Aspects of signal transduction in the gastrointestinal tract

This study was undertaken to increase knowledge of the mechanisms of inter- and intracellular signalling in the gastrointestinal tract. Specific aims were: to use cell lines to elucidate factors affecting growth of gastric cells, to investigate the distribution and aspects of function of isoforms of protein kinase C in a gastric cell line and in the rat gastrointestinal tract and to determine the presence and regulation of nitric oxide synthase in gastrointestinal tissues from the rat and in cell lines. The gastric cancer cell line HGT-1 was used to investigate control of growth. Increases in cell number were found to be dependent on the seeding density of the cells. In cells plated at low density insulin, epidermal growth factor and gastrin all increased cell number. Gastrin produced a bell-shaped dose response curve with a maximum activity at 5nM. No effect of gastrin was apparent in cells plated at high density. α and β isoforms of protein kinase C were found, by immunoblotting procedures, to be widespread in the gastrointestinal tract of the rat, but protein kinase Cε was confined to the gastric mucosa and gastrointestinal smooth muscle. HGT-1 cells contained protein kinase C α and ε but β or γ were not detected. Preincubation of HGT-1 cells for 24h with 1μM phorbol-12,13-dibutyrate down-regulated protein kinase C α but not ε. The inhibition by the activator of protein kinase C, 12-O-tetradecanoylphorbol 13-acetate (TPA) of the histamine-stimulated increase in cAMP in HGT-1 cells was down regulated by phorbol-12,13-dibutyrate. Inhibition of histamine-stimulation of adenylate cyclase by TPA was Ca2+-dependent and inhibited by the addition of an antibody to protein kinase C α. A role for protein kinase C α in modulating the effect of histamine on adenylate cyclase in HGT-1 cells is suggested. No nitric oxide synthase activity was detected in the gastrointestinal cell lines HGT-l, MKN-45 or CaCo-2. Ca2+-dependent nitric oxide synthase activity was observed in the gastric mucosa and the gastrointestinal smooth muscle from stomach to colon. The gastric: mucosal enzyme was soluble and showed half-maximal activity at 400nM Ca2+. Pretreatment of rats with endotoxin (3mg/kg body weight) induced nitric oxide synthase activity in both jejunal, ileal and colonic mucosa and muscle. A major portion of the induced activity in ileal and colonic mucosa was Ca2+-independent. Nitric oxide synthase activity in a high-density fraction of gastric mucosal cells was inhibited in a dose-dependent fashion by L-nitroarginine, NG-monomethyl-L-arginine, trifluoperazine and L-canavanine (in descending order of potency). Preincubation with okadaic acid and addition of ATPlMg2+ to the homogenisation buffer inhibited enzyme activity, which implies that phosphorylation inhibits gastric mucosal nitric oxide synthase.

Control of the endocrine pancreas by gastrointestinal peptides

This thesis concerns the mechanism through which enteral delivery of glucose results in a larger insulin response than an equivalent parenteral glucose load. Preliminary studies in which mice received a glucose solution either intragastrically or intraperitoneally confirmed this phenomenon. An important regulatory system in this respect is the entero-insular axis, through which insulin secretion is influenced by neural and endocrine communication between the gastrointestinal tract and the pancreatic islets of Langerhans. Using an in vitro system involving static incubation of isolated (by collagenase digestion) islets of Langerhans, the effect of a variety of gastrointestinal peptides on the secretion of the four main islet hormones, namely insulin, glucagon, somatostatin and pancreatic polypeptide, was studied. The gastrointestinal peptides investigated in this study were the secretin family, comprising secretin, glucagon, gastric inhibitory polypeptide (GIP), vasoactive intestinal polypeptide (VIP), peptide histidine isoleucine (PHI) and growth hormone releasing factor (GRF). Gastrin releasing peptide (GRP) was also studied. The results showed that insulin release was stimulated by all peptides studied except PHI, glucagon release was stimulated by all peptides tested, except GRF which suppressed glucagon release, somatostatin release was stimulated by GIP and GRF but suppressed by VIP, PHI, glucagon and secretin, and PP release was stimulated by GIP and GRF, but suppressed by PHI. The insulinotropic effect of GRP was investigated further. A perifusion system was used to examine the time-course of insulin release from isolated islets after stimulation with GRP. GRP was shown to be insulinotropic only in the presence of physiologically elevated glucose concentrations and both first and second phases of insulin release were augmented. There was no effect at substimulatory or very high glucose concentrations. Studies using a cultured insulin-secreting islet cell line, the RINm5F cell line, were undertaken to elucidate the intracellular mechanism of action of GRP. This peptide did not enhance insulin release via an augmentation of glucose metabolism, or via the adenylate cyclase/cyclic AMP secondary messenger system. The pattern of changes of cytosolic free calcium in response to GRP, which involved both mobilization of intracellular stores and an influx of extracellular calcium, suggested the involvement of phosphatidylinositol bisphosphate breakdown as a mediator of the effect of GRP on insulin secretion.

Metformin and the gastrointestinal tract

Metformin is an effective agent with a good safety profile that is widely used as a first-line treatment for type 2 diabetes, yet its mechanisms of action and variability in terms of efficacy and side effects remain poorly understood. Although the liver is recognised as a major site of metformin pharmacodynamics, recent evidence also implicates the gut as an important site of action. Metformin has a number of actions within the gut. It increases intestinal glucose uptake and lactate production, increases GLP-1 concentrations and the bile acid pool within the intestine, and alters the microbiome. A novel delayed-release preparation of metformin has recently been shown to improve glycaemic control to a similar extent to immediate-release metformin, but with less systemic exposure. We believe that metformin response and tolerance is intrinsically linked with the gut. This review examines the passage of metformin through the gut, and how this can affect the efficacy of metformin treatment in the individual, and contribute to the side effects associated with metformin intolerance.

Design, synthesis and evaluation of dipeptides as probes for studies of gastrointestinal tract dipeptide transport system

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Effect of nitric oxide on apoptotic activity in the rat gastrointestinal tract

The effect of nitric oxide (NO) on apoptosis in the gastrointestinal mucosa was investigated. Experiments involved long-term exposure of rat gastric mucosal cells in vitro to exogenous NO delivered from the NO, donor S-nitroso-N-acetyl-penicillamine, and the effect of intravenous administration of lipopolysaccharide in vivo, in the presence and absence of the selective inhibitor of inducible NO synthase N-(3-(aminomethyl)benzyl) acetamidine (1400 W). S-nitroso-N-acetyl-penicillamine produced a dose-related inhibition of caspase 3-like activity and DNA fragmentation in isolated gastric mucosal cells. Caspase 3-like activity and DNA fragmentation in gastric, ileal and colonic mucosa were increased both 5 and 24 h after injection of lipopolysaccharide (3 mg/kg, i.v.) to rats in vivo. Administration of 1400 W (5 mg/kg, i.v.) immediately after lipopolysaccharide enhanced caspase 3-like activity and DNA fragmentation above that found with lipopolysaccharide alone. In conclusion, data obtained both in vitro and in vivo suggest that NO exerts an anti-apoptotic effect on rat gastrointestinal mucosal cells. © 2001 Elsevier Science B.V.

A prática do enfermeiro da atenção primária à saúde nas consultas ao paciente com tuberculose

This study aimed to analyze the practice of nurses regarding the development of the nursing process in the consultation to the patient with tuberculosis. This is a descriptive study with quantitative approach, performed with 60 nurses of the Primary units of the city of Natal, RN Health. The project was approved by the Ethics Committee of the Federal University of Rio Grande do Norte. To collect data, we used a structured questionnaire, developed from the "Consultation of Nursing," the Nursing Protocol for the Treatment of Tuberculosis Directly Observed in Primary Care, Ministry of Health. The instrument was subjected to pre- -test and contained questions regarding the elements used by the nurse in consultation with the patient with tuberculosis and an open question about the feasibility of implementing the Nursing Process in Primary Health Care. data collection was conducted between September and October 2014, in health units work of each participant. Data were analyzed using SPSS 20. The answers to the open question were analyzed for themes and quantified for analysis. With respect to the elements of nursing process used in consultation with the patient with tuberculosis, were on the history of nursing at the expense of survey nursing diagnosis, action planning, implementation and evaluation. Step in the history of nursing, however, the actions were toward complaints and symptoms of the disease (100% of the nurses always investigating). Social and cultural aspects involved in for tuberculosis, as stigma and difficulties in routine work, were less addressed by nurses (43.3% never investigated suffering stigma; 46.7% sometimes investigating changes in the work routine patient ). The physical examination was focused on measuring patient weight (100% held). To the understanding of nurses on the implementation of the nursing process Primary Health Care, favorable factors were identified, such as that this implementation can promote greater scientific basis for nursing (36.7%); and hindering aspects, such as the understanding that Primary Health Care is pervaded by bureaucratic issues and high demand (13.3%). Be established in consultation with the nurse fragmentations, since elements as identification of nursing diagnoses, action planning and evaluation were not made in full by the professionals. Highlights the need for continuing education for nurses who are included in Primary Health Care, seeking to maximize the autonomy of these professionals in developing a practice grounded in scientific knowledge

O controle da tuberculose no contexto da atenção primária à saúde no Brasil

O Brasil é um dos países que concentram 80% da carga de tuberculose no mundo. No contexto da atenção primária brasileira, fatores interferem para que as equipes de saúde da família possam incorporar as atividades de controle da doença no processo de trabalho. O controle da doença depende da forma como os serviços de saúde estão organizados para garantir o acesso ao diagnóstico precoce e ao tratamento. Esse estudo tem como objetivo geral analisar o controle da tuberculose no contexto da atenção primária à saúde no Brasil. Os objetivos específicos são comparar o tratamento diretamente observado com o regime autoadministrado em pessoas com tuberculose; Verificar se o Programa Nacional de Controle da Tuberculose é avaliável e elaborar um modelo teórico e lógico para avaliação deste programa; avaliar a relação entre porte populacional dos municípios e as características de estrutura e processo de cuidado a pacientes de tuberculose na atenção primária no Brasil. Realizou-se uma revisão sistemática, seguida de um estudo de avaliabilidade e de um estudo transversal. Os achados da revisão sistemática revelam que não houve diferença significativa entre os grupos de tratamento (observado e não observado) para cura (OR 1,06. IC95% 0,75 - 1,50) e para conclusão do tratamento (OR 1,64, IC 95% 0,79 - 3,42). Menor abandono no grupo com tratamento supervisionado e não houve diferença estatisticamente significativa entre os grupos (OR 0,73, CI 95% 0,58-0,92). O risco de morte foi maior no regime de tratamento autoadministrado (OR 1,49 IC 95% 1,03 - 2,45). A hetorogeinadade entre os estudos analisados não permite afirmar que nao há diferença estatisticamente significativa para cura e tratamento concluído. A pré-avaliação do Programa de Controle de Tuberculose possibilitou a descrição do Programa, elaboração e pactuação do modelo lógico e a matriz de relevância dos indicadores. Caracterizou-se os seus elementos estruturantes, definição de indicadores de estrutura e processo, além das perguntas avaliativas. Uma avaliação somativa com enfoque na análise dos efeitos da intervenção de controle da tuberculose é recomendada. A avaliação das características de estrutura e processo de cuidado à pessoa com tuberculose revelou melhor desempenho para as equipes de atenção básica de municípios classificados como metrópole no acesso, coordenação do cuidado e qualidade técnica da atenção. Em relação ao acesso: 98,5% acolhimento a demanda espontânea; 95,8% programação de consultas. Na coordenação do cuidado, 93,2% existência de protocolo para tuberculose. Quanto a qualidade técnica da atenção à tuberculose verifica-se que 93,4% acompanhamento de tratamento diretamente observado, 95,8% com busca ativa de faltosos ao tratamento, 64,0% oferta de ações educativas, 91,3% busca ativa de sintomáticos respiratórios. Cabe destacar que metrópoles apresentaram maior tempo médio de espera para escuta/acolhimento (24,41 minutos); para consulta previamente agendada (23,52 dias); para consulta em pneumologia (87,12 dias). Percebem-se fragilidades na estrutura e processo da atenção à tuberculose, principalmente no controle especializado da doença e na qualidade técnica entre os municípios. Recomenda-se reforço, particularmente na qualidade técnica para aumentar a cobertura de acompanhamento do tratamento, busca de sintomáticos respiratórios e das ações educativas.

Genome-wide association and genome partitioning reveal novel genomic regions underlying variation in gastrointestinal nematode burden in a wild bird

Acknowledgements This study was funded by a BBSRC studentship (MA Wenzel) and NERC grants NE/H00775X/1 and NE/D000602/1 (SB Piertney). The authors are grateful to Fiona Leckie, Andrew MacColl, Jesús Martínez-Padilla, François Mougeot, Steve Redpath, Pablo Vergara† and Lucy M.I. Webster for samples; Keliya Bai, Daisy Brickhill, Edward Graham, Alyson Little, Daniel Mifsud, Lizzie Molyneux and Mario Röder for fieldwork assistance; Gillian Murray-Dickson and Laura Watt for laboratory assistance; Heather Ritchie for helpful comments on manuscript drafts; and all estate owners, factors and keepers for access to field sites, most particularly Stuart Young and Derek Calder (Edinglassie), Simon Blackett, Jim Davidson and Liam Donald (Invercauld and Glas Choille), Richard Cooke and Fred Taylor† (Invermark) and T. Helps (Catterick).

Impact of mash feeding versus pellets on propionic/butyric acid levels and on total Escherichia coli load in the gastrointestinal tract of growing pigs

Feed characteristics may influence the bacterial community composition and metabolic activities in the pig gastrointestinal tract, known to be associated with positive effects on the gut. Use of mash feed is associated with reduced Salmonella excretion, but little is known of its effect on the Escherichia coli population or of the mechanism of action. Our objectives were to assess the effect of feed texture combined with feed particle size on VFA profiles and levels, total E. coli count, and the presence of genes encoding virulence factors of pathogenic E. coli strains in the digestive tract along with their impact on pig performance of fattening pigs. Pigs (n = 840) on a commercial farm received mash or pellet diets of different particle sizes during the fattening period. Caecal and colon contents from 164 pigs were sampled at the slaughterhouse for enumeration of E. coli by quantitative PCR (qPCR) and for VFA quantification by capillary gas chromatography. The yccT gene was used to enumerate total E. coli. Improved pig performances associated with pellet texture and a 500-μm size were observed. Caecal (P = 0.02) and colon (P < 0.01) propionic acid concentrations were lower for pigs receiving pellet rather than mash feed. Similarly, caecal (P = 0.01) and colon (P < 0.001) butyric acid concentrations were also lower for pigs receiving pellet rather than mash feed, as determined by capillary gas chromatography. Moreover, caecal (P = 0.03) and colon (P < 0.001) butyric acid concentrations were higher for pigs receiving a feed with a 1,250-μm particle size rather than a 500-μm particle size. On the other hand, total caecal and colon E. coli levels were higher for pigs receiving pellet feed than for those receiving mash feed. For total E. coli enumeration, caecal (P < 0.01) and colon (P < 0.01) yccT gene copies were higher for pigs receiving pellet rather than mash feed. No effect of particle size on fatty acid concentrations or on E. coli numbers was observed. Virulence gene quantification revealed no trend. Taken together, results showed that mash feed is associated with lower growth performance but with favorable intestinal changes linked to VFA levels and E. coli reduction in the intestine.

Histoire de l'Institut Bruchési et son engagement dans la lutte contre la tuberculose à Montréal (1911-1945)

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

Impact of mash feeding versus pellets on propionic/butyric acid levels and on total Escherichia coli load in the gastrointestinal tract of growing pigs

Feed characteristics may influence the bacterial community composition and metabolic activities in the pig gastrointestinal tract, known to be associated with positive effects on the gut. Use of mash feed is associated with reduced Salmonella excretion, but little is known of its effect on the Escherichia coli population or of the mechanism of action. Our objectives were to assess the effect of feed texture combined with feed particle size on VFA profiles and levels, total E. coli count, and the presence of genes encoding virulence factors of pathogenic E. coli strains in the digestive tract along with their impact on pig performance of fattening pigs. Pigs (n = 840) on a commercial farm received mash or pellet diets of different particle sizes during the fattening period. Caecal and colon contents from 164 pigs were sampled at the slaughterhouse for enumeration of E. coli by quantitative PCR (qPCR) and for VFA quantification by capillary gas chromatography. The yccT gene was used to enumerate total E. coli. Improved pig performances associated with pellet texture and a 500-μm size were observed. Caecal (P = 0.02) and colon (P < 0.01) propionic acid concentrations were lower for pigs receiving pellet rather than mash feed. Similarly, caecal (P = 0.01) and colon (P < 0.001) butyric acid concentrations were also lower for pigs receiving pellet rather than mash feed, as determined by capillary gas chromatography. Moreover, caecal (P = 0.03) and colon (P < 0.001) butyric acid concentrations were higher for pigs receiving a feed with a 1,250-μm particle size rather than a 500-μm particle size. On the other hand, total caecal and colon E. coli levels were higher for pigs receiving pellet feed than for those receiving mash feed. For total E. coli enumeration, caecal (P < 0.01) and colon (P < 0.01) yccT gene copies were higher for pigs receiving pellet rather than mash feed. No effect of particle size on fatty acid concentrations or on E. coli numbers was observed. Virulence gene quantification revealed no trend. Taken together, results showed that mash feed is associated with lower growth performance but with favorable intestinal changes linked to VFA levels and E. coli reduction in the intestine.

Histoire de l'Institut Bruchési et son engagement dans la lutte contre la tuberculose à Montréal (1911-1945)

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