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BACKGROUND: To eliminate some of the potential late limitations of permanent metallic stents, the bioresorbable coronary stents or 'bioresorbable vascular scaffolds' (BVS) have been developed. METHODS: We reviewed all currently available clinical data on BVS implantation. RESULTS: Since the 2015 position statement on the appropriateness of BVS in percutaneous coronary interventions, several large randomised trials have been presented. These have demonstrated that achieving adequate 1 and 2 year outcomes with these first-generation BVS is not straightforward. These first adequately powered studies in non-complex lesions showed worse results if standard implantation techniques were used for these relatively thick scaffolds. Post-hoc analyses hypothesise that outcomes similar to current drug-eluting stents are still possible if aggressive lesion preparation, adequate sizing and high-pressure postdilatation are implemented rigorously. As long as this has not been confirmed in prospective studies the usage should be restricted to experienced centres with continuous outcome monitoring. For more complex lesions, results are even more disappointing and usage should be discouraged. When developed, newer generation scaffolds with thinner struts or faster resorption rates are expected to improve outcomes. In the meantime prolonged dual antiplatelet therapy (DAPT, beyond one year) is recommended in an individualised approach for patients treated with current generation BVS. CONCLUSION: The new 2017 recommendations downgrade and limit the use of the current BVS to experienced centres within dedicated registries using the updated implantation protocol and advise the prolonged usage of DAPT. In line with these recommendations the manufacturer does not supply devices to the hospitals without such registries in place.
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Microencapsulation processes may be divided into three steps, namely: incorporation of the bioactive substance in the matrix, dispersion of the matrix in droplets, and conversion in microcapsules. This contribution is focused on the second step and more specifically using the dripping approach to form droplets by extrusion of liquid through a nozzle. Different technologies of dripping are described, using as an example the production of alginate beads.
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Alginatos/química , Composición de Medicamentos/métodos , Algoritmos , Cápsulas/química , Composición de Medicamentos/instrumentación , Diseño de Equipo , Ácido Glucurónico/química , Gravitación , Ácidos Hexurónicos/química , Microesferas , Tamaño de la Partícula , Electricidad EstáticaRESUMEN
Resistance to third-generation cephalosporins in Gram-negative bacteria is emerging in Asia. We report the prevalence and distribution of extended-spectrum beta-lactamase (ESBL), AmpC beta-lactamase and carbapenemase-coding genes in cefotaxime-resistant Enterobacteriaceae isolates from bloodstream infections (BSI) in Cambodia. All Enterobacteriaceae isolated from BSI in adult patients at Sihanouk Hospital Centre of HOPE, Phnom Penh, Cambodia (2007-2010) were assessed. Antimicrobial susceptibility testing was carried out by disc diffusion and MicroScan according to Clinical and Laboratory Standards Institute (CLSI) guidelines. Screening for ESBL, plasmidic AmpC and carbapenemase-coding genes was performed by multiplex polymerase chain reaction (PCR) sequencing assays. Identification of the ST131 clone was performed in all CTX-M-positive Escherichia coli, using PCR targeting the papB gene. Out of 183 Enterobacteriaceae, 91 (49.7 %) isolates (84 BSI episodes) were cefotaxime-resistant: E. coli (n = 68), Klebsiella pneumoniae (n = 17) and Enterobacter spp. (n = 6). Most episodes were community-acquired (66/84; 78.3 %). ESBLs were present in 89/91 (97.8 %) cefotaxime-resistant isolates: 86 (96.6 %) were CTX-M, mainly CTX-M-15 (n = 41) and CTX-M-14 (n = 21). CTX-M of group 1 were frequently associated with TEM and/or OXA-1/30 coding genes and with phenotypic combined resistance to ciprofloxacin, sulphamethoxazole-trimethoprim and gentamicin (39/50, 78.0 %). Plasmidic AmpC (CMY-2 and DHA-1 types) were found alone (n = 2) or in combination with ESBL (n = 4). Eighteen E. coli isolates were identified as B2-ST131-O25B: 11 (61.1 %) carried CTX-M-14. No carbapenemase-coding genes were detected. ESBL among Enterobacteriaceae from BSI in Cambodia is common, mainly associated with CTX-M-15 and CTX-M-14. These findings warrant urgent action for the containment of antibiotic resistance in Cambodia.
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Antibacterianos/farmacología , Bacteriemia/epidemiología , Cefalosporinas/farmacología , Infecciones por Enterobacteriaceae/epidemiología , Enterobacteriaceae/enzimología , Resistencia betalactámica , beta-Lactamasas/genética , Adolescente , Adulto , Anciano , Bacteriemia/microbiología , Cambodia/epidemiología , Cefotaxima/farmacología , Enterobacteriaceae/genética , Enterobacteriaceae/aislamiento & purificación , Infecciones por Enterobacteriaceae/microbiología , Escherichia coli , Femenino , Humanos , Klebsiella pneumoniae , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa Multiplex , Prevalencia , Estudios Prospectivos , Análisis de Secuencia de ADN , Adulto JovenRESUMEN
We report an increased number of Salmonella enterica Paratyphi A infections in adults in Cambodia. Between January 2011 and August 2013, 71 S. Paratyphi A isolates were recovered from blood cultures, representing a 44-fold increase compared to July 2007 to December 2010, while monthly numbers of cultures did not change. Infections with S. Typhi increased two-fold in the same period. Most cases came from the capital Phnom Penh. These findings warrant epidemiological investigation to support public health measures.
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Fiebre Paratifoidea/diagnóstico , Fiebre Paratifoidea/epidemiología , Salmonella paratyphi A/aislamiento & purificación , Adolescente , Adulto , Antibacterianos/farmacología , Cambodia/epidemiología , Niño , Farmacorresistencia Bacteriana Múltiple , Femenino , Humanos , Incidencia , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Fiebre Paratifoidea/tratamiento farmacológico , Fiebre Paratifoidea/microbiología , Vigilancia de la Población , Factores de Riesgo , Salmonella paratyphi A/efectos de los fármacos , Adulto JovenRESUMEN
BACKGROUND: Ghrelin is the only known peripherally active orexigenic hormone produced by the stomach that activates vagal afferents to stimulate food intake and to accelerate gastric emptying. Vagal sensory neurons within the nodose ganglia are surrounded by glial cells, which are able to receive and transmit chemical signals. We aimed to investigate whether ghrelin activates or influences the interaction between both types of cells. The effect of ghrelin was compared with that of leptin and cholecystokinin (CCK). METHODS: Cultures of rat nodose ganglia were characterized by immunohistochemistry and the functional effects of peptides, neurotransmitters, and pharmacological blockers were measured by Ca(2+) imaging using Fluo-4-AM as an indicator. KEY RESULTS: Neurons responded to KCl and were immunoreactive for PGP-9.5 whereas glial cells responded to lysophosphatidic acid and had the typical SOX-10-positive nuclear staining. Neurons were only responsive to CCK (31 ± 5%) whereas glial cells responded equally to the applied stimuli: ghrelin (27 ± 2%), leptin (21 ± 2%), and CCK (30 ± 2%). In contrast, neurons stained more intensively for the ghrelin receptor than glial cells. ATP induced [Ca(2+) ]i rises in 90% of the neurons whereas ACh and the NO donor, SIN-1, mainly induced [Ca(2+) ]i changes in glial cells (41 and 51%, respectively). The percentage of ghrelin-responsive glial cells was not affected by pretreatment with suramin, atropine, hexamethonium or 1400 W, but was reduced by l-NAME and by tetrodotoxin. Neurons were shown to be immunoreactive for neuronal NO-synthase (nNOS). CONCLUSIONS & INFERENCES: Our data show that ghrelin induces Ca(2+) signaling in glial cells of the nodose ganglion via the release of NO originating from the neurons.
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Señalización del Calcio/fisiología , Ghrelina/metabolismo , Neuroglía/metabolismo , Neuronas/metabolismo , Comunicación Paracrina/fisiología , Animales , Señalización del Calcio/efectos de los fármacos , Células Cultivadas , Técnica del Anticuerpo Fluorescente , Ghrelina/farmacología , Inmunohistoquímica , Neuroglía/efectos de los fármacos , Neuronas/efectos de los fármacos , Ganglio Nudoso , Comunicación Paracrina/efectos de los fármacos , Ratas , Ratas WistarRESUMEN
The First National Workshop on Antibiotic Resistance in Cambodia was organised by the Cambodian Ministry of Health with support from several national and international partner institutions. It brought together policy-makers, clinicians, pharmacists, laboratory technicians and other professionals dealing with the problems of bacterial infection and antibiotic resistance across the country. Antibiotic resistance data from starting up and experienced laboratories were presented, showing high rates of resistance in key pathogens to most antibiotics currently available in Cambodia, e.g. 70-90% multidrug resistance and 70-80% decreased ciprofloxacin susceptibility in Salmonella enterica serovar Typhi, 20-40% meticillin resistance rates in Staphylococcus aureus and 30-50% extended-spectrum ß-lactamase production in Escherichia coli. A five-point plan was discussed, which included initiatives from government and non-governmental partners, focusing on rational prescribing, clinical practice guidelines, improved laboratory services, infection prevention and enhanced education at all levels. Implementation, however challenging, is a priority given the high levels of resistance seen in key pathogens and the overall health needs in the country.
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The Burkholderia cepacia complex is a group of Gram-negative bacteria known as respiratory pathogens in cystic fibrosis patients, but also increasingly reported as a cause of healthcare associated infections. We describe an outbreak of B. cepacia bloodstream infections in a referral hospital in Phnom Penh, Cambodia. Over a 1.5-month period, blood cultures from eight adult patients grew B. cepacia. Bloodstream infection occurred after a median of 2.5 days of hospitalisation. Three patients died: 7, 10 and 17 days after blood cultures were sampled. As part of the outbreak investigation, patient files were reviewed and environmental sampling was performed. All patients had peripheral venous catheters that were flushed with Ringer lactate drawn from a 1 L bag, used as multiple-dose vial at the ward. Cultures of unopened Ringer lactate and disinfectants remained sterile but an in-use bag of Ringer lactate solution and the dispensing pin grew B. cepacia. The isolates from patients and flushing solution were identified as B. cepacia by recA gene sequence analysis, and random amplified polymorphic DNA typing confirmed clonal relatedness. The onset of the outbreak had coincided with the introduction of a dispensing pin with a screw fit that did not allow proper disinfection. Re-enforcement of aseptic procedures with sterile syringe and needle has ended the outbreak. Growth of B. cepacia should alert the possibility of healthcare associated infection also in tropical resource-limited settings. The use of multiple-dose vials should be avoided and newly introduced procedures should be assessed for infection control risks.
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Bacteriemia/epidemiología , Infecciones por Burkholderia/epidemiología , Burkholderia cepacia/aislamiento & purificación , Infecciones Relacionadas con Catéteres/epidemiología , Infección Hospitalaria/epidemiología , Contaminación de Medicamentos , Soluciones Isotónicas , Adulto , Anciano , Bacteriemia/microbiología , Técnicas de Tipificación Bacteriana , Infecciones por Burkholderia/microbiología , Infecciones por Burkholderia/prevención & control , Burkholderia cepacia/genética , Cambodia/epidemiología , Infecciones Relacionadas con Catéteres/microbiología , Infección Hospitalaria/prevención & control , Brotes de Enfermedades , Femenino , Humanos , Control de Infecciones/métodos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Técnica del ADN Polimorfo Amplificado Aleatorio , Lactato de Ringer , Dispositivos de Acceso VascularRESUMEN
Ghrelin is an important orexigenic peptide that not only exerts gastroprokinetic but also immunoregulatory effects. This study aimed to assess the role of endogenous and exogenous ghrelin in the pathogenesis of colitis and in the disturbances of gastric emptying and colonic contractility during this process. Dextran sodium sulphate colitis was induced for 5 days in (i) ghrelin(+/+) and ghrelin(-/-) mice and clinical and histological parameters were monitored at days 5, 10 and 26 and (ii) in Naval Medical Research Institute non-inbred Swiss (NMRI) mice treated with ghrelin (100 nmol kg(-1)) twice daily for 5 or 10 days. Neural contractility changes were measured in colonic smooth muscle strips, whereas gastric emptying was measured with the (14)C octanoic acid breath test. Inflammation increased ghrelin plasma levels. Body weight loss, histological damage, myeloperoxidase activity and IL-1beta levels were attenuated in ghrelin(-/-) mice. Whereas absence of ghrelin did not affect changes in colonic contractility, gastric emptying in the acute phase was accelerated in ghrelin(+/+) but not in ghrelin(-/-) mice. In agreement with the studies in ghrelin knockout mice, 10 days treatment of NMRI mice with exogenous ghrelin enhanced the clinical disease activity and promoted infiltration of neutrophils and colonic IL-1beta levels. Unexpectedly, ghrelin treatment decreased excitatory and inhibitory neural responses in the colon of healthy but not of inflamed NMRI mice. Endogenous ghrelin enhances the course of the inflammatory process and is involved in the disturbances of gastric emptying associated with colitis. Treatment with exogenous ghrelin aggravates colitis, thereby limiting the potential therapeutic properties of ghrelin during intestinal inflammation.
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Colitis/fisiopatología , Ghrelina/metabolismo , Animales , Colitis/inducido químicamente , Colitis/patología , Sulfato de Dextran/toxicidad , Vaciamiento Gástrico/efectos de los fármacos , Vaciamiento Gástrico/fisiología , Ghrelina/farmacología , Masculino , Ratones , Ratones Noqueados , Contracción Muscular/efectos de los fármacos , Contracción Muscular/fisiología , Músculo Liso/efectos de los fármacos , Músculo Liso/fisiologíaRESUMEN
PURPOSE: To explore the hypothesis that stent placement decreases dilator function of various arteries outside the stented segment and that angiotensin- (1-7) improves this function, and to assess the contribution of dilator signal compounds. A further objective was to test the hypothesis that on-stent delivery of Ang-(1-7) reduces neointima formation and improves endothelial function. METHODS: Abdominal aortic stenting or sham operation was performed in the rat four weeks after stenting and treatment with intravenous saline or Ang-(1-7) infusion (24 mug/kg/h); vasomotor function in isolated thoracic aorta and brachial and iliac artery was measured in organ baths. Furthermore, Ang-(1-7)-eluting stents were designed and placed in rat abdominal aorta. Neointima formation and aortic function were tested after four weeks. RESULTS: Relaxation of the thoracic aorta to metacholine was decreased after stenting compared with shams due to a decrease in nitric oxide-mediated response (67% reduction in maximal NO-dependent response). Ang-(1-7) restored the response mainly through increased prostaglandin- and possibly also endothelial-derived hyperpolarising factor-mediated relaxation. Relaxation in the brachial artery decreased after stenting (maximal response dropped by 50%), whilst contractions to phenylephrine increased. Ang-(1-7) normalised vasomotor function. Iliac artery function remained unaltered after stenting but Ang-(1-7) increased maximal relaxations by 65%. Delivery of Ang-(1-7) by means of a drug-eluting stent improved endothelial function. CONCLUSION: Stenting differentially affects dilator and contractile function in various arterial beds. Ang-(1-7) both improves dilator function and normalises contractile function. Delivery of protective peptides such as Ang-(1-7) from the stent is a new therapy option that merits further development and exploration. (Neth Heart J 2008;16:293-8.).
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OBJECTIVES: To compare Angio-Seal (AS) and StarClose (SC) and manual compression (MC) on efficacy of hemostasis, complication rate, safety of early mobilization, and patient comfort. BACKGROUND: Closure of the femoral artery after cardiac catheterization can be obtained through different methods. Today, physicians can choose from a number of different devices to achieve arterial closure. METHODS: In a prospective trial 450 patients were randomized to AS, SC, or MC. Patients were mobilized 1 to 2 hr after device placement, and 6 hr after MC. Data were collected during hospital admission and by telephone at one month after hospital discharge. RESULTS: Devices were used in 138/150 allocated to AS and 124/150 allocated to SC patients (92% vs. 83%, P = 0.015) Patients with MC experienced more pain during sheath removal than patients receiving a device, and rated their period of bed rest as less comfortable. Oozing and need for pressure bandage at the puncture site were observed in 37 AS patients and 57 SC patients (25% vs. 38%, P = 0.002). Hematoma occurred in 15 AS patients, in 17 SC patients, and in 14 MC patients (11 vs. 14 vs. 9%, ns). CONCLUSION: There is no difference in safety between the three methods of arterial closure. SC was more often not used or successfully deployed. SC patients more often had continuing oozing. On patient comfort, closure devices performed better than MC. Early ambulation in patients with a closure device is safe. AS is the preferred method of arterial closure after cardiac catheterization.
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Cateterismo Cardíaco/efectos adversos , Arteria Femoral , Hemorragia/prevención & control , Técnicas Hemostáticas , Presión , Punciones/efectos adversos , Anciano , Ambulación Precoz , Diseño de Equipo , Femenino , Hematoma/etiología , Hemorragia/etiología , Técnicas Hemostáticas/efectos adversos , Técnicas Hemostáticas/instrumentación , Humanos , Masculino , Persona de Mediana Edad , Dolor/etiología , Dimensión del Dolor , Satisfacción del Paciente , Estudios Prospectivos , Proyectos de Investigación , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND AND PURPOSE: The finding that obestatin, a peptide encoded by the ghrelin gene, opposes ghrelin's stimulatory effect on food intake and gastric emptying has been questioned. The effect of obestatin has been mostly investigated in fasted rodents, a condition associated with high blood levels of ghrelin which may mask the effect of obestatin. We therefore investigated the effect of obestatin on food intake, gastric emptying and gastric contractility in ghrelin knockout mice. EXPERIMENTAL APPROACH: The effect of obestatin on 6-h cumulative food intake was studied in fasted wildtype (ghrelin+/+) and ghrelin knockout (ghrelin-/-) mice. In both genotypes, the effect of obestatin and/or ghrelin was studied in vivo on gastric emptying measured with the (14)C-octanoic acid breath test and in vitro on neural responses elicited by electrical field stimulation (EFS) of fundic smooth muscle strips. KEY RESULTS: Administration of obestatin did not influence fasting-induced hyperphagia or gastric emptying in both genotypes. Injection of ghrelin accelerated gastric emptying in ghrelin+/+ and ghrelin-/- mice but the effect was not reversed by co-injection with obestatin. In fundic strips from ghrelin+/+ and ghrelin-/- mice, ghrelin increased EFS-induced contractions, but obestatin was without effect. However, co-administration with obestatin tended to reduce the excitatory effect of ghrelin in both genotypes. CONCLUSIONS AND IMPLICATIONS: In ghrelin-/- mice, obestatin failed to affect food intake and gastric motility. These results suggest that endogenous ghrelin does not mask the effect of obestatin and confirm that obestatin administered peripherally is not a major regulator of satiety signalling or gut motility.
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Ingestión de Alimentos/efectos de los fármacos , Vaciamiento Gástrico/efectos de los fármacos , Ghrelina/farmacología , Animales , Pruebas Respiratorias , Caprilatos , Estudios Cruzados , Estimulación Eléctrica , Fundus Gástrico/efectos de los fármacos , Fundus Gástrico/metabolismo , Genotipo , Ghrelina/administración & dosificación , Ghrelina/genética , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Contracción Muscular/efectos de los fármacos , Contracción Muscular/fisiología , Respuesta de Saciedad/efectos de los fármacos , Respuesta de Saciedad/fisiología , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiologíaRESUMEN
Obestatin has recently been discovered in the rat stomach. It is encoded by the ghrelin gene and has been claimed to be a functional opponent of ghrelin and to be the natural ligand of the GPR39 receptor. The latter could not be confirmed by Holst et al. (Endocrinology, 2006). Yet, in GPR39 knockout mice, gastric emptying is accelerated. We verified the effects of obestatin on gastric emptying and intestinal contractility in rodents. Gastric emptying was measured with the (14)C octanoic breath test in mice. In vitro, the effect of obestatin was studied on electrically stimulated and non-stimulated strips from the fundus and small intestine of mice and rats. Obestatin (60, 125, 250 nmol kg(-1)) did not affect gastric emptying parameters (T(half) and T(lag)) and did not inhibit the prokinetic effects of ghrelin. Mouse and rat intestinal and fundic smooth muscle strips did not respond to obestatin either in the absence or in the presence of electrical field stimulation. Obestatin (125 nmol kg(-1)) did not inhibit fasting-induced hyperphagia. Our results suggest that peripheral obestatin is not a satiety signal that plays a role in the regulation of gastric emptying and do not support the concept that obestatin is a physiological opponent of ghrelin.
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Vaciamiento Gástrico/fisiología , Motilidad Gastrointestinal/fisiología , Músculo Liso/fisiología , Hormonas Peptídicas/metabolismo , Animales , Masculino , Ratones , Ratones Endogámicos C57BL , Contracción Muscular/fisiología , Ratas , Ratas WistarRESUMEN
Ghrelin is an orexigenic peptide involved in the regulation of energy homeostasis. To investigate the role of ghrelin in the hyperphagia associated with uncontrolled streptozotocin-induced diabetes, food intake was followed in diabetic ghrelin knockout (ghrelin(-/-)) and control wild-type (ghrelin(+/+)) mice and diabetic Naval Medical Research Institute noninbred Swiss mice treated with either saline or the ghrelin receptor antagonist, D-Lys3-GH-releasing peptide-6 (D-Lys3-GHRP-6) for 5 d. In diabetic ghrelin(-/-) mice, hyperphagia was attenuated, and the maximal increase in food intake was 50% lower in mutant than in wild-type mice. The increased food intake observed during the light period (1000-1200 h) in ghrelin(+/+) mice was abolished in mutant mice. Diabetic ghrelin(-/-) mice lost 12.4% more body weight than ghrelin(+/+) mice. In diabetic ghrelin(+/+) mice, but not in ghrelin(-/-) mice, the number of neuropeptide Y (NPY)-immunoreactive neurons was significantly increased. Diabetic Naval Medical Research Institute noninbred Swiss mice were hyperphagic and had increased plasma ghrelin levels. Treatment with D-Lys3-GHRP-6 reduced daily food intake by 23% and reversed the increased food intake observed during the light period. The change in the number of NPY- (2.4-fold increase) and alpha-MSH (1.7-fold decrease)-immunoreactive hypothalamic neurons induced by diabetes was normalized by D-Lys3-GHRP-6 treatment. Our results suggest that enhanced NPY and reduced alpha-MSH expression are secondary to the release of ghrelin, which should be considered the underlying trigger of hyperphagia associated with uncontrolled diabetes.
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Diabetes Mellitus Experimental/complicaciones , Hiperfagia/etiología , Hormonas Peptídicas/fisiología , Animales , Núcleo Arqueado del Hipotálamo/fisiología , Glucemia/análisis , Peso Corporal , Ghrelina , Glucagón/sangre , Masculino , Ratones , Ratones Endogámicos C57BL , Neuropéptido Y/análisis , Neuropéptido Y/fisiología , Oligopéptidos/farmacología , Hormonas Peptídicas/sangre , Estreptozocina , alfa-MSH/análisisRESUMEN
To elucidate the role of endogenous ghrelin in the regulation of energy homeostasis and gastric emptying, ghrelin knockout mice (ghrelin(-/-)) were generated. Body weight, food intake, respiratory quotient, and heat production (indirect calorimetry), and gastric emptying ((14)C breath test) were compared between ghrelin(+/+) and ghrelin(-/-) mice. In both strains, the effect of exogenous ghrelin on gastric emptying and food intake was determined. Ghrelin(-/-) mice showed some subtle phenotypic changes. Body weight gain and 24-h food intake were not affected, but interruption of the normal light/dark cycle triggered additional food intake in old ghrelin(+/+) but not in ghrelin(-/-) mice. Exogenous ghrelin increased food intake in both genotypes with a bell-shaped dose-response curve that was shifted to the left in ghrelin(-/-) mice. During the dark period, young ghrelin(-/-) mice had a lower respiratory quotient, whereas their heat production was higher than that of the wild-type littermates, inferring a leaner body composition of the ghrelin(-/-) mice. Absence of ghrelin did not affect gastric emptying, and the bell-shaped dose-response curves of the acceleration of gastric emptying by exogenous ghrelin were not shifted between both strains. In conclusion, ghrelin is not an essential regulator of food intake and gastric emptying, but its loss may be compensated by other redundant inputs. In old mice, meal initiation triggered by the light/dark cue may be related to ghrelin. In young animals, ghrelin seems to be involved in the selection of energy stores and in the partitioning of metabolizable energy between storage and dissipation as heat.
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Metabolismo Energético/genética , Vaciamiento Gástrico/genética , Homeostasis/genética , Hormonas Peptídicas/genética , Hormonas Peptídicas/fisiología , Envejecimiento/fisiología , Animales , Regulación de la Temperatura Corporal/genética , Regulación de la Temperatura Corporal/fisiología , Peso Corporal/genética , Peso Corporal/fisiología , Pruebas Respiratorias , Rastreo Diferencial de Calorimetría , Caprilatos , Ingestión de Alimentos/efectos de los fármacos , Ingestión de Alimentos/genética , Ingestión de Alimentos/fisiología , Metabolismo Energético/fisiología , Vaciamiento Gástrico/fisiología , Motilidad Gastrointestinal/genética , Motilidad Gastrointestinal/fisiología , Ghrelina , Homeostasis/fisiología , Inmunohistoquímica , Ratones , Ratones Noqueados , Consumo de Oxígeno/genética , Consumo de Oxígeno/fisiología , Hormonas Peptídicas/farmacología , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Receptores de GhrelinaRESUMEN
BACKGROUND AND AIMS: The gastroprokinetic activities of ghrelin, the natural ligand of the growth hormone secretagogue receptor (GHS-R), prompted us to compare the effect of ghrelin with that of synthetic peptide (growth hormone releasing peptide 6 (GHRP-6)) and non-peptide (capromorelin) GHS-R agonists both in vivo and in vitro. METHODS: In vivo, the dose dependent effects (1-150 nmol/kg) of ghrelin, GHRP-6, and capromorelin on gastric emptying were measured by the 14C octanoic breath test which was adapted for use in mice. The effect of atropine, N(G)-nitro-L-arginine methyl ester hydrochloride (L-NAME), or D-Lys3-GHRP-6 (GHS-R antagonist) on the gastroprokinetic effect of capromorelin was also investigated. In vitro, the effect of the GHS-R agonists (1 microM) on electrical field stimulation (EFS) induced responses was studied in fundic strips in the absence and presence of L-NAME. RESULTS: Ghrelin, GHRP-6, and capromorelin accelerated gastric emptying in an equipotent manner, with bell-shaped dose-response relationships. In the presence of atropine or l-NAME, which delayed gastric emptying, capromorelin failed to accelerate gastric emptying. D-Lys3-GHRP-6 also delayed gastric emptying but did not effectively block the action of the GHS-R agonists, but this may be related to interactions with other receptors. EFS of fundic strips caused frequency dependent relaxations that were not modified by the GHS-R agonists. L-NAME turned EFS induced relaxations into cholinergic contractions that were enhanced by ghrelin, GHRP-6, and capromorelin. CONCLUSION: The 14C octanoic breath test is a valuable technique to evaluate drug induced effects on gastric emptying in mice. Peptide and non-peptide GHS-R agonists accelerate gastric emptying of solids in an equipotent manner through activation of GHS receptors, possibly located on local cholinergic enteric nerves.
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Oligopéptidos/farmacología , Hormonas Peptídicas/farmacología , Piperidinas/farmacología , Pirazoles/farmacología , Estómago/efectos de los fármacos , Animales , Atropina/farmacología , Betanecol/farmacología , Pruebas Respiratorias , Colinérgicos/farmacología , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/farmacología , Vaciamiento Gástrico/efectos de los fármacos , Ghrelina , Hormona Liberadora de Hormona del Crecimiento/metabolismo , Masculino , Ratones , Ratones Endogámicos , Contracción Muscular/efectos de los fármacos , NG-Nitroarginina Metil Éster/farmacología , Hormonas Peptídicas/agonistasRESUMEN
BACKGROUND: Restenosis after balloon angioplasty is in part due to remodelling, whereas restenosis after stenting is entirely due to neointima formation. Nonmuscle myosin heavy chain-B (NMMHC-B) is expressed by vascular smooth muscle cells and because of its overexpression in restenotic lesions after balloon angioplasty, NMMHC-B is proposed as a potential therapeutic target. Because the mechanisms underlying restenosis after balloon angioplasty or after stenting are different we hypothesised that the expression of NMMHC-B would differ in balloon-dilated versus stented arteries. METHODS: To study the localisation and time course of expression of NMMHC-B, we performed stenting or balloon dilation in peripheral arteries of 16 atherosclerotic Yucatan micropigs and used serial intravascular ultrasound (IVUS) and angiography to measure geometric dimensions following balloon angioplasty or stenting. In situ hybridisation techniques were used to detect NMMHC-B mRNA. 5'-bromo-2'-deoxyuridine (BrdU) was administered to detect proliferating cells. By counting the number of silver grains in the different layers of the artery, we could compare the amount of expression at the different time points between the groups. RESULTS: In intima and media, NMMHC-B expression increased after balloon dilation and stenting and peaked at 7 days. In stented arteries, the expression of NMMHC-B remained high for up to 42 days after injury, whereas in balloon-dilated arteries it had normalised. In the adventitia of balloon-dilated arteries, but not of stented arteries, NMMHC-B expression peaked at 7 days. NMMHC-B expression was not limited to proliferating cells. CONCLUSION: NMMHC-B is expressed near sites of active repair after arterial injury, but not limited to proliferating cells. The different pattern of NMMHC-B expression after balloon dilation compared with stenting may be related to arterial remodelling, because stented arteries that do not remodel lack this conspicuous adventitial expression at 7 days.
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In 1997 the Flemish Environmental Agency (FEA) started a monitoring program "Pesticides in Rain in Flanders, Belgium". The original purpose of the monitoring program was to examine the possible occurrence of dichlorvos in rainwater and subsequent deposition. However, it was thought necessary from the beginning to monitor a wide range of pesticides. During the first year some 62 pesticides and metabolites and 9 polychlorinated biphenyls, were monitored at 4 locations. Nowadays the monitoring program has grown up to more than 100 pesticides and metabolites and 11 polychlorinated biphenyls examined at 8 different locations. Rainwater is collected continuously and samples are examined for pesticides and PCB's on a weekly basis. In agreement with other European studies pesticides are found in rainwater samples during times of application. Pesticides which are most frequently detected are [small alpha]-, [small beta]-endosulfan and endosulfan sulfate, [gamma]-HCH (lindane), dichlorvos, atrazine, diuron, DNOC, glyphosate and AMPA and isoproturon. Furthermore it was seen that most pesticides showed a deposition pattern related to local spraying operations.