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Intestinal hormones and growth factors:Effects on the small intestine

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World Journal of Gastroenterology 2009年第4期15卷 385-406页

作者： Laurie Drozdowski alan br thomson Division of Gastroenterology University of Alberta

There are various hormones and growth factors which may modify the intestinal absorption of nutrients, and which might thereby be useful in a therapeutic setting, such as in persons with short bowel syndrome. In part I, we focus first on insulin-like growth factors, epidermal and transferring growth factors, thyroid hormones and glucocorticosteroids. Part Ⅱ will detail the effects of glucagon-like peptide （GLP）-2 on intestinal absorption and adaptation, and the potential for an additive effect of GLP2 plus steroids.

关键词： Epidermal growth factor Glucocortico-steroids Insulin-like growth factor-I/Ⅱ Intestinalgrowth Transforming growth factor-α-2 Hepatocytegrowth factor Keratinocyte growth factor

Aging and the intestine

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World Journal of Gastroenterology 2006年第47期12卷 7578-7584页

作者： Laurie Drozdowski alan br thomson Nutrition and Metabolism Group University of Alberta Canada

Over the lifetime of the animal, there are many changes in the function of the body’s organ systems. In the gastrointestinal tract there is a general modest decline in the function of the esophagus, stomach, colon, pancreas and liver. In the small intestine, there may be subtle alterations in the intestinal morphology, as well as a decline in the uptake of fatty acids and sugars. The malabsorption may be partially reversed by aging glucagon-like peptide 2 (GLP2) or dexamethasone. Modifications in the type of lipids in the diet will influence the intestinal absorption of nutrients: for example, in mature rats a diet enriched with saturated as compared with polysaturated fatty acids will enhance lipid and sugar uptake, whereas in older animals the opposite effect is observed. Thus, the results of studies of the intestinal adaptation performed in mature rats does not necessarily apply in older animals. The age-associated malabsorption of nutrients that occurs with aging may be one of the several factors which contribute to the malnutrition that occurs with aging.

关键词： Aging Gastrointestinal tract Intestine Absorption Malnutrition

Intestinal sugar transport

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World Journal of Gastroenterology 2006年第11期12卷 1657-1670页

作者： Laurie A Drozdowski alan br thomson Division of Gastroenterology Department of Medicine University of Alberta5150 Dentistry Pharmacy BuildingEdmontonABT6G 2N8Canada 130 University Campus Division of Gastroenterology Department of MedicineUniversity of AlbertaZeidler Ledcor CenterEdmontonABT6G 2X8Canada

Carbohydrates are an important component of the diet. The carbohydrates that we ingest range from simple monosaccharides （glucose, fructose and galactose） to disaccharides （lactose, sucrose） to complex polysaccharides. Most carbohydrates are digested by salivary and pancreatic amylases, and are further broken down into monosaccharides by enzymes in the brush border membrane （BBM） of enterocytes. For example, lactase-phloridzin hydrolase and sucraseisomaltase are two disaccharidases involved in the hydrolysis of nutritionally important disaccharides. Once monosaccharides are presented to the BBM, mature enterocytes expressing nutrient transporters transport the sugars into the enterocytes. This paper reviews the early studies that contributed to the development of a working model of intestinal sugar transport, and details the recent advances made in understanding the process by which sugars are absorbed in the intestine.

关键词： Glucose Fructose SGLT1 GLUT2 GLUT5 Transport Intestine Enterocytes Sugar

Ontogeny,growth and development of the small intestine:Understanding pediatric gastroenterology

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World Journal of Gastroenterology 2010年第7期16卷 787-799页

作者： Laurie A Drozdowski Tom Clandinin alan br thomson Medical Affairs Mead Johnson NutritionalsOttawaOntarioK1S 5N4Canada Department of Agricultural Food and Nutritional ScienceUniversity of AlbertaAlbertaT6G 2B7Canada Division of General Internal Medicine Department of MedicineUniversity of AlbertaAlbertaT6G 2B7Canada

Throughout our lifetime,the intestine *** alterations in its form and function may be genetically determined,and some are the result of adaptation to diet,temperature,or *** 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 *** early forced adaptation may persist in later life,such as the unwanted increased intestinal absorption of sugars,fatty acids and ***,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.

关键词： Intestinal development Ontogeny Pediatrics

Morphological,kinetic,membrane biochemical and genetic aspects of intestinal enteroplasticity

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World Journal of Gastroenterology 2009年第7期15卷 774-787页

作者： Laurie A Drozdowski M Tom Clandinin alan br thomson Medical Affairs Mead Johnson Nutritionals Department of Agriculture Food and Nutritional SciencesUniversity of Alberta Division of Internal Medicine Department of MedicineUniversity of Alberta

The process of intestinal adaptation("enteroplasticity") is complex and *** a number of trophic nutrients and non-nutritive factors have been identified in animal studies,successful,reproducible clinical trials in humans are *** 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 *** 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 *** most of the data is derived from rodent studies,wherever possible,the results of human studies of intestinal enteroplasticity are provided.

关键词： Diabetes Diet Hormonal regulation Intestinal resection Mechanisms Morphology Nutrientabsorption Short bowel syndrome Signals

Celiac disease:Prevalence,diagnosis,pathogenesis and treatment

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World Journal of Gastroenterology 2012年第42期18卷 6036-6059页

作者： Naiyana Gujral Hugh J Freeman alan br thomson Faculty of Pharmacy and Pharmaceutical Sciences University of AlbertaEdmontonAB T6G 2E1Canada Department of Medicine University of British ColumbiaVancouverBC V6T 2B5Canada Division of Gastroenterology Department of MedicineUniversity of Western OntarioLondonON N6A 5A5Canada

Celiac disease(CD) is one of the most common diseases,resulting from both environmental(gluten) and genetic factors [human leukocyte antigen(HLA) and nonHLA genes].The prevalence of CD has been estimated to approximate 0.5%-1% in different parts of the ***,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 *** gains access to the basal surface of the epithelium,and interact directly with the immune system,via both trans-and para-cellular *** 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 *** anti-tissue transglutaminase antibody or antiendomysial 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 ***,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.

关键词： Celiac disease Demography Diagnosis Pathogenesis Treatment

Use of the tumor necrosis factor-blockers for Crohn's disease

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World Journal of Gastroenterology 2012年第35期18卷 4823-4854页

作者： alan br thomson Milli Gupta Hugh J Freeman Division of Gastroenterology Department of MedicineUniversity of Western Ontario Department of Medicine University of Alberta Department of Medicine University of British Columbia

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-c~ 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 ther- apy, and when or if TNFB may be weaned and discon- tinued. 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 accept- able 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 ben- efits to TNFB are modest from a population perspec- tive and the cost of therapy is very high, the ultimate application of use of TNFBs will likely be established by cost/benefit studies.

关键词： Adalimumab Adverse effects Certolizum-ab pegol Crohn's disease Economic evaluation Inflix-imab Secondary lack of response Ulcerative colitis

Safety of the long-term use of proton pump inhibitors

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World Journal of Gastroenterology 2010年第19期16卷 2323-2330页

作者： alan br thomson Michel D Sauve Narmin Kassam Holly Kamitakahara Division of General Internal Medicine Faculty of Medicine University of Alberta Edmonton AB T6G 2B7 Alberta Canada

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 enterochromaff in-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-termuse of PPIs. Long-term use of PPIs does not lead to vitamin B12 def iciencies, 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 longterm in persons in whom there is a clear need for the maintenance of extensive acid inhibition.

关键词： Acid inhibition Drug safety Osteoporosis Pneumonia Enteric infections

Recent advances in small bowel diseases:Part Ⅰ

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World Journal of Gastroenterology 2012年第26期18卷 3336-3352页

作者： alan br thomson Angeli Chopra Michael Tom Clandinin Hugh Freeman Department of Medicine University of Western OntarioLondonON N6A 5A5Canada Division of General Internal Medicine University of AlbertaEdmontonAB T6G 2X8Canada Department of Agricultural Foodand Nutritional ScienceUniversity of AlbertaEdmontonAB T6G 2R1Canada Division of Gastroenterology University of British ColumbiaVancouverBC V6T 2B5Canada

As is the case in all parts of gastroenterology and hepatology,there have been many advances in our knowledge and understanding of small intestinal *** 1000 publications were reviewed for 2008 and 2009,and the important advances in basic science as well as clinical applications were *** Part Ⅰ 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/*** topics were chosen because of their importance to the practicing physician.

关键词： Diarrhea Infectious diarrhea Intestinal development Intestinal proliferation and repair Intestinalpermeability Microbiotica Necrotizing enterocolitis Probiotics