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Background and Aims: Dietary gangliosides are present in human milk and consumed in low amounts from organ meats. Clinical and animal studies indicate that dietary gangliosides attenuate signaling processes that are a hallmark of inflammatory bowel disease (IBD). Gangliosides decrease pro-inflammatory markers, improve intestinal permeability, and reduce symptoms characteristic in patients with IBD. The objective of this study was to examine mechanisms by which dietary gangliosides exert beneficial effects on intestinal health. Methods: Studies were conducted in vitro using CaCo-2 intestinal epithelial cells. Gangliosides were extracted from milk powder and incubated with differentiated CaCo-2 cells after exposure to pro-inflammatory stimuli. Gut barrier integrity was assessed by electron microscopy, epithelial barrier function was examined by measuring transepithelial electric resistance, and content of HBD-2, IL-23, NF-κB, and sPLA2 was assessed by ELISA. Results: Ganglioside attenuated the decrease in integrity of tight junctions induced by pro-inflammatory stimuli and improved epithelial barrier function (P < 0.05). Ganglioside decreased the basolateral secretion of sPLA2 (P ≤ 0.05), lowered HBD-2 and IL-23 levels (P ≤ 0.05), and inhibited NF-κB activation (P ≤ 0.05). Conclusions: In summary, the present study indicates that ganglioside GD3 improves intestinal integrity by altering sPLA2 trafficking, and the production of pro-inflammatory mediators is mitigated by decreasing assembly of the NF-κB complex. Dietary gangliosides may have promising potential beneficial effects in IBD as decreased inflammatory signaling, improved intestinal integrity, and maintenance of epithelial barrier function have been demonstrated in vitro.
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BACKGROUND: Preclinical studies reveal associations between intestinal ganglioside content and inflammatory bowel disease (IBD). Since a low level of ganglioside is associated with higher production of proinflammatory signals in the intestine, it is important to determine safety and bioavailability of dietary ganglioside for application as a potential therapeutic agent. MATERIALS AND METHODS: Healthy volunteers (HVs; n = 18) completed an 8-week supplementation study to demonstrate safety and bioavailabity of ganglioside consumption. HVs were randomized to consume a milk fat fraction containing 43 mg/d ganglioside or placebo, and patients with IBD (n = 5) consumed ganglioside supplement in a small pilot study. Plasma gangliosides were characterized using reverse-phase liquid chromatography-QQQ mass spectrometry. Intestinal permeability was assessed by oral lactulose/mannitol, and quality of life was assessed by quality of life in the IBD questionnaire. RESULTS: There were no adverse events associated with dietary ganglioside intake. Ganglioside consumption increased ( P < .05) plasma content of total GD3 by 35% over 8 weeks. HVs consuming ganglioside exhibited a 19% decrease in intestinal permeability ( P = .04). Consumption of ganglioside was associated with a 39% increase ( P < .01) in emotional health and a 36% improvement ( P < .02) in systemic symptoms in patients with IBD. CONCLUSION: Impaired intestinal integrity characteristic of IBD results in increased permeability to bacterial antigens and decreased nutrient absorption. Intestinal integrity may be improved by dietary treatment with specific species of ganglioside. Ganglioside is a safe, bioavailable dietary compound that can be consumed to potentially improve quality of life in patients with IBD and treat other disorders involving altered ganglioside metabolism. This study was registered at clinicaltrials.gov as NCT02139709.
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Gangliósidos/administración & dosificación , Gangliósidos/sangre , Adulto , Biomarcadores/sangre , Citocinas/sangre , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Glucolípidos/administración & dosificación , Glucolípidos/sangre , Glicoproteínas/administración & dosificación , Glicoproteínas/sangre , Humanos , Enfermedades Inflamatorias del Intestino/sangre , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Mucosa Intestinal/metabolismo , Intestinos/efectos de los fármacos , Gotas Lipídicas , Masculino , Permeabilidad , Proyectos Piloto , Calidad de Vida , Encuestas y CuestionariosRESUMEN
AIM: To investigate whether accelerated catabolism of ganglioside and decreased ganglioside content contribute to the etiology of pro-inflammatory intestinal disease. METHODS: Intestinal mucosa from terminal ileum or colon was obtained from patients with ulcerative colitis or inflammatory Crohn's disease (n = 11) undergoing bowel resection and compared to control samples of normal intestine from patients with benign colon polyps (n = 6) and colorectal cancer (n = 12) in this observational case-control study. Gangliosides and phospholipids of intestinal mucosa were characterized by class and ceramide or fatty acid composition using liquid chromatography triple-quad mass spectrometry. Content and composition of ganglioside classes GM1, GM3, GD3, GD1a, GT1 and GT3 were compared among subject groups. Content and composition of phospholipid classes phosphatidylcholine (PC) and phosphatidylethanolamine were compared among subject groups. Unsaturation index of individual ganglioside and phospholipid classes was computed and compared among subject groups. Ganglioside catabolism enzymes beta-hexosaminidase A (HEXA) and sialidase-3 (NEU3) were measured in intestinal mucosa using western blot and compared among subject groups. RESULTS: Relative GM3 ganglioside content was 2-fold higher (P < 0.05) in intestine from patients with inflammatory bowel disease (IBD) compared to control intestine. The quantity of GM3 and ratio of GM3/GD3 was also higher in IBD intestine than control tissue (P < 0.05). Control intestine exhibited 3-fold higher (P < 0.01) relative GD1a ganglioside content than IBD intestine. GD3 and GD1a species of ganglioside containing three unsaturated bonds were present in control intestine, but were not detected in IBD intestine. The relative content of PC containing more than two unsaturated bonds was 30% lower in IBD intestine than control intestine (P < 0.05). The relative content of HEXA in IBD intestine was increased 1.7-fold (P < 0.05) and NEU3 was increased 8.3-fold (P < 0.01) compared to normal intestine. Intestinal mucosa in IBD is characterized by increased GM3 content, decreased GD1a, and a reduction in polyunsaturated fatty acid constituents in GD3, GD1a and PC. CONCLUSION: This study suggests a new paradigm by proposing that IBD occurs as a consequence of increased metabolism of specific gangliosides.
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Colitis Ulcerosa/metabolismo , Colon/química , Enfermedad de Crohn/metabolismo , Ácidos Grasos Insaturados/análisis , Gangliósidos/análisis , Íleon/química , Mucosa Intestinal/química , Estudios de Casos y Controles , Colitis Ulcerosa/cirugía , Colon/cirugía , Enfermedad de Crohn/cirugía , Gangliósido G(M3)/análisis , Humanos , Íleon/cirugía , Mucosa Intestinal/cirugía , Neuraminidasa/análisis , Fosfatidilcolinas/análisis , Fosfatidiletanolaminas/análisis , Cadena alfa de beta-Hexosaminidasa/análisisRESUMEN
BACKGROUND: Synthesis of lipid species, including fatty acids (FA) and cholesterol, can contribute to pathological disease. The purpose of this study was to investigate FA and cholesterol synthesis in individuals with type 1 diabetes, a group at elevated risk for vascular disease, using stable isotope analysis. METHODS: Individuals with type 1 diabetes (n = 9) and age-, sex-, and BMI-matched non-diabetic subjects (n = 9) were recruited. On testing day, meals were provided to standardize food intake and elicit typical feeding responses. Blood samples were analyzed at fasting (0 and 24 h) and postprandial (2, 4, 6, and 8 hours after breakfast) time points. FA was isolated from VLDL to estimate hepatic FA synthesis, whereas free cholesterol (FC) and cholesteryl ester (CE) was isolated from plasma and VLDL to estimate whole-body and hepatic cholesterol synthesis, respectively. Lipid synthesis was measured using deuterium incorporation and isotope ratio mass spectrometry. RESULTS: Fasting total hepatic lipogenesis (3.91 ± 0.90% vs. 5.30 ± 1.22%; P = 0.41) was not significantly different between diabetic and control groups, respectively, nor was synthesis of myristic (28.60 ± 4.90% vs. 26.66 ± 4.57%; P = 0.76), palmitic (12.52 ± 2.75% vs. 13.71 ± 2.64%; P = 0.65), palmitoleic (3.86 ± 0.91% vs. 4.80 ± 1.22%; P = 0.65), stearic (5.55 ± 1.04% vs. 6.96 ± 0.97%; P = 0.29), and oleic acid (1.45 ± 0.28% vs. 2.10 ± 0.51%; P = 0.21). Postprandial lipogenesis was also not different between groups (P = 0.38). Similarly, fasting synthesis of whole-body FC (8.2 ± 1.3% vs. 7.3 ± 0.8%/day; P = 0.88) and CE (1.9 ± 0.4% vs. 2.0 ± 0.3%/day; P = 0.96) and hepatic FC (8.2 ± 2.0% vs. 8.1 ± 0.8%/day; P = 0.72) was not significantly different between diabetic and control subjects. CONCLUSIONS: Despite long-standing disease, lipogenesis and cholesterol synthesis was not different in individuals with type 1 diabetes compared to healthy non-diabetic humans.
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Colesterol/biosíntesis , Diabetes Mellitus Tipo 1/metabolismo , Lipogénesis , Estudios de Casos y Controles , Ésteres del Colesterol/metabolismo , Diabetes Mellitus Tipo 1/sangre , Ayuno/sangre , Ácidos Grasos/biosíntesis , Femenino , Humanos , Lipoproteínas VLDL/sangre , Hígado/metabolismo , Masculino , Persona de Mediana Edad , Periodo Posprandial , Triglicéridos/sangreRESUMEN
UNLABELLED: Hepatitis C virus (HCV) exerts a profound influence on host lipid metabolism. It has been suggested that the synthesis of both fatty acids (FA) and cholesterol is dysregulated in HCV but this has not been directly quantified in humans. The purpose of this study was to measure lipogenesis and cholesterol synthesis using stable isotopes in patients with HCV (n = 5) and healthy control (n = 9) subjects recruited from the University of Alberta hospital. Blood samples were taken at fasting (0 and 24 hours) and after meals over the day to mimic typical food consumption and postprandial metabolism. Isolation of free cholesterol (FC), cholesteryl ester (CE), and triglyceride (TG) from plasma and very low-density lipoproteins (VLDL) was used to measure FA and cholesterol synthesis using deuterium uptake and isotope ratio mass spectrometry. FA composition was analyzed by gas chromatography. VLDL-TG levels of polyunsaturated fatty acids (PUFA), including linoleic and linolenic acid, were lower in HCV compared to control (P < 0.05 for both). Fasting hepatic lipogenesis was significantly higher in HCV (2.80 ± 0.55%) compared to control (1.19 ± 0.27%; P = 0.03). Conversely, fasting whole-body synthesis of FC (HCV 1.64 ± 0.28% versus control 8.78 ± 1.59%) and CE (HCV 0.26 ± 0.08% versus control 1.92 ± 0.25%), as well as hepatic FC synthesis (HCV 1.68 ± 0.26% versus control 8.12 ± 0.77%) was lower in HCV (P < 0.001 for all). CONCLUSION: These data provide evidence that lipogenesis is elevated while cholesterol synthesis is impaired in HCV, supporting previous findings from cellular and animal models. Low PUFA levels combined with elevated lipogenesis suggests a role for dietary PUFA supplementation in HCV patients.
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Colesterol/metabolismo , Hepacivirus , Hepatitis C/metabolismo , Lipogénesis/fisiología , Estudios de Casos y Controles , Ésteres del Colesterol/sangre , Ácidos Grasos Insaturados/sangre , Femenino , Humanos , Lipoproteínas VLDL/sangre , Masculino , Persona de Mediana Edad , Triglicéridos/sangreRESUMEN
Celiac disease (CD) is one of the most common diseases, resulting from both environmental (gluten) and genetic factors [human leukocyte antigen (HLA) and non-HLA genes]. The prevalence of CD has been estimated to approximate 0.5%-1% in different parts of the world. However, the population with diabetes, autoimmune disorder or relatives of CD individuals have even higher risk for the development of CD, at least in part, because of shared HLA typing. Gliadin gains access to the basal surface of the epithelium, and interact directly with the immune system, via both trans- and para-cellular routes. From a diagnostic perspective, symptoms may be viewed as either "typical" or "atypical". In both positive serological screening results suggestive of CD, should lead to small bowel biopsy followed by a favourable clinical and serological response to the gluten-free diet (GFD) to confirm the diagnosis. Positive anti-tissue transglutaminase antibody or anti-endomysial antibody during the clinical course helps to confirm the diagnosis of CD because of their over 99% specificities when small bowel villous atrophy is present on biopsy. Currently, the only treatment available for CD individuals is a strict life-long GFD. A greater understanding of the pathogenesis of CD allows alternative future CD treatments to hydrolyse toxic gliadin peptide, prevent toxic gliadin peptide absorption, blockage of selective deamidation of specific glutamine residues by tissue, restore immune tolerance towards gluten, modulation of immune response to dietary gliadin, and restoration of intestinal architecture.
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Enfermedad Celíaca , Animales , Autoinmunidad , Enfermedad Celíaca/diagnóstico , Enfermedad Celíaca/etnología , Enfermedad Celíaca/genética , Enfermedad Celíaca/inmunología , Enfermedad Celíaca/terapia , Dieta Sin Gluten , Interacción Gen-Ambiente , Predisposición Genética a la Enfermedad , Gliadina/inmunología , Humanos , Intestino Delgado/inmunología , Prevalencia , Factores de Riesgo , Resultado del TratamientoRESUMEN
The use of anti-tumor necrosis factor-α therapy for inflammatory bowel disease represents the most important advance in the care of these patients since the publication of the National Co-operative Crohn's disease study thirty years ago. The recommendations of numerous consensus groups worldwide are now supported by a wealth of clinical trials and several meta-analyses. In general, it is suggested that tumor necrosis factor-α blockers (TNFBs) are indicated (1) for persons with moderately-severe Crohn's disease or ulcerative colitis (UC) who have failed two or more causes of glucocorticosteroids and an acceptably long cause (8 wk to 12 wk) of an immune modulator such as azathioprine or methotrexate; (2) non-responsive perianal disease; and (3) severe UC not responding to a 3-d to 5-d course of steroids. Once TNFBs have been introduced and the patient is responsive, therapy given by the IV and SC rate must be continued. It remains open to definitive evidence if concomitant immune modulators are required with TNFB maintenance therapy, and when or if TNFB may be weaned and discontinued. The supportive evidence from a single study on the role of early versus later introduction of TNFB in the course of a patient's illness needs to be confirmed. The risk/benefit profile of TNFB appears to be acceptable as long as the patient is immunized and tested for tuberculosis and viral hepatitis before the initiation of TNFB, and as long as the long-term adverse effects on the development of lymphoma and other tumors do not prone to be problematic. Because the rates of benefits to TNFB are modest from a population perspective and the cost of therapy is very high, the ultimate application of use of TNFBs will likely be established by cost/benefit studies.
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Enfermedad de Crohn/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Animales , Análisis Costo-Beneficio , Enfermedad de Crohn/diagnóstico , Enfermedad de Crohn/economía , Enfermedad de Crohn/inmunología , Costos de los Medicamentos , Quimioterapia Combinada , Humanos , Inmunosupresores/efectos adversos , Inmunosupresores/economía , Selección de Paciente , Guías de Práctica Clínica como Asunto , Inducción de Remisión , Medición de Riesgo , Factores de Riesgo , Insuficiencia del Tratamiento , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
As is the case in all parts of gastroenterology and hepatology, there have been many advances in our knowledge and understanding of small intestinal diseases. Over 1000 publications were reviewed for 2008 and 2009, and the important advances in basic science as well as clinical applications were considered. In Partâ Iâ of this Editorial Review, seven topics are considered: intestinal development; proliferation and repair; intestinal permeability; microbiotica, infectious diarrhea and probiotics; diarrhea; salt and water absorption; necrotizing enterocolitis; and immunology/allergy. These topics were chosen because of their importance to the practicing physician.
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Gastroenterología/métodos , Gastroenterología/tendencias , Enfermedades Intestinales/diagnóstico , Enfermedades Intestinales/terapia , Intestino Delgado/patología , Animales , Proliferación Celular , Enterocolitis Necrotizante/metabolismo , Homeostasis , Humanos , Recién Nacido , Enfermedades Intestinales/patología , Mucosa Intestinal/metabolismo , Neovascularización Patológica , Células de Paneth/citología , Permeabilidad , Fagocitosis , ProbióticosRESUMEN
As is the case in all areas of gastroenterology and hepatology, in 2009 and 2010 there were many advances in our knowledge and understanding of small intestinal diseases. Over 1000 publications were reviewed, and the important advances in basic science as well as clinical applications were considered. In Part II we review six topics: absorption, short bowel syndrome, smooth muscle function and intestinal motility, tumors, diagnostic imaging, and cystic fibrosis.
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Gastroenterología/métodos , Enfermedades Intestinales/diagnóstico , Enfermedades Intestinales/terapia , Absorción , Animales , Transporte Biológico , Colesterol/química , Fibrosis Quística/diagnóstico , Fibrosis Quística/terapia , Gangliósidos/metabolismo , Gastroenterología/tendencias , Motilidad Gastrointestinal , Humanos , Enfermedades Intestinales/patología , Intestino Delgado/fisiología , Intestino Delgado/fisiopatología , Modelos Biológicos , Músculo Liso/patología , Síndrome del Intestino Corto/diagnóstico , Síndrome del Intestino Corto/terapiaRESUMEN
OBJECTIVE: To investigate policosanol absorption by brush border membrane (BBM), metabolism in CaCo-2 enterocytes, and transport of policosanol metabolites across the basolateral membrane (BLM). It was hypothesized that policosanol is partially oxidized into fatty acids and then is incorporated into other lipids. METHODS: Policosanol was emulsified with phosphatidylcholine in the culture medium. The viability of cells was assessed via an MTT (3-[4,5]dimethylthiazol-2-yl-2,5-diphenyltetrazolim) assay. Control cells received only the same amount of "vehicle" (phosphatidylcholine) without policosanol. CaCo-2 cell monolayer and medium were collected; lipid was extracted and analyzed by thin-layer chromatography (TLC) and gas liquid chromatography (GLC). RESULTS: Eighty-six percent of policosanol added to the cell culture medium was absorbed after 48 hours' incubation. The amount of cholesterol ester fatty acid was significantly increased both in the cells and in the basolateral medium, and was reduced in the apical medium. Policosanol increased the quantity of free fatty acids in the basolateral medium and reduced the free fatty acid content of CaCo-2 cells. Further evaluation of lipid profiles indicated that policosanol modulated the fatty acid profile of cholesterol ester in the basolateral medium. CONCLUSION: It was concluded that policosanol or policosanol metabolites may modulate lipid metabolism and/or transport following absorption by the BBM, partial oxidation by the intestinal epithelium, and transport of policosanol metabolites across the BLM.
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Anticolesterolemiantes/farmacocinética , Ésteres del Colesterol/metabolismo , Ácidos Grasos no Esterificados/metabolismo , Alcoholes Grasos/farmacocinética , Absorción , Transporte Biológico , Células CACO-2 , Supervivencia Celular/efectos de los fármacos , Cromatografía de Gases , Cromatografía en Capa Delgada , Humanos , Mucosa Intestinal/metabolismo , Metabolismo de los Lípidos/efectos de los fármacos , Fosfatidilcolinas/metabolismoRESUMEN
The proton pump inhibitors (PPIs) as a class are remarkably safe and effective for persons with peptic ulcer disorders. Serious adverse events are extremely rare for PPIs, with case reports of interstitial nephritis with omeprazole, hepatitis with omeprazole and lansoprazole, and disputed visual disturbances with pantoprazole and omeprazole. PPI use is associated with the development of fundic gland polyps (FGP); stopping PPIs is associated with regression of FGP. In the absence of Helicobacter pylori infection, the long-term use of PPIs has not been convincingly proven to cause or be associated with the progression of pre-existing chronic gastritis or gastric atrophy or intestinal metaplasia. Mild/modest hypergastrinemia is a physiological response to the reduction in gastric acid secretion due to any cause. The long-term use of PPIs has not been convincingly proven to cause enterochromaffin-like cell hyperplasia or carcinoid tumors. PPIs increase the risk of community acquired pneumonia, but not of hospital acquired (nosocomial) pneumonia. There is no data to support particular care in prescribing PPI therapy due to concerns about risk of hip fracture with the long-term use of PPIs. Long-term use of PPIs does not lead to vitamin B12 deficiencies, except possibly in the elderly, or in persons with Zollinger-Ellison Syndrome who are on high doses of PPI for prolonged periods of time. There is no convincingly proven data that PPIs increase the risk of Clostridium difficile-associated diarrhea in persons in the community. The discontinuation of PPIs may result in rebound symptoms requiring further and even continuous PPI use for suppression of symptoms. As with all medications, the key is to use PPIs only when clearly indicated, and to reassess continued use so that long-term therapy is used judiciously. Thus, in summary, the PPIs are a safe class of medications to use long-term in persons in whom there is a clear need for the maintenance of extensive acid inhibition.
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Antiulcerosos/administración & dosificación , Úlcera Péptica/tratamiento farmacológico , Inhibidores de la Bomba de Protones/administración & dosificación , Antiulcerosos/efectos adversos , Comorbilidad , Seguridad de Productos para el Consumidor , Esquema de Medicación , Interacciones Farmacológicas , Medicina Basada en la Evidencia , Humanos , Inhibidores de la Bomba de Protones/efectos adversos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
OBJECTIVES: Intestinal permeability and barrier function are regulated by expression of tight junction proteins. Lipopolysaccharide (LPS), tumor necrosis factor-alpha, and interleukin-1beta induce expression of nitric oxide (NO) and reduce the expression of gut tight junction proteins. The purpose of this study was to determine whether dietary gangliosides (GGs) increase the concentration of the anti-inflammatory cytokine interleukin-10 (IL-10) in response to LPS, thereby inhibiting NO production and protecting gut occludin tight junction protein from degradation. MATERIALS AND METHODS: Rats were fed semipurified diets with (n = 16) or without (n = 16) GGs (0.1% w/w of total lipid). After 2 weeks of feeding, animals were injected with saline (n = 8/diet group) or LPS (n = 8/diet group) (IP, 3 mg mL(-1) kg(-1)). Intestinal tissue, mucosa, and blood sample were collected 6 hours post-LPS exposure. The effect of dietary GGs on production/expression of IL-10, NO, inducible NO synthase, and occludin protein was determined. RESULTS: Dietary GGs increased IL-10 content in intestinal mucosa significantly by 32-fold (P < 0.0001) and in plasma by 2.4-fold (P < 0.001). Feeding animals a ganglioside-enriched diet decreased total NO content in intestinal mucosa and plasma by 44% and 30%, respectively, and inhibited inducible NO synthase expression following LPS exposure compared with control animals. Dietary GGs reduced the degradation of occludin tight junction protein in response to LPS. CONCLUSIONS: Dietary GGs inhibit degradation of gut occludin tight junction protein during LPS-induced acute inflammation. Thus, dietary GGs have a role in protecting the integrity of the intestinal barrier during acute gut inflammation.
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Antiinflamatorios/farmacología , Grasas de la Dieta/administración & dosificación , Gangliósidos/farmacología , Inflamación/tratamiento farmacológico , Mucosa Intestinal/efectos de los fármacos , Proteínas de la Membrana/metabolismo , Uniones Estrechas/efectos de los fármacos , Enfermedad Aguda , Animales , Permeabilidad de la Membrana Celular/efectos de los fármacos , Inflamación/inducido químicamente , Inflamación/metabolismo , Interleucina-10/sangre , Interleucina-10/metabolismo , Absorción Intestinal , Mucosa Intestinal/metabolismo , Lipopolisacáridos , Masculino , Óxido Nítrico/sangre , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Ocludina , Ratas , Ratas Sprague-Dawley , Uniones Estrechas/metabolismoRESUMEN
Throughout our lifetime, the intestine changes. Some alterations in its form and function may be genetically determined, and some are the result of adaptation to diet, temperature, or stress. The critical period programming of the intestine can be modified, such as from subtle differences in the types and ratios of n3:m6 fatty acids in the diet of the pregnant mother, or in the diet of the weanlings. This early forced adaptation may persist in later life, such as the unwanted increased intestinal absorption of sugars, fatty acids and cholesterol. Thus, the ontogeny, early growth and development of the intestine is important for the adult gastroenterologist to appreciate, because of the potential for these early life events to affect the responsiveness of the intestine to physiological or pathological challenges in later life.
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Absorción Intestinal , Mucosa Intestinal/crecimiento & desarrollo , Intestino Delgado/crecimiento & desarrollo , Adaptación Fisiológica , Adulto , Animales , Transporte Biológico , Diferenciación Celular , Proliferación Celular , Niño , Carbohidratos de la Dieta/metabolismo , Grasas de la Dieta/metabolismo , Proteínas en la Dieta/metabolismo , Femenino , Humanos , Recién Nacido , Mucosa Intestinal/embriología , Mucosa Intestinal/metabolismo , Intestino Delgado/embriología , Intestino Delgado/metabolismo , Proteínas de la Leche/metabolismo , Estado Nutricional , EmbarazoRESUMEN
BACKGROUND: Dietary fiber reduces the intestinal absorption of nutrients and the blood concentrations of cholesterol and triglycerides. AIM: We wished to test the hypothesis that high-viscosity (HV) and low-viscosity preparations of barley and oat beta-glucan modify the expression of selected genes of lipid-binding proteins in the intestinal mucosa and reduce the intestinal in vitro uptake of lipids. METHODS: Five different beta-glucan extracts were separately added to test solutions at concentrations of 0.1-0.5% (wt/wt), and the in vitro intestinal uptake of lipids into the intestine of rats was assessed. An intestinal cell line was used to determine the effect of beta-glucan extracts on the expression of intestinal genes involved in lipid metabolism and fatty acid transport. RESULTS: All extracts reduced the uptake of 18:2 when the effective resistance of the unstirred water layer was high. When the unstirred layer resistance was low, the HV oat beta-glucan extract reduced jejunal 18:2 uptake, while most extracts reduced ileal 18:2 uptake. Ileal 18:0 uptake was reduced by the HV barley extract, while both jejunal and ileal cholesterol uptakes were reduced by the medium-purity HV barley extract. The inhibitory effect of HV barley beta-glucan on 18:0 and 18:2 uptake was more pronounced at higher fatty acid concentrations. The expression of genes involved in fatty acid synthesis and cholesterol metabolism was down-regulated with the HV beta-glucan extracts. beta-Glucan extracts also reduced intestinal fatty-acid-binding protein and fatty acid transport protein 4 mRNA. CONCLUSIONS: The reduced intestinal fatty acid uptake observed with beta-glucan is associated with inhibition of genes regulating intestinal uptake and synthesis of lipids. The inhibitory effect of beta-glucan on intestinal lipid uptake raises the possibility of their selective use to reduce their intestinal absorption.
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Colesterol/metabolismo , Regulación hacia Abajo/efectos de los fármacos , Ácidos Grasos/metabolismo , Yeyuno/efectos de los fármacos , Metabolismo de los Lípidos , Lipogénesis/efectos de los fármacos , beta-Glucanos/farmacología , Animales , Secuencia de Bases , Cartilla de ADN , Femenino , Yeyuno/metabolismo , Masculino , RatasRESUMEN
The topic of gastroenterology (GI) in the elderly has been extensively reviewed. It takes special skill, patience and insight to interview the elderly, as well as to appreciate their altered physiology and interpretation of their presenting symptoms and signs, often against an extreme background of complex medical problems. The maldigestion and malabsorption coupled with altered motility contributes to the development of malnutrition. There generally a decrease of function of the GI tract, but there may be loss of adaptability in response to changes in diet or nutritional stress. Pathological alterations which might lead to minor overall intestinal functional variations in the young because of a normal process of adaptation, may lead to much more serious events in the elderly.
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Envejecimiento , Enfermedades Intestinales/fisiopatología , Intestino Delgado/fisiopatología , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Animales , Enfermedad Celíaca/etiología , Enfermedad Celíaca/fisiopatología , Proliferación Celular , Diarrea/etiología , Diarrea/fisiopatología , Motilidad Gastrointestinal , Humanos , Inmunidad Mucosa , Absorción Intestinal , Enfermedades Intestinales/diagnóstico , Enfermedades Intestinales/etiología , Enfermedades Intestinales/patología , Enfermedades Intestinales/terapia , Intestino Delgado/irrigación sanguínea , Intestino Delgado/inmunología , Intestino Delgado/microbiología , Intestino Delgado/patología , Microvellosidades/patología , Persona de Mediana Edad , Estado Nutricional , Medición de Riesgo , Factores de Riesgo , Circulación EsplácnicaRESUMEN
Ganglioside GD3 is a glycosphingolipid found in colostrum, developing tissues, and tumors and is known to regulate cell growth, differentiation, apoptosis, and inflammation. Feeding a GD3-enriched diet to rats increases GD3 in intestinal lipid rafts and blood. The mechanism, efficiency, and fate of ganglioside absorption by human enterocytes have not been investigated. A model to study GD3 uptake by human intestinal cells was developed to test the hypothesis that enterocyte GD3 uptake is time and concentration dependent, with uptake efficiency and fate influenced by route of delivery. Caco-2 cells were exposed to GD3 on the apical or basolateral membrane (BLM) side for 6, 24, and 48 h. GD3 uptake, retention, transfer, and metabolism was determined. GD3 uptake across the apical and BLM was time and concentration dependent and reached a plateau. GD3 uptake across the BLM was more efficient than apical delivery. Apical GD3 was metabolized with some cell retention and transfer, whereas basolateral GD3 was mostly metabolized. This study demonstrates efficient GD3 uptake by enterocytes and suggests that the route of delivery influences ganglioside uptake and fate.
Asunto(s)
Polaridad Celular , Enterocitos/metabolismo , Gangliósidos/metabolismo , Transporte Biológico , Biotransformación , Células CACO-2 , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Enterocitos/efectos de los fármacos , Enterocitos/patología , Gangliósidos/toxicidad , Humanos , Cinética , NecrosisRESUMEN
Galactomannan, a soluble fiber, has been reported to reduce postprandial blood glucose response. Using this fiber, extracted from Canadian-grown fenugreek seeds (Trigonella foenum graecum L), we conducted an in vitro study to determine if galactomannan affects intestinal glucose uptake in genetically determined lean and obese rats. The segments of jejunum and ileum from these animals were incubated with labeled glucose (2 or 32 mmol/L) in the presence of different concentrations of galactomannan ranging from 0.1% to 0.5% (wt/wt). The uptake of low or high concentration of glucose was significantly and progressively reduced by increasing concentrations of galactomannan in both lean and obese rats. No significant difference was observed in the uptake of glucose between the 2 groups. The viscosity of various concentrations of galactomannan solutions was determined after stirring for 60 minutes at a temperature-controlled (37 degrees C) fixed sheer rate of 1.29 (1/s). The inhibitory effect of galactomannan on glucose uptake was found to be in parallel with the degree of viscosity of the fiber solutions. These results suggest that the galactomannan, because of its viscous property, has the potential to reduce intestinal absorption of low or high concentrations of glucose and hence for the benefit of blood glucose management.
Asunto(s)
Glucosa/farmacocinética , Absorción Intestinal/efectos de los fármacos , Intestino Delgado/metabolismo , Mananos/farmacología , Extractos Vegetales/farmacología , Trigonella , Animales , Peso Corporal , Galactosa/análogos & derivados , Síndrome Metabólico/metabolismo , Obesidad/metabolismo , Fitoterapia , Ratas , Ratas Endogámicas , Semillas , ViscosidadRESUMEN
The process of intestinal adaptation ("enteroplasticity") is complex and multifaceted. Although a number of trophic nutrients and non-nutritive factors have been identified in animal studies, successful, reproducible clinical trials in humans are awaited. Understanding mechanisms underlying this adaptive process may direct research toward strategies that maximize intestinal function and impart a true clinical benefit to patients with short bowel syndrome, or to persons in whom nutrient absorption needs to be maximized. In this review, we consider the morphological, kinetic and membrane biochemical aspects of enteroplasticity, focus on the importance of nutritional factors, provide an overview of the many hormones that may alter the adaptive process, and consider some of the possible molecular profiles. While most of the data is derived from rodent studies, wherever possible, the results of human studies of intestinal enteroplasticity are provided.