to be the principal mechanisms of combined treatment. Considering the different, but complementary mechanisms of action by which AC and STGP induce lower glucose and insulin levels, combination therapy with both these agents offers great potential for treating diabetic cats in the future. Copyright © 2016 Elsevier Ltd. All rights reserved.

Mechanisms Regulating Insulin Response to Intragastric Glucose in Lean and Non-Diabetic Obese Subjects: A Randomized, Double-Blind, Parallel-Group Trial

PubMed Central

Meyer-Gerspach, Anne Christin; Cajacob, Lucian; Riva, Daniele; Herzog, Raphael; Drewe, Juergen; Beglinger, Christoph; Wölnerhanssen, Bettina K.

2016-01-01

Background/Objectives The changes in blood glucose concentrations that result from an oral glucose challenge are dependent on the rate of gastric emptying, the rate of glucose absorption and the rate of insulin-driven metabolism that include the incretins, glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1). The rate of insulin-driven metabolism is clearly altered in obese subjects, but it is controversial which of these factors is predominant. We aimed to quantify gastric emptying, plasma insulin, C-peptide, glucagon and glucose responses, as well as incretin hormone secretions in obese subjects and healthy controls during increasing glucose loads. Subjects/Methods The study was conducted as a randomized, double-blind, parallel-group trial in a hospital research unit. A total of 12 normal weight (6 men and 6 women) and 12 non-diabetic obese (BMI > 30, 6 men and 6 women) participants took part in the study. Subjects received intragastric loads of 10 g, 25 g and 75 g glucose dissolved in 300 ml tap water. Results Main outcome measures were plasma GLP-1 and GIP, plasma glucagon, glucose, insulin, C-peptide and gastric emptying. The primary findings are: i) insulin resistance (P < 0.001) and hyperinsulinemia (P < 0.001); ii) decreased insulin disposal (P < 0.001); iii) trend for reduced GLP-1 responses at 75 g glucose; and iv) increased fasting glucagon levels (P < 0.001) in obese subjects. Conclusions It seems that, rather than changes in incretin secretion, fasting hyperglucagonemia and consequent hyperglycemia play a role in reduced disposal of insulin, contributing to hyperinsulinemia and insulin resistance. Trial Registration ClinicalTrials.gov NCT01875575 PMID:26942445

Cut to the chase: a review of CD26/dipeptidyl peptidase‐4's (DPP4) entanglement in the immune system

PubMed Central

Wagner, L.; Stephan, M.; von Hörsten, S.

2016-01-01

Summary CD26/DPP4 (dipeptidyl peptidase 4/DP4/DPPIV) is a surface T cell activation antigen and has been shown to have DPP4 enzymatic activity, cleaving‐off amino‐terminal dipeptides with either L‐proline or L‐alanine at the penultimate position. It plays a major role in glucose metabolism by N‐terminal truncation and inactivation of the incretins glucagon‐like peptide‐1 (GLP) and gastric inhibitory protein (GIP). In 2006, DPP4 inhibitors have been introduced to clinics and have been demonstrated to efficiently enhance the endogenous insulin secretion via prolongation of the half‐life of GLP‐1 and GIP in patients. However, a large number of studies demonstrate clearly that CD26/DPP4 also plays an integral role in the immune system, particularly in T cell activation. Therefore, inhibition of DPP4 might represent a double‐edged sword. Apart from the metabolic benefit, the associated immunological effects of long term DPP4 inhibition on regulatory processes such as T cell homeostasis, maturation and activation are not understood fully at this stage. The current data point to an important role for CD26/DPP4 in maintaining lymphocyte composition and function, T cell activation and co‐stimulation, memory T cell generation and thymic emigration patterns during immune‐senescence. In rodents, critical immune changes occur at baseline levels as well as after in‐vitro and in‐vivo challenge. In patients receiving DPP4 inhibitors, evidence of immunological side effects also became apparent. The scope of this review is to recapitulate the role of CD26/DPP4 in the immune system regarding its pharmacological inhibition and T cell‐dependent immune regulation. PMID:26919392

Characteristics of iron corrosion scales and water quality variations in drinking water distribution systems of different pipe materials.

PubMed

Li, Manjie; Liu, Zhaowei; Chen, Yongcan; Hai, Yang

2016-12-01

Interaction between old, corroded iron pipe surfaces and bulk water is crucial to the water quality protection in drinking water distribution systems (WDS). Iron released from corrosion products will deteriorate water quality and lead to red water. This study attempted to understand the effects of pipe materials on corrosion scale characteristics and water quality variations in WDS. A more than 20-year-old hybrid pipe section assembled of unlined cast iron pipe (UCIP) and galvanized iron pipe (GIP) was selected to investigate physico-chemical characteristics of corrosion scales and their effects on water quality variations. Scanning Electron Microscope (SEM), Energy Dispersive X-ray Spectroscopy (EDS), Inductively Coupled Plasma (ICP) and X-ray Diffraction (XRD) were used to analyze micromorphology and chemical composition of corrosion scales. In bench testing, water quality parameters, such as pH, dissolved oxygen (DO), oxidation reduction potential (ORP), alkalinity, conductivity, turbidity, color, Fe 2+ , Fe 3+ and Zn 2+ , were determined. Scale analysis and bench-scale testing results demonstrated a significant effect of pipe materials on scale characteristics and thereby water quality variations in WDS. Characteristics of corrosion scales sampled from different pipe segments show obvious differences, both in physical and chemical aspects. Corrosion scales were found highly amorphous. Thanks to the protection of zinc coatings, GIP system was identified as the best water quality stability, in spite of high zinc release potential. It is deduced that the complicated composition of corrosion scales and structural break by the weld result in the diminished water quality stability in HP system. Measurement results showed that iron is released mainly in ferric particulate form. Copyright © 2016 Elsevier Ltd. All rights reserved.

Cardiovascular pleiotropic actions of DPP-4 inhibitors: a step at the cutting edge in understanding their additional therapeutic potentials.

PubMed

Balakumar, Pitchai; Dhanaraj, Sokkalingam A

2013-09-01

Dipeptidyl peptidase 4 (DPP-4) is a serine protease enzyme expressed widely in many tissues, including the cardiovascular system. The incretin hormones such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are released from the small intestine into the vasculature during a meal, and these incretins have a potential to release insulin from pancreatic beta cells of islets of Langerhans, affording a glucose-lowering action. However, both incretins are hurriedly degraded by the DPP-4. Inhibitors of DPP-4, therefore, enhance the bioavailability of GLP-1 and GIP, and thus have been approved for better glycemic management in patients afflicted with type 2 diabetes mellitus (T2DM). Five different DPP-4 inhibitors, often called as 'gliptins', namely sitagliptin, vildagliptin, saxagliptin, linagliptin and alogliptin have been approved hitherto for clinical use. These drugs are used along with diet and exercise to lower blood sugar in diabetic subjects. T2DM is intricately related with an increased risk of cardiovascular disease. Growing body of evidence suggests that gliptins, in addition to their persuasive anti-diabetic action, have a beneficial pleiotropic action on the heart and vessels. In view of the fact of cardiovascular disease susceptibility of patients afflicted with T2DM, gliptins might offer additional therapeutic benefits in treating diabetic cardiovascular complications. Exploring further the cardiovascular pleiotropic potentials of gliptins might open a panorama in impeccably employing these agents for the dual management of T2DM and T2DM-associated perilous cardiovascular complications. This review will shed lights on the newly identified beneficial pleiotropic actions of gliptins on the cardiovascular system. Copyright © 2013 Elsevier Inc. All rights reserved.

Who Really Wants an Ambitious Large-Scale Restoration of the Seine Estuary? A Strategic Analysis of a Science-Policy Interface Locked in a Stalemate.

PubMed

Coreau, Audrey; Narcy, Jean-Baptiste; Lumbroso, Sarah

2018-05-01

The development of ecosystem knowledge is an essential condition for effective environmental management but using available knowledge to solve environmental controversies is still difficult in "real" situations. This paper explores the conditions under which ecological knowledge could contribute to the environmental strategies and actions of stakeholders at science-policy interface. Ecological restoration of the Seine estuary is an example of an environmental issue whose overall management has run into difficulties despite the production of a large amount of knowledge by a dedicated organization, GIP Seine Aval. Thanks to an action-research project, based on a futures study, we analyze the reasons of these difficulties and help the GIP Seine Aval adopt a robust strategy to overcome them. According to our results, most local stakeholders involved in the large-scale restoration project emphasize the need for a clear divide between knowledge production and environmental action. This kind of divide may be strategic in a context where the robustness of environmental decisions is strongly depending on the mobilization of "neutral" scientific knowledge. But in our case study, this rather blocks action because some powerful stakeholders continuously ask for more knowledge before taking action. The construction and analysis of possible future scenarios has led to three alternative strategies being identified to counter this stalemate situation: (1) to circumvent difficulties by creating indirect links between knowledge and actions; (2) to use knowledge to sustain advocacy for the interests of each and every stakeholder; (3) to involve citizens in decisions about knowledge production and use, so that environmental issues weight more on the local political agenda.

Role of nutrient-sensing taste 1 receptor (T1R) family members in gastrointestinal chemosensing.

PubMed

Shirazi-Beechey, Soraya P; Daly, Kristian; Al-Rammahi, Miran; Moran, Andrew W; Bravo, David

2014-06-01

Luminal nutrient sensing by G-protein-coupled receptors (GPCR) expressed on the apical domain of enteroendocrine cells activates intracellular pathways leading to secretion of gut hormones that control vital physiological processes such as digestion, absorption, food intake and glucose homeostasis. The taste 1 receptor (T1R) family of GPCR consists of three members: T1R1; T1R2; T1R3. Expression of T1R1, T1R2 and T1R3 at mRNA and protein levels has been demonstrated in the intestinal tissue of various species. It has been shown that T1R2-T1R3, in association with G-protein gustducin, is expressed in intestinal K and L endocrine cells, where it acts as the intestinal glucose (sweet) sensor. A number of studies have demonstrated that activation of T1R2-T1R3 by natural sugars and artificial sweeteners leads to secretion of glucagon-like peptides 1&2 (GLP-1 and GLP-2) and glucose dependent insulinotropic peptide (GIP). GLP-1 and GIP enhance insulin secretion; GLP-2 increases intestinal growth and glucose absorption. T1R1-T1R3 combination co-expressed on the apical domain of cholecystokinin (CCK) expressing cells is a luminal sensor for a number of L-amino acids; with amino acid-activation of the receptor eliciting CCK secretion. This article focuses on the role of the gut-expressed T1R1, T1R2 and T1R3 in intestinal sweet and L-amino acid sensing. The impact of exploiting T1R2-T1R3 as a nutritional target for enhancing intestinal glucose absorption and gut structural maturity in young animals is also highlighted.

Soya milk exerts different effects on plasma amino acid responses and incretin hormone secretion compared with cows' milk in healthy, young men.

PubMed

Sun, Lijuan; Tan, Kevin Wei Jie; Siow, Phei Ching; Henry, Christiani Jeyakumar

2016-10-01

Apart from the well-known action of insulin, the mechanism by which soya and cows' milk improve postprandial glycaemia control was examined. In total, twelve healthy, young, Chinese men were studied on three separate occasions, in random order with isovolumetric (322 ml) control water, soya milk and cows' milk. Plasma total amino acid concentrations increased 30 min after test meals consumption and were higher after soya milk (230 %) and cow milk (240 %) consumption compared with water. Cows' milk ingestion induced higher branched-chain amino acids (BCAA) (40 %) than soya milk. Postprandial incretin concentrations increased after meal consumption. Cows' milk meal was accompanied by higher incremental AUC (iAUC) (170 %) for glucagon-like peptide-1 (GLP-1) compared with soya milk and control (P=0·06). However, glucose-dependent insulinotropic polypeptide (GIP) concentrations increased to significantly greater levels after soya milk consumption (iAUC 60 % higher) compared with cows' milk and control. Consumption of both soya and cows' milk with carbohydrates induced a similar reduction in glycaemic response through a different mechanism, beyond insulin action. Plasma amino acids (alanine and arginine), and incretins in particular (GIP was stimulated), may be involved in the hyperinsulinaemia after soya milk meals. However, BCAA and GLP-1 release may be responsible for the reduced glycaemia after cows' milk consumption by delaying gastric emptying. This could be the result of different milk protein/amino acid composition, but also differences in milk carbohydrate composition (i.e. lactose v. sucrose). It can be concluded that soya milk is a good alternative to cows' milk with regard to glycaemic regulation, with different mechanisms involved.

Inhibition of dipeptidyl-peptidase IV catalyzed peptide truncation by Vildagliptin ((2S)-{[(3-hydroxyadamantan-1-yl)amino]acetyl}-pyrrolidine-2-carbonitrile).

PubMed

Brandt, Inger; Joossens, Jurgen; Chen, Xin; Maes, Marie-Berthe; Scharpé, Simon; De Meester, Ingrid; Lambeir, Anne-Marie

2005-07-01

Vildagliptin (NVP-LAF237/(2S)-{[(3-hydroxyadamantan-1-yl)amino]acetyl}-pyrrolidine-2-carbonitrile) was described as a potent, selective and orally bio-available dipeptidyl-peptidase IV (DPP IV, EC 3.4.14.5) inhibitor [Villhauer EB, Brinkman JA, Naderi GB, Burkey BF, Dunning BE, Prasad K, et al.1-[[(3-Hydroxy-1-adamantyl)amino]acetyl]-2-cyano-(S)-pyrrolidine: a potent, selective, and orally bioavailable dipeptidyl peptidase IV inhibitor with antihyperglycemic properties. J Med Chem 2003;46:2774-89]. Phase III clinical trials for the use of this compound in the treatment of Type 2 diabetes were started in the first quarter of 2004. In this paper, we report on (1) the kinetics of binding, (2) the type of inhibition, (3) the selectivity with respect to other peptidases, and (4) the inhibitory potency on the DPP IV catalyzed degradation of glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and substance P. Vildagliptin behaved as a slow-binding DPP IV inhibitor with an association rate constant of 1.4x10(5)M(-1)s(-1) and a K(i) of 17nM. It is a micromolar inhibitor for dipeptidyl-peptidase 8 and does not significantly inhibit dipeptidyl-peptidase II (EC 3.4.11.2), prolyl oligopeptidase (EC 3.4.21.26), aminopeptidase P (EC 3.4.11.9) or aminopeptidase M (EC 3.4.11.2). There was no evidence for substrate specific inhibition of DPP IV by Vildagliptin or for important allosteric factors affecting the inhibition constant in presence of GIP and GLP-1.

The Role of SGLT1 and GLUT2 in Intestinal Glucose Transport and Sensing

PubMed Central

Röder, Pia V.; Geillinger, Kerstin E.; Zietek, Tamara S.; Thorens, Bernard; Koepsell, Hermann; Daniel, Hannelore

2014-01-01

Intestinal glucose absorption is mediated by SGLT1 whereas GLUT2 is considered to provide basolateral exit. Recently, it was proposed that GLUT2 can be recruited into the apical membrane after a high luminal glucose bolus allowing bulk absorption of glucose by facilitated diffusion. Moreover, SGLT1 and GLUT2 are suggested to play an important role in intestinal glucose sensing and incretin secretion. In mice that lack either SGLT1 or GLUT2 we re-assessed the role of these transporters in intestinal glucose uptake after radiotracer glucose gavage and performed Western blot analysis for transporter abundance in apical membrane fractions in a comparative approach. Moreover, we examined the contribution of these transporters to glucose-induced changes in plasma GIP, GLP-1 and insulin levels. In mice lacking SGLT1, tissue retention of tracer glucose was drastically reduced throughout the entire small intestine whereas GLUT2-deficient animals exhibited higher tracer contents in tissue samples than wild type animals. Deletion of SGLT1 resulted also in reduced blood glucose elevations and abolished GIP and GLP-1 secretion in response to glucose. In mice lacking GLUT2, glucose-induced insulin but not incretin secretion was impaired. Western blot analysis revealed unchanged protein levels of SGLT1 after glucose gavage. GLUT2 detected in apical membrane fractions mainly resulted from contamination with basolateral membranes but did not change in density after glucose administration. SGLT1 is unequivocally the prime intestinal glucose transporter even at high luminal glucose concentrations. Moreover, SGLT1 mediates glucose-induced incretin secretion. Our studies do not provide evidence for GLUT2 playing any role in either apical glucose influx or incretin secretion. PMID:24587162

Long-term etanercept therapy favors weight gain and ameliorates cachexia in rheumatoid arthritis patients: roles of gut hormones and leptin.

PubMed

Chen, Chih-Yen; Tsai, Chang-Youh; Lee, Pui-Ching; Lee, Shou-Dong

2013-01-01

Rheumatoid arthritis (RA) is a chronic inflammatory disease that damages the synovial joints, and patients with it are often anorexic and cachectic with high morbidity and mortality. Biological therapy with anti-tumor necrosis factor (TNF)-α has been proven effective as a treatment for RA. However, the long-term effects of anti-TNF-α therapy on body weight, appetite, plasma gut hormones and leptin have not been investigated. Twenty RA patients received subcutaneous injections of etanercept, a chimeric protein of human IgG1 Fc and TNF receptor p75, twice weekly for 12 consecutive months. Sequential changes in body weight, body fat, appetite rating, lipid profiles, gut hormones and leptin were measured at baseline and at 3 and 12 months after treatment. Ten RA patients who received non-biological disease modifying anti-rheumatic drugs were enrolled as the controls and were appraised at baseline and at 12 months after treatment (a nonrandomized study). Significant weight gain, hyperuricemia, decreased fasting plasma glucose-dependent insulinotropic polypeptide (GIP) levels, and loss of post-oral glucose suppression of plasma leptin concentration were found in the patients after the 12-month course of etanercept therapy, but not in the controls. A transient decrease in fasting plasma acyl ghrelin occurred at 3 months during etanercept treatment. Appetite score and serum lipid profiles did not change in either group. Long-term therapy with anti-TNF-α is promising in ameliorating body mass decrease in patients with active RA. Plasma levels of ghrelin, GIP and leptin may play significant roles in maintaining energy homeostasis in the anti-inflammatory responses during RA remission.

The Impact of Food Viscosity on Eating Rate, Subjective Appetite, Glycemic Response and Gastric Emptying Rate

PubMed Central

Zhu, Yong; Hsu, Walter H.; Hollis, James H.

2013-01-01

Understanding the impact of rheological properties of food on postprandial appetite and glycemic response helps to design novel functional products. It has been shown that solid foods have a stronger satiating effect than their liquid equivalent. However, whether a subtle change in viscosity of a semi-solid food would have a similar effect on appetite is unknown. Fifteen healthy males participated in the randomized cross-over study. Each participant consumed a 1690 kJ portion of a standard viscosity (SV) and a high viscosity (HV) semi-solid meal with 1000 mg acetaminophen in two separate sessions. At regular intervals during the three hours following the meal, subjective appetite ratings were measured and blood samples collected. The plasma samples were assayed for insulin, glucose-dependent insulinotropic peptide (GIP), glucose and acetaminophen. After three hours, the participants were provided with an ad libitum pasta meal. Compared with the SV meal, HV was consumed at a slower eating rate (P = 0.020), with postprandial hunger and desire to eat being lower (P = 0.019 and P<0.001 respectively) while fullness was higher (P<0.001). In addition, consuming the HV resulted in lower plasma concentration of GIP (P<0.001), higher plasma concentration of glucose (P<0.001) and delayed gastric emptying as revealed by the acetaminophen absorption test (P<0.001). However, there was no effect of food viscosity on insulin or food intake at the subsequent meal. In conclusion, increasing the viscosity of a semi-solid food modulates glycemic response and suppresses postprandial satiety, although the effect may be short-lived. A slower eating rate and a delayed gastric emptying rate can partly explain for the stronger satiating properties of high viscous semi-solid foods. PMID:23818981

Multimodel comparison of the ionosphere variability during the 2009 sudden stratosphere warming

NASA Astrophysics Data System (ADS)

Pedatella, N. M.; Fang, T.-W.; Jin, H.; Sassi, F.; Schmidt, H.; Chau, J. L.; Siddiqui, T. A.; Goncharenko, L.

2016-07-01

A comparison of different model simulations of the ionosphere variability during the 2009 sudden stratosphere warming (SSW) is presented. The focus is on the equatorial and low-latitude ionosphere simulated by the Ground-to-topside model of the Atmosphere and Ionosphere for Aeronomy (GAIA), Whole Atmosphere Model plus Global Ionosphere Plasmasphere (WAM+GIP), and Whole Atmosphere Community Climate Model eXtended version plus Thermosphere-Ionosphere-Mesosphere-Electrodynamics General Circulation Model (WACCMX+TIMEGCM). The simulations are compared with observations of the equatorial vertical plasma drift in the American and Indian longitude sectors, zonal mean F region peak density (NmF2) from the Constellation Observing System for Meteorology, Ionosphere, and Climate (COSMIC) satellites, and ground-based Global Positioning System (GPS) total electron content (TEC) at 75°W. The model simulations all reproduce the observed morning enhancement and afternoon decrease in the vertical plasma drift, as well as the progression of the anomalies toward later local times over the course of several days. However, notable discrepancies among the simulations are seen in terms of the magnitude of the drift perturbations, and rate of the local time shift. Comparison of the electron densities further reveals that although many of the broad features of the ionosphere variability are captured by the simulations, there are significant differences among the different model simulations, as well as between the simulations and observations. Additional simulations are performed where the neutral atmospheres from four different whole atmosphere models (GAIA, HAMMONIA (Hamburg Model of the Neutral and Ionized Atmosphere), WAM, and WACCMX) provide the lower atmospheric forcing in the TIME-GCM. These simulations demonstrate that different neutral atmospheres, in particular, differences in the solar migrating semidiurnal tide, are partly responsible for the differences in the simulated ionosphere variability in GAIA, WAM+GIP, and WACCMX+TIMEGCM.

Increased postprandial glycaemia, insulinemia, and lipidemia after 10 weeks’ sucrose-rich diet compared to an artificially sweetened diet: a randomised controlled trial

PubMed Central

Raben, Anne; Møller, Bente K.; Flint, Anne; Vasilaras, Tatjana H.; Christina Møller, A.; Juul Holst, Jens; Astrup, Arne

2011-01-01

Background The importance of exchanging sucrose for artificial sweeteners on risk factors for developing diabetes and cardiovascular diseases is not yet clear. Objective To investigate the effects of a diet high in sucrose versus a diet high in artificial sweeteners on fasting and postprandial metabolic profiles after 10 weeks. Design Healthy overweight subjects were randomised to consume drinks and foods sweetened with either sucrose (∼2 g/kg body weight) (n = 12) or artificial sweeteners (n = 11) as supplements to their usual diet. Supplements were similar on the two diets and consisted of beverages (∼80 weight%) and solid foods (yoghurts, marmalade, ice cream, stewed fruits). The rest of the diet was free of choice and ad libitum. Before (week 0) and after the intervention (week 10) fasting blood samples were drawn and in week 10, postprandial blood was sampled during an 8-hour meal test (breakfast and lunch). Results After 10 weeks postprandial glucose, insulin, lactate, triglyceride, leptin, glucagon, and GLP-1 were all significantly higher in the sucrose compared with the sweetener group. After adjusting for differences in body weight changes and fasting values (week 10), postprandial glucose, lactate, insulin, GIP, and GLP-1 were significantly higher and after further adjusting for differences in energy and sucrose intake, postprandial lactate, insulin, GIP, and GLP-1 levels were still significantly higher on the sucrose-rich diet. Conclusion A sucrose-rich diet consumed for 10 weeks resulted in significant elevations of postprandial glycaemia, insulinemia, and lipidemia compared to a diet rich in artificial sweeteners in slightly overweight healthy subjects. PMID:21799667

The antidiabetic action of camel milk in experimental type 2 diabetes mellitus: an overview on the changes in incretin hormones, insulin resistance, and inflammatory cytokines.

PubMed

Korish, A A

2014-06-01

Folk medicine stories accredited the aptitude of camel milk (CMK) as a hypoglycemic agent and recent studies have confirmed this in the diabetic patients and experimental animals. However, the mechanism(s) by which CMK influences glucose homeostasis is yet unclear. The current study investigated the changes in the glucose homeostatic parameters, the incretin hormones, and the inflammatory cytokines in the CMK-treated diabetic animals. A model of type 2 diabetes mellitus was induced in rats by intraperitoneal injection of streptozotocin 40 mg/kg/day for 4 repeated doses. Camel milk treatment was administered for 8 weeks. The changes in glucagon like peptide-1 (GLP-1), glucose dependent insulinotropic peptide (GIP), glucose tolerance, fasting and glucose-stimulated insulin secretion, insulin resistance (IR), TNF-α, TGF-β1, lipid profile, atherogenic index (AI), and body weight were investigated. The untreated diabetic animals showed hyperglycemia, increased HOMA-IR, hyperlipidemia, elevated AI, high serum incretins [GLP-1 and GIP], TNF-α, and TGF-β1 levels and weight loss as compared with the control group. Camel milk treatment to the diabetic animals resulted in significant lowered fasting glucose level, hypolipidemia, decreased HOMA-IR, recovery of insulin secretion, weight gain, and no mortality during the study. Additionally, CMK inhibits the diabetes-induced elevation in incretin hormones, TNF-α and TGF-β1 levels. The increase in glucose-stimulated insulin secretion, decreased HOMA-IR, modulation of the secretion and/or the action of incretins, and the anti-inflammatory effect are anticipated mechanisms to the antidiabetic effect of CMK and suggest it as a valuable adjuvant antidiabetic therapy. © Georg Thieme Verlag KG Stuttgart · New York.

Viking planetary quarantine procedures and implementation

NASA Technical Reports Server (NTRS)

Howell, R.

1974-01-01

Some of the techniques and methodology that were used on Viking to implement planetary quarantine requirements are reported. Special attention was given to techniques and approaches used to implement sterilization of the Viking probe. Quarantine procedures for unmanned planetary missions and procedures for microbiological contamination of space hardware are included. A probability of contamination of the biological instruments onboard by terrestrial organisms was examined.

28 CFR 19.6 - Responsibility of DOJ organizational units for program implementation and implementation procedures.

Code of Federal Regulations, 2010 CFR

2010-07-01

... consent to use the photograph and biographical information. See 28 CFR 0.1, Organizational Structure of... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Responsibility of DOJ organizational... Responsibility of DOJ organizational units for program implementation and implementation procedures. (a) The...

28 CFR 61.1 - Background.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Administration DEPARTMENT OF JUSTICE (CONTINUED) PROCEDURES FOR IMPLEMENTING THE NATIONAL ENVIRONMENTAL POLICY... 102(2) of NEPA contains certain procedural requirements directed toward the attainment of such goals... regulations to implement the procedural provisions of NEPA. Accordingly, CEQ issued final NEPA regulations, 40...

28 CFR 61.1 - Background.

Code of Federal Regulations, 2012 CFR

2012-07-01

... Administration DEPARTMENT OF JUSTICE (CONTINUED) PROCEDURES FOR IMPLEMENTING THE NATIONAL ENVIRONMENTAL POLICY... 102(2) of NEPA contains certain procedural requirements directed toward the attainment of such goals... regulations to implement the procedural provisions of NEPA. Accordingly, CEQ issued final NEPA regulations, 40...

28 CFR 61.1 - Background.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Administration DEPARTMENT OF JUSTICE (CONTINUED) PROCEDURES FOR IMPLEMENTING THE NATIONAL ENVIRONMENTAL POLICY... 102(2) of NEPA contains certain procedural requirements directed toward the attainment of such goals... regulations to implement the procedural provisions of NEPA. Accordingly, CEQ issued final NEPA regulations, 40...

28 CFR 61.1 - Background.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Administration DEPARTMENT OF JUSTICE (CONTINUED) PROCEDURES FOR IMPLEMENTING THE NATIONAL ENVIRONMENTAL POLICY... 102(2) of NEPA contains certain procedural requirements directed toward the attainment of such goals... regulations to implement the procedural provisions of NEPA. Accordingly, CEQ issued final NEPA regulations, 40...

28 CFR 61.1 - Background.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Administration DEPARTMENT OF JUSTICE (CONTINUED) PROCEDURES FOR IMPLEMENTING THE NATIONAL ENVIRONMENTAL POLICY... 102(2) of NEPA contains certain procedural requirements directed toward the attainment of such goals... regulations to implement the procedural provisions of NEPA. Accordingly, CEQ issued final NEPA regulations, 40...

Designing Flightdeck Procedures

NASA Technical Reports Server (NTRS)

Barshi, Immanuel; Mauro, Robert; Degani, Asaf; Loukopoulou, Loukia

2016-01-01

The primary goal of this document is to provide guidance on how to design, implement, and evaluate flight deck procedures. It provides a process for developing procedures that meet clear and specific requirements. This document provides a brief overview of: 1) the requirements for procedures, 2) a process for the design of procedures, and 3) a process for the design of checklists. The brief overview is followed by amplified procedures that follow the above steps and provide details for the proper design, implementation and evaluation of good flight deck procedures and checklists.

32 CFR 21.320 - Are there areas in which DoD Components must establish policies and procedures to implement the...

Code of Federal Regulations, 2012 CFR

2012-07-01

... under awards, if the DoD Component makes any awards to institutions of higher education or to other... establish policies and procedures to implement the DoDGARs? 21.320 Section 21.320 National Defense... Components must establish policies and procedures to implement the DoDGARs? Yes, Heads of DoD Components or...

32 CFR 21.320 - Are there areas in which DoD Components must establish policies and procedures to implement the...

Code of Federal Regulations, 2011 CFR

2011-07-01

... under awards, if the DoD Component makes any awards to institutions of higher education or to other... establish policies and procedures to implement the DoDGARs? 21.320 Section 21.320 National Defense... Components must establish policies and procedures to implement the DoDGARs? Yes, Heads of DoD Components or...

32 CFR 21.320 - Are there areas in which DoD Components must establish policies and procedures to implement the...

Code of Federal Regulations, 2014 CFR

2014-07-01

... under awards, if the DoD Component makes any awards to institutions of higher education or to other... establish policies and procedures to implement the DoDGARs? 21.320 Section 21.320 National Defense... Components must establish policies and procedures to implement the DoDGARs? Yes, Heads of DoD Components or...

32 CFR 21.320 - Are there areas in which DoD Components must establish policies and procedures to implement the...

Code of Federal Regulations, 2010 CFR

2010-07-01

... under awards, if the DoD Component makes any awards to institutions of higher education or to other... establish policies and procedures to implement the DoDGARs? 21.320 Section 21.320 National Defense... Components must establish policies and procedures to implement the DoDGARs? Yes, Heads of DoD Components or...

32 CFR 21.320 - Are there areas in which DoD Components must establish policies and procedures to implement the...

Code of Federal Regulations, 2013 CFR

2013-07-01

... under awards, if the DoD Component makes any awards to institutions of higher education or to other... establish policies and procedures to implement the DoDGARs? 21.320 Section 21.320 National Defense... Components must establish policies and procedures to implement the DoDGARs? Yes, Heads of DoD Components or...

23 CFR 630.1014 - Implementation.

Code of Federal Regulations, 2014 CFR

2014-04-01

... FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION ENGINEERING AND TRAFFIC OPERATIONS PRECONSTRUCTION PROCEDURES Work Zone Safety and Mobility § 630.1014 Implementation. Each State shall work in partnership with the FHWA in the implementation of its policies and procedures to improve work zone safety and...

23 CFR 630.1014 - Implementation.

Code of Federal Regulations, 2013 CFR

2013-04-01

... FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION ENGINEERING AND TRAFFIC OPERATIONS PRECONSTRUCTION PROCEDURES Work Zone Safety and Mobility § 630.1014 Implementation. Each State shall work in partnership with the FHWA in the implementation of its policies and procedures to improve work zone safety and...

23 CFR 630.1014 - Implementation.

Code of Federal Regulations, 2012 CFR

2012-04-01

... FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION ENGINEERING AND TRAFFIC OPERATIONS PRECONSTRUCTION PROCEDURES Work Zone Safety and Mobility § 630.1014 Implementation. Each State shall work in partnership with the FHWA in the implementation of its policies and procedures to improve work zone safety and...

23 CFR 630.1014 - Implementation.

Code of Federal Regulations, 2011 CFR

2011-04-01

... FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION ENGINEERING AND TRAFFIC OPERATIONS PRECONSTRUCTION PROCEDURES Work Zone Safety and Mobility § 630.1014 Implementation. Each State shall work in partnership with the FHWA in the implementation of its policies and procedures to improve work zone safety and...

10 CFR 1021.300 - General requirements.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 4 2013-01-01 2013-01-01 false General requirements. 1021.300 Section 1021.300 Energy DEPARTMENT OF ENERGY (GENERAL PROVISIONS) NATIONAL ENVIRONMENTAL POLICY ACT IMPLEMENTING PROCEDURES Implementing Procedures § 1021.300 General requirements. (a) DOE shall determine, under the procedures in the...

Label-free SPR detection of gluten peptides in urine for non-invasive celiac disease follow-up.

PubMed

Soler, Maria; Estevez, M-Carmen; Moreno, Maria de Lourdes; Cebolla, Angel; Lechuga, Laura M

2016-05-15

Motivated by the necessity of new and efficient methods for dietary gluten control of celiac patients, we have developed a simple and highly sensitive SPR biosensor for the detection of gluten peptides in urine. The sensing methodology enables rapid and label-free quantification of the gluten immunogenic peptides (GIP) by using G12 mAb. The overall performance of the biosensor has been in-depth optimized and evaluated in terms of sensitivity, selectivity and reproducibility, reaching a limit of detection of 0.33 ng mL(-1). Besides, the robustness and stability of the methodology permit the continuous use of the biosensor for more than 100 cycles with excellent repeatability. Special efforts have been focused on preventing and minimizing possible interferences coming from urine matrix enabling a direct analysis in this fluid without requiring extraction or purification procedures. Our SPR biosensor has proven to detect and identify gluten consumption by evaluating urine samples from healthy and celiac individuals with different dietary gluten conditions. This novel biosensor methodology represents a novel approach to quantify the digested gluten peptides in human urine with outstanding sensitivity in a rapid and non-invasive manner. Our technique should be considered as a promising opportunity to develop Point-of-Care (POC) devices for an efficient, simple and accurate gluten free diet (GFD) monitoring as well as therapy follow-up of celiac disease patients. Copyright © 2015 Elsevier B.V. All rights reserved.

40 CFR 142.80 - Review procedures.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 22 2010-07-01 2010-07-01 false Review procedures. 142.80 Section 142...) NATIONAL PRIMARY DRINKING WATER REGULATIONS IMPLEMENTATION Administrator's Review of State Decisions that Implement Criteria Under Which Filtration Is Required § 142.80 Review procedures. (a) The Administrator may...

Standardized patient walkthroughs in the National Drug Abuse Treatment Clinical Trials Network: common challenges to protocol implementation.

PubMed

Fussell, Holly E; Kunkel, Lynn E; McCarty, Dennis; Lewy, Colleen S

2011-09-01

Training research staff to implement clinical trials occurring in community-based addiction treatment programs presents unique challenges. Standardized patient walkthroughs of study procedures may enhance training and protocol implementation. Examine and discuss cross-site and cross-study challenges of participant screening and data collection procedures identified during standardized patient walkthroughs of multi-site clinical trials. Actors portrayed clients and "walked through" study procedures with protocol research staff. The study completed 57 walkthroughs during implementation of 4 clinical trials. Observers and walkthrough participants identified three areas of concern (consent procedures, screening and assessment processes, and protocol implementation) and made suggestions for resolving the concerns. Standardized patient walkthroughs capture issues with study procedures previously unidentified with didactic training or unscripted rehearsals. Clinical trials within the National Drug Abuse Treatment Clinical Trials Network are conducted in addiction treatment centers that vary on multiple dimensions. Based on walkthrough observations, the national protocol team and local site leadership modify standardized operating procedures and resolve cross-site problems prior to recruiting study participants. The standardized patient walkthrough improves consistency across study sites and reduces potential site variation in study outcomes.

Implementing an Integrated Commitment Management System at the Savannah River Site Tank Farms

DOE Office of Scientific and Technical Information (OSTI.GOV)

Blanchard, A.

1999-06-16

Recently, the Savannah River Site Tank Farms have been transitioning from pre-1990 Authorization Basis requirements to new 5480.22/.23 requirements. Implementation of the new Authorization Basis has resulted in more detailed requirements, a completely new set of implementing procedures, and the expectation of even more disciplined operations. Key to the success of this implementation has been the development of an Integrated Commitment Management System (ICMS) by Westinghouse Safety Management Solutions. The ICMS has two elements: the Authorization Commitment Matrix (ACM), and a Procedure Consistency Review methodology. The Authorization Commitment Matrix is a linking database, which ties requirements and implementing documents together.more » The associated Procedure Consistency Review process ensures that the procedures to be credited in the ACM do in fact correctly and completely meet all intended commitments. This Integrated Commitment Management System helps Westinghouse Safety Management Solutions and the facility operations and engineering organizations take ownership in the implementation of the requirements that have been developed.« less

77 FR 47862 - National Environmental Policy Act: Implementing Procedures; Addition to Categorical Exclusions...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-10

... DEPARTMENT OF THE INTERIOR Office of the Secretary National Environmental Policy Act: Implementing... Interior. ACTION: Notice of Final National Environmental Policy Act Implementing Procedures. SUMMARY: This notice announces the addition of a new categorical exclusion under the National Environmental Policy Act...

Interprofessional and interdisciplinary simulation-based training leads to safe sedation procedures in the emergency department.

PubMed

Sauter, Thomas C; Hautz, Wolf E; Hostettler, Simone; Brodmann-Maeder, Monika; Martinolli, Luca; Lehmann, Beat; Exadaktylos, Aristomenis K; Haider, Dominik G

2016-08-02

Sedation is a procedure required for many interventions in the Emergency department (ED) such as reductions, surgical procedures or cardioversions. However, especially under emergency conditions with high risk patients and rapidly changing interdisciplinary and interprofessional teams, the procedure caries important risks. It is thus vital but difficult to implement a standard operating procedure for sedation procedures in any ED. Reports on both, implementation strategies as well as their success are currently lacking. This study describes the development, implementation and clinical evaluation of an interprofessional and interdisciplinary simulation-based sedation training concept. All physicians and nurses with specialised training in emergency medicine at the Berne University Department of Emergency Medicine participated in a mandatory interdisciplinary and interprofessional simulation-based sedation training. The curriculum consisted of an individual self-learning module, an airway skill training course, three simulation-based team training cases, and a final practical learning course in the operating theatre. Before and after each training session, self-efficacy, awareness of emergency procedures, knowledge of sedation medication and crisis resource management were assessed with a questionnaire. Changes in these measures were compared via paired tests, separately for groups formed based on experience and profession. To assess the clinical effect of training, we collected patient and team satisfaction as well as duration and complications for all sedations in the ED within the year after implementation. We further compared time to beginning of procedure, time for duration of procedure and time until discharge after implementation with the one year period before the implementation. Cohen's d was calculated as effect size for all statistically significant tests. Fifty staff members (26 nurses and 24 physicians) participated in the training. In all subgroups, there is a significant increase in self-efficacy and knowledge with high effect size (d z  = 1.8). The learning is independent of profession and experience level. In the clinical evaluation after implementation, we found no major complications among the sedations performed. Time to procedure significantly improved after the introduction of the training (d = 0.88). Learning is independent of previous working experience and equally effective in raising the self-efficacy and knowledge in all professional groups. Clinical outcome evaluation confirms the concepts safety and feasibility. An interprofessional and interdisciplinary simulation-based sedation training is an efficient way to implement a conscious sedation concept in an ED.

Developing Flowcharted Procedures Manuals for School District Administration within the ISO 9000 Context.

ERIC Educational Resources Information Center

Schoch, Robert

2002-01-01

Describes how the School District of Lancaster, Pennsylvania, implemented a districtwide quality-management system based on the Geneva-based International Standards Organization 9001, a major component of which is the documentation of procedures. Includes sections on implementation, procedure manuals, quality management, uniformity, formatting,…

23 CFR 630.1014 - Implementation.

Code of Federal Regulations, 2010 CFR

2010-04-01

... PRECONSTRUCTION PROCEDURES Work Zone Safety and Mobility § 630.1014 Implementation. Each State shall work in partnership with the FHWA in the implementation of its policies and procedures to improve work zone safety and mobility. At a minimum, this shall involve an FHWA review of conformance of the State's policies and...

24 CFR 51.206 - Implementation.

Code of Federal Regulations, 2011 CFR

2011-04-01

... Conventional Fuels or Chemicals of an Explosive or Flammable Nature § 51.206 Implementation. This subpart C... entity responsible for review of the project. The implementation procedure will be part of the environmental review process in accordance with the procedures set forth in 24 CFR parts 50 and 58. [61 FR 13334...

24 CFR 51.206 - Implementation.

Code of Federal Regulations, 2013 CFR

2013-04-01

... Conventional Fuels or Chemicals of an Explosive or Flammable Nature § 51.206 Implementation. This subpart C... entity responsible for review of the project. The implementation procedure will be part of the environmental review process in accordance with the procedures set forth in 24 CFR parts 50 and 58. [61 FR 13334...

24 CFR 51.206 - Implementation.

Code of Federal Regulations, 2012 CFR

2012-04-01

... Conventional Fuels or Chemicals of an Explosive or Flammable Nature § 51.206 Implementation. This subpart C... entity responsible for review of the project. The implementation procedure will be part of the environmental review process in accordance with the procedures set forth in 24 CFR parts 50 and 58. [61 FR 13334...

24 CFR 51.206 - Implementation.

Code of Federal Regulations, 2014 CFR

2014-04-01

... Conventional Fuels or Chemicals of an Explosive or Flammable Nature § 51.206 Implementation. This subpart C... entity responsible for review of the project. The implementation procedure will be part of the environmental review process in accordance with the procedures set forth in 24 CFR parts 50 and 58. [61 FR 13334...

24 CFR 51.206 - Implementation.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Conventional Fuels or Chemicals of an Explosive or Flammable Nature § 51.206 Implementation. This subpart C... entity responsible for review of the project. The implementation procedure will be part of the environmental review process in accordance with the procedures set forth in 24 CFR parts 50 and 58. [61 FR 13334...

Using Video Modeling with Voiceover Instruction Plus Feedback to Train Staff to Implement Direct Teaching Procedures.

PubMed

Giannakakos, Antonia R; Vladescu, Jason C; Kisamore, April N; Reeve, Sharon A

2016-06-01

Direct teaching procedures are often an important part of early intensive behavioral intervention for consumers with autism spectrum disorder. In the present study, a video model with voiceover (VMVO) instruction plus feedback was evaluated to train three staff trainees to implement a most-to-least direct (MTL) teaching procedure. Probes for generalization were conducted with untrained direct teaching procedures (i.e., least-to-most, prompt delay) and with an actual consumer. The results indicated that VMVO plus feedback was effective in training the staff trainees to implement the MTL procedure. Although additional feedback was required for the staff trainees to show mastery of the untrained direct teaching procedures (i.e., least-to-most and prompt delay) and with an actual consumer, moderate to high levels of generalization were observed.

NHEXAS PHASE I ARIZONA STUDY--STANDARD OPERATING PROCEDURE FOR PREPARATION OF STANDARD OPERATING PROCEDURES (SOPS) (UA-G-1.0)

EPA Science Inventory

The purpose of this SOP is to establish a uniform format for the preparation of SOPs. Use of these protocols ensures consistent implementation of project tasks, documents the preparation and implementation of the procedures used, describes quality control measures and the limits...

NHEXAS PHASE I ARIZONA STUDY--STANDARD OPERATING PROCEDURE FOR RECEIPT OF EQUIPMENT AND IMPLEMENTATION SUPPLIES (UA-G-5.0)

EPA Science Inventory

The purpose of this SOP is to outline procedures for the receipt of equipment and field implementation supplies at the NHEXAS Arizona research project. This procedure was followed to ensure consistent data custody, storage, transfer, and analysis of a high quality during the Ari...

17 CFR 39.4 - Procedures for implementing derivatives clearing organization rules and clearing new products.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 17 Commodity and Securities Exchanges 1 2010-04-01 2010-04-01 false Procedures for implementing derivatives clearing organization rules and clearing new products. 39.4 Section 39.4 Commodity and Securities Exchanges COMMODITY FUTURES TRADING COMMISSION DERIVATIVES CLEARING ORGANIZATIONS § 39.4 Procedures for...

Internal quality control: planning and implementation strategies.

PubMed

Westgard, James O

2003-11-01

The first essential in setting up internal quality control (IQC) of a test procedure in the clinical laboratory is to select the proper IQC procedure to implement, i.e. choosing the statistical criteria or control rules, and the number of control measurements, according to the quality required for the test and the observed performance of the method. Then the right IQC procedure must be properly implemented. This review focuses on strategies for planning and implementing IQC procedures in order to improve the quality of the IQC. A quantitative planning process is described that can be implemented with graphical tools such as power function or critical-error graphs and charts of operating specifications. Finally, a total QC strategy is formulated to minimize cost and maximize quality. A general strategy for IQC implementation is recommended that employs a three-stage design in which the first stage provides high error detection, the second stage low false rejection and the third stage prescribes the length of the analytical run, making use of an algorithm involving the average of normal patients' data.

Measurement of the Thermal Expansion Coefficient for Ultra-High Temperatures up to 3000 K

NASA Astrophysics Data System (ADS)

Kompan, T. A.; Kondratiev, S. V.; Korenev, A. S.; Puhov, N. F.; Inochkin, F. M.; Kruglov, S. K.; Bronshtein, I. G.

2018-03-01

The paper is devoted to a new high-temperature dilatometer, a part of the State Primary Standard of the thermal expansion coefficient (TEC) unit. The dilatometer is designed for investigation and certification of materials for TEC standards in the range of extremely high temperatures. The critical review of existing methods of TEC measurements is given. Also, the design, principles of operation and metrological parameters of the new device are described. The main attention is paid to the system of machine vision that allows accurate measurement of elongation at high temperatures. The results of TEC measurements for graphite GIP-4, single crystal Al2O3, and some other materials are also presented.

Product-based Safety Certification for Medical Devices Embedded Software.

PubMed

Neto, José Augusto; Figueiredo Damásio, Jemerson; Monthaler, Paul; Morais, Misael

2015-01-01

Worldwide medical device embedded software certification practices are currently focused on manufacturing best practices. In Brazil, the national regulatory agency does not hold a local certification process for software-intensive medical devices and admits international certification (e.g. FDA and CE) from local and international industry to operate in the Brazilian health care market. We present here a product-based certification process as a candidate process to support the Brazilian regulatory agency ANVISA in medical device software regulation. Center of Strategic Technology for Healthcare (NUTES) medical device embedded software certification is based on a solid safety quality model and has been tested with reasonable success against the Class I risk device Generic Infusion Pump (GIP).

Account of the intratrack radiolytic processes for interpretation of the AMOC spectrum of liquid water

NASA Astrophysics Data System (ADS)

Zvezhinskiy, D. S.; Butterling, M.; Wagner, A.; Krause-Rehberg, R.; Stepanov, S. V.

2013-06-01

Recent development of the Gamma-induced Positron Spectroscopy (GiPS) setup significantly extends applicability of the Age-Momentum Correlation technique (AMOC) for studies of the bulk samples. It also provides many advantages comparing with conventional positron annihilation experiments in liquids, such as extremely low annihilation fraction in vessel walls, absence of a positron source and positron annihilations in it. We have developed a new approach for processing and interpretation of the AMOC-GiPS data based on the diffusion recombination model of the intratrack radiolytic processes. This approach is verified in case of liquid water, which is considered as a reference medium in the positron and positronium chemistry.

Policies and Procedures That Facilitate Implementation of Evidence-Based Clinical Guidelines in U.S. Dental Schools.

PubMed

Polk, Deborah E; Nolan, Beth A D; Shah, Nilesh H; Weyant, Robert J

2016-01-01

The aim of this study was to determine the degree to which dental schools in the United States have policies and procedures in place that facilitate the implementation of evidence-based clinical guidelines. The authors sent surveys to all 65 U.S. dental schools in 2014; responses were obtained from 38 (58%). The results showed that, of the nine policies and procedures examined, only two were fully implemented by 50% or more of the responding schools: guidelines supported through clinical faculty education or available chairside (50%), and students informed of guidelines in both the classroom and clinic (65.8%). Although 92% of the respondents reported having an electronic health record, 80% of those were not using it to track compliance with guidelines. Five schools reported implementing more policies than the rest of the schools. The study found that the approach to implementing guidelines at most of the responding schools did not follow best practices although five schools had an exemplary set of policies and procedures to support guideline implementation. These results suggest that most dental schools are currently not implementing guidelines effectively and efficiently, but that the goal of schools' having a comprehensive implementation program for clinical guidelines is achievable since some are doing so. Future studies should determine whether interventions to improve implementation in dental schools are needed.

U.S.-MEXICO BORDER PROGRAM ARIZONA BORDER STUDY--STANDARD OPERATING PROCEDURE FOR RECEIPT OF EQUIPMENT AND FIELD IMPLEMENTATION SUPPLIES (UA-G-5.0)

EPA Science Inventory

The purpose of this SOP is to outline procedures for the receipt of equipment and field implementation supplies for the Arizona Border Study. This procedure was followed to ensure consistent data custody, storage, transfer, and analysis of a high quality during the Arizona NHEXA...

U.S.-MEXICO BORDER PROGRAM ARIZONA BORDER STUDY--STANDARD OPERATING PROCEDURE FOR PREPARATION OF STANDARD OPERATING PROCEDURES (SOPS) (UA-G-1.0)

EPA Science Inventory

The purpose of this SOP is to establish a uniform format for the preparation of SOPs. Use of these protocols ensures consistent implementation of project tasks, documents the preparation and implementation of the procedures used, describes quality control measures and the limits...

28 CFR Appendix B to Part 61 - Drug Enforcement Administration Procedures Relating to the Implementation of the National...

Code of Federal Regulations, 2013 CFR

2013-07-01

... appropriate. 3. Environmental Information Interested persons may contact the Office of Science and Technology... Procedures Relating to the Implementation of the National Environmental Policy Act B Appendix B to Part 61... ENVIRONMENTAL POLICY ACT Pt. 61, App. B Appendix B to Part 61—Drug Enforcement Administration Procedures...

28 CFR Appendix B to Part 61 - Drug Enforcement Administration Procedures Relating to the Implementation of the National...

Code of Federal Regulations, 2012 CFR

2012-07-01

... appropriate. 3. Environmental Information Interested persons may contact the Office of Science and Technology... Procedures Relating to the Implementation of the National Environmental Policy Act B Appendix B to Part 61... ENVIRONMENTAL POLICY ACT Pt. 61, App. B Appendix B to Part 61—Drug Enforcement Administration Procedures...

28 CFR Appendix B to Part 61 - Drug Enforcement Administration Procedures Relating to the Implementation of the National...

Code of Federal Regulations, 2014 CFR

2014-07-01

... appropriate. 3. Environmental Information Interested persons may contact the Office of Science and Technology... Procedures Relating to the Implementation of the National Environmental Policy Act B Appendix B to Part 61... ENVIRONMENTAL POLICY ACT Pt. 61, App. B Appendix B to Part 61—Drug Enforcement Administration Procedures...

Implementation guide for monitoring work zone safety and mobility impacts

DOT National Transportation Integrated Search

2009-01-01

This implementation guide describes the conceptual framework, data requirements, and computational procedures for determining the safety and mobility impacts of work zones in Texas. Researchers designed the framework and procedures to assist district...

Kernel and System Procedures in Flex.

DTIC Science & Technology

1983-08-01

System procedures on which the operating system for the Flex computer is based. These are the low level rOCedures Whbich are used to implement the compilers, file-store* coummand interpreters etc on Flex. 168 ... System procedures on which the operating system for the Flex computer is based. These are the low level procedures which are used to implement the...privileged mode. They form the interface between the user and a particular operating system written on top of the Kernel.

The Krigifier: A Procedure for Generating Pseudorandom Nonlinear Objective Functions for Computational Experimentation

NASA Technical Reports Server (NTRS)

Trosset, Michael W.

1999-01-01

Comprehensive computational experiments to assess the performance of algorithms for numerical optimization require (among other things) a practical procedure for generating pseudorandom nonlinear objective functions. We propose a procedure that is based on the convenient fiction that objective functions are realizations of stochastic processes. This report details the calculations necessary to implement our procedure for the case of certain stationary Gaussian processes and presents a specific implementation in the statistical programming language S-PLUS.

Parent-Implemented Procedural Modification of Escape Extinction in the Treatment of Food Selectivity in a Young Child with Autism

ERIC Educational Resources Information Center

Tarbox, Jonathan; Schiff, Averil; Najdowski, Adel C.

2010-01-01

Fool selectivity is characterized by the consumption of an inadequate variety of foods. The effectiveness of behavioral treatment procedures, particularly nonremoval of the spoon, is well validated by research. The role of parents in the treatment of feeding disorders and the feasibility of behavioral procedures for parent implementation in the…

Incretin responses to oral glucose and mixed meal tests and changes in fasting glucose levels during 7 years of follow-up: The Hoorn Meal Study.

PubMed

Koopman, A D M; Rutters, F; Rauh, S P; Nijpels, G; Holst, J J; Beulens, J W; Alssema, M; Dekker, J M

2018-01-01

We conducted the first prospective observational study in which we examined the association between incretin responses to an oral glucose tolerance test (OGTT) and mixed meal test (MMT) at baseline and changes in fasting glucose levels 7 years later, in individuals who were non-diabetic at baseline. We used data from the Hoorn Meal Study; a population-based cohort study among 121 subjects, aged 61.0±6.7y. GIP and GLP-1 responses were determined at baseline and expressed as total and incremental area under the curve (tAUC and iAUC). The association between incretin response at baseline and changes in fasting glucose levels was assessed using linear regression. The average change in glucose over 7 years was 0.43 ± 0.5 mmol/l. For GIP, no significant associations were observed with changes in fasting glucose levels. In contrast, participants within the middle and highest tertile of GLP-1 iAUC responses to OGTT had significantly smaller increases (actually decreases) in fasting glucose levels; -0.28 (95% confidence interval: -0.54;-0.01) mmol/l and -0.39 (-0.67;-0.10) mmol/l, respectively, compared to those in the lowest tertile. The same trend was observed for tAUC GLP-1 following OGTT (highest tertile: -0.32 (0.61;-0.04) mmol/l as compared to the lowest tertile). No significant associations were observed for GLP-1 responses following MMT. In conclusion, within our non-diabetic population-based cohort, a low GLP-1 response to OGTT was associated with a steeper increase in fasting glucose levels during 7 years of follow-up. This suggests that a reduced GLP-1 response precedes glucose deterioration and may play a role in the etiology of type 2 diabetes mellitus.

A Protein Preload Enhances the Glucose-Lowering Efficacy of Vildagliptin in Type 2 Diabetes.

PubMed

Wu, Tongzhi; Little, Tanya J; Bound, Michelle J; Borg, Malcolm; Zhang, Xiang; Deacon, Carolyn F; Horowitz, Michael; Jones, Karen L; Rayner, Christopher K

2016-04-01

Nutrient "preloads" given before meals can attenuate postprandial glycemic excursions, at least partly by slowing gastric emptying and stimulating secretion of the incretins (i.e., glucagon-like peptide-1 [GLP-1] and glucose-dependent insulinotropic polypeptide [GIP]). This study was designed to evaluate whether a protein preload could improve the efficacy of the dipeptidyl peptidase-4 (DPP-4) inhibitor vildagliptin to increase incretin concentrations, slow gastric emptying, and lower postprandial glycemia in type 2 diabetes. Twenty-two patients with type 2 diabetes treated with metformin were studied on four occasions, receiving either 50 mg vildagliptin (VILD) or placebo (PLBO) on both the evening before and the morning of each study day. The latter dose was followed after 60 min by a preload drink containing either 25 g whey protein (WHEY) or control flavoring (CTRL), and after another 30 min by a (13)C-octanoate-labeled mashed potato meal. Plasma glucose and hormones, and gastric emptying, were evaluated. Compared with PLBO/CTRL, PLBO/WHEY reduced postprandial peak glycemia, increased plasma insulin, glucagon, and incretin hormones (total and intact), and slowed gastric emptying, whereas VILD/CTRL reduced both the peak and area under the curve for glucose, increased plasma intact incretins, and slowed gastric emptying but suppressed plasma glucagon and total incretins (P < 0.05 each). Compared with both PLBO/WHEY and VILD/CTRL, VILD/WHEY was associated with higher plasma intact GLP-1 and GIP, slower gastric emptying, and lower postprandial glycemia (P < 0.05 each). In metformin-treated type 2 diabetes, a protein preload has the capacity to enhance the efficacy of vildagliptin to slow gastric emptying, increase plasma intact incretins, and reduce postprandial glycemia. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Prebiotic Fiber Increases Hepatic Acetyl CoA Carboxylase Phosphorylation and Suppresses Glucose-Dependent Insulinotropic Polypeptide Secretion More Effectively When Used with Metformin in Obese Rats1,2

PubMed Central

Pyra, Kim A.; Saha, Dolan C.; Reimer, Raylene A.

2013-01-01

Independently, metformin (MET) and the prebiotic, oligofructose (OFS), have been shown to increase glucagon-like peptide (GLP-1) secretion. Our objective was to determine whether using OFS as an adjunct with MET augments GLP-1 secretion in obese rats. Male, diet-induced obese Sprague Dawley rats were randomized to: 1) high-fat/-sucrose diet [HFHS; control (C); 20% fat, 50% sucrose wt:wt]; 2) HFHS+10% OFS (OFS); 3) HFHS + MET [300 mg/kg/d (MET)]; 4) HFHS+10% OFS+MET (OFS +MET). Body composition, glycemia, satiety hormones, and mechanisms related to dipeptidyl peptidase 4 (DPP4) activity in plasma, hepatic AMP-activated protein kinase (AMPK; Western blots), and gut microbiota (qPCR) were examined. Direct effects of MET and SCFA were examined in human enteroendocrine cells. The interaction between OFS and MET affected fat mass, hepatic TG, secretion of glucose-dependent insulinotropic polypeptide (GIP) and leptin, and AMPKα2 mRNA and phosphorylated acetyl CoA carboxylase (pACC) levels (P < 0.05). Combined, OFS and MET reduced GIP secretion to a greater extent than either treatment alone (P < 0.05). The hepatic pACC level was increased by OFS+MET by at least 50% above all other treatments, which did not differ from each other (P < 0.05). OFS decreased plasma DPP4 activity (P < 0.001). Cecal Bifidobacteria (P < 0.001) were markedly increased and C. leptum decreased (P < 0.001) with OFS consumption. In human enteroendocrine cells, the interaction between MET and SCFA affected GLP-1 secretion (P < 0.04) but was not associated with higher GLP-1 than the highest individual doses. In conclusion, the combined actions of OFS and MET were associated with important interaction effects that have the potential to improve metabolic outcomes associated with obesity. PMID:22223580

A common variant upstream of the PAX6 gene influences islet function in man.

PubMed

Ahlqvist, E; Turrini, F; Lang, S T; Taneera, J; Zhou, Y; Almgren, P; Hansson, O; Isomaa, B; Tuomi, T; Eriksson, K; Eriksson, J G; Lyssenko, V; Groop, L

2012-01-01

Impaired glucose tolerance and impaired insulin secretion have been reported in families with PAX6 mutations and it is suggested that they result from defective proinsulin processing due to lack of prohormone convertase 1/3, encoded by PCSK1. We investigated whether a common PAX6 variant would mimic these findings and explored in detail its effect on islet function in man. A PAX6 candidate single nucleotide polymorphism (rs685428) was associated with fasting insulin levels in the Diabetes Genetics Initiative genome-wide association study. We explored its potential association with glucose tolerance and insulin processing and secretion in three Scandinavian cohorts (N = 8,897 individuals). In addition, insulin secretion and the expression of PAX6 and transcriptional target genes were studied in human pancreatic islets. rs685428 G allele carriers had lower islet mRNA expression of PAX6 (p = 0.01) and PCSK1 (p = 0.001) than AA homozygotes. The G allele was associated with increased fasting insulin (p (replication) = 0.02, p (all) = 0.0008) and HOMA-insulin resistance (p (replication) = 0.02, p (all) = 0.001) as well as a lower fasting proinsulin/insulin ratio (p (all) = 0.008) and lower fasting glucagon (p = 0.04) and gastric inhibitory peptide (GIP) (p = 0.05) concentrations. Arginine-stimulated (p = 0.02) insulin secretion was reduced in vivo, which was further reflected by a reduction of glucose- and potassium-stimulated insulin secretion (p = 0.002 and p = 0.04, respectively) in human islets in vitro. A common variant in PAX6 is associated with reduced PAX6 and PCSK1 expression in human islets and reduced insulin response, as well as decreased glucagon and GIP concentrations and decreased insulin sensitivity. These findings emphasise the central role of PAX6 in the regulation of islet function and glucose metabolism in man.

Enteroendocrine K and L cells in healthy and type 2 diabetic individuals.

PubMed

Jorsal, Tina; Rhee, Nicolai A; Pedersen, Jens; Wahlgren, Camilla D; Mortensen, Brynjulf; Jepsen, Sara L; Jelsing, Jacob; Dalbøge, Louise S; Vilmann, Peter; Hassan, Hazem; Hendel, Jakob W; Poulsen, Steen S; Holst, Jens J; Vilsbøll, Tina; Knop, Filip K

2018-02-01

Enteroendocrine K and L cells are pivotal in regulating appetite and glucose homeostasis. Knowledge of their distribution in humans is sparse and it is unknown whether alterations occur in type 2 diabetes. We aimed to evaluate the distribution of enteroendocrine K and L cells and relevant prohormone-processing enzymes (using immunohistochemical staining), and to evaluate the mRNA expression of the corresponding genes along the entire intestinal tract in individuals with type 2 diabetes and healthy participants. In this cross-sectional study, 12 individuals with type 2 diabetes and 12 age- and BMI-matched healthy individuals underwent upper and lower double-balloon enteroscopy with mucosal biopsy retrieval from approximately every 30 cm of the small intestine and from seven specific anatomical locations in the large intestine. Significantly different densities for cells positive for chromogranin A (CgA), glucagon-like peptide-1, glucose-dependent insulinotropic polypeptide, peptide YY, prohormone convertase (PC) 1/3 and PC2 were observed along the intestinal tract. The expression of CHGA did not vary along the intestinal tract, but the mRNA expression of GCG, GIP, PYY, PCSK1 and PCSK2 differed along the intestinal tract. Lower counts of CgA-positive and PC1/3-positive cells, respectively, were observed in the small intestine of individuals with type 2 diabetes compared with healthy participants. In individuals with type 2 diabetes compared with healthy participants, the expression of GCG and PYY was greater in the colon, while the expression of GIP and PCSK1 was greater in the small intestine and colon, and the expression of PCSK2 was greater in the small intestine. Our findings provide a detailed description of the distribution of enteroendocrine K and L cells and the expression of their products in the human intestinal tract and demonstrate significant differences between individuals with type 2 diabetes and healthy participants. NCT03044860.

Effect of additional administration of acarbose on blood glucose fluctuations and postprandial hyperglycemia in patients with type 2 diabetes mellitus under treatment with alogliptin.

PubMed

Kusunoki, Yoshiki; Katsuno, Tomoyuki; Myojin, Makiko; Miyakoshi, Kana; Ikawa, Takashi; Matsuo, Toshihiro; Ochi, Fumihiro; Tokuda, Masaru; Murai, Kazuki; Miuchi, Masayuki; Hamaguchi, Tomoya; Miyagawa, Jun-ichiro; Namba, Mitsuyoshi

2013-01-01

Acarbose was administered at 300 mg/day to patients with type 2 diabetes mellitus (T2DM) who had been taking 25 mg/day of alogliptin, and levels of blood glucose were analyzed by continuous glucose monitoring (CGM) for 3 days. The mean blood glucose level with acarbose (136.4 ± 30.7 mg/dL) did not differ significantly from that without acarbose (141.7 ± 28.3 mg/dL). However, in the condition of the combination therapy, there were significant decreases in the standard deviation of the mean blood glucose levels for the 24-hour period (27.6 ± 9.1 vs. 16.2 ± 6.9 mg/dL, p<0.001) and mean amplitude of glycemic excursions (MAGE) (65.8 ± 26.1 vs. 38.8 ± 19.2 mg/dL, p=0.010). In addition, a meal tolerance test was conducted to monitor changes in insulin secretion and active GLP-1 and total GIP values. Ten subjects (5 males, 5 females) of 54.9 ± 6.9 years with BMI 25.9 ± 5.2 kg/m² and HbAlc 9.2 ± 1.2% were enrolled. In the meal tolerance test, active GLP-1 values before and after acarbose administration were 17.0 ± 5.8 and 24.1 ± 9.3 pmol·hr/mL (p=0.054), respectively, showing an increasing tendency, and total GIP(AUC0-180) values were 685.9 ± 209.7 and 404.4 ± 173.7 pmol·hr/mL, respectively, showing a significant decrease (p=0.010). The results indicate that the combined administration of both inhibitors is effective not only in decreasing blood glucose fluctuations and preventing postprandial insulin secretion. The beneficial effects may also protect the endocrine pancreas and inhibit body weight gain.

Plant-rich mixed meals based on Palaeolithic diet principles have a dramatic impact on incretin, peptide YY and satiety response, but show little effect on glucose and insulin homeostasis: an acute-effects randomised study.

PubMed

Bligh, H Frances J; Godsland, Ian F; Frost, Gary; Hunter, Karl J; Murray, Peter; MacAulay, Katrina; Hyliands, Della; Talbot, Duncan C S; Casey, John; Mulder, Theo P J; Berry, Mark J

2015-02-28

There is evidence for health benefits from 'Palaeolithic' diets; however, there are a few data on the acute effects of rationally designed Palaeolithic-type meals. In the present study, we used Palaeolithic diet principles to construct meals comprising readily available ingredients: fish and a variety of plants, selected to be rich in fibre and phyto-nutrients. We investigated the acute effects of two Palaeolithic-type meals (PAL 1 and PAL 2) and a reference meal based on WHO guidelines (REF), on blood glucose control, gut hormone responses and appetite regulation. Using a randomised cross-over trial design, healthy subjects were given three meals on separate occasions. PAL2 and REF were matched for energy, protein, fat and carbohydrates; PAL1 contained more protein and energy. Plasma glucose, insulin, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP) and peptide YY (PYY) concentrations were measured over a period of 180 min. Satiation was assessed using electronic visual analogue scale (EVAS) scores. GLP-1 and PYY concentrations were significantly increased across 180 min for both PAL1 (P= 0·001 and P< 0·001) and PAL2 (P= 0·011 and P= 0·003) compared with the REF. Concomitant EVAS scores showed increased satiety. By contrast, GIP concentration was significantly suppressed. Positive incremental AUC over 120 min for glucose and insulin did not differ between the meals. Consumption of meals based on Palaeolithic diet principles resulted in significant increases in incretin and anorectic gut hormones and increased perceived satiety. Surprisingly, this was independent of the energy or protein content of the meal and therefore suggests potential benefits for reduced risk of obesity.

Differential acute postprandial effects of processed meat and isocaloric vegan meals on the gastrointestinal hormone response in subjects suffering from type 2 diabetes and healthy controls: a randomized crossover study.

PubMed

Belinova, Lenka; Kahleova, Hana; Malinska, Hana; Topolcan, Ondrej; Vrzalova, Jindra; Oliyarnyk, Olena; Kazdova, Ludmila; Hill, Martin; Pelikanova, Terezie

2014-01-01

The intake of meat, particularly processed meat, is a dietary risk factor for diabetes. Meat intake impairs insulin sensitivity and leads to increased oxidative stress. However, its effect on postprandial gastrointestinal hormone (GIH) secretion is unclear. We aimed to investigate the acute effects of two standardized isocaloric meals: a processed hamburger meat meal rich in protein and saturated fat (M-meal) and a vegan meal rich in carbohydrates (V-meal). We hypothesized that the meat meal would lead to abnormal postprandial increases in plasma lipids and oxidative stress markers and impaired GIH responses. In a randomized crossover study, 50 patients suffering from type 2 diabetes (T2D) and 50 healthy subjects underwent two 3-h meal tolerance tests. For statistical analyses, repeated-measures ANOVA was performed. The M-meal resulted in a higher postprandial increase in lipids in both groups (p<0.001) and persistent postprandial hyperinsulinemia in patients with diabetes (p<0.001). The plasma glucose levels were significantly higher after the V-meal only at the peak level. The plasma concentrations of glucose-dependent insulinotropic peptide (GIP), peptide tyrosine-tyrosine (PYY) and pancreatic polypeptide (PP) were higher (p<0.05, p<0.001, p<0.001, respectively) and the ghrelin concentration was lower (p<0.001) after the M-meal in healthy subjects. In contrast, the concentrations of GIP, PYY and PP were significantly lower after the M-meal in T2D patients (p<0.001). Compared with the V-meal, the M-meal was associated with a larger increase in lipoperoxidation in T2D patients (p<0.05). Our results suggest that the diet composition and the energy content, rather than the carbohydrate count, should be important considerations for dietary management and demonstrate that processed meat consumption is accompanied by impaired GIH responses and increased oxidative stress marker levels in diabetic patients. ClinicalTrials.gov NCT01572402.

Mucosal glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide cell numbers in the super-obese human foregut after gastric bypass.

PubMed

Nergård, Bent J; Lindqvist, Andreas; Gislason, Hjörtur G; Groop, Leif; Ekelund, Mikael; Wierup, Nils; Hedenbro, Jan L

2015-01-01

Super-obesity, a body mass index>50 kg/m(2), is difficult to treat. Many studies have focused on the anatomic changes of the intestines; the physiologic background is not clearly identified. It is established that Roux-en-Y gastric bypass (RYGB) augments secretion of glucagon-like peptide-1 (GLP-1), peptide tyrosine tyrosine (PYY), and insulin, but other aspects of gut hormone cell function in the alimentary limb are unknown. To study the effects of laparoscopic RYGB on enteroendocrine cells. University-affiliated, high-volume bariatric surgery center. Eighteen nondiabetic patients were drawn from the present study (NCT 01514799), randomizing between biliopancreatic (BP) limbs of either 60 cm (BP60) or 200 cm (BP200). Demographic characteristics did not differ at baseline or 12 months. Pouch and jejunal biopsies were obtained intraoperatively and using endoscopy at 12 months. Mucosal height and density of hormone-producing cell populations were assessed and mRNA expression measured with real-time polymerase chain reaction. In perianastomotic jejunum, a 4.9-fold increase in GLP-1 cell density was evident 12 months after RYGB, most pronounced in the BP200-group. The densities of glucose-dependent insulinotropic polypeptide (GIP) cells and PYY immunoreactive cells were doubled after 12 months. GIP mRNA was unaffected, but GLP-1 and PYY mRNA were lower 12 months after RYGB. RYGB had no impact on villi length or density of ghrelin-, cholecystokinin-, neurotensin-, secretin-, or serotonin-producing cells after 12 months. Pouch mucosal height and cell densities of ghrelin-, histamine-, serotonin-, and somatostatin-producing cells remained unaffected by RYGB in both groups. RYGB selectively increased the density of incretin-producing cell populations in the jejunum. This may provide anatomic explanation for the observed increased plasma levels of incretins. Copyright © 2015 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

The effect of high-molecular-weight guar gum on net apparent glucose absorption and net apparent insulin and gastric inhibitory polypeptide production in the growing pig: relationship to rheological changes in jejunal digesta.

PubMed

Ellis, P R; Roberts, F G; Low, A G; Morgan, L M

1995-10-01

The present study was designed to determine the quantitative effects of starchy meals containing guar gum on rates of net apparent glucose absorption and net apparent insulin and gastric inhibitory polypeptide (GIP) production in growing pigs. The effects of these meals on the viscosity of jejunal digesta were also examined and correlated to changes in glucose absorption. Four growing pigs were each given either a low-fat semi-purified diet (control) or the same diet supplemented with a high-molecular-weight guar gum at concentrations in the diet of 20 or 40 g/kg. Blood samples were removed simultaneously via indwelling catheters from the mesenteric artery and the hepatic portal vein. Samples of jejunal digesta were removed via a T-piece cannula and used immediately for viscosity measurements at 39 degrees. The 'zero-shear' viscosity of each sample was then calculated. Blood-flow measurements were made using an ultrasonic flow probe fitted to the hepatic portal vein. All measurements were made at intervals of 10 or 30 min during a 4 h postprandial period. Meals containing guar gum significantly increased (P < 0.05) the viscosity of jejunal digesta, an effect that was strongly dependent on the concentration of guar gum in the original diet. No significant differences in blood-flow rates were found between the control and guar-containing diets. Both concentrations of guar gum significantly reduced (P < 0.05) glucose absorption and insulin and GIP secretion rates over the 4 h postprandial period. An inverse relationship between the rate of glucose absorption and the 'zero-shear' viscosity of jejunal digesta was found. This study also provides direct evidence for the important role played by the enteroinsular axis in modifying the glycaemic response to a meal containing guar gum.

Incretin responses to oral glucose and mixed meal tests and changes in fasting glucose levels during 7 years of follow-up: The Hoorn Meal Study

PubMed Central

Rutters, F.; Rauh, S. P.; Nijpels, G.; Holst, J. J.; Beulens, J. W.; Alssema, M.; Dekker, J. M.

2018-01-01

We conducted the first prospective observational study in which we examined the association between incretin responses to an oral glucose tolerance test (OGTT) and mixed meal test (MMT) at baseline and changes in fasting glucose levels 7 years later, in individuals who were non-diabetic at baseline. We used data from the Hoorn Meal Study; a population-based cohort study among 121 subjects, aged 61.0±6.7y. GIP and GLP-1 responses were determined at baseline and expressed as total and incremental area under the curve (tAUC and iAUC). The association between incretin response at baseline and changes in fasting glucose levels was assessed using linear regression. The average change in glucose over 7 years was 0.43 ± 0.5 mmol/l. For GIP, no significant associations were observed with changes in fasting glucose levels. In contrast, participants within the middle and highest tertile of GLP-1 iAUC responses to OGTT had significantly smaller increases (actually decreases) in fasting glucose levels; -0.28 (95% confidence interval: -0.54;-0.01) mmol/l and -0.39 (-0.67;-0.10) mmol/l, respectively, compared to those in the lowest tertile. The same trend was observed for tAUC GLP-1 following OGTT (highest tertile: -0.32 (0.61;-0.04) mmol/l as compared to the lowest tertile). No significant associations were observed for GLP-1 responses following MMT. In conclusion, within our non-diabetic population-based cohort, a low GLP-1 response to OGTT was associated with a steeper increase in fasting glucose levels during 7 years of follow-up. This suggests that a reduced GLP-1 response precedes glucose deterioration and may play a role in the etiology of type 2 diabetes mellitus. PMID:29324870

Gastrin-Releasing Peptide and Glucose Metabolism Following Pancreatitis.

PubMed

Pendharkar, Sayali A; Drury, Marie; Walia, Monika; Korc, Murray; Petrov, Maxim S

2017-08-01

Gastrin-releasing peptide (GRP) is a pluripotent peptide that has been implicated in both gastrointestinal inflammatory states and classical chronic metabolic diseases such as diabetes. Abnormal glucose metabolism (AGM) after pancreatitis, an exemplar inflammatory disease involving the gastrointestinal tract, is associated with persistent low-grade inflammation and altered secretion of pancreatic and gut hormones as well as cytokines. While GRP is involved in secretion of many of them, it is not known whether GRP has a role in AGM. Therefore, we aimed to investigate the association between GRP and AGM following pancreatitis. Fasting blood samples were collected to measure GRP, blood glucose, insulin, amylin, glucagon, pancreatic polypeptide (PP), somatostatin, cholecystokinin, gastric-inhibitory peptide (GIP), gastrin, ghrelin, glicentin, glucagon-like peptide-1 and 2, oxyntomodulin, peptide YY (PYY), secretin, vasoactive intestinal peptide, tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein (MCP)-1, and interleukin-6. Modified Poisson regression analysis and linear regression analyses were conducted. Four statistical models were used to adjust for demographic, metabolic, and pancreatitis-related risk factors. A total of 83 individuals after an episode of pancreatitis were recruited. GRP was significantly associated with AGM, consistently in all four models (P -trend < 0.05), and fasting blood glucose contributed 17% to the variance of GRP. Further, GRP was significantly associated with glucagon (P < 0.003), MCP-1 (P < 0.025), and TNF-α (P < 0.025) - consistently in all four models. GRP was also significantly associated with PP and PYY in three models (P < 0.030 for both), and with GIP and glicentin in one model (P = 0.001 and 0.024, respectively). Associations between GRP and other pancreatic and gut hormones were not significant. GRP is significantly increased in patients with AGM after pancreatitis and is associated with increased levels of pro-inflammatory cytokines, as well as certain pancreatic and gut hormones. Detailed mechanistic studies are now warranted to investigate the exact role of GRP in derangements of glucose homeostasis following pancreatitis.

Gastrin-Releasing Peptide and Glucose Metabolism Following Pancreatitis

PubMed Central

Pendharkar, Sayali A.; Drury, Marie; Walia, Monika; Korc, Murray; Petrov, Maxim S.

2017-01-01

Background Gastrin-releasing peptide (GRP) is a pluripotent peptide that has been implicated in both gastrointestinal inflammatory states and classical chronic metabolic diseases such as diabetes. Abnormal glucose metabolism (AGM) after pancreatitis, an exemplar inflammatory disease involving the gastrointestinal tract, is associated with persistent low-grade inflammation and altered secretion of pancreatic and gut hormones as well as cytokines. While GRP is involved in secretion of many of them, it is not known whether GRP has a role in AGM. Therefore, we aimed to investigate the association between GRP and AGM following pancreatitis. Methods Fasting blood samples were collected to measure GRP, blood glucose, insulin, amylin, glucagon, pancreatic polypeptide (PP), somatostatin, cholecystokinin, gastric-inhibitory peptide (GIP), gastrin, ghrelin, glicentin, glucagon-like peptide-1 and 2, oxyntomodulin, peptide YY (PYY), secretin, vasoactive intestinal peptide, tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein (MCP)-1, and interleukin-6. Modified Poisson regression analysis and linear regression analyses were conducted. Four statistical models were used to adjust for demographic, metabolic, and pancreatitis-related risk factors. Results A total of 83 individuals after an episode of pancreatitis were recruited. GRP was significantly associated with AGM, consistently in all four models (P -trend < 0.05), and fasting blood glucose contributed 17% to the variance of GRP. Further, GRP was significantly associated with glucagon (P < 0.003), MCP-1 (P < 0.025), and TNF-α (P < 0.025) - consistently in all four models. GRP was also significantly associated with PP and PYY in three models (P < 0.030 for both), and with GIP and glicentin in one model (P = 0.001 and 0.024, respectively). Associations between GRP and other pancreatic and gut hormones were not significant. Conclusion GRP is significantly increased in patients with AGM after pancreatitis and is associated with increased levels of pro-inflammatory cytokines, as well as certain pancreatic and gut hormones. Detailed mechanistic studies are now warranted to investigate the exact role of GRP in derangements of glucose homeostasis following pancreatitis. PMID:28912908

Improving Implementation of Function-Based Interventions: Self-Monitoring, Data Collection, and Data Review

ERIC Educational Resources Information Center

Pinkelman, Sarah E.; Horner, Robert H.

2017-01-01

The success of function-based interventions depends not just on the quality of procedures but also on the extent to which procedures are implemented as planned. Too often in schools, effort is committed to functional assessment and behavior support plan design, only to be followed by weak implementation. This study used a multiple baseline across…

The importance of employee participation and perceptions of changes in procedures in a teamworking intervention

PubMed Central

Nielsen, Karina; Randall, Raymond

2012-01-01

The powerful positive results of implementing teamwork are not always achieved. It has been suggested that attempts to implement theories regarding teamwork do not always lead to those theories being put into practice, and as a result positive outcomes are not always found. The participation of employees in the development and implementation of an intervention may help to ensure that changes take place. In this longitudinal study (N = 583) of teamwork implementation in Denmark we examined the links between pre-intervention working conditions and well-being, levels of participation in planning and implementation, employees’ reports of changes in procedures, and intervention outcomes. Pre-intervention levels of autonomy and job satisfaction predicted the degree of employee participation in the planning and implementation of the intervention. Pre-intervention well-being and social support were linked directly to the degree to which employees reported changes in existing work practices concerning teamwork. In addition, participation and changes in work procedures were significantly associated with post-intervention autonomy, social support and well-being. The results indicate that employee participation in intervention processes is crucial in what appears to be an important association with perceived changes in procedures and, therefore, in intervention outcomes. PMID:22745519

28 CFR 61.11 - Environmental information.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Environmental information. 61.11 Section 61.11 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) PROCEDURES FOR IMPLEMENTING THE NATIONAL ENVIRONMENTAL POLICY ACT Implementing Procedures § 61.11 Environmental information. Interested...

28 CFR 61.11 - Environmental information.

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2011-07-01

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28 CFR Appendix C to Part 61 - Immigration and Naturalization Service Procedures Relating to the Implementation of the National...

Code of Federal Regulations, 2013 CFR

2013-07-01

... Procedures Relating to the Implementation of the National Environmental Policy Act C Appendix C to Part 61... ENVIRONMENTAL POLICY ACT Pt. 61, App. C Appendix C to Part 61—Immigration and Naturalization Service Procedures... published pursuant to the National Environmental Policy Act of 1969 (NEPA), as amended (42 U.S.C. 4321 et...

28 CFR Appendix C to Part 61 - Immigration and Naturalization Service Procedures Relating to the Implementation of the National...

Code of Federal Regulations, 2010 CFR

2010-07-01

... Procedures Relating to the Implementation of the National Environmental Policy Act C Appendix C to Part 61... ENVIRONMENTAL POLICY ACT Pt. 61, App. C Appendix C to Part 61—Immigration and Naturalization Service Procedures... published pursuant to the National Environmental Policy Act of 1969 (NEPA), as amended (42 U.S.C. 4321 et...

32 CFR 148.14 - Procedures.

Code of Federal Regulations, 2010 CFR

2010-07-01

... POLICY AND IMPLEMENTATION OF RECIPROCITY OF FACILITIES Guidelines for the Implementation and Oversight of the Policy on Reciprocity of use and Inspections of Facilities § 148.14 Procedures. (a) Agencies that... maximize interagency reciprocity shall be based primarily upon existing organizational reporting channels...

32 CFR 148.14 - Procedures.

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2013-07-01

... POLICY AND IMPLEMENTATION OF RECIPROCITY OF FACILITIES Guidelines for the Implementation and Oversight of the Policy on Reciprocity of use and Inspections of Facilities § 148.14 Procedures. (a) Agencies that... maximize interagency reciprocity shall be based primarily upon existing organizational reporting channels...

32 CFR 148.14 - Procedures.

Code of Federal Regulations, 2014 CFR

2014-07-01

... POLICY AND IMPLEMENTATION OF RECIPROCITY OF FACILITIES Guidelines for the Implementation and Oversight of the Policy on Reciprocity of use and Inspections of Facilities § 148.14 Procedures. (a) Agencies that... maximize interagency reciprocity shall be based primarily upon existing organizational reporting channels...

32 CFR 148.14 - Procedures.

Code of Federal Regulations, 2012 CFR

2012-07-01

... POLICY AND IMPLEMENTATION OF RECIPROCITY OF FACILITIES Guidelines for the Implementation and Oversight of the Policy on Reciprocity of use and Inspections of Facilities § 148.14 Procedures. (a) Agencies that... maximize interagency reciprocity shall be based primarily upon existing organizational reporting channels...

32 CFR 148.14 - Procedures.

Code of Federal Regulations, 2011 CFR

2011-07-01

... POLICY AND IMPLEMENTATION OF RECIPROCITY OF FACILITIES Guidelines for the Implementation and Oversight of the Policy on Reciprocity of use and Inspections of Facilities § 148.14 Procedures. (a) Agencies that... maximize interagency reciprocity shall be based primarily upon existing organizational reporting channels...

10 CFR 1021.320 - Environmental assessments.

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2010-01-01

... 10 Energy 4 2010-01-01 2010-01-01 false Environmental assessments. 1021.320 Section 1021.320 Energy DEPARTMENT OF ENERGY (GENERAL PROVISIONS) NATIONAL ENVIRONMENTAL POLICY ACT IMPLEMENTING PROCEDURES Implementing Procedures § 1021.320 Environmental assessments. DOE shall prepare and circulate EAs...

10 CFR 1021.320 - Environmental assessments.

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2011-01-01

... 10 Energy 4 2011-01-01 2011-01-01 false Environmental assessments. 1021.320 Section 1021.320 Energy DEPARTMENT OF ENERGY (GENERAL PROVISIONS) NATIONAL ENVIRONMENTAL POLICY ACT IMPLEMENTING PROCEDURES Implementing Procedures § 1021.320 Environmental assessments. DOE shall prepare and circulate EAs...

10 CFR 1021.314 - Supplemental environmental impact statements.

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2010-01-01

... 10 Energy 4 2010-01-01 2010-01-01 false Supplemental environmental impact statements. 1021.314 Section 1021.314 Energy DEPARTMENT OF ENERGY (GENERAL PROVISIONS) NATIONAL ENVIRONMENTAL POLICY ACT IMPLEMENTING PROCEDURES Implementing Procedures § 1021.314 Supplemental environmental impact statements. (a...

10 CFR 1021.310 - Environmental impact statements.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 4 2010-01-01 2010-01-01 false Environmental impact statements. 1021.310 Section 1021.310 Energy DEPARTMENT OF ENERGY (GENERAL PROVISIONS) NATIONAL ENVIRONMENTAL POLICY ACT IMPLEMENTING PROCEDURES Implementing Procedures § 1021.310 Environmental impact statements. DOE shall prepare and...

45 CFR 164.530 - Administrative requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... privacy official who is responsible for the development and implementation of the policies and procedures... workforce on the policies and procedures with respect to protected health information required by this...) Implementation specification: Safeguards. A covered entity must reasonably safeguard protected health information...

45 CFR 164.530 - Administrative requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... privacy official who is responsible for the development and implementation of the policies and procedures... workforce on the policies and procedures with respect to protected health information required by this...) Implementation specification: Safeguards. A covered entity must reasonably safeguard protected health information...

Training shelter volunteers to teach dog compliance.

PubMed

Howard, Veronica J; DiGennaro Reed, Florence D

2014-01-01

This study examined the degree to which training procedures influenced the integrity of behaviorally based dog training implemented by volunteers of an animal shelter. Volunteers were taught to implement discrete-trial obedience training to teach 2 skills (sit and wait) to dogs. Procedural integrity during the baseline and written instructions conditions was low across all participants. Although performance increased with use of a video model, integrity did not reach criterion levels until performance feedback and modeling were provided. Moreover, the integrity of the discrete-trial training procedure was significantly and positively correlated with dog compliance to instructions for all dyads. Correct implementation and compliance were observed when participants were paired with a novel dog and trainer, respectively, although generalization of procedural integrity from the discrete-trial sit procedure to the discrete-trial wait procedure was not observed. Shelter consumers rated the behavior change in dogs and trainers as socially significant. Implications of these findings and future directions for research are discussed. © Society for the Experimental Analysis of Behavior.

An Examination of the Effects of a Video-Based Training Package on Professional Staff's Implementation of a Brief Functional Analysis and Data Analysis

ERIC Educational Resources Information Center

Fleming, Courtney V.

2011-01-01

Minimal research has investigated training packages used to teach professional staff how to implement functional analysis procedures and to interpret data gathered during functional analysis. The current investigation used video-based training with role-play and feedback to teach six professionals in a clinical setting to implement procedures of a…

Cost reduction with successful implementation of an antibiotic prophylaxis program in a private hospital in Ribeirão Preto, Brazil.

PubMed

Fonseca, S N; Melon Kunzle, S R; Barbosa Silva, S A; Schmidt, J G; Mele, R R

1999-01-01

To describe the implementation and results of a perioperative antibiotic prophylaxis (PAP) program. A protocol for correct use of PAP was implemented in December 1994. For selected months we measured the PAP protocol compliance of a random sample of clean and clean-contaminated procedures and calculated the cost of incorrect use of PAP. SELLING: A 180-bed general hospital in Ribeirão Preto, Brazil. The cost of unnecessary PAP in the obstetric and gynecologic, cardiothoracic, and orthopedic services dropped from $4,224.54 ($23.47/procedure) in November 1994 to $1,147.24 ($6.17/procedure, January 1995), $544.42 ($3.58/procedure, May 1995), $99.06 ($0.50/procedure, August 1995), and $30 ($0.12/procedure, March 1996). In November 1994, only 13.6% of all surgical procedures were done with correct use of PAP, compared to 59% in January 1995, 73% in August 1995, 78% in March 1996, 92% in November 1996, and 98% in May 1997. Incorrect PAP use wastes resources, which is a particular problem in developing countries. Our program is simple and can be implemented without the use of computers and now is being adopted in other hospitals in our region. We credit the success of our program to the commitment of all participants and to the strong support of the hospital directors.

A management system for evaluating the Virginia periodic motor vehicle inspection program : software manual and implementation procedures : final report.

DOT National Transportation Integrated Search

1978-01-01

This report deals with the Periodic Motor Vehicle Inspection Management Evaluation System software documentation and implementation procedures. A companion report entitled "A Management System for Evaluating the Virginia Periodic Motor Vehicle Inspec...

Policy and Procedures for Managing Dual Use Research of Concern

EPA Pesticide Factsheets

The DURC and iDURC Policies require all federal departments and agencies that conduct life sciences research to implement their provisions. EPA Order 1000.19, Policy and Procedures for Managing Dual Use Research of Concern, implements both policies at EPA.

Development, implementation and evaluation of a pedestrian safety zone for elderly pedestrians

DOT National Transportation Integrated Search

1998-02-01

The objectives of this study were to develop and apply procedures for defining pedestrian safety zones for the older (age 65+) adult and to develop, implement and evaluate a countermeasure program in the defined zones. Zone definition procedures were...

Thorium-232 fission induced by light charged particles up to 70 MeV

NASA Astrophysics Data System (ADS)

Métivier, Vincent; Duchemin, Charlotte; Guertin, Arnaud; Michel, Nathalie; Haddad, Férid

2017-09-01

Studies have been devoted to the production of alpha emitters for medical application in collaboration with the GIP ARRONAX that possesses a high energy and high intensity multi-particle cyclotron. The productions of Ra-223, Ac-225 and U-230 have been investigated from the Th-232(p,x) and Th-232(d,x) reactions using the stacked-foils method and gamma spectrometry measurements. These reactions have led to the production of several fission products, including some with a medical interest like Mo-99, Cd-115g and I-131. This article presents cross section data of fission products obtained from these undedicated experiments. These data have been also compared with the TALYS code results.

Mode-Stirred Method Implementation for HIRF Susceptibility Testing and Results Comparison with Anechoic Method

NASA Technical Reports Server (NTRS)

Nguyen, Truong X.; Ely, Jay J.; Koppen, Sandra V.

2001-01-01

This paper describes the implementation of mode-stirred method for susceptibility testing according to the current DO-160D standard. Test results on an Engine Data Processor using the implemented procedure and the comparisons with the standard anechoic test results are presented. The comparison experimentally shows that the susceptibility thresholds found in mode-stirred method are consistently higher than anechoic. This is consistent with the recent statistical analysis finding by NIST that the current calibration procedure overstates field strength by a fixed amount. Once the test results are adjusted for this value, the comparisons with the anechoic results are excellent. The results also show that test method has excellent chamber to chamber repeatability. Several areas for improvements to the current procedure are also identified and implemented.

Systems development and difficulties in implementing procedures for elder abuse prevention among private community general support centers in Japan.

PubMed

Nakanishi, Miharu; Nakashima, Taeko; Yamaoka, Yukako; Hada, Keiko; Tanaka, Hideaki

2014-01-01

The present study examines differences in systems development and difficulties in implementing procedures for elder abuse prevention in 1,119 private and 606 public community general support centers under the public long-term care insurance program in Japan. The private community general support centers showed more difficulty implementing procedures than the public community general support centers. Controlling for the type of municipality, progress in systems development did not differ between the private and public community general support centers. Further research should examine how the characteristics of municipal governments are related to systems development in community general support centers.

32 CFR 57.1 - Purpose.

Code of Federal Regulations, 2013 CFR

2013-07-01

...) Authorizes implementing instructions, a DoD Manual entitled “Standard Operating Procedures for the Provision...) Implements policy, assigns responsibilities, and prescribes procedures under 20 U.S.C. chapter 33 and 20 U.S... forms consistent with DoD 8910.1-M, DoD Instruction 7750.7, and Hospital Accreditation Standards. ...

32 CFR 57.1 - Purpose.

Code of Federal Regulations, 2012 CFR

2012-07-01

...) Authorizes implementing instructions, a DoD Manual entitled “Standard Operating Procedures for the Provision...) Implements policy, assigns responsibilities, and prescribes procedures under 20 U.S.C. chapter 33 and 20 U.S... forms consistent with DoD 8910.1-M, DoD Instruction 7750.7, and Hospital Accreditation Standards. ...

32 CFR 57.1 - Purpose.

Code of Federal Regulations, 2014 CFR

2014-07-01

...) Authorizes implementing instructions, a DoD Manual entitled “Standard Operating Procedures for the Provision...) Implements policy, assigns responsibilities, and prescribes procedures under 20 U.S.C. chapter 33 and 20 U.S... forms consistent with DoD 8910.1-M, DoD Instruction 7750.7, and Hospital Accreditation Standards. ...

78 FR 66648 - Approval and Promulgation of Implementation Plans; Texas; Procedures for Stringency...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-06

... ENVIRONMENTAL PROTECTION AGENCY 40 CFR Part 52 [EPA-R06-OAR-2010-0335; FRL-9902-50-Region 6] Approval and Promulgation of Implementation Plans; Texas; Procedures for Stringency Determinations and Minor Permit Revisions for Federal Operating Permits AGENCY: Environmental Protection Agency (EPA...

78 FR 55234 - Approval and Promulgation of Implementation Plans; Texas; Procedures for Stringency...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-10

... ENVIRONMENTAL PROTECTION AGENCY 40 CFR Part 52 [EPA-R06-OAR-2010-0335; FRL-9900-81-Region6] Approval and Promulgation of Implementation Plans; Texas; Procedures for Stringency Determinations and Minor Permit Revisions for Federal Operating Permits AGENCY: Environmental Protection Agency (EPA...

10 CFR 1021.313 - Public review of environmental impact statements.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 4 2010-01-01 2010-01-01 false Public review of environmental impact statements. 1021.313 Section 1021.313 Energy DEPARTMENT OF ENERGY (GENERAL PROVISIONS) NATIONAL ENVIRONMENTAL POLICY ACT IMPLEMENTING PROCEDURES Implementing Procedures § 1021.313 Public review of environmental impact statements. (a...

24 CFR 901.45 - Indicator #8, security.

Code of Federal Regulations, 2010 CFR

2010-04-01

... of crime to local law enforcement agencies, the adoption and implementation of tough applicant screening and resident eviction policies and procedures, and, as applicable, PHA performance under any HUD... policies and the PHA has implemented procedures and can document that it (1) tracks crime and crime-related...

Overcoming Barriers to Implementing Outdoor and Environmental Education (Continued): Safety/Legal Liability.

ERIC Educational Resources Information Center

Hanna, Glenda

1994-01-01

A risk management plan for outdoor education programs should include procedures for regular program implementation, as well as rescue, first aid, and accident follow-up procedures. Stresses understanding legal and ethical responsibilities and the importance of sufficient insurance protection. Includes suggestions for dealing with conflicts in…

Evaluating Community College Personnel: A Research Report.

ERIC Educational Resources Information Center

Deegan, William L.; And Others

A statewide survey was conducted of local evaluation policies, procedures, and problems of implementing evaluation programs on the campuses of California community colleges. The following areas were studied: (1) the process of development of the evaluation program; (2) procedures utilized in the first year of implementing Senate Bill 696…

77 FR 235 - Approval and Promulgation of Air Quality Implementation Plans; Colorado; Procedural Rules...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-04

... Promulgation of Air Quality Implementation Plans; Colorado; Procedural Rules; Conflicts of Interest AGENCY... its members of potential conflicts of interest. We are also reproposing approval of a portion of... federally mandate that Commission members disclose any potential conflicts of interest that arise during...

77 FR 21451 - Approval and Promulgation of Air Quality Implementation Plans; Colorado; Procedural Rules...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-10

... Promulgation of Air Quality Implementation Plans; Colorado; Procedural Rules; Conflicts of Interest AGENCY... potential conflicts of interest. We are also approving the remaining portion of Colorado's January 7, 2008... of potential conflicts of interest. (i) Incorporation by reference. (A) Department of Public Health...

Training Shelter Volunteers to Teach Dog Compliance

ERIC Educational Resources Information Center

Howard, Veronica J.; DiGennaro Reed, Florence D.

2014-01-01

This study examined the degree to which training procedures influenced the integrity of behaviorally based dog training implemented by volunteers of an animal shelter. Volunteers were taught to implement discrete-trial obedience training to teach 2 skills (sit and wait) to dogs. Procedural integrity during the baseline and written instructions…

17 CFR 39.4 - Procedures for implementing derivatives clearing organization rules and clearing new products.

Code of Federal Regulations, 2011 CFR

2011-04-01

... derivatives clearing organization rules and clearing new products. 39.4 Section 39.4 Commodity and Securities Exchanges COMMODITY FUTURES TRADING COMMISSION DERIVATIVES CLEARING ORGANIZATIONS § 39.4 Procedures for implementing derivatives clearing organization rules and clearing new products. (a) Request for approval of...

78 FR 9651 - Approval and Promulgation of Implementation Plans; Oregon: Heat Smart Program and Enforcement...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-11

... Promulgation of Implementation Plans; Oregon: Heat Smart Program and Enforcement Procedures AGENCY... submission contains revisions to the Heat Smart program and to the enforcement procedures and civil penalties... submission contains additional revisions to the Heat Smart program, along with minor revisions and...

Guide for Implementing State Adopted Texts, 1969-1970.

ERIC Educational Resources Information Center

Sanchis, Robert A.; And Others

The materials and procedures used by the Fountain Valley School District, California, to implement their reading program are described. Included are a description of the reading principles on which the program is based and information on methodology and organizational procedures. Also described are lists of state-adopted texts, summaries of basic…

Security breaches: tips for assessing and limiting your risks.

PubMed

Coons, Leeanne R

2011-01-01

As part of their compliance planning, medical practices should undergo a risk assessment to determine any vulnerability within the practice relative to security breaches. Practices should also implement safeguards to limit their risks. Such safeguards include facility access controls, information and electronic media management, use of business associate agreements, and education and enforcement. Implementation of specific policies and procedures to address security incidents is another critical step that medical practices should take as part of their security incident prevention plan. Medical practices should not only develop policies and procedures to prevent, detect, contain, and correct security violations, but should make sure that such policies and procedures are actually implemented in their everyday operations.

Consulting report on the NASA technology utilization network system

NASA Technical Reports Server (NTRS)

Hlava, Marjorie M. K.

1992-01-01

The purposes of this consulting effort are: (1) to evaluate the existing management and production procedures and workflow as they each relate to the successful development, utilization, and implementation of the NASA Technology Utilization Network System (TUNS) database; (2) to identify, as requested by the NASA Project Monitor, the strengths, weaknesses, areas of bottlenecking, and previously unaddressed problem areas affecting TUNS; (3) to recommend changes or modifications of existing procedures as necessary in order to effect corrections for the overall benefit of NASA TUNS database production, implementation, and utilization; and (4) to recommend the addition of alternative procedures, routines, and activities that will consolidate and facilitate the production, implementation, and utilization of the NASA TUNS database.

Moving to patient reported collection of race and ethnicity data: implementation and impact in ten hospitals.

PubMed

Berry, Carolyn; Kaplan, Sue A; Mijanovich, Tod; Mayer, Andrea

2014-01-01

The purpose of this paper is to examine the feasibility of collecting standardized, patient reported race and ethnicity (RE) data in hospitals, and to assess the impact on data quality and utility. Part of a larger evaluation that included a comprehensive assessment. Sites documented RE data collection procedures before and after program implementation. Primary data collected through qualitative interviewing with key respondents in ten hospitals to assess implementation. Nine hospitals provided RE data on the same patients before and after implementation new data collection procedures were implemented to assess impact. Implementation went smoothly in nine of ten hospitals and had substantial effects on the hospital staff awareness on the potential for disparities within their hospitals. New procedures had minimal impact on characterization of readmitted patients. This study demonstrated that it is feasible for staff in a diverse group of hospitals to implement systematic, internally standardized methods to collect self-reported RE data from patients. Although this study found little impact patients' demographic characterizations, other benefits included greater awareness of and attention to disparities, uncovering small pockets of minorities, and dramatically increased RE data use in quality improvement efforts.

Caregiver preference for reinforcement-based interventions for problem behavior maintained by positive reinforcement.

PubMed

Gabor, Anne M; Fritz, Jennifer N; Roath, Christopher T; Rothe, Brittany R; Gourley, Denise A

2016-06-01

Social validity of behavioral interventions typically is assessed with indirect methods or by determining preferences of the individuals who receive treatment, and direct observation of caregiver preference rarely is described. In this study, preferences of 5 caregivers were determined via a concurrent-chains procedure. Caregivers were neurotypical, and children had been diagnosed with developmental disabilities and engaged in problem behavior maintained by positive reinforcement. Caregivers were taught to implement noncontingent reinforcement (NCR), differential reinforcement of alternative behavior (DRA), and differential reinforcement of other behavior (DRO), and the caregivers selected interventions to implement during sessions with the child after they had demonstrated proficiency in implementing the interventions. Three caregivers preferred DRA, 1 caregiver preferred differential reinforcement procedures, and 1 caregiver did not exhibit a preference. Direct observation of implementation in concurrent-chains procedures may allow the identification of interventions that are implemented with sufficient integrity and preferred by caregivers. © 2016 Society for the Experimental Analysis of Behavior.

Reflections on the implementation of governance structures for early-stage clinical innovation.

PubMed

Cowie, Luke; Sandall, Jane; Ehrich, Kathryn

2013-12-01

This paper seeks to further explore the question of how best to monitor and govern innovative clinical procedures in their earliest phase of development. We examine the potential value of proposed governance frameworks, such as the IDEAL model, and examine the functioning of a novel procedures review committee. The paper draws upon 20 qualitative, semi-structured interviews. Nine interviews were conducted with members of a committee that was established as a means of governing innovative procedures within a large National Health Service Foundation Trust hospital in the UK. Eleven interviews were conducted with health providers involved with the development of a variety of novel clinical procedures. Prominent themes from the data include the potential willingness of clinicians to engage with regulatory frameworks for innovative procedures, existing ways in which clinicians and others attempt to ensure patient's safety and manage uncertainty in the context of novel procedures, views on the potential benefits and drawbacks of engaging with a review committee for novel procedures, and the pragmatic considerations and potential unintended consequences that are entailed in the implementation of regulatory requirements for the monitoring of innovative procedures. The views of committee members and clinical innovators help us to understand the practical issues of implementing governance structures for novel clinical procedures. The data illustrate those factors that must be taken into account if governance is to support innovation rather than act as an inhibiting factor in the development of new clinical procedures. © 2012 John Wiley & Sons Ltd.

Implementation of a Self-Management System for Students with Disabilities in General Education Settings

ERIC Educational Resources Information Center

Schulze, Margaret A.

2016-01-01

Despite the fact that self-management procedures have a robust literature base attesting to their efficacy with students with disabilities, the use of these strategies in general education settings remains limited. This mixed methods study examined the implementation of self-management procedures using both quantitative and qualitative methods.…

24 CFR 70.4 - Procedure for implementing prevailing wage exemptions for volunteers.

Code of Federal Regulations, 2010 CFR

2010-04-01

... prevailing wage exemptions for volunteers. 70.4 Section 70.4 Housing and Urban Development Office of the... AND HUD-DETERMINED WAGE RATES § 70.4 Procedure for implementing prevailing wage exemptions for... otherwise subject to Davis-Bacon or HUD-determined prevailing wage rates which propose to use volunteers and...

QUALITY SYSTEMS AND IMPLEMENTATION PLAN FOR A PILOT STUDY OF CHILDREN'S TOTAL EXPOSURE TO PERSISTENT PESTICIDES AND OTHER PERSISTENT ORGANIC PESTICIDES (CTEPP)

EPA Science Inventory

The Quality System Implementation Plan (QSIP) describes the quality assurance and quality control procedures developed for the CTEPP study. It provides the QA/QC procedures used in recruitment of subjects, sample field collection, sample extraction and analysis, data storage, and...

Enhancing E-Learning Quality through the Application of the AKUE Procedure Model

ERIC Educational Resources Information Center

Bremer, C.

2012-01-01

The paper describes the procedure model AKUE, which aims at the improvement and assurance of quality and cost efficiency in the context of the introduction of e-learning and the development of digital learning material. AKUE divides the whole planning and implementation process into four different phases: analysis, conception, implementation, and…

40 CFR 93.118 - Criteria and procedures: Motor vehicle emissions budget.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 20 2011-07-01 2011-07-01 false Criteria and procedures: Motor vehicle... Projects Developed, Funded or Approved Under Title 23 U.S.C. or the Federal Transit Laws § 93.118 Criteria...(s) in the applicable implementation plan (or implementation plan submission). This criterion applies...

On the role of the gut in diabetic hyperglucagonaemia.

PubMed

Lund, Asger

2017-04-01

Patients with type 2 diabetes are characterised not only by compromised insulin secretion and action, but also by elevated plasma concentrations of the 29-amino acid peptide hormone glucagon, which generally is thought of as a pancreas-derived hormone (produced in and secreted from alpha cells in the islet of Langerhans). In patients with diabetes, circulating glucagon concentrations are elevated in the fasting state and fail to decrease appropriately or even increase in response to ingestion of nutrients. Glucagon is known to be a potent stimulator of hepatic glucose production, and, thus, the elevated glucagon concentrations in diabetes contribute decisively to the predominating trait of patients with diabetes namely hyperglycaemia. Interestingly, studies have shown that while oral intake of glucose results in inappropriately high plasma concentrations of glucagon in patients with diabetes, intravenous (iv) infusion of glucose does not. The mechanisms behind these differential glucagon responses to oral vs. iv glucose administration are currently unexplained. Three hypotheses were tested in the present thesis: 1) Could the inappropriate glucagon response to oral glucose ingestion in patients with diabetes be attributed to the release of glucagonotropic/glucagonostatic peptides secreted from the gut? 2) Could the inappropriate glucagon response to oral glucose ingestion in diabetes be a result of extrapancreatic glucagon secretion (possibly originating from the gut)? And 3) Does the differential glucagon responses between oral and iv glucose administration affect endogenous glucose production (EGP). The overall aim of this PhD thesis was, thus, to investigate the role of the gut in diabetic hyperglucagonaemia and hyperglycaemia. In Study I we examined the effect of the three gut-derived hormones glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2) on glucagon secretion in patients with type 2 diabetes. We applied a 50 g-oral glucose tolerance test (OGTT), and five isoglycaemic iv glucose infusions (IIGIs) with either saline, GIP, GLP-1, GLP-2 or a combination of the three hormones. We show that these gut-derived hormones affect glucagon secretion differently and that OGTT-induced secretion of these hormones may play a role in the inappropriate glucagon response to orally ingested glucose in patients with type 2 diabetes with especially GIP acting to increase glucagon secretion. In Study II we examined totally pancreatectomised patients and non-diabetic control subjects during a 75 g-OGTT and an IIGI. We applied sandwich enzyme-linked immunosorbent assay (ELISA) and mass spectrometry-based proteomics for plasma glucagon analysis and show that 29-amino acid glucagon circulates in patients without a pancreas and that glucose stimulation of the gut results in significant hyperglucagonemia in these patients - ultimately confirming the existence of extrapancreatic glucagon secretion in humans. In Study III we examined whether the different responses of insulin and glucagon, respectively, between oral and iv glucose administration translate into differences in EGP and glucose disappearance in patients with type 2 diabetes and non-diabetic control subjects. We applied glucose tracer methodology during a 75 g-OGTT, IIGI and IIGI + iv glucagon (to isolate the effect of glucagon) and show that EGP is less suppressed during OGTT than during IIGI in both patients with type 2 diabetes and non-diabetic control subjects. Articles published in the Danish Medical Journal are “open access”. This means that the articles are distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits any non-commercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.

28 CFR 42.733 - Enforcement procedures.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 28 Judicial Administration 1 2014-07-01 2014-07-01 false Enforcement procedures. 42.733 Section 42.733 Judicial Administration DEPARTMENT OF JUSTICE NONDISCRIMINATION; EQUAL EMPLOYMENT OPPORTUNITY...; Implementation of the Age Discrimination Act of 1975 Compliance Procedures § 42.733 Enforcement procedures. (a...

Association of Reference Payment for Colonoscopy With Consumer Choices, Insurer Spending, and Procedural Complications.

PubMed

Robinson, James C; Brown, Timothy T; Whaley, Christopher; Finlayson, Emily

2015-11-01

Regulatory limits on consumer cost sharing permit wide variation in the prices charged for screening and diagnostic tests such as colonoscopy. Employers are experimenting with reference payment initiatives that offer full insurance coverage at low-priced facilities but require substantial cost sharing if patients select high-priced alternatives. To ascertain the effect of reference payment on facility choice, insurer spending, consumer cost sharing, and procedural complications for colonoscopy. The California Public Employees' Retirement System (CalPERS) implemented reference payment in January 2012. We obtained data on 21 644 CalPERS enrollees who underwent colonoscopy in the 3 years prior to implementation and on 13 551 patients in the 2 years after implementation. Control group data were obtained on 258 616 Anthem Blue Cross enrollees who underwent colonoscopy and who were not subject to reference payment initiatives during this 5-year period. Consumer choice of facility, price paid per procedure, total insurer spending, consumer cost sharing, and procedural complications. Choices, prices, and complications were compared for CalPERS and Anthem patients before and after implementation of reference payments, using difference-in-difference multivariable regressions to adjust for patient demographic characteristics and comorbidities, procedure indications, and geographic location. Utilization of low-priced facilities for CalPERS members increased from 68.6% in 2009 to 90.5% in 2013. After adjusting for patient demographic characteristics, comorbidities, and other factors, the implementation of reference payment increased use of low-priced facilities by 17.6 percentage points (95% CI, 11.8 to 23.4; P < .001). The mean price paid for colonoscopy for the CalPERS population increased from $1587 (95% CI, $1555-$1618) in 2009 to $1716 (95% CI, $1678-$1753) in 2011 and then decreased to $1508 (95% CI, $1469-$1548) in 2013 for patients subject to reference payment. After adjustment for other relevant factors, reference payment was responsible for a 21.0% (95% CI, -26.0% to -15.6%, P < .001) reduction in the price. Reference payment was associated with a small but statistically insignificant decline in procedural complications, from 2.1% in 2009 to 2.0% in 2013 (P = .47). In the first 2 years after implementation, CalPERS saved $7.0 million (28%) on spending for the procedure. Implementation of reference payment for colonoscopy was associated with reduced spending and no change in complications.

Extravasation management in the pediatric oncology ward of Children's Hospital of Fudan University: a best practice implementation project.

PubMed

Wang, Yingwen; Kong, Meijing; Ge, Youhong

2016-12-01

Extravasation in a pediatric patient can cause a serious adverse event, but many nurses have insufficient experience to deal with it during intravenous administration. Our division implemented a best practice project, which included extravasation kit instruction preparation, staff education and an update of institutional policy and procedures. The project focused on auditing the extent to which the protocol was implemented and promoting its implementation. The objective of the project was to establish an evidence-based policy and procedure for extravasation management, improve knowledge regarding best practice of extravasation management among staff and formalize the documentation template for extravasation events. The Joanna Briggs Institute's Practical Application of Clinical Evidence System and Getting Research into Practice were used to examine compliance with criteria based on the best available evidence before and after the implementation of strategies to promote the use of the evidence-based practice protocol. Four criteria showed a noticeable improvement in compliance: increased use of extravasation kit (0-100%), updated policies and procedure (0-94%), staff education (19-94%) and documented outcomes (13-88%). The project successfully established effective strategies for establishing an extravasation kit instruction sheet, updating policies and procedures, continuous staff education and nursing documentation to ensure best practice and improve patient outcomes.

[Standard operating procedures in ethic committees].

PubMed

Czarkowski, Marek

2006-02-01

Polish ethic committees should have to work together in order to maintain and develop high quality standards in the protection of human subjects. Exchanging knowledge, know-how and information polish ethic committees should have to implement standard operating procedures. Procedures should improve quality and proficiency of all types of ethic committee's activities. Standard operating procedures should cover as important problems as conflict of interest, trial's insurance or elections of ethic committees. The opinions of experts who have been reviewing medical research projects for several years may prove to be especially valuable in this setting. Governmental initiatives and creation of forum for polish ethic committees are essential in the effective standardisation, coordination and implementation of procedures in regional ethic committees. These projects need support via public funding from our authorities.

10 CFR 835.104 - Written procedures.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 4 2012-01-01 2012-01-01 false Written procedures. 835.104 Section 835.104 Energy DEPARTMENT OF ENERGY OCCUPATIONAL RADIATION PROTECTION Management and Administrative Requirements § 835.104 Written procedures. Written procedures shall be developed and implemented as necessary to ensure...

10 CFR 835.104 - Written procedures.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 4 2010-01-01 2010-01-01 false Written procedures. 835.104 Section 835.104 Energy DEPARTMENT OF ENERGY OCCUPATIONAL RADIATION PROTECTION Management and Administrative Requirements § 835.104 Written procedures. Written procedures shall be developed and implemented as necessary to ensure...

10 CFR 835.104 - Written procedures.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 4 2011-01-01 2011-01-01 false Written procedures. 835.104 Section 835.104 Energy DEPARTMENT OF ENERGY OCCUPATIONAL RADIATION PROTECTION Management and Administrative Requirements § 835.104 Written procedures. Written procedures shall be developed and implemented as necessary to ensure...

10 CFR 835.104 - Written procedures.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 4 2013-01-01 2013-01-01 false Written procedures. 835.104 Section 835.104 Energy DEPARTMENT OF ENERGY OCCUPATIONAL RADIATION PROTECTION Management and Administrative Requirements § 835.104 Written procedures. Written procedures shall be developed and implemented as necessary to ensure...

10 CFR 835.104 - Written procedures.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 4 2014-01-01 2014-01-01 false Written procedures. 835.104 Section 835.104 Energy DEPARTMENT OF ENERGY OCCUPATIONAL RADIATION PROTECTION Management and Administrative Requirements § 835.104 Written procedures. Written procedures shall be developed and implemented as necessary to ensure...

10 CFR 26.127 - Procedures.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 1 2011-01-01 2011-01-01 false Procedures. 26.127 Section 26.127 Energy NUCLEAR REGULATORY COMMISSION FITNESS FOR DUTY PROGRAMS Licensee Testing Facilities § 26.127 Procedures. (a) Licensee testing facilities shall develop, implement, and maintain clear and well-documented procedures for...

10 CFR 26.127 - Procedures.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Procedures. 26.127 Section 26.127 Energy NUCLEAR REGULATORY COMMISSION FITNESS FOR DUTY PROGRAMS Licensee Testing Facilities § 26.127 Procedures. (a) Licensee testing facilities shall develop, implement, and maintain clear and well-documented procedures for...

7 CFR Exhibit D to Subpart G of... - Implementation Procedures for the Endangered Species Act

Code of Federal Regulations, 2014 CFR

2014-01-01

... for the Endangered Species Act 1. FmHA or its successor agency under Public Law 103-354 shall implement the consultation procedures required under Section 7 of the Endangered Species Act as specified in... State Director that a request for an exemption from section 7 of the Endangered Species Act is not...

7 CFR Exhibit D to Subpart G of... - Implementation Procedures for the Endangered Species Act

Code of Federal Regulations, 2011 CFR

2011-01-01

... for the Endangered Species Act 1. FmHA or its successor agency under Public Law 103-354 shall implement the consultation procedures required under Section 7 of the Endangered Species Act as specified in... State Director that a request for an exemption from section 7 of the Endangered Species Act is not...

7 CFR Exhibit D to Subpart G of... - Implementation Procedures for the Endangered Species Act

Code of Federal Regulations, 2013 CFR

2013-01-01

... for the Endangered Species Act 1. FmHA or its successor agency under Public Law 103-354 shall implement the consultation procedures required under Section 7 of the Endangered Species Act as specified in... State Director that a request for an exemption from section 7 of the Endangered Species Act is not...

7 CFR Exhibit D to Subpart G of... - Implementation Procedures for the Endangered Species Act

Code of Federal Regulations, 2010 CFR

2010-01-01

... for the Endangered Species Act 1. FmHA or its successor agency under Public Law 103-354 shall implement the consultation procedures required under Section 7 of the Endangered Species Act as specified in... State Director that a request for an exemption from section 7 of the Endangered Species Act is not...

7 CFR Exhibit D to Subpart G of... - Implementation Procedures for the Endangered Species Act

Code of Federal Regulations, 2012 CFR

2012-01-01

... for the Endangered Species Act 1. FmHA or its successor agency under Public Law 103-354 shall implement the consultation procedures required under Section 7 of the Endangered Species Act as specified in... State Director that a request for an exemption from section 7 of the Endangered Species Act is not...

77 FR 63245 - Rules of Practice in Air Safety Proceedings; Rules Implementing the Equal Access to Justice Act...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-16

... of Practice in Air Safety Proceedings; Rules Implementing the Equal Access to Justice Act of 1980... procedure concerning applications for fees and expenses under the Equal Access to Justice Act of 1980 (EAJA... procedure, Airmen, Aviation safety. 49 CFR Part 826 Claims, Equal access to justice, Lawyers. For the...

2 CFR 1125.40 - What policies and procedures must I follow?

Code of Federal Regulations, 2011 CFR

2011-01-01

... 2 Grants and Agreements 1 2011-01-01 2011-01-01 false What policies and procedures must I follow... OMB guidance in subparts A through I of 2 CFR part 180, as implemented by this part. (b) Specific sections of OMB guidance that this part supplements. In implementing the OMB guidance in 2 CFR part 180...

Implementing Behavior Modification Procedures in an Elementary School: Problems and Issues.

ERIC Educational Resources Information Center

Elardo, Richard

This paper represents a report of a year-long case study of the implementation of a token economy in an entire elementary school. The effort was intended to provide teachers with an alternative to corporal punishment as a form of school discipline. In this report, both the successful and unsuccessful procedures are described in chronological…

7 CFR Exhibit E to Subpart G of... - Implementation Procedures for the Wild and Scenic Rivers Act

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 13 2012-01-01 2012-01-01 false Implementation Procedures for the Wild and Scenic... for the Wild and Scenic Rivers Act 1. Each application for financial assistance or subdivision... included in the National Wild and Scenic Rivers System, designated for potential addition to the system, or...

7 CFR Exhibit E to Subpart G of... - Implementation Procedures for the Wild and Scenic Rivers Act

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 13 2011-01-01 2009-01-01 true Implementation Procedures for the Wild and Scenic... for the Wild and Scenic Rivers Act 1. Each application for financial assistance or subdivision... included in the National Wild and Scenic Rivers System, designated for potential addition to the system, or...

7 CFR Exhibit E to Subpart G of... - Implementation Procedures for the Wild and Scenic Rivers Act

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 13 2013-01-01 2013-01-01 false Implementation Procedures for the Wild and Scenic... for the Wild and Scenic Rivers Act 1. Each application for financial assistance or subdivision... included in the National Wild and Scenic Rivers System, designated for potential addition to the system, or...

7 CFR Exhibit E to Subpart G of... - Implementation Procedures for the Wild and Scenic Rivers Act

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 13 2014-01-01 2013-01-01 true Implementation Procedures for the Wild and Scenic... for the Wild and Scenic Rivers Act 1. Each application for financial assistance or subdivision... included in the National Wild and Scenic Rivers System, designated for potential addition to the system, or...

A SAS(®) macro implementation of a multiple comparison post hoc test for a Kruskal-Wallis analysis.

PubMed

Elliott, Alan C; Hynan, Linda S

2011-04-01

The Kruskal-Wallis (KW) nonparametric analysis of variance is often used instead of a standard one-way ANOVA when data are from a suspected non-normal population. The KW omnibus procedure tests for some differences between groups, but provides no specific post hoc pair wise comparisons. This paper provides a SAS(®) macro implementation of a multiple comparison test based on significant Kruskal-Wallis results from the SAS NPAR1WAY procedure. The implementation is designed for up to 20 groups at a user-specified alpha significance level. A Monte-Carlo simulation compared this nonparametric procedure to commonly used parametric multiple comparison tests. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

23 CFR 630.1008 - State-level processes and procedures.

Code of Federal Regulations, 2011 CFR

2011-04-01

..., data and information resources, training, and periodic evaluation enable a systematic approach for... management procedures. States should develop and implement systematic procedures to assess work zone impacts... practices and State processes and procedures. (e) Process review. In order to assess the effectiveness of...

10 CFR 26.157 - Procedures.

Code of Federal Regulations, 2010 CFR

2010-01-01

... of standard operating procedures for each assay performed for licensees and other entities for drug... 10 Energy 1 2010-01-01 2010-01-01 false Procedures. 26.157 Section 26.157 Energy NUCLEAR... Services § 26.157 Procedures. (a) HHS-certified laboratories shall develop, implement, and maintain clear...

10 CFR 26.157 - Procedures.

Code of Federal Regulations, 2013 CFR

2013-01-01

... of standard operating procedures for each assay performed for licensees and other entities for drug... 10 Energy 1 2013-01-01 2013-01-01 false Procedures. 26.157 Section 26.157 Energy NUCLEAR... Services § 26.157 Procedures. (a) HHS-certified laboratories shall develop, implement, and maintain clear...

10 CFR 26.157 - Procedures.

Code of Federal Regulations, 2011 CFR

2011-01-01

... of standard operating procedures for each assay performed for licensees and other entities for drug... 10 Energy 1 2011-01-01 2011-01-01 false Procedures. 26.157 Section 26.157 Energy NUCLEAR... Services § 26.157 Procedures. (a) HHS-certified laboratories shall develop, implement, and maintain clear...

10 CFR 26.157 - Procedures.

Code of Federal Regulations, 2014 CFR

2014-01-01

... of standard operating procedures for each assay performed for licensees and other entities for drug... 10 Energy 1 2014-01-01 2014-01-01 false Procedures. 26.157 Section 26.157 Energy NUCLEAR... Services § 26.157 Procedures. (a) HHS-certified laboratories shall develop, implement, and maintain clear...

10 CFR 26.157 - Procedures.

Code of Federal Regulations, 2012 CFR

2012-01-01

... of standard operating procedures for each assay performed for licensees and other entities for drug... 10 Energy 1 2012-01-01 2012-01-01 false Procedures. 26.157 Section 26.157 Energy NUCLEAR... Services § 26.157 Procedures. (a) HHS-certified laboratories shall develop, implement, and maintain clear...

45 CFR 164.316 - Policies and procedures and documentation requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Electronic Protected Health Information § 164.316 Policies and procedures and documentation requirements. A... reasonable and appropriate policies and procedures to comply with the standards, implementation... 45 Public Welfare 1 2010-10-01 2010-10-01 false Policies and procedures and documentation...

45 CFR 164.316 - Policies and procedures and documentation requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Electronic Protected Health Information § 164.316 Policies and procedures and documentation requirements. A... reasonable and appropriate policies and procedures to comply with the standards, implementation... 45 Public Welfare 1 2011-10-01 2011-10-01 false Policies and procedures and documentation...

Development and applications of two computational procedures for determining the vibration modes of structural systems. [aircraft structures - aerospaceplanes

NASA Technical Reports Server (NTRS)

Kvaternik, R. G.

1975-01-01

Two computational procedures for analyzing complex structural systems for their natural modes and frequencies of vibration are presented. Both procedures are based on a substructures methodology and both employ the finite-element stiffness method to model the constituent substructures. The first procedure is a direct method based on solving the eigenvalue problem associated with a finite-element representation of the complete structure. The second procedure is a component-mode synthesis scheme in which the vibration modes of the complete structure are synthesized from modes of substructures into which the structure is divided. The analytical basis of the methods contains a combination of features which enhance the generality of the procedures. The computational procedures exhibit a unique utilitarian character with respect to the versatility, computational convenience, and ease of computer implementation. The computational procedures were implemented in two special-purpose computer programs. The results of the application of these programs to several structural configurations are shown and comparisons are made with experiment.

Concept of Draft International Standard for a Unified Approach to Space Program Quality Assurance

NASA Astrophysics Data System (ADS)

Stryzhak, Y.; Vasilina, V.; Kurbatov, V.

2002-01-01

For want of the unified approach to guaranteed space project and product quality assurance, implementation of many international space programs has become a challenge. Globalization of aerospace industry and participation of various international ventures with diverse quality assurance requirements in big international space programs requires for urgent generation of unified international standards related to this field. To ensure successful fulfillment of space missions, aerospace companies should design and process reliable and safe products with properties complying or bettering User's (or Customer's) requirements. Quality of the products designed or processed by subcontractors (or other suppliers) should also be in compliance with the main user (customer)'s requirements. Implementation of this involved set of unified requirements will be made possible by creating and approving a system (series) of international standards under a generic title Space Product Quality Assurance based on a system consensus principle. Conceptual features of the baseline standard in this system (series) should comprise: - Procedures for ISO 9000, CEN and ECSS requirements adaptation and introduction into space product creation, design, manufacture, testing and operation; - Procedures for quality assurance at initial (design) phases of space programs, with a decision on the end product made based on the principle of independence; - Procedures to arrange incoming inspection of products delivered by subcontractors (including testing, audit of supplier's procedures, review of supplier's documentation), and space product certification; - Procedures to identify materials and primary products applied; - Procedures for quality system audit at the component part, primary product and materials supplier facilities; - Unified procedures to form a list of basic performances to be under configuration management; - Unified procedures to form a list of critical space product components, and unified procedures to define risks related to the specific component application and evaluate safety for the entire program implementation. In the eyes of the authors, those features together with a number of other conceptual proposals should constitute a unified standard-technical basis for implementing international space programs.

The in vitro effect of selected essential oils on the growth and mycotoxin production of Aspergillus species.

PubMed

Císarová, Miroslava; Tančinová, Dana; Medo, Juraj; Kačániová, Miroslava

2016-10-02

The aim of the present study was to assess the antifungal and anti-toxinogenic activity of 15 essential oils (EOs) against three fungi of the genus Aspergillus (A. parasiticus KMi-227-LR, A. parasiticus KMi-220-LR and A. flavus KMi-202-LR). The minimum inhibitory doses (MIDs) of the tested essential oils and their antifungal activity were determined using the micro-atmosphere method. The original commercial essential oil samples of Jasminum officinale L., Thymus vulgaris L., Syzygium aromaticum (L.) Merrill & Perry, Rosmarinus officinalis L., Ocimum basilicum L., Eucalyptus globulus Labill., Salvia officinalis L., Citrus limon (L.) Burm, Origanum vulgare L., Lavandula angustifolia Mill., Carum carvi L., Citrus sinensis (L.) Osbeck., Zingiber officinalis Rosc., Mentha piperita L. and Cinnamomum zeylanicum Nees. (C. verum J.S.Presl.) were produced in Slovakia (Calendula a.s., Nová Ľubovňa, Slovakia). All essential oils exhibited activity against all tested strains of fungi. After 14 days of incubation, A. flavus (KMi-202-LR) showed the highest susceptibility with a growth inhibition percentage (GIP) of 18.70% to C. limon and 5.92% to C. sinensis, while A. parasiticus (KMi-220-LR) exhibited a GIP of 20.56% to J. officinale. The minimum inhibitory doses (MIDs) of EOs with the most significant activity were recorded. The best antifungal activity, using the micro-atmosphere method was found in S. aromaticum with an MID of 62.5 μL L -1 air, T. vulgaris (MID of 62.5 μL L -1 air) and O. vulgare (MID of 31.5 μL L -1 air) against all tested strains. Mycotoxin production of the tested strains was evaluated by the thin layer chromatography (TLC) method. Mycotoxin production of AFB 1 and AFG 1 was inhibited following all treatments with C. carvi, R. officinale and S. officinale, Eucalyptus globulus L. and O. basilicum L. Essential oils exhibited a potential inhibition activity against toxic fungi, although, these affected only the production of AFB 1 .

Differential Acute Postprandial Effects of Processed Meat and Isocaloric Vegan Meals on the Gastrointestinal Hormone Response in Subjects Suffering from Type 2 Diabetes and Healthy Controls: A Randomized Crossover Study

PubMed Central

Belinova, Lenka; Kahleova, Hana; Malinska, Hana; Topolcan, Ondrej; Vrzalova, Jindra; Oliyarnyk, Olena; Kazdova, Ludmila; Hill, Martin; Pelikanova, Terezie

2014-01-01

Background The intake of meat, particularly processed meat, is a dietary risk factor for diabetes. Meat intake impairs insulin sensitivity and leads to increased oxidative stress. However, its effect on postprandial gastrointestinal hormone (GIH) secretion is unclear. We aimed to investigate the acute effects of two standardized isocaloric meals: a processed hamburger meat meal rich in protein and saturated fat (M-meal) and a vegan meal rich in carbohydrates (V-meal). We hypothesized that the meat meal would lead to abnormal postprandial increases in plasma lipids and oxidative stress markers and impaired GIH responses. Methods In a randomized crossover study, 50 patients suffering from type 2 diabetes (T2D) and 50 healthy subjects underwent two 3-h meal tolerance tests. For statistical analyses, repeated-measures ANOVA was performed. Results The M-meal resulted in a higher postprandial increase in lipids in both groups (p<0.001) and persistent postprandial hyperinsulinemia in patients with diabetes (p<0.001). The plasma glucose levels were significantly higher after the V-meal only at the peak level. The plasma concentrations of glucose-dependent insulinotropic peptide (GIP), peptide tyrosine-tyrosine (PYY) and pancreatic polypeptide (PP) were higher (p<0.05, p<0.001, p<0.001, respectively) and the ghrelin concentration was lower (p<0.001) after the M-meal in healthy subjects. In contrast, the concentrations of GIP, PYY and PP were significantly lower after the M-meal in T2D patients (p<0.001). Compared with the V-meal, the M-meal was associated with a larger increase in lipoperoxidation in T2D patients (p<0.05). Conclusion/Interpretation Our results suggest that the diet composition and the energy content, rather than the carbohydrate count, should be important considerations for dietary management and demonstrate that processed meat consumption is accompanied by impaired GIH responses and increased oxidative stress marker levels in diabetic patients. Trial Registration ClinicalTrials.gov NCT01572402 PMID:25222490

Glucagon dynamics during hypoglycaemia and food-re-challenge following treatment with vildagliptin in insulin-treated patients with type 2 diabetes.

PubMed

Farngren, J; Persson, M; Schweizer, A; Foley, J E; Ahrén, B

2014-09-01

To determine the effects of dipeptidyl peptidase-4 (DPP-4) inhibition on glucagon dynamics in patients with insulin-treated type 2 diabetes (T2D). The study was a single-centre, double-blind, randomized, placebo controlled crossover study in patients with T2D, mean age 59 ± 6 (s.d.) years and mean haemoglobin A1c 7.7 ± 0.8%, treated with exogenous insulin with or without oral antihyperglycaemic agents. Patients received vildagliptin (50 mg BID) or placebo as add-on to insulin for 4 weeks in random order with a 4-week washout in-between. On day 28 of the respective treatment, patients were served a standard meal (500 kcal) followed by a hyperinsulinaemic hypoglycaemic clamp (target 2.5 mmol/l) and a subsequent food re-challenge (700 kcal). The completers population (n = 29) was analysed. Glucose levels were lower with vildagliptin than with placebo during the meal [areas under the curve (AUC) 1.23 ± 0.07 vs. 1.46 ± 0.05 mol/l min, P < 0.001] and similar between the groups during the clamp. During the meal, glucagon levels were lower with vildagliptin (AUC 1.98 ± 0.15 vs. 2.15 ± 0.17 nmol/l min, P = 0.016). In contrast, the glucagon counter-regulation to the insulin-induced hypoglycaemia was sustained by vildagliptin (6.05 ± 1.20 pmol/l during vildagliptin vs.6.94 ± 1.09 pmol/l during placebo, NS). During the food re-challenge after hypoglycaemia, glucagon levels were, again, significantly lower after vildagliptin (AUC 1.30 ± 0.11 vs. 1.52 ± 0.12 nmol/l min, P < 0.039). Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) levels were significantly elevated by vildagliptin compared to placebo during meal, hypoglycaemia and food re-challenge. Vildagliptin action to block GLP-1 and GIP inactivation by DPP-4 improves glucagon dynamics during hypoglycaemia, hyperglycaemia and food re-challenge. © 2014 John Wiley & Sons Ltd.

Effect of soya protein on digestive enzymes, gut hormone and anti-soya antibody plasma levels in the preruminant calf.

PubMed

Guilloteau, P; Corring, T; Chayvialle, J A; Bernard, C; Sissons, J W; Toullec, R

1986-01-01

The effect of a milk substitute diet containing concentrated soya protein on secretory functions of the abomasum and pancreas and on plasma concentrations of gut hormones and soya antibodies was studied. Sixteen calves aged 12-19 weeks were given a milk substitute in which a major part of the protein source was either soya concentrate (soya diet) or skim milk (control diet). The soya diet was prepared by hot aqueous ethanol extraction of soya bean meal to remove oligosaccharides and inactivate antigenic constituents. Circulatory IgG antibodies against soya proteins were found in all of the calves when they were 16 weeks of age. Their titres increased slightly between 16 and 19 weeks, irrespective of the diet. It seems unlikely that the presence of these antibodies was related specifically to the feeding of the soya concentrate. At slaughter the weight of the gastric mucosa and pancreas and quantities of pancreatic protein together with specific activities of trypsin and chymotrypsin were significantly lower (17, 20, 16, 30 and 36%, respectively) with the soya diet. The quantities of enzymes in the gastric mucosa or the specific activity of pancreatic amylase were not affected, whereas that of lipase increased by 26%. Total enzyme activities as well as units per kg live weight gave significant differences only for trypsin and chymotrypsin which were reduced by 43 and 38%, respectively. With the soya diet, fasting concentrations of gastric inhibitory peptide (GIP) and secretin in plasma samples were significantly lower (49 and 34%, respectively). Values of GIP were also lower (54%) 1 h after feeding. In contrast, postprandial values of cholecystokinin (CCK) were 1.4 times greater. No significant differences were found between the two diets for gastrin, vasoactive intestinal peptide (VIP), bovine pancreatic polypeptide (BPP), somatostatine and motilin. In general these observations could be explained, in part, by the more rapid passage of protein and fat from the abomasum to the duodenum following feeds containing soya concentrate. However, these differences in concentrations of gut hormones did not seem to be related to variations in the weights of gastric mucosa and pancreas or activities of pancreatic enzymes.

Development of small intestinal enzyme activities and their relationship with some gut regulatory peptides in grazing sheep.

PubMed

Wang, C L; Lang, X; Wu, P J; Casper, D P; Li, F D

2017-08-01

Growth depends on an animal's capacity to digest and assimilate ingested nutrients, and insufficient supply and impairment will constrain lamb growth. Eight groups of Alpine Finewool lambs were harvested on 0, 3, 7, 14, 21, 28, 42, and 56 d to measure pH and enzymatic activities in the duodenum, proximal jejunum, middle jejunum, distal jejunum, and ileum mucosa or digesta. From the duodenum to the ileum the pH of intestinal mucosa and digesta increased, whereas pH changed very little with age. The trypsin, chymotrypsin, lipase, lactase, and α-amylase activities observed at birth decreased by d 3, followed by a nonuniform enzymatic response in the small intestine. The trypsin activity increased from d 3 to peak, at d 21, followed by a decline. Chymotrypsin activity followed the same general trend but with smaller responses in activities. Trypsin demonstrated greater enzymatic activity than chymotrypsin at the same age. The lipase activity of small intestinal mucosa and digesta changed little with age. The lactase activity was high at birth, decreased by d 3, and then increased, followed by a decrease as lambs approached weaning. α-Amylase activity was similar in the small intestinal mucosa and digesta at birth but increased with age for the duodenum and proximal jejunum. Plasma concentrations of cholecystokinin (CCK), secretin, and gastrin were positively correlated ( < 0.05) with ileal mucosa lipase activity. Plasma concentration of CCK, secretin, gastrin, and gastric inhibitory polypeptide (GIP) were positively correlated ( < 0.05) with ileal mucosa lactase activity. Plasma concentration of pancreatic polypeptide (PP) was negatively correlated ( < 0.05) with lactase activity in the middle jejunum and ileal mucosa. Plasma concentrations of CCK, secretin, gastrin, and GIP were positively correlated ( < 0.05) with α-amylase activity in the ileal mucosa but negatively correlated ( < 0.05) with duodenum, prejejunum, and middle jejunum. Plasma PP concentrations were positively correlated ( < 0.01) with α-amylase activity of duodenum, middle jejunum, and postjejunum mucosa but not with the enzyme activity of postjejunum and ileal mucosa ( > 0.05). Small intestinal enzymatic activities exist and may be sufficient to enhance lamb growth via appropriate nutrient supplementation.

Modulation of postprandial lipaemia by a single meal containing a commonly consumed interesterified palmitic acid-rich fat blend compared to a non-interesterified equivalent.

PubMed

Hall, Wendy L; Iqbal, Sara; Li, Helen; Gray, Robert; Berry, Sarah E E

2017-12-01

Interesterification of palm stearin and palm kernal (PSt/PK) is widely used by the food industry to create fats with desirable functional characteristics for applications in spreads and bakery products, negating the need for trans fatty acids. Previous studies have reported reduced postprandial lipaemia, an independent risk factor for CVD, following interesterified (IE) palmitic and stearic acid-rich fats that are not currently widely used by the food industry. The current study investigates the effect of the most commonly consumed PSt/PK IE blend on postprandial lipaemia. A randomised, controlled, crossover (1 week washout) double-blind design study (n = 12 healthy males, 18-45 years), compared the postprandial (0-4 h) effects of meals containing 50 g fat [PSt/PK (80:20); IE vs. non-IE] on changes in plasma triacylglycerol (TAG), glucose, glucose-dependent insulinotropic polypeptide (GIP), peptide YY (PYY), insulin, gastric emptying (paracetamol concentrations) and satiety (visual analogue scales). The postprandial increase in plasma TAG was higher following the IE PSt/PK versus the non-IE PSt/PK, with a 51 % greater incremental area under the curve [mean difference with 95 % CI 41 (23, 58) mmol/L min P = 0.001]. The pattern of lipaemia was different between meals; at 4-h plasma TAG concentrations declined following the IE fat but continued to rise following the non-IE fat. Insulin, glucose, paracetamol, PYY and GIP concentrations increased significantly after the test meals (time effect; P < 0.001 for all), but did not differ between test meals. Feelings of fullness were higher following the non-IE PSt/PK meal (diet effect; P = 0.034). No other significant differences were noted. Interesterification of PSt/PK increases early phase postprandial lipaemia (0-4 h); however, further investigation during the late postprandial phase (4-8 h) is warranted to determine the rate of return to baseline values. Clinicaltrials.gov as NCT02365987.

10 CFR 712.12 - HRP implementation.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 4 2011-01-01 2011-01-01 false HRP implementation. 712.12 Section 712.12 Energy... Program Procedures § 712.12 HRP implementation. (a) The implementation of the HRP is the responsibility of... by April 22, 2004. (b) The HRP Management Official must: (1) Prepare an initial HRP implementation...

10 CFR 712.12 - HRP implementation.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 4 2010-01-01 2010-01-01 false HRP implementation. 712.12 Section 712.12 Energy... Program Procedures § 712.12 HRP implementation. (a) The implementation of the HRP is the responsibility of... by April 22, 2004. (b) The HRP Management Official must: (1) Prepare an initial HRP implementation...

Application of the Flood-IMPAT procedure in the Valle d'Aosta Region, Italy

NASA Astrophysics Data System (ADS)

Minucci, Guido; Mendoza, Marina Tamara; Molinari, Daniela; Atun, Funda; Menoni, Scira; Ballio, Francesco

2016-04-01

Flood Risk Management Plans (FRMPs) established by European "Floods" Directive (Directive 2007/60/EU) to Member States in order to address all aspects of flood risk management, taking into account costs and benefits of proposed mitigation tools must be reviewed by the same law every six years. This is aimed at continuously increasing the effectiveness of risk management, on the bases of the most advanced knowledge of flood risk and most (economically) feasible solutions, also taking into consideration achievements of the previous management cycle. Within this context, the Flood-IMPAT (i.e. Integrated Meso-scale Procedure to Assess Territorial flood risk) procedure has been developed aiming at overcoming limits of risk maps produced by the Po River Basin Authority and adopted for the first version of the Po River FRMP. The procedure allows the estimation of flood risk at the meso-scale and it is characterized by three main peculiarities. First is its feasibility for the entire Italian territory. Second is the possibility to express risk in monetary terms (i.e. expected damage), at least for those categories of damage for which suitable models are available. Finally, independent modules compose the procedure: each module allows the estimation of a certain type of damage (i.e. direct, indirect, intangibles) on a certain sector (e.g. residential, industrial, agriculture, environment, etc.) separately, guaranteeing flexibility in the implementation. This paper shows the application of the Flood-IMPAT procedure and the recent advancements in the procedure, aiming at increasing its reliability and usability. Through a further implementation of the procedure in the Dora Baltea River Basin (North of Italy), it was possible to test the sensitivity of risk estimates supplied by Flood-IMPAT with respect to different damage models and different approaches for the estimation of assets at risk. Risk estimates were also compared with observed damage data in the investigated areas to identify the most suitable damage model/exposure assessment approach to be implemented in the procedure. In the end, the procedure was adapted to be applied at the micro-scale, in such a way to supply risk estimates, which are coherent with those at the meso-scale. This way the procedure can be first implemented in the whole catchment to identify hotspots; the micro-scale approach can be implemented in a second run to investigate in depth (i) the most risk prone areas and (ii) the possible risk mitigation strategies.

The Effect of the Extinction Procedure in Function-Based Intervention

ERIC Educational Resources Information Center

Janney, Donna M.; Umbreit, John; Ferro, Jolenea B.; Liaupsin, Carl J.; Lane, Kathleen L.

2013-01-01

In this study, we examined the contribution of the extinction procedure in function-based interventions implemented in the general education classrooms of three at-risk elementary-aged students. Function-based interventions included antecedent adjustments, reinforcement procedures, and function-matched extinction procedures. Using a combined ABC…

An SPSS implementation of the nonrecursive outlier deletion procedure with shifting z score criterion (Van Selst & Jolicoeur, 1994).

PubMed

Thompson, Glenn L

2006-05-01

Sophisticated univariate outlier screening procedures are not yet available in widely used statistical packages such as SPSS. However, SPSS can accept user-supplied programs for executing these procedures. Failing this, researchers tend to rely on simplistic alternatives that can distort data because they do not adjust to cell-specific characteristics. Despite their popularity, these simple procedures may be especially ill suited for some applications (e.g., data from reaction time experiments). A user friendly SPSS Production Facility implementation of the shifting z score criterion procedure (Van Selst & Jolicoeur, 1994) is presented in an attempt to make it easier to use. In addition to outlier screening, optional syntax modules can be added that will perform tedious database management tasks (e.g., restructuring or computing means).

Steepest descent method implementation on unconstrained optimization problem using C++ program

NASA Astrophysics Data System (ADS)

Napitupulu, H.; Sukono; Mohd, I. Bin; Hidayat, Y.; Supian, S.

2018-03-01

Steepest Descent is known as the simplest gradient method. Recently, many researches are done to obtain the appropriate step size in order to reduce the objective function value progressively. In this paper, the properties of steepest descent method from literatures are reviewed together with advantages and disadvantages of each step size procedure. The development of steepest descent method due to its step size procedure is discussed. In order to test the performance of each step size, we run a steepest descent procedure in C++ program. We implemented it to unconstrained optimization test problem with two variables, then we compare the numerical results of each step size procedure. Based on the numerical experiment, we conclude the general computational features and weaknesses of each procedure in each case of problem.

15 CFR 23.7 - Notice to Department of Commerce organizational units of implementation and procedures.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 15 Commerce and Foreign Trade 1 2014-01-01 2014-01-01 false Notice to Department of Commerce organizational units of implementation and procedures. 23.7 Section 23.7 Commerce and Foreign Trade Office of the Secretary of Commerce USE OF PENALTY MAIL IN THE LOCATION AND RECOVERY OF MISSING CHILDREN § 23.7 Notice to...

15 CFR 23.7 - Notice to Department of Commerce organizational units of implementation and procedures.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 15 Commerce and Foreign Trade 1 2013-01-01 2013-01-01 false Notice to Department of Commerce organizational units of implementation and procedures. 23.7 Section 23.7 Commerce and Foreign Trade Office of the Secretary of Commerce USE OF PENALTY MAIL IN THE LOCATION AND RECOVERY OF MISSING CHILDREN § 23.7 Notice to...

15 CFR 23.7 - Notice to Department of Commerce organizational units of implementation and procedures.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 15 Commerce and Foreign Trade 1 2011-01-01 2011-01-01 false Notice to Department of Commerce organizational units of implementation and procedures. 23.7 Section 23.7 Commerce and Foreign Trade Office of the Secretary of Commerce USE OF PENALTY MAIL IN THE LOCATION AND RECOVERY OF MISSING CHILDREN § 23.7 Notice to...

Peer-Implemented Time Delay Procedures on the Acquisition of Chained Tasks by Students with Moderate and Severe Disabilities

ERIC Educational Resources Information Center

Godsey, Janet Read; Schuster, John W.; Lingo, Amy Shearer; Collins, Belva C.; Kleinert, Harold L.

2008-01-01

This study evaluated the effectiveness of and reliability of peer tutors implementing a constant time delay procedure when teaching four high school students with moderate and severe disabilities to prepare foods using picture recipes. We used a multiple probe design across subjects to determine the effectiveness of the peer tutor implemented…

Response of School Districts to the New York State Concussion Awareness and Management Act: Review of Policies and Procedures

ERIC Educational Resources Information Center

Kajankova, Maria; Oswald, Jennifer M.; Terranova, Lauren M.; Kaplen, Michael V.; Ambrose, Anne F.; Spielman, Lisa A.; Gordon, Wayne A.

2017-01-01

Background: By 2014, all states implemented concussion laws that schools must translate into daily practice; yet, limited knowledge exists regarding implementation of these laws. We examined the extent to which concussion management policies and procedure (P&P) documents of New York State school districts comply with the State's Concussion…

Strategies for controlling item exposure in computerized adaptive testing with the partial credit model.

PubMed

Davis, Laurie Laughlin; Dodd, Barbara G

2008-01-01

Exposure control research with polytomous item pools has determined that randomization procedures can be very effective for controlling test security in computerized adaptive testing (CAT). The current study investigated the performance of four procedures for controlling item exposure in a CAT under the partial credit model. In addition to a no exposure control baseline condition, the Kingsbury-Zara, modified-within-.10-logits, Sympson-Hetter, and conditional Sympson-Hetter procedures were implemented to control exposure rates. The Kingsbury-Zara and the modified-within-.10-logits procedures were implemented with 3 and 6 item candidate conditions. The results show that the Kingsbury-Zara and modified-within-.10-logits procedures with 6 item candidates performed as well as the conditional Sympson-Hetter in terms of exposure rates, overlap rates, and pool utilization. These two procedures are strongly recommended for use with partial credit CATs due to their simplicity and strength of their results.

Multi-response permutation procedure as an alternative to the analysis of variance: an SPSS implementation.

PubMed

Cai, Li

2006-02-01

A permutation test typically requires fewer assumptions than does a comparable parametric counterpart. The multi-response permutation procedure (MRPP) is a class of multivariate permutation tests of group difference useful for the analysis of experimental data. However, psychologists seldom make use of the MRPP in data analysis, in part because the MRPP is not implemented in popular statistical packages that psychologists use. A set of SPSS macros implementing the MRPP test is provided in this article. The use of the macros is illustrated by analyzing example data sets.

23 CFR 200.11 - Procedures for processing Title VI reviews.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 23 Highways 1 2010-04-01 2010-04-01 false Procedures for processing Title VI reviews. 200.11 Section 200.11 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION CIVIL RIGHTS TITLE VI PROGRAM AND RELATED STATUTES-IMPLEMENTATION AND REVIEW PROCEDURES § 200.11 Procedures for processing Title...

23 CFR 200.11 - Procedures for processing Title VI reviews.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 23 Highways 1 2014-04-01 2014-04-01 false Procedures for processing Title VI reviews. 200.11 Section 200.11 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION CIVIL RIGHTS TITLE VI PROGRAM AND RELATED STATUTES-IMPLEMENTATION AND REVIEW PROCEDURES § 200.11 Procedures for processing Title...

23 CFR 200.11 - Procedures for processing Title VI reviews.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 23 Highways 1 2011-04-01 2011-04-01 false Procedures for processing Title VI reviews. 200.11 Section 200.11 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION CIVIL RIGHTS TITLE VI PROGRAM AND RELATED STATUTES-IMPLEMENTATION AND REVIEW PROCEDURES § 200.11 Procedures for processing Title...

23 CFR 200.11 - Procedures for processing Title VI reviews.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 23 Highways 1 2013-04-01 2013-04-01 false Procedures for processing Title VI reviews. 200.11 Section 200.11 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION CIVIL RIGHTS TITLE VI PROGRAM AND RELATED STATUTES-IMPLEMENTATION AND REVIEW PROCEDURES § 200.11 Procedures for processing Title...

42 CFR 413.122 - Payment for hospital outpatient radiology services and other diagnostic procedures.

Code of Federal Regulations, 2011 CFR

2011-10-01

... and other diagnostic procedures. 413.122 Section 413.122 Public Health CENTERS FOR MEDICARE & MEDICAID... radiology services and other diagnostic procedures. (a) Basis and purpose. (1) This section implements... services and other diagnostic procedures performed by a hospital on an outpatient basis. (2) For purposes...

21 CFR 123.11 - Sanitation control procedures.

Code of Federal Regulations, 2012 CFR

2012-04-01

... procedures. (a) Sanitation SOP. Each processor should have and implement a written sanitation standard operating procedure (herein referred to as SSOP) or similar document that is specific to each location where... 21 Food and Drugs 2 2012-04-01 2012-04-01 false Sanitation control procedures. 123.11 Section 123...

21 CFR 123.11 - Sanitation control procedures.

Code of Federal Regulations, 2014 CFR

2014-04-01

... procedures. (a) Sanitation SOP. Each processor should have and implement a written sanitation standard operating procedure (herein referred to as SSOP) or similar document that is specific to each location where... 21 Food and Drugs 2 2014-04-01 2014-04-01 false Sanitation control procedures. 123.11 Section 123...

23 CFR 630.1012 - Project-level procedures.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 23 Highways 1 2010-04-01 2010-04-01 false Project-level procedures. 630.1012 Section 630.1012... PRECONSTRUCTION PROCEDURES Work Zone Safety and Mobility § 630.1012 Project-level procedures. (a) This section... maintained at an equivalent or better level than existed prior to project implementation. The scope of the...

44 CFR 59.30 - A pilot inspection procedure.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 44 Emergency Management and Assistance 1 2011-10-01 2011-10-01 false A pilot inspection procedure... PROVISIONS Pilot Inspection Program § 59.30 A pilot inspection procedure. (a) Purpose. This section sets forth the criteria for implementing a pilot inspection procedure in Monroe County and the Village of...

44 CFR 59.30 - A pilot inspection procedure.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false A pilot inspection procedure... PROVISIONS Pilot Inspection Program § 59.30 A pilot inspection procedure. (a) Purpose. This section sets forth the criteria for implementing a pilot inspection procedure in Monroe County and the Village of...

Improved telescope focus using only two focus images

NASA Astrophysics Data System (ADS)

Barrick, Gregory; Vermeulen, Tom; Thomas, James

2008-07-01

In an effort to reduce the amount of time spent focusing the telescope and to improve the quality of the focus, a new procedure has been investigated and implemented at the Canada-France-Hawaii Telescope (CFHT). The new procedure is based on a paper by Tokovinin and Heathcote and requires only two out-of-focus images to determine the best focus for the telescope. Using only two images provides a great time savings over the five or more images required for a standard through-focus sequence. In addition, it has been found that this method is significantly less sensitive to seeing variations than the traditional through-focus procedure, so the quality of the resulting focus is better. Finally, the new procedure relies on a second moment calculation and so is computationally easier and more robust than methods using a FWHM calculation. The new method has been implemented for WIRCam for the past 18 months, for MegaPrime for the past year, and has recently been implemented for ESPaDOnS.

Object oriented development of engineering software using CLIPS

NASA Technical Reports Server (NTRS)

Yoon, C. John

1991-01-01

Engineering applications involve numeric complexity and manipulations of a large amount of data. Traditionally, numeric computation has been the concern in developing an engineering software. As engineering application software became larger and more complex, management of resources such as data, rather than the numeric complexity, has become the major software design problem. Object oriented design and implementation methodologies can improve the reliability, flexibility, and maintainability of the resulting software; however, some tasks are better solved with the traditional procedural paradigm. The C Language Integrated Production System (CLIPS), with deffunction and defgeneric constructs, supports the procedural paradigm. The natural blending of object oriented and procedural paradigms has been cited as the reason for the popularity of the C++ language. The CLIPS Object Oriented Language's (COOL) object oriented features are more versatile than C++'s. A software design methodology based on object oriented and procedural approaches appropriate for engineering software, and to be implemented in CLIPS was outlined. A method for sensor placement for Space Station Freedom is being implemented in COOL as a sample problem.

Real-time implementation of second generation of audio multilevel information coding

NASA Astrophysics Data System (ADS)

Ali, Murtaza; Tewfik, Ahmed H.; Viswanathan, V.

1994-03-01

This paper describes real-time implementation of a novel wavelet- based audio compression method. This method is based on the discrete wavelet (DWT) representation of signals. A bit allocation procedure is used to allocate bits to the transform coefficients in an adaptive fashion. The bit allocation procedure has been designed to take advantage of the masking effect in human hearing. The procedure minimizes the number of bits required to represent each frame of audio signals at a fixed distortion level. The real-time implementation provides almost transparent compression of monophonic CD quality audio signals (samples at 44.1 KHz and quantized using 16 bits/sample) at bit rates of 64-78 Kbits/sec. Our implementation uses two ASPI Elf boards, each of which is built around a TI TMS230C31 DSP chip. The time required for encoding of a mono CD signal is about 92 percent of real time and that for decoding about 61 percent.

The impact of OSHA regulations on nursing care cost and compliance.

PubMed

Raltz, S; Kozarek, R A; Kim-Deobald, J; Pethigal, P; Moorhouse, M A

1994-01-01

The Occupational Safety and Health Administration (OSHA) requires health care facilities to protect employees from bloodborne pathogens. One of the mandates is to provide personal protective equipment (PPE) to employees at no cost to the employee. In this article, the authors explore the cost and compliance of implementing the new OSHA regulations for nursing staff assisting with colonoscopies over a 6-month period. The data were collected on a total of 461 procedures. The cost of implementing PPE for the nursing staff was $2.98 per procedure. The PPE available for the nursing staff included goggles, splash-proof gown, face mask, shoe covers, and latex gloves. The total cost of implementing the new regulations for the nursing staff assisting with colonoscopies was $2,747.56 and was projected to cost approximately $50,000 yearly if implemented for all GI procedures in the institution. Staff compliance rates for the five pieces of PPE ranged from 6.5 to 97.8%.

Discovery of ((4R,5S)-5-amino-4-(2,4,5- trifluorophenyl)cyclohex-1-enyl)-(3- (trifluoromethyl)-5,6-dihydro- [1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)methanone (ABT-341), a highly potent, selective, orally efficacious, and safe dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes.

PubMed

Pei, Zhonghua; Li, Xiaofeng; von Geldern, Thomas W; Madar, David J; Longenecker, Kenton; Yong, Hong; Lubben, Thomas H; Stewart, Kent D; Zinker, Bradley A; Backes, Bradley J; Judd, Andrew S; Mulhern, Mathew; Ballaron, Stephen J; Stashko, Michael A; Mika, Amanda K; Beno, David W A; Reinhart, Glenn A; Fryer, Ryan M; Preusser, Lee C; Kempf-Grote, Anita J; Sham, Hing L; Trevillyan, James M

2006-11-02

Dipeptidyl peptidase IV (DPP4) deactivates glucose-regulating hormones such as GLP-1 and GIP, thus, DPP4 inhibition has become a useful therapy for type 2 diabetes. Optimization of the high-throughput screening lead 6 led to the discovery of 25 (ABT-341), a highly potent, selective, and orally bioavailable DPP4 inhibitor. When dosed orally, 25 dose-dependently reduced glucose excursion in ZDF rats. Amide 25 is safe in a battery of in vitro and in vivo tests and may represent a new therapeutic agent for the treatment of type 2 diabetes.

Observance of Sterilization Protocol Guideline Procedures of Critical Instruments for Preventing Iatrogenic Transmission of Creutzfeldt-Jakob Disease in Dental Practice in France, 2017

PubMed Central

Bourgeois, Denis; Dussart, Claude; Saliasi, Ina; Laforest, Laurent; Tramini, Paul; Carrouel, Florence

2018-01-01

Effective sterilization of reusable instruments contaminated by Creutzfeldt–Jakob disease in dental care is a crucial issue for public health. The present cross-sectional study investigated how the recommended procedures for sterilization were implemented by French dental practices in real-world settings. A sample of dental practices was selected in the French Rhône-Alpes region. Data were collected by a self-questionnaire in 2016. Sterilization procedures (n = 33) were classified into 4 groups: (1) Pre-sterilization cleaning of reusable instruments; (2) Biological verification of sterilization cycles—Monitoring steam sterilization procedures; (3) Autoclave performance and practitioner knowledge of autoclave use; (4) Monitoring and documentation of sterilization procedures—Tracking and tracing the instrumentation. Answers were provided per procedure, along with the global implementation of procedures within a group (over 80% correctly performed). Then it was verified how adherence to procedure groups varied with the size of the dental practice and the proportion of dental assistants within the team. Among the 179 questionnaires available for the analyses, adherence to the recommended procedures of sterilization noticeably varied between practices, from 20.7% to 82.6%. The median percentages of procedures correctly implemented per practice were 58.1%, 50.9%, 69.2% and 58.2%, in Groups 1, 2, 3 and 4, respectively (corresponding percentages for performing over 80% of the procedures in the group: 23.4%, 6.6%, 46.6% and 38.6%). Dental practices ≥ 3 dental units performed significantly better (>80%) procedures of Groups 2 and 4 (p = 0.01 and p = 0.002, respectively), while no other significant associations emerged. As a rule, practices complied poorly with the recommended procedures, despite partially improved results in bigger practices. Specific training regarding sterilization procedures and a better understanding of the reasons leading to their non-compliance are needed. PMID:29693615

Implementation of a partitioned algorithm for simulation of large CSI problems

NASA Technical Reports Server (NTRS)

Alvin, Kenneth F.; Park, K. C.

1991-01-01

The implementation of a partitioned numerical algorithm for determining the dynamic response of coupled structure/controller/estimator finite-dimensional systems is reviewed. The partitioned approach leads to a set of coupled first and second-order linear differential equations which are numerically integrated with extrapolation and implicit step methods. The present software implementation, ACSIS, utilizes parallel processing techniques at various levels to optimize performance on a shared-memory concurrent/vector processing system. A general procedure for the design of controller and filter gains is also implemented, which utilizes the vibration characteristics of the structure to be solved. Also presented are: example problems; a user's guide to the software; the procedures and algorithm scripts; a stability analysis for the algorithm; and the source code for the parallel implementation.

2 CFR 1401.110 - What policies and procedures must I follow?

Code of Federal Regulations, 2011 CFR

2011-01-01

... 2 Grants and Agreements 1 2011-01-01 2011-01-01 false What policies and procedures must I follow... F of 2 CFR part 182, as implemented by this part. (b) In implementing OMB guidance in 2 CFR part 182... clarifies (1) 2 CFR 182.225(a) § 1401.335 Whom in the DOI a recipient other than an individual must notify...

A Comparison of Staff Training Methods for Effective Implementation of Discrete Trial Teaching for Learners with Developmental Disabilities

ERIC Educational Resources Information Center

Geiger, Kaneen Barbara

2012-01-01

Discrete trial teaching is an effective procedure for teaching a variety of skills to children with autism. However, it must be implemented with high integrity to produce optimal learning. Behavioral Skills Training (BST) is a staff training procedure that has been demonstrated to be effective. However, BST is time and labor intensive, and with…

Developing Policy and Practice for Implementation of the Individuals with Disabilities Education Act--Innovative Approaches to State and National Issues: Invasive Procedures. Final Report.

ERIC Educational Resources Information Center

Krajicek, Marilyn J.

This final report discusses the activities and outcomes of a federally funded project designed to address the safe and legal implementation of the Individuals with Disabilities Education Act for young children who required invasive health care procedures. To accomplish the project objectives three annual, interdisciplinary conferences were held to…

Radiation safety protocol using real-time dose reporting reduces patient exposure in pediatric electrophysiology procedures.

PubMed

Patel, Akash R; Ganley, Jamie; Zhu, Xiaowei; Rome, Jonathan J; Shah, Maully; Glatz, Andrew C

2014-10-01

Radiation exposure during pediatric catheterization is significant. We sought to describe radiation exposure and the effectiveness of radiation safety protocols in reducing exposure during catheter ablations with electrophysiology studies in children and patients with congenital heart disease. We additionally sought to identify at-risk patients. We retrospectively reviewed all interventional electrophysiology procedures performed from April 2009 to September 2011 (6 months preceding intervention, 12 months following implementation of initial radiation safety protocol, and 8 months following implementation of modified protocol). The protocols consisted of low pulse rate fluoroscopy settings, operator notification of skin entrance dose every 1,000 mGy, adjusting cameras by >5 at every 1,000 mGy, and appropriate collimation. The cohort consisted of 291 patients (70 pre-intervention, 137 after initial protocol implementation, 84 after modified protocol implementation) at a median age of 14.9 years with congenital heart disease present in 11 %. Diagnoses included atrioventricular nodal reentrant tachycardia (25 %), atrioventricular reentrant tachycardia (61 %), atrial tachycardias (12 %), and ventricular tachycardia (2 %). There were no differences between groups based on patient, arrhythmia, and procedural characteristics. Following implementation of the protocols, there were significant reductions in all measures of radiation exposure: fluoroscopy time (17.8 %), dose area product (80.2 %), skin entry dose (81.0 %), and effective dose (76.9 %), p = 0.0001. Independent predictors of increased radiation exposure included larger patient weight, longer fluoroscopy time, and lack of radiation safety protocol. Implementation of a radiation safety protocol for pediatric and congenital catheter ablations can drastically reduce radiation exposure to patients without affecting procedural success.

"Heidelberg standard examination" and "Heidelberg standard procedures" - Development of faculty-wide standards for physical examination techniques and clinical procedures in undergraduate medical education.

PubMed

Nikendei, C; Ganschow, P; Groener, J B; Huwendiek, S; Köchel, A; Köhl-Hackert, N; Pjontek, R; Rodrian, J; Scheibe, F; Stadler, A-K; Steiner, T; Stiepak, J; Tabatabai, J; Utz, A; Kadmon, M

2016-01-01

The competent physical examination of patients and the safe and professional implementation of clinical procedures constitute essential components of medical practice in nearly all areas of medicine. The central objective of the projects "Heidelberg standard examination" and "Heidelberg standard procedures", which were initiated by students, was to establish uniform interdisciplinary standards for physical examination and clinical procedures, and to distribute them in coordination with all clinical disciplines at the Heidelberg University Hospital. The presented project report illuminates the background of the initiative and its methodological implementation. Moreover, it describes the multimedia documentation in the form of pocketbooks and a multimedia internet-based platform, as well as the integration into the curriculum. The project presentation aims to provide orientation and action guidelines to facilitate similar processes in other faculties.

Therapeutic apheresis in Asia: An Indonesia single center experience.

PubMed

Triyono, Teguh; Vrielink, Hans

2015-06-01

In developing countries, like Indonesia, apheresis is still a relative new procedure. Nowadays, therapeutic apheresis procedures are performed in the field of hematology and neurology, especially in the teaching hospitals in Indonesia. Therapeutic apheresis procedure, that is, leukocytapheresis, therapeutic plasma exchange (TPE), and thrombocytapheresis are already performed. In the period 2009-2013, 204 apheresis procedures in 137 patients to reduce the leukocytes, 72 TPE procedures in 17 patients, and 14 thrombocyte reductions were performed in the Sardjito hospital, Yogyakarta, Indonesia. In the future, to improve the therapeutic apheresis implementation, it is important to increase the insurance coverage and also should be considered to introduce the apheresis medicine into the curriculum of appropriate physician programs in Indonesia. Especially in Indonesia, a lot of efforts are still being needed to improve implementation of therapeutic apheresis. © 2014 Wiley Periodicals, Inc.

Comparing the Teaching Interaction Procedure to Social Stories: A Replication Study

ERIC Educational Resources Information Center

Kassardjian, Alyne; Leaf, Justin B.; Ravid, Daniel; Leaf, Jeremy A.; Alcalay, Aditt; Dale, Stephanie; Tsuji, Kathleen; Taubman, Mitchell; Leaf, Ronald; McEachin, John; Oppenheim-Leaf, Misty L.

2014-01-01

This study compared the teaching interaction procedure to social stories implemented in a group setting to teach social skills to three children diagnosed with autism spectrum disorder. The researchers taught each participant one social skill with the teaching interaction procedure, one social skill with the social story procedure, and one social…

33 CFR 230.20 - Integration with State and local procedures.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 33 Navigation and Navigable Waters 3 2010-07-01 2010-07-01 false Integration with State and local procedures. 230.20 Section 230.20 Navigation and Navigable Waters CORPS OF ENGINEERS, DEPARTMENT OF THE ARMY, DEPARTMENT OF DEFENSE PROCEDURES FOR IMPLEMENTING NEPA § 230.20 Integration with State and local procedures...

5 CFR 2601.202 - Procedure.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 5 Administrative Personnel 3 2013-01-01 2013-01-01 false Procedure. 2601.202 Section 2601.202 Administrative Personnel OFFICE OF GOVERNMENT ETHICS ORGANIZATION AND PROCEDURES IMPLEMENTATION OF OFFICE OF GOVERNMENT ETHICS STATUTORY GIFT ACCEPTANCE AUTHORITY Guidelines for Solicitation and Acceptance of Gifts...

5 CFR 2601.202 - Procedure.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 5 Administrative Personnel 3 2014-01-01 2014-01-01 false Procedure. 2601.202 Section 2601.202 Administrative Personnel OFFICE OF GOVERNMENT ETHICS ORGANIZATION AND PROCEDURES IMPLEMENTATION OF OFFICE OF GOVERNMENT ETHICS STATUTORY GIFT ACCEPTANCE AUTHORITY Guidelines for Solicitation and Acceptance of Gifts...

5 CFR 2601.202 - Procedure.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 5 Administrative Personnel 3 2011-01-01 2011-01-01 false Procedure. 2601.202 Section 2601.202 Administrative Personnel OFFICE OF GOVERNMENT ETHICS ORGANIZATION AND PROCEDURES IMPLEMENTATION OF OFFICE OF GOVERNMENT ETHICS STATUTORY GIFT ACCEPTANCE AUTHORITY Guidelines for Solicitation and Acceptance of Gifts...

5 CFR 2601.202 - Procedure.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 5 Administrative Personnel 3 2012-01-01 2012-01-01 false Procedure. 2601.202 Section 2601.202 Administrative Personnel OFFICE OF GOVERNMENT ETHICS ORGANIZATION AND PROCEDURES IMPLEMENTATION OF OFFICE OF GOVERNMENT ETHICS STATUTORY GIFT ACCEPTANCE AUTHORITY Guidelines for Solicitation and Acceptance of Gifts...

40 CFR 6.203 - Public participation.

Code of Federal Regulations, 2014 CFR

2014-07-01

....203 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GENERAL PROCEDURES FOR IMPLEMENTING THE NATIONAL ENVIRONMENTAL POLICY ACT AND ASSESSING THE ENVIRONMENTAL EFFECTS ABROAD OF EPA ACTIONS EPA's NEPA Environmental Review Procedures § 6.203 Public participation. (a) General requirements. (1) The procedures in...

40 CFR 6.203 - Public participation.

Code of Federal Regulations, 2013 CFR

2013-07-01

....203 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GENERAL PROCEDURES FOR IMPLEMENTING THE NATIONAL ENVIRONMENTAL POLICY ACT AND ASSESSING THE ENVIRONMENTAL EFFECTS ABROAD OF EPA ACTIONS EPA's NEPA Environmental Review Procedures § 6.203 Public participation. (a) General requirements. (1) The procedures in...

40 CFR 6.203 - Public participation.

Code of Federal Regulations, 2011 CFR

2011-07-01

....203 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GENERAL PROCEDURES FOR IMPLEMENTING THE NATIONAL ENVIRONMENTAL POLICY ACT AND ASSESSING THE ENVIRONMENTAL EFFECTS ABROAD OF EPA ACTIONS EPA's NEPA Environmental Review Procedures § 6.203 Public participation. (a) General requirements. (1) The procedures in...

40 CFR 6.203 - Public participation.

Code of Federal Regulations, 2010 CFR

2010-07-01

....203 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GENERAL PROCEDURES FOR IMPLEMENTING THE NATIONAL ENVIRONMENTAL POLICY ACT AND ASSESSING THE ENVIRONMENTAL EFFECTS ABROAD OF EPA ACTIONS EPA's NEPA Environmental Review Procedures § 6.203 Public participation. (a) General requirements. (1) The procedures in...

40 CFR 6.203 - Public participation.

Code of Federal Regulations, 2012 CFR

2012-07-01

....203 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GENERAL PROCEDURES FOR IMPLEMENTING THE NATIONAL ENVIRONMENTAL POLICY ACT AND ASSESSING THE ENVIRONMENTAL EFFECTS ABROAD OF EPA ACTIONS EPA's NEPA Environmental Review Procedures § 6.203 Public participation. (a) General requirements. (1) The procedures in...

50 CFR 82.3 - Supplementary information and procedures.

Code of Federal Regulations, 2011 CFR

2011-10-01

... INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE PROCEDURES... governments these regulations are intended to implement and be read as consistent with Federal Management... standards and procedures set forth therein, and other referenced Federal management circulars, will, to the...

50 CFR 82.3 - Supplementary information and procedures.

Code of Federal Regulations, 2012 CFR

2012-10-01

... INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE PROCEDURES... governments these regulations are intended to implement and be read as consistent with Federal Management... standards and procedures set forth therein, and other referenced Federal management circulars, will, to the...

50 CFR 82.3 - Supplementary information and procedures.

Code of Federal Regulations, 2010 CFR

2010-10-01

... INTERIOR (CONTINUED) FINANCIAL ASSISTANCE-WILDLIFE SPORT FISH RESTORATION PROGRAM ADMINISTRATIVE PROCEDURES... governments these regulations are intended to implement and be read as consistent with Federal Management... standards and procedures set forth therein, and other referenced Federal management circulars, will, to the...

How personal and standardized coordination impact implementation of integrated care.

PubMed

Benzer, Justin K; Cramer, Irene E; Burgess, James F; Mohr, David C; Sullivan, Jennifer L; Charns, Martin P

2015-10-02

Integrating health care across specialized work units has the potential to lower costs and increase quality and access to mental health care. However, a key challenge for healthcare managers is how to develop policies, procedures, and practices that coordinate care across specialized units. The purpose of this study was to identify how organizational factors impacted coordination, and how to facilitate implementation of integrated care. Semi-structured interviews were conducted in August 2009 with 30 clinic leaders and 35 frontline staff who were recruited from a convenience sample of 16 primary care and mental health clinics across eight medical centers. Data were drawn from a management evaluation of primary care-mental health integration in the US Department of Veterans Affairs. To protect informant confidentiality, the institutional review board did not allow quotations. Interviews identified antecedents of organizational coordination processes, and highlighted how these antecedents can impact the implementation of integrated care. Overall, implementing new workflow practices were reported to create conflicts with pre-existing standardized coordination processes. Personal coordination (i.e., interpersonal communication processes) between primary care leaders and staff was reported to be effective in overcoming these barriers both by working around standardized coordination barriers and modifying standardized procedures. This study identifies challenges to integrated care that might be solved with attention to personal and standardized coordination. A key finding was that personal coordination both between primary care and mental health leaders and between frontline staff is important for resolving barriers related to integrated care implementation. Integrated care interventions can involve both new standardized procedures and adjustments to existing procedures. Aligning and integrating procedures between primary care and specialty care requires personal coordination amongst leaders. Interpersonal relationships should be strengthened between staff when personal connections are important for coordinating patient care across clinical settings.

Monitoring process hygiene in Serbian retail establishments

NASA Astrophysics Data System (ADS)

Vesković Moračanin, S.; Baltić, T.; Milojević, L.

2017-09-01

The present study was conducted to estimate the effectiveness of sanitary procedures on food contact surfaces and food handlers’ hands in Serbian retail establishments. For that purpose, a total of 970 samples from food contact surfaces and 525 samples from workers’ hands were microbiologically analyzed. Results of total aerobic plate count and total Enterobacteriaceae count showed that the implemented washing and disinfection procedures, as a part of HACCP plans, were not effective enough in most retail facilities. Constant and intensive education of employees on proper implementation of sanitation procedures are needed in order to ensure food safety in the retail market.

Fuzzy Structures Analysis of Aircraft Panels in NASTRAN

NASA Technical Reports Server (NTRS)

Sparrow, Victor W.; Buehrle, Ralph D.

2001-01-01

This paper concerns an application of the fuzzy structures analysis (FSA) procedures of Soize to prototypical aerospace panels in MSC/NASTRAN, a large commercial finite element program. A brief introduction to the FSA procedures is first provided. The implementation of the FSA methods is then disclosed, and the method is validated by comparison to published results for the forced vibrations of a fuzzy beam. The results of the new implementation show excellent agreement to the benchmark results. The ongoing effort at NASA Langley and Penn State to apply these fuzzy structures analysis procedures to real aircraft panels is then described.

Civilian Health and Medical Program of the Uniformed Services (CHAMPUS); TRICARE Reserve Select for certain members of the selected reserve; Transitional Assistance Management Program; early eligibility for TRICARE for certain reserve component members. Interim final rule with comment period.

PubMed

2005-03-16

This interim final rule establishes requirements and procedures for implementation of TRICARE Reserve Select. It also revises requirements and procedures for the Transitional Assistance Management Program. In addition, it establishes requirements and procedures for implementation of the earlier TRICARE eligibility for certain reserve component members. The rule is being published as an interim final rule with comment period in order to comply with statutory effective dates.

7 CFR 1465.2 - Administration.

Code of Federal Regulations, 2010 CFR

2010-01-01

... leadership for AMA; (2) Establish policies, procedures, priorities, and guidance for implementation; (3... and contracts with selected participants; (6) Provide technical leadership for implementation, quality...

7 CFR 1465.2 - Administration.

Code of Federal Regulations, 2011 CFR

2011-01-01

... leadership for AMA; (2) Establish policies, procedures, priorities, and guidance for implementation; (3... and contracts with selected participants; (6) Provide technical leadership for implementation, quality...

7 CFR 1465.2 - Administration.

Code of Federal Regulations, 2014 CFR

2014-01-01

... leadership for AMA; (2) Establish policies, procedures, priorities, and guidance for implementation; (3... and contracts with selected participants; (6) Provide technical leadership for implementation, quality...

7 CFR 1465.2 - Administration.

Code of Federal Regulations, 2012 CFR

2012-01-01

... leadership for AMA; (2) Establish policies, procedures, priorities, and guidance for implementation; (3... and contracts with selected participants; (6) Provide technical leadership for implementation, quality...

7 CFR 1465.2 - Administration.

Code of Federal Regulations, 2013 CFR

2013-01-01

... leadership for AMA; (2) Establish policies, procedures, priorities, and guidance for implementation; (3... and contracts with selected participants; (6) Provide technical leadership for implementation, quality...

Atmospheric model development in support of SEASAT. Volume 1: Summary of findings

NASA Technical Reports Server (NTRS)

Kesel, P. G.

1977-01-01

Atmospheric analysis and prediction models of varying (grid) resolution were developed. The models were tested using real observational data for the purpose of assessing the impact of grid resolution on short range numerical weather prediction. The discretionary model procedures were examined so that the computational viability of SEASAT data might be enhanced during the conduct of (future) sensitivity tests. The analysis effort covers: (1) examining the procedures for allowing data to influence the analysis; (2) examining the effects of varying the weights in the analysis procedure; (3) testing and implementing procedures for solving the minimization equation in an optimal way; (4) describing the impact of grid resolution on analysis; and (5) devising and implementing numerous practical solutions to analysis problems, generally.

40 CFR 6.406 - Implementation.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GENERAL PROCEDURES FOR IMPLEMENTING THE NATIONAL ENVIRONMENTAL POLICY ACT AND ASSESSING THE ENVIRONMENTAL EFFECTS ABROAD OF EPA ACTIONS Assessing the Environmental Effects Abroad of EPA Actions § 6.406 Implementation. (a) Oversight. OFA is responsible for...

Policy Implementation: Implications for Evaluation

ERIC Educational Resources Information Center

DeGroff, Amy; Cargo, Margaret

2009-01-01

Policy implementation reflects a complex change process where government decisions are transformed into programs, procedures, regulations, or practices aimed at social betterment. Three factors affecting contemporary implementation processes are explored: networked governance, sociopolitical context and the democratic turn, and new public…

The transcatheter aortic valve implementation (TAVI)--a qualitative approach to the implementation and diffusion of a minimally invasive surgical procedure.

PubMed

Merkel, Sebastian; Eikermann, Michaela; Neugebauer, Edmund A; von Bandemer, Stephan

2015-10-06

The transcatheter aortic valve implantation (TAVI), a minimally invasive surgical procedure to treat patients with severe symptomatic aortic stenosis, showed a rapid diffusion in Germany compared to the international level. The aim of this study is to identify and analyze factors affecting the implementation and diffusion of the procedure in hospitals using a qualitative application of the diffusion of innovations theory. We conducted problem-centered interviews with cardiologists and cardiac surgeons working in German hospitals. The multi-level model "diffusion of innovations in health services organizations" developed by Greenhalgh et al. was used to guide the research. Data was analyzed using content and a thematic analysis. Among the ten participants who were interviewed, we found both barriers and facilitators related to the innovation itself, system readiness and antecedents, communication and influence, and the outer context. Key issues were the collaboration between cardiologists and cardiac surgeons, reimbursement policies, requirements needed to conduct the procedure, and medical advantages of the method. The findings show that there are multiple factors influencing the diffusion of TAVI that go beyond the reimbursement and cost issues. The diffusion of innovations model proved to be helpful in understanding the different aspects of the uptake of the procedure. A central theme that affected the implementation of TAVI was the collaboration and competition between involved medical departments: cardiology and cardiac surgery. Against this background, it seems especially important to moderate and coordinate the cooperation of the different medical disciplines.

A Two-Stage Procedure Toward the Efficient Implementation of PANS and Other Hybrid Turbulence Models

NASA Technical Reports Server (NTRS)

Abdol-Hamid, Khaled S.; Girimaji, Sharath S.

2004-01-01

The main objective of this article is to introduce and to show the implementation of a novel two-stage procedure to efficiently estimate the level of scale resolution possible for a given flow on a given grid for Partial Averaged Navier-Stokes (PANS) and other hybrid models. It has been found that the prescribed scale resolution can play a major role in obtaining accurate flow solutions. The first step is to solve the unsteady or steady Reynolds Averaged Navier-Stokes (URANS/RANS) equations. From this preprocessing step, the turbulence length-scale field is obtained. This is then used to compute the characteristic length-scale ratio between the turbulence scale and the grid spacing. Based on this ratio, we can assess the finest scale resolution that a given grid for a given flow can support. Along with other additional criteria, we are able to analytically identify the appropriate hybrid solver resolution for different regions of the flow. This procedure removes the grid dependency issue that affects the results produced by different hybrid procedures in solving unsteady flows. The formulation, implementation methodology, and validation example are presented. We implemented this capability in a production Computational Fluid Dynamics (CFD) code, PAB3D, for the simulation of unsteady flows.

A Checklist to Improve Patient Safety in Interventional Radiology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Koetser, Inge C. J.; Vries, Eefje N. de; Delden, Otto M. van

2013-04-15

To develop a specific RADiological Patient Safety System (RADPASS) checklist for interventional radiology and to assess the effect of this checklist on health care processes of radiological interventions. On the basis of available literature and expert opinion, a prototype checklist was developed. The checklist was adapted on the basis of observation of daily practice in a tertiary referral centre and evaluation by users. To assess the effect of RADPASS, in a series of radiological interventions, all deviations from optimal care were registered before and after implementation of the checklist. In addition, the checklist and its use were evaluated by interviewingmore » all users. The RADPASS checklist has two parts: A (Planning and Preparation) and B (Procedure). The latter part comprises checks just before starting a procedure (B1) and checks concerning the postprocedural care immediately after completion of the procedure (B2). Two cohorts of, respectively, 94 and 101 radiological interventions were observed; the mean percentage of deviations of the optimal process per intervention decreased from 24 % before implementation to 5 % after implementation (p < 0.001). Postponements and cancellations of interventions decreased from 10 % before implementation to 0 % after implementation. Most users agreed that the checklist was user-friendly and increased patient safety awareness and efficiency. The first validated patient safety checklist for interventional radiology was developed. The use of the RADPASS checklist reduced deviations from the optimal process by three quarters and was associated with less procedure postponements.« less

Standard operating procedures improve acute neurologic care in a sub-Saharan African setting

PubMed Central

Jaiteh, Lamin E.S.; Helwig, Stefan A.; Jagne, Abubacarr; Ragoschke-Schumm, Andreas; Sarr, Catherine; Walter, Silke; Lesmeister, Martin; Manitz, Matthias; Blaß, Sebastian; Weis, Sarah; Schlund, Verena; Bah, Neneh; Kauffmann, Jil; Fousse, Mathias; Kangankan, Sabina; Ramos Cabrera, Asmell; Kronfeld, Kai; Ruckes, Christian; Liu, Yang; Nyan, Ousman

2017-01-01

Objective: Quality of neurologic emergency management in an under-resourced country may be improved by standard operating procedures (SOPs). Methods: Neurologic SOPs were implemented in a large urban (Banjul) and a small rural (Brikama) hospital in the Gambia. As quality indicators of neurologic emergency management, performance of key procedures was assessed at baseline and in the first and second implementation years. Results: At Banjul, 100 patients of the first-year intervention group exhibited higher rates of general procedures of emergency management than 105 control patients, such as neurologic examination (99.0% vs 91.4%; p < 0.05) and assessments of respiratory rate (98.0% vs 81.9%, p < 0.001), temperature (60.0% vs 36.2%; p < 0.001), and glucose levels (73.0% vs 58.1%; p < 0.05), in addition to written directives by physicians (96.0% vs 88.6%, p < 0.05), whereas assessments of other vital signs remained unchanged. In stroke patients, rates of stroke-related procedures increased: early CT scanning (24.3% vs 9.9%; p < 0.05), blood count (73.0% vs 49.3%; p < 0.01), renal and liver function tests (50.0% vs 5.6%, p < 0.001), aspirin prophylaxis (47.3% vs 9.9%; p < 0.001), and physiotherapy (41.9% vs 4.2%; p < 0.001). Most effects persisted until the second-year evaluation. SOP implementation was similarly feasible and beneficial at the Brikama hospital. However, outcomes did not significantly differ in the hospitals. Conclusions: Implementing SOPs is a realistic, low-cost option for improving process quality of neurologic emergency management in under-resourced settings. Classification of evidence: This study provides Class IV evidence that, for patients with suspected neurologic emergencies in sub-Saharan Africa, neurologic SOPs increase the rate of performance of guideline-recommended procedures. PMID:28600460

TU-FG-201-12: Designing a Risk-Based Quality Assurance Program for a Newly Implemented Y-90 Microspheres Procedure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vile, D; Zhang, L; Cuttino, L

2016-06-15

Purpose: To create a quality assurance program based upon a risk-based assessment of a newly implemented SirSpheres Y-90 procedure. Methods: A process map was created for a newly implemented SirSpheres procedure at a community hospital. The process map documented each step of this collaborative procedure, as well as the roles and responsibilities of each member. From the process map, different potential failure modes were determined as well as any current controls in place. From this list, a full failure mode and effects analysis (FMEA) was performed by grading each failure mode’s likelihood of occurrence, likelihood of detection, and potential severity.more » These numbers were then multiplied to compute the risk priority number (RPN) for each potential failure mode. Failure modes were then ranked based on their RPN. Additional controls were then added, with failure modes corresponding to the highest RPNs taking priority. Results: A process map was created that succinctly outlined each step in the SirSpheres procedure in its current implementation. From this, 72 potential failure modes were identified and ranked according to their associated RPN. Quality assurance controls and safety barriers were then added for failure modes associated with the highest risk being addressed first. Conclusion: A quality assurance program was created from a risk-based assessment of the SirSpheres process. Process mapping and FMEA were effective in identifying potential high-risk failure modes for this new procedure, which were prioritized for new quality assurance controls. TG 100 recommends the fault tree analysis methodology to design a comprehensive and effective QC/QM program, yet we found that by simply introducing additional safety barriers to address high RPN failure modes makes the whole process simpler and safer.« less

7 CFR 1491.2 - Administration.

Code of Federal Regulations, 2010 CFR

2010-01-01

... implementation leadership for FRPP; (2) Develop, maintain, and ensure that policies, guidelines, and procedures... CFR part 12; and (10) Provide leadership for establishing, implementing, and overseeing administrative...

7 CFR 1491.2 - Administration.

Code of Federal Regulations, 2011 CFR

2011-01-01

... implementation leadership for FRPP; (2) Develop, maintain, and ensure that policies, guidelines, and procedures... CFR part 12; and (10) Provide leadership for establishing, implementing, and overseeing administrative...

An Analysis of Policies and Procedures for Obtaining New Course Approval at Oakton Community College.

ERIC Educational Resources Information Center

Woloshin, Phyllis Lerman

Procedures and policies by which a new course is introduced into the Oakton Community College curriculum were analyzed in order to discover appropriate procedures for attaining course approval from the internal college governance structure, to implement those procedures in obtaining final approval, and to make recommendations for improvement of…

A Quantitative Review of Functional Analysis Procedures in Public School Settings

ERIC Educational Resources Information Center

Solnick, Mark D.; Ardoin, Scott P.

2010-01-01

Functional behavioral assessments can consist of indirect, descriptive and experimental procedures, such as a functional analysis. Although the research contains numerous examples demonstrating the effectiveness of functional analysis procedures, experimental conditions are often difficult to implement in classroom settings and analog conditions…

34 CFR 303.419 - Mediation.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 34 Education 2 2010-07-01 2010-07-01 false Mediation. 303.419 Section 303.419 Education... DISABILITIES Procedural Safeguards Mediation and Due Process Procedures for Parents and Children § 303.419 Mediation. (a) General. Each State shall ensure that procedures are established and implemented to allow...

10 CFR 26.137 - Quality assurance and quality control.

Code of Federal Regulations, 2013 CFR

2013-01-01

... validation of analytical procedures. Quality assurance procedures must be designed, implemented, and reviewed... resolving any technical, methodological, or administrative errors in the licensee testing facility's testing...

10 CFR 26.137 - Quality assurance and quality control.

Code of Federal Regulations, 2010 CFR

2010-01-01

... validation of analytical procedures. Quality assurance procedures must be designed, implemented, and reviewed... resolving any technical, methodological, or administrative errors in the licensee testing facility's testing...

10 CFR 26.137 - Quality assurance and quality control.

Code of Federal Regulations, 2011 CFR

2011-01-01

... validation of analytical procedures. Quality assurance procedures must be designed, implemented, and reviewed... resolving any technical, methodological, or administrative errors in the licensee testing facility's testing...

10 CFR 26.137 - Quality assurance and quality control.

Code of Federal Regulations, 2012 CFR

2012-01-01

... validation of analytical procedures. Quality assurance procedures must be designed, implemented, and reviewed... resolving any technical, methodological, or administrative errors in the licensee testing facility's testing...

10 CFR 26.137 - Quality assurance and quality control.

Code of Federal Regulations, 2014 CFR

2014-01-01

... validation of analytical procedures. Quality assurance procedures must be designed, implemented, and reviewed... resolving any technical, methodological, or administrative errors in the licensee testing facility's testing...

33 CFR 277.5 - General.

Code of Federal Regulations, 2010 CFR

2010-07-01

... has established implementing procedures based on those previously adopted and utilized by the Chief of Engineers prior to 15 October 1966. This regulation adapts these cost apportionment procedures, found in...

33 CFR 277.5 - General.

Code of Federal Regulations, 2011 CFR

2011-07-01

... has established implementing procedures based on those previously adopted and utilized by the Chief of Engineers prior to 15 October 1966. This regulation adapts these cost apportionment procedures, found in...

75 FR 35497 - Updated Guidance: Prevention Strategies for Seasonal Influenza in Healthcare Settings

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-22

...-generating procedure precautions, surveillance, and environmental and engineering controls. CDC will consider... procedures. Implementing environmental and engineering infection control measures. [[Page 35499

7 CFR 7.36 - Implementation.

Code of Federal Regulations, 2010 CFR

2010-01-01

... part, the Deputy Administrator, State and County Operations, or the Deputy Administrator, Management, ASCS, is authorized to issue the instructions and procedures referred to herein which implement the...

Guidelines for Implementing NCHRP 1-37A M-E Design Procedures in Ohio : Volume 1 -- Summary of Findings, Implementation Plan, and Next Steps

DOT National Transportation Integrated Search

2009-11-01

Highway agencies across the nation are moving towards implementation of the new AASHTO Mechanistic-Empirical Pavement Design Guide (MEPDG) for pavement design. The benefits of implementing the MEPDG for routine use in Ohio includes (1) achieving more...

[Implementation of a patient data management system. Effects on intensive care documentation].

PubMed

Castellanos, I; Ganslandt, T; Prokosch, H U; Schüttler, J; Bürkle, T

2013-11-01

Patient data management systems (PDMS) enable digital documentation on intensive care units (ICU). A commercial PDMS was implemented in a 25-bed ICU replacing paper-based patient charting. The ICU electronic patient record is completely managed inside the PDMS. It compiles data from vital signs monitors, ventilators and further medical devices and facilitates some drug dose and fluid balance calculations as well as data reuse for administrative purposes. Ventilation time and patient severity scoring as well as coding of diagnoses and procedures is supported. Billing data transferred via interface to the central billing system of the hospital. Such benefits should show in measurable parameters, such as documented ventilator time, number of coded diagnoses and procedures and others. These parameters influence reimbursement in the German DRG system. Therefore, measurable changes in cost and reimbursement data of the ICU were expected. A retrospective analysis of documentation quality parameters, cost data and mortality rate of a 25-bed surgical ICU within a German university hospital 3 years before (2004-2006) and 5 years after (2007-2011) PDMS implementation. Selected parameters were documented electronically, consistently and reproducibly for the complete time span of 8 years including those years where no electronic patient recording was available. The following parameters were included: number of cleared DRG, cleared ventilator time, case mix (CM), case mix index (CMI), length of stay, number of coded diagnoses and procedures, detailed overview of a specific procedure code based on daily Apache II and TISS Core 10 scores, mortality, total ICU costs and revenues and partial profits for specific ICU procedures, such as renal replacement therapy and blood products. Systematic shifts were detected over the study period, such as increasing case numbers and decreasing length of stay as well as annual fluctuations in severity of disease seen in the CM and CMI. After PDMS introduction, the total number of coded diagnoses increased but the proportion of DRG relevant diagnoses dropped significantly. The number of procedures increased (not significantly) and the number of procedures per case did not rise significantly. The procedure 8-980 showed a significant increase after PDMS introduction whereas the DRG-relevant proportion of those procedures dropped insignificantly. The number of ventilator-associated DRG cases as well as the total ventilator time increased but not significantly. Costs and revenues increased slightly but profit varied considerably from year to year in the 5 years after system implementation. A small increase was observed per case, per nursing day and per case mix point. Additional revenues for specific ICU procedures increased in the years before and dropped after PDMS implementation. There was an insignificant increase in ICU mortality rate from 7.4 % in the year 2006 (before) to 8.5 % in 2007 (after PDMS implementation). In the following years mortality dropped below the base level. The implementation of the PDMS showed only small effects on documentation of reimbursement-relevant parameters which were too small to set off against the total investment. The method itself, a long-term follow-up of different parameters proved successful and can be adapted by other organizations. The quality of results depends on the availability of long-term parameters in good quality. No significant influence of PDMS on mortality was found.

Implementation of alanine/EPR as transfer dosimetry system in a radiotherapy audit programme in Belgium.

PubMed

Schaeken, B; Cuypers, R; Lelie, S; Schroeyers, W; Schreurs, S; Janssens, H; Verellen, D

2011-04-01

A measurement procedure based on alanine/electron paramagnetic resonance (EPR) dosimetry was implemented successfully providing simple, stable, and accurate dose-to-water (D(w)) measurements. The correspondence between alanine and ionization chamber measurements in reference conditions was excellent. Alanine/EMR dosimetry might be a valuable alternative to thermoluminescent (TLD) and ionization chamber based measuring procedures in radiotherapy audits. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

77 FR 44121 - Procedures for the Handling of Retaliation Complaints Under the Employee Protection Provision of...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-27

...This document provides the final text of regulations governing employee protection (or ``whistleblower'') claims under the Surface Transportation Assistance Act of 1982 (STAA), as amended, implementing statutory changes to STAA enacted into law on August 3, 2007, as part of the Implementing Recommendations of the 9/11 Commission Act of 2007. On August 31, 2010, the Occupational Safety and Health Administration (OSHA) published an interim final rule (IFR) for STAA whistleblower complaints in the Federal Register and requested public comment on the IFR. This final rule implements changes to the IFR in response to comments received, where appropriate. This final rule also finalizes changes to the procedures for handling whistleblower complaints under STAA that were designed to make them more consistent with OSHA's procedures for handling retaliation complaints under Section 211 of the Energy Reorganization Act of 1974, and other whistleblower provisions. It also sets forth interpretations of STAA.

PLA realizations for VLSI state machines

NASA Technical Reports Server (NTRS)

Gopalakrishnan, S.; Whitaker, S.; Maki, G.; Liu, K.

1990-01-01

A major problem associated with state assignment procedures for VLSI controllers is obtaining an assignment that produces minimal or near minimal logic. The key item in Programmable Logic Array (PLA) area minimization is the number of unique product terms required by the design equations. This paper presents a state assignment algorithm for minimizing the number of product terms required to implement a finite state machine using a PLA. Partition algebra with predecessor state information is used to derive a near optimal state assignment. A maximum bound on the number of product terms required can be obtained by inspecting the predecessor state information. The state assignment algorithm presented is much simpler than existing procedures and leads to the same number of product terms or less. An area-efficient PLA structure implemented in a 1.0 micron CMOS process is presented along with a summary of the performance for a controller implemented using this design procedure.

Development of methodologies for the estimation of thermal properties associated with aerospace vehicles

NASA Technical Reports Server (NTRS)

Scott, Elaine P.

1993-01-01

Thermal stress analyses are an important aspect in the development of aerospace vehicles such as the National Aero-Space Plane (NASP) and the High-Speed Civil Transport (HSCT) at NASA-LaRC. These analyses require knowledge of the temperature within the structures which consequently necessitates the need for thermal property data. The initial goal of this research effort was to develop a methodology for the estimation of thermal properties of aerospace structural materials at room temperature and to develop a procedure to optimize the estimation process. The estimation procedure was implemented utilizing a general purpose finite element code. In addition, an optimization procedure was developed and implemented to determine critical experimental parameters to optimize the estimation procedure. Finally, preliminary experiments were conducted at the Aircraft Structures Branch (ASB) laboratory.

An automation-assisted generic approach for biological sample preparation and LC-MS/MS method validation.

PubMed

Zhang, Jie; Wei, Shimin; Ayres, David W; Smith, Harold T; Tse, Francis L S

2011-09-01

Although it is well known that automation can provide significant improvement in the efficiency of biological sample preparation in quantitative LC-MS/MS analysis, it has not been widely implemented in bioanalytical laboratories throughout the industry. This can be attributed to the lack of a sound strategy and practical procedures in working with robotic liquid-handling systems. Several comprehensive automation assisted procedures for biological sample preparation and method validation were developed and qualified using two types of Hamilton Microlab liquid-handling robots. The procedures developed were generic, user-friendly and covered the majority of steps involved in routine sample preparation and method validation. Generic automation procedures were established as a practical approach to widely implement automation into the routine bioanalysis of samples in support of drug-development programs.

Development of methodologies for the estimation of thermal properties associated with aerospace vehicles

NASA Astrophysics Data System (ADS)

Scott, Elaine P.

1993-12-01

Thermal stress analyses are an important aspect in the development of aerospace vehicles such as the National Aero-Space Plane (NASP) and the High-Speed Civil Transport (HSCT) at NASA-LaRC. These analyses require knowledge of the temperature within the structures which consequently necessitates the need for thermal property data. The initial goal of this research effort was to develop a methodology for the estimation of thermal properties of aerospace structural materials at room temperature and to develop a procedure to optimize the estimation process. The estimation procedure was implemented utilizing a general purpose finite element code. In addition, an optimization procedure was developed and implemented to determine critical experimental parameters to optimize the estimation procedure. Finally, preliminary experiments were conducted at the Aircraft Structures Branch (ASB) laboratory.

17 CFR 8.02 - Implementing exchange rules.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 17 Commodity and Securities Exchanges 1 2010-04-01 2010-04-01 false Implementing exchange rules. 8.02 Section 8.02 Commodity and Securities Exchanges COMMODITY FUTURES TRADING COMMISSION EXCHANGE PROCEDURES FOR DISCIPLINARY, SUMMARY, AND MEMBERSHIP DENIAL ACTIONS General Provisions § 8.02 Implementing...

12 CFR 1250.2 - Procedural requirements.

Code of Federal Regulations, 2010 CFR

2010-01-01

... requirements. (a) Procedures. An Enterprise shall implement procedures reasonably designed to ensure for any loan that is secured by improved real estate or a mobile home located in an area that has been... amended and purchased by the Enterprise, the building or mobile home and any personal property securing...

29 CFR 2400.6 - Procedures for requesting records.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 29 Labor 9 2010-07-01 2010-07-01 false Procedures for requesting records. 2400.6 Section 2400.6 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH REVIEW COMMISSION REGULATIONS IMPLEMENTING THE PRIVACY ACT § 2400.6 Procedures for requesting records. The purpose of this...

29 CFR 2400.6 - Procedures for requesting records.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 29 Labor 9 2011-07-01 2011-07-01 false Procedures for requesting records. 2400.6 Section 2400.6 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH REVIEW COMMISSION REGULATIONS IMPLEMENTING THE PRIVACY ACT § 2400.6 Procedures for requesting records. The purpose of this...

75 FR 17874 - Digital Audio Broadcasting Systems and Their Impact on the Terrestrial Radio Broadcast Service

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-08

... power (ERP), and implements interference mitigation and remediation procedures to resolve promptly..., and the interference mitigation and remediation procedures will make certain that permissible... ERP to more than 4% of authorized analog ERP. 4. Establishes interference remediation procedures that...

[TANDEM (TAsk force oN long Duration unemployment of Elderly People and Mental health) implementation of a cross-institutional pilot project for elderly long-term unemployed persons - presentation of the project procedure and the utilisation].

PubMed

Steil, C; Meiler, B; Wiesten, I; Wiltfang, J; Kis, B

2013-08-01

The aim of this study is to implement and examine the feasibility of a cross-institutional mental health intervention to comprehend and advance mental health of elderly long-term unemployed persons. Report on the procedure and on the observational study utilisation in a 14-month period. The structure and processes chosen could be implemented into practice successfully. Utilisation was high but 30% dropped out during the procedure. Of the unemployed persons surveyed, 96% received a psychiatric diagnosis. 85% were not having psychiatric treatment. The method chosen is feasible and was accepted by the target group. Project structure and processes proved to be applicable for the implementation of the project aims. The method chosen reaches an up to now "psychiatry-inexperienced" target group characterised by frequent incidence of mental disorders and low utilisation of psychiatric care. Thus, vocational reintegration programmes should be supported by psychiatric services. © Georg Thieme Verlag KG Stuttgart · New York.

Social Thinking®: Science, Pseudoscience, or Antiscience?

PubMed

Leaf, Justin B; Kassardjian, Alyne; Oppenheim-Leaf, Misty L; Cihon, Joseph H; Taubman, Mitchell; Leaf, Ronald; McEachin, John

2016-06-01

Today, there are several interventions that can be implemented with individuals diagnosed with autism spectrum disorder. Most of these interventions have limited to no empirical evidence demonstrating their effectiveness, yet they are widely implemented in home, school, university, and community settings. In 1996, Green wrote a chapter in which she outlined three levels of science: evidence science, pseudoscience, and antiscience; professionals were encouraged to implement and recommend only those procedures that would be considered evidence science. Today, an intervention that is commonly implemented with individuals diagnosed with autism spectrum disorder is Social Thinking®. This intervention has been utilized by behaviorists and non-behaviorists. This commentary will outline Social Thinking® and provide evidence that the procedure, at the current time, qualifies as a pseudoscience and, therefore, should not be implemented with individuals diagnosed with autism spectrum disorder, especially given the availability of alternatives which clearly meet the standard of evidence science.

The digital implementation of control compensators: The coefficient wordlength issue

NASA Technical Reports Server (NTRS)

Moroney, P.; Willsky, A. S.; Houpt, P. K.

1979-01-01

There exists a number of mathematical procedures for designing discrete-time compensators. However, the digital implementation of these designs, with a microprocessor for example, has not received nearly as thorough an investigation. The finite-precision nature of the digital hardware makes it necessary to choose an algorithm (computational structure) that will perform 'well-enough' with regard to the initial objectives of the design. This paper describes a procedure for estimating the required fixed-point coefficient wordlength for any given computational structure for the implementation of a single-input single-output LOG design. The results are compared to the actual number of bits necessary to achieve a specified performance index.

Development of novel ligands for peptide GPCRs.

PubMed

Moran, Brian M; McKillop, Aine M; O'Harte, Finbarr Pm

2016-12-01

Incretin based glucagon-like peptide-1 receptor (GLP-1R) agonists which target a G-protein coupled receptor (GPCR) are currently used in the treatment of type 2 diabetes. This review focuses on GPCRs from pancreatic β-cells, including GLP-1, glucose-dependent insulinotropic polypeptide (GIP), glucagon, somatostatin, pancreatic polypeptide (PP), cholecystokinin (CCK), peptide YY (PYY), oxyntomodulin (OXM) and ghrelin receptors. In addition, fatty acids GPCRs are thought to have an increasing role in regulating peptide secretions namely short fatty acids GPCR (GPR41, GPR43), medium chain fatty acid GPCR (GPR84), long chain fatty acid GPCR (GPR40, GPR120) and cannabinoid-like GPCR (GPR55, GPR119). Several pre-clinical and clinical trials are currently ongoing in peptide GPCR based therapies, including dual and triple agonist peptides which activate two or more GPCRs simultaneously. Copyright © 2016 Elsevier Ltd. All rights reserved.

17 CFR 23.605 - Conflicts of interest policies and procedures.

Code of Federal Regulations, 2014 CFR

2014-04-01

... subject to this rule must adopt and implement written policies and procedures reasonably designed to... information in the research report, to provide for non-substantive editing, to format the layout or style of... swap participant must establish written policies and procedures reasonably designed to ensure the...

Item Purification in Differential Item Functioning Using Generalized Linear Mixed Models

ERIC Educational Resources Information Center

Liu, Qian

2011-01-01

For this dissertation, four item purification procedures were implemented onto the generalized linear mixed model for differential item functioning (DIF) analysis, and the performance of these item purification procedures was investigated through a series of simulations. Among the four procedures, forward and generalized linear mixed model (GLMM)…

23 CFR 750.304 - State policies and procedures.

Code of Federal Regulations, 2011 CFR

2011-04-01

... one company or those located along a single route, all of the signs in a single county or other... BEAUTIFICATION Outdoor Advertising (Acquisition of Rights of Sign and Sign Site Owners) § 750.304 State policies and procedures. The State's written policies and operating procedures for implementing its sign...

23 CFR 750.304 - State policies and procedures.

Code of Federal Regulations, 2010 CFR

2010-04-01

... one company or those located along a single route, all of the signs in a single county or other... BEAUTIFICATION Outdoor Advertising (Acquisition of Rights of Sign and Sign Site Owners) § 750.304 State policies and procedures. The State's written policies and operating procedures for implementing its sign...