WorldWideScience

Sample records for achlorhydria

  1. Watery diarrhea, hypokalemia and achlorhydria syndrome due to an adrenal pheochromocytoma

    Institute of Scientific and Technical Information of China (English)

    Shin-ichi Ikuta; Chiaki Yasui; Masahiro Kawanaka; Tsukasa Aihara; Hidenori Yoshie; Hidenori Yanagi; Masao Mitsunobu; Ayako Sugihara; Naoki Yamanaka

    2007-01-01

    Watery diarrhea, hypokalemia and achlorhydria (WDHA)syndrome caused by vasoactive intestinal polypeptide (VIP) -producing tumor only rarely occurs in patients with nonpancreatic disease. A 49-year-old woman was referred for evaluation of a right adrenal tumor incidentally diagnosed by abdominal ultrasound during the investigation of chronic watery diarrhea. Laboratory findings showed hypokalemia and excessive production of VIP and catecholamines. After surgical resection of the tumor, diarrhea subsided and both electrolytes and affected hormone levels normalized. Immunohistochemical examination confirmed a diagnosis of pheochromocytoma,which contained VIP-positive ganglion-like cells. We herein present the clinical and histogenetic implications of this rare clinical entity, with literature review.

  2. Pancreatic metaplasia in the gastro-achlorhydria in WTC-dfk rat, a potassium channel Kcnq1 mutant.

    Science.gov (United States)

    Kuwamura, M; Okajima, R; Yamate, J; Kotani, T; Kuramoto, T; Serikawa, T

    2008-07-01

    The WTC-deafness Kyoto (dfk) rat is a new mutant characterized by deafness and abnormal, imbalanced behavior. WTC-dfk rats carry an intragenic deletion at the Kcnq1 gene; KCNQ1 plays an important role in K(+) homeostasis, and the mutation of Kcnq1 causes a cardiac long QT syndrome in humans. Here, we studied stomach lesions in these WTC-dfk rats. The most characteristic pathologic feature in the stomach was the appearance of hypertrophic gastric glands in the stomach body. The hypertrophic cells had many eosinophilic granules in their cytoplasm, and these granules were stained red with Azan stain; stained positively for trypsinogen, amylase, and chymotrypsin; and did not stain positively for pepsinogen when using immunohistochemical analysis. These staining results suggested a metaplasia toward a pancreatic acinar cells. Extensive fibrosis was found in the bottom part of the mucosa of 34-week-old WTC-dfk rats, suggesting a progression of stomach lesions with aging. Although cells that were positive for proliferating cell nuclear antigen were restricted in the area of the glandular neck in WTC control rats, positive cells in WTC-dfk rats were scattered throughout the mucosa. The parietal cells in WTC-dfk rats were negative for KCNQ1 immunohistochemical analysis. These findings indicate that a deficiency in rat Kcnq1 provokes an abnormal proliferation and differentiation of gastric glandular cells.

  3. Gastric cancer risk in achlorhydric patients. A long-term follow-up study

    DEFF Research Database (Denmark)

    Svendsen, Jesper Hastrup; Dahl, C; Svendsen, L B

    1986-01-01

    Achlorhydria, determined by the augmented histamine test, is the functional expression of the most severe atrophic gastritis and is followed by a 4- to 6-fold increased risk of gastric cancer, as we found 5 cancers in 114 patients after a mean observation period of 8.4 years. The cancers developed...... from 1 to 17 years after achlorhydria diagnosis--three cases after more than 9 years. The study showed no difference in gastric cancer risk between patients with and without pernicious anaemia. Spontaneous achlorhydria is the late result of atrophic gastritis, which should be regarded the premalignant...... condition. The development of gastric cancer from pharmacologically reduced acid secretion must be regarded as highly hypothetical, since this is not followed by atrophic gastritis....

  4. Enterococcus faecalis Infection Causes Inflammation, Intracellular Oxphos-Independent ROS Production, and DNA Damage in Human Gastric Cancer Cells

    DEFF Research Database (Denmark)

    Strickertsson, Jesper A. B; Desler, Claus; Martin-Bertelsen, Tomas;

    2013-01-01

    Background Achlorhydria caused by e.g. atrophic gastritis allows for bacterial overgrowth, which induces chronic inflammation and damage to the mucosal cells of infected individuals driving gastric malignancies and cancer. Enterococcus faecalis (E. faecalis) can colonize achlohydric stomachs and we...

  5. Mujer joven con diarrea crónica

    Directory of Open Access Journals (Sweden)

    María Vares González

    2013-12-01

    Chronic diarrhea is frequent. The causes are multiple, so reaching the definitive diagnosis can be complex. The diagnostic delay can be deadly. We describe the case of a young woman who developed severe hypokalemia secondary to VIPoma, neuroendocrine tumor secreting vasoactive intestinal peptide, a hormone responsible for the clinical: watery diarrhea, hypokalemia and achlorhydria

  6. Dynamic gadolinium-enhanced MR imaging of pancreatic VIPoma in a patient with Verner-Morrison syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Mortele, K.J. [Dept. of Radiology, University Hospital Gent (Belgium); Dept. of Radiology, Brigham and Women' s Hospital, Bosotn, MA (United States); Oei, A.; Bauters, W.; Kunnen, M. [Dept. of Radiology, University Hospital Gent (Belgium); Timmermans, F. [Dept. of Gastroenterology, University Hospital Gent (Belgium); Cuvelier, C. [Dept. of Pathology, University Hospital Gent (Belgium); Ros, P.R. [Dept. of Radiology, Brigham and Women' s Hospital, Bosotn, MA (United States)

    2001-10-01

    We describe a rare case of a pancreatic VIPoma diagnosed in a patient presenting with watery diarrhea, hypokalemia, and achlorhydria, the so-called WDHA or Verner-Morrison syndrome. Emphasis is placed on the dynamic gadolinium-enhanced MR profile of the tumor, characteristics which have not been illustrated previously, to the best of our knowledge. (orig.)

  7. Angiographic diagnosis of a pancreatic islet tumor in a patient with the WDHA syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Inamoto, K.; Yoshino, F.; Nakao, N.; Kawanaka, M.

    1980-01-01

    A patient with an islet cell tumor of the pancreas that produced the watery diarrhea, hypokalemia, achlorhydria syndrome is presented. On celiac angiography an extremely vascular mass was seen in the body of pancreas with hypertrophied arteries and persistent, dense tumor staining.

  8. Autoimmune gastritis and parietal cell reactivity in two children with abnormal intestinal permeability

    NARCIS (Netherlands)

    Greenwood, Deanne L. V.; Crock, Patricia; Braye, Stephen; Davidson, Patricia; Sentry, John W.

    2008-01-01

    Autoimmune gastritis is characterised by lymphocytic infiltration of the gastric submucosa, with loss of parietal and chief cells and achlorhydria. Often, gastritis is expressed clinically as cobalamin deficiency with megaloblastic anaemia, which is generally described as a disease of the elderly. H

  9. Comparative Analysis of Gastrointestinal Microbiota Between Normal and Caudal-Related Homeobox 2 (Cdx2) Transgenic Mice

    OpenAIRE

    Sakamoto, Hirotsugu; Asahara, Takashi; Chonan, Osamu; Yuki, Norikatsu; Mutoh, Hiroyuki; Hayashi, Shunji; Yamamoto, Hironori; Sugano, Kentaro

    2015-01-01

    Background/Aims Caudal-related homeobox 2 (Cdx2) is expressed in the human intestinal metaplastic mucosa and induces intestinal metaplastic mucosa in the Cdx2 transgenic mouse stomach. Atrophic gastritis and intestinal metaplasia commonly lead to gastric achlorhydria, which predisposes the stomach to bacterial overgrowth. In the present study, we determined the differences in gut microbiota between normal and Cdx2 transgenic mice, using quantitative reverse transcription-polymerase chain reac...

  10. Lack of Commensal Flora in Helicobacter pylori–Infected INS-GAS Mice Reduces Gastritis and Delays Intraepithelial Neoplasia

    OpenAIRE

    Lofgren, Jennifer L.; Whary, Mark T.; Ge, Zhongming; Muthupalani, Sureshkumar; Taylor, Nancy S.; Mobley, Melissa W.; Potter, Amanda; Varro, Andrea; Eibach, Daniel; Suerbaum, Sebastian; Wang, Timothy C.; James G. Fox

    2010-01-01

    Background & Aims Transgenic FVB/N insulin-gastrin (INS-GAS) mice have high circulating gastrin levels, and develop spontaneous atrophic gastritis and gastrointestinal intraepithelial neoplasia (GIN) with 80% prevalence 6 months after Helicobacter pylori infection. GIN is associated with gastric atrophy and achlorhydria, predisposing mice to nonhelicobacter microbiota overgrowth. We determined if germfree INS-GAS mice spontaneously develop GIN and if H pylori accelerates GIN in gnotobiotic...

  11. Lysosomal Localization of TRPML3 Depends on TRPML2 and the Mucolipidosis-associated Protein TRPML1*S

    OpenAIRE

    2006-01-01

    Mucolipidosis type IV is an autosomal recessive lysosomal storage disorder characterized by severe neurodegeneration, achlorhydria, and visual impairments such as corneal opacity and strabismus. The disease arises due to mutations in a group 2 transient receptor potential (TRP)-related cation channel, TRPML1. Mammals encode two additional TRPML proteins named TRPML2 and TRPML3. Information regarding the propensity of these proteins to multimerize, their subcellular distribution and mechanisms...

  12. Is radiofrequency ablation justified for liver metastatic VIPoma patient undergoing Whipple procedure?

    Institute of Scientific and Technical Information of China (English)

    LI Jiang-tao; LIU Ying-bin; PENG Shu-you; FANG He-qing; LIU Xiao-lei; TANG Zhe; XU Jun; ZHANG Song-zhao; MA Rui; ZHANG Li-yong; WANG Jian-wei

    2010-01-01

    @@ Vasoactive intestinal polypeptide secreting tumors (VIPoma) are one kind of rare endocrine tumor which is mostly located in the pancreas.The annual incidence was estimated to be about 1 per 10 000 000 individuals in general population.1 The VIPoma is usually associated with Verner-Morrison syndrome following tremendous over-secretion of vasoactive intestinal polypeptide (VIP), which consisted of water diarrhea,hypokalemia and achlorhydria.This syndrome has been termed pancreatic cholera, watery diarrhea syndrome.

  13. Effects of an acidic beverage (Coca-Cola) on absorption of ketoconazole.

    Science.gov (United States)

    Chin, T W; Loeb, M; Fong, I W

    1995-08-01

    Absorption of ketoconazole is impaired in patients with achlorhydria. The purpose of this study was to determine the effectiveness of a palatable acidic beverage (Coca-Cola Classic, pH 2.5) in improving the absorption of ketoconazole in the presence of drug-induced achlorhydria. A prospective, randomized, three-way crossover design with a 1-week wash-out period between each treatment was employed. Nine healthy nonsmoking, nonobese volunteers between 22 and 41 years old were studied. Each subject was randomized to receive three treatments: (A) ketoconazole 200-mg tablet with water (control), (B) omeprazole (60 mg) followed by ketoconazole (200 mg) taken with water, and (C) omeprazole (60 mg) followed by ketoconazole (200 mg) taken with 240 ml of Coca-Cola Classic. The pH values of gastric aspirates were checked after omeprazole was administered to confirm attainment of a pH of > 6. Multiple serum samples were obtained for measurements of ketoconazole concentrations by high-pressure liquid chromatography. The mean area under the ketoconazole concentration-time curve from zero to infinity for the control treatment (17.9 +/- 13.1 mg.h/liter) was significantly greater than that for treatment B (3.5 +/- 5.1 mg.h/liter; 16.6% +/- 15.0% of control). The mean peak concentration was highest for the control treatment (4.1 +/- 1.9 micrograms/ml), for which the mean peak concentration showed a significant increase over that for treatment B. The absorption of ketoconazole was reduced in the presence of omeprazole-induced achlorhydria. However, drug absorption was significantly increased, to approximately 65% of the mean for the control treatment, when the drug was taken with an acidic beverage, such as Coca-Cola.

  14. Enterococcus faecalis Infection Causes Inflammation, Intracellular Oxphos-Independent ROS Production, and DNA Damage in Human Gastric Cancer Cells

    DEFF Research Database (Denmark)

    Strickertsson, Jesper A. B; Desler, Claus; Martin-Bertelsen, Tomas

    2013-01-01

    Background Achlorhydria caused by e.g. atrophic gastritis allows for bacterial overgrowth, which induces chronic inflammation and damage to the mucosal cells of infected individuals driving gastric malignancies and cancer. Enterococcus faecalis (E. faecalis) can colonize achlohydric stomachs and we...... therefore wanted to study the impact of E. faecalis infection on inflammatory response, reactive oxygen species (ROS) formation, mitochondrial respiration, and mitochondrial genetic stability in gastric mucosal cells. Methods To separate the changes induced by bacteria from those of the inflammatory cells...... we established an in vitro E. faecalis infection model system using the gastric carcinoma cell line MKN74. Total ROS and superoxide was measured by fluorescence microscopy. Cellular oxygen consumption was characterized non-invasively using XF24 microplate based respirometry. Gene expression...

  15. Gastric adenocarcinoma in the context of X-linked agammaglobulinemia: case report and review of the literature.

    Science.gov (United States)

    Staines Boone, Aidé Tamara; Torres Martínez, María Guadalupe; López Herrera, Gabriela; de Leija Portilla, Julia O; Espinosa Padilla, Sara Elva; Espinosa Rosales, Francisco J; Lugo Reyes, Saúl Oswaldo

    2014-02-01

    The hallmarks of X-linked Agammaglobulinemia (XLA) are panhypogammaglobulinemia, absent B-cells, and recurrent sinopulmonary and gastrointestinal infections starting at an early age, as well as other infections like cellulitis, meningitis, arthritis and sepsis. A number of non-infectious complications have been reported in these patients, including autoimmune diseases and malignancy, especially lymphomas. Here, we report the case of a 30-year old man who developed gastric adenocarcinoma in the context of XLA. Previous reports of, and hypotheses addressing the development of cancer in patients with XLA, are also summarized. Solid cancer in XLA affects mainly the gastrointestinal tract and seems to be related to chronic infection. A natural evolution can be traced back from gastric adenocarcinoma to megaloblastic anemia due to achlorhydria in the context of chronic infection; periodic endoscopy thus seems justified to detect and treat carcinoma in early stages.

  16. Kcne2 deletion causes early-onset nonalcoholic fatty liver disease via iron deficiency anemia

    Science.gov (United States)

    Lee, Soo Min; Nguyen, Dara; Anand, Marie; Kant, Ritu; Köhncke, Clemens; Lisewski, Ulrike; Roepke, Torsten K.; Hu, Zhaoyang; Abbott, Geoffrey W.

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) is an increasing health problem worldwide, with genetic, epigenetic, and environmental components. Here, we describe the first example of NAFLD caused by genetic disruption of a mammalian potassium channel subunit. Mice with germline deletion of the KCNE2 potassium channel β subunit exhibited NAFLD as early as postnatal day 7. Using mouse genetics, histology, liver damage assays and transcriptomics we discovered that iron deficiency arising from KCNE2-dependent achlorhydria is a major factor in early-onset NAFLD in Kcne2─/─ mice, while two other KCNE2-dependent defects did not initiate NAFLD. The findings uncover a novel genetic basis for NAFLD and an unexpected potential factor in human KCNE2-associated cardiovascular pathologies, including atherosclerosis. PMID:26984260

  17. Lysosomal trafficking functions of mucolipin-1 in murine macrophages

    Directory of Open Access Journals (Sweden)

    Dang Hope

    2007-12-01

    Full Text Available Abstract Background Mucolipidosis Type IV is currently characterized as a lysosomal storage disorder with defects that include corneal clouding, achlorhydria and psychomotor retardation. MCOLN1, the gene responsible for this disease, encodes the protein mucolipin-1 that belongs to the "Transient Receptor Potential" family of proteins and has been shown to function as a non-selective cation channel whose activity is modulated by pH. Two cell biological defects that have been described in MLIV fibroblasts are a hyperacidification of lysosomes and a delay in the exit of lipids from lysosomes. Results We show that mucolipin-1 localizes to lysosomal compartments in RAW264.7 mouse macrophages that show subcompartmental accumulations of endocytosed molecules. Using stable RNAi clones, we show that mucolipin-1 is required for the exit of lipids from these compartments, for the transport of endocytosed molecules to terminal lysosomes, and for the transport of the Major Histocompatibility Complex II to the plasma membrane. Conclusion Mucolipin-1 functions in the efficient exit of molecules, destined for various cellular organelles, from lysosomal compartments.

  18. [Plummer-Vinson syndrome or related syndrome in 3 black African women].

    Science.gov (United States)

    Aubry, P; Oddes, B; Chazouillères, O; Lebourgeois, M; Delanoue, G; Seurat, P L

    1985-01-01

    The Plummer-Vinson syndrome or "sideropenic dysphagia" is exceptional among Blacks. One case was recently reported in a female patient from Guadeloupe. This study pertains to three cases observed in Senegalese Black women aged 28, 27, and 41 years. These three women were admitted for a dysphagia, in fact in evidence 10, 4, and 7 years respectively before the diagnosis was made. A clinical anemia was noted twice in addition to mucocutaneous disorders (cases 1 and 2). The laboratory tests showed in all three cases a hypochromic microcytic sideropenic anemia (serum iron levels at 32, 14, and 31 mcg 100 ml respectively). Barium swallow films showed esophageal rings in front of C5-C6 (case 1) of T2-T3 (case 2) and a web of fine mucosal folds in front of C5-C6 (case 3). These films were confirmed cineradiographically by esophagoscopy. The treatment consisted of blood transfusions (cases 1 and 2) and administration of iron by injections and or per os. The endoscopic exams were repeated two or three times. Medical treatment rapidly changed the course of disease for the better. No cause for bleeding was found. A chemical achlorhydria (case 1), a provoked hypoachlorhydria (cases 2 and 3) can be retained as associated factors. In light of the frequency of esophageal membranes in the general population and the incidence of sideropenic anemias among African women, the Plummer-Vinson syndrome should be more often detected in Black Africa.

  19. Lysosomal localization of TRPML3 depends on TRPML2 and the mucolipidosis-associated protein TRPML1.

    Science.gov (United States)

    Venkatachalam, Kartik; Hofmann, Thomas; Montell, Craig

    2006-06-23

    Mucolipidosis type IV is an autosomal recessive lysosomal storage disorder characterized by severe neurodegeneration, achlorhydria, and visual impairments such as corneal opacity and strabismus. The disease arises due to mutations in a group 2 transient receptor potential (TRP)-related cation channel, TRPML1. Mammals encode two additional TRPML proteins named TRPML2 and TRPML3. Information regarding the propensity of these proteins to multimerize, their subcellular distribution and mechanisms that regulate their trafficking are limited. Here we demonstrate that TRPMLs interact to form homo- and heteromultimers. Moreover, the presence of either TRPML1 or TRPML2 specifically influences the spatial distribution of TRPML3. TRPML1 and TRPML2 homomultimers are lysosomal proteins, whereas TRPML3 homomultimers are in the endoplasmic reticulum. However, TRPML3 localizes to lysosomes when coexpressed with either TRPML1 or TRPML2 and is comparably mislocalized when lysosomal targeting of TRPML1 and TRPML2 is disrupted. Conversely, TRPML3 does not cause retention of TRPML1 or TRPML2 in the endoplasmic reticulum. These data demonstrate that there is a hierarchy controlling the subcellular distributions of the TRPMLs such that TRPML1 and TRPML2 dictate the localization of TRPML3 and not vice versa.

  20. Impaired myelination and reduced brain ferric iron in the mouse model of mucolipidosis IV.

    Science.gov (United States)

    Grishchuk, Yulia; Peña, Karina A; Coblentz, Jessica; King, Victoria E; Humphrey, Daniel M; Wang, Shirley L; Kiselyov, Kirill I; Slaugenhaupt, Susan A

    2015-12-01

    Mucolipidosis type IV (MLIV) is a lysosomal storage disease caused by mutations in the MCOLN1 gene, which encodes the lysosomal transient receptor potential ion channel mucolipin-1 (TRPML1). MLIV causes impaired motor and cognitive development, progressive loss of vision and gastric achlorhydria. How loss of TRPML1 leads to severe psychomotor retardation is currently unknown, and there is no therapy for MLIV. White matter abnormalities and a hypoplastic corpus callosum are the major hallmarks of MLIV brain pathology. Here, we report that loss of TRPML1 in mice results in developmental aberrations of brain myelination as a result of deficient maturation and loss of oligodendrocytes. Defective myelination is evident in Mcoln1(-/-) mice at postnatal day 10, an active stage of postnatal myelination in the mouse brain. Expression of mature oligodendrocyte markers is reduced in Mcoln1(-/-) mice at postnatal day 10 and remains lower throughout the course of the disease. We observed reduced Perls' staining in Mcoln1(-/-) brain, indicating lower levels of ferric iron. Total iron content in unperfused brain is not significantly different between Mcoln1(-/-) and wild-type littermate mice, suggesting that the observed maturation delay or loss of oligodendrocytes might be caused by impaired iron handling, rather than by global iron deficiency. Overall, these data emphasize a developmental rather than a degenerative disease course in MLIV, and suggest that there should be a stronger focus on oligodendrocyte maturation and survival to better understand MLIV pathogenesis and aid treatment development.

  1. A knockin mouse model for human ATP4aR703C mutation identified in familial gastric neuroendocrine tumors recapitulates the premalignant condition of the human disease and suggests new therapeutic strategies

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    Oriol Calvete

    2016-09-01

    Full Text Available By whole exome sequencing, we recently identified a missense mutation (p.R703C in the human ATP4a gene, which encodes the proton pump responsible for gastric acidification. This mutation causes an aggressive familial type I gastric neuroendocrine tumor in homozygous individuals. Affected individuals show an early onset of the disease, characterized by gastric hypoacidity, hypergastrinemia, iron-deficiency anemia, gastric intestinal metaplasia and, in one case, an associated gastric adenocarcinoma. Total gastrectomy was performed as the definitive treatment in all affected individuals. We now describe the generation and characterization of a knockin mouse model for the ATP4aR703C mutation to better understand the tumorigenesis process. Homozygous mice recapitulated most of the phenotypical alterations that were observed in human individuals, strongly suggesting that this mutation is the primary alteration responsible for disease development. Homozygous mice developed premalignant condition with severe hyperplasia, dysplasia and glandular metaplasia in the stomach. Interestingly, gastric acidification in homozygous mice, induced by treatment with 3% HCl acid in the drinking water, prevented (if treated from birth or partially reverted (if treated during adulthood the development of glandular metaplasia and dysplasia in the stomach and partially rescued the abnormal biochemical parameters. We therefore suggest that, in this model, achlorhydria contributes to tumorigenesis to a greater extent than hypergastrinemia. Furthermore, our mouse model represents a unique and novel tool for studying the pathologies associated with disturbances in gastric acid secretion.

  2. Nutritional vitamin-B12 deficiency. Possible contributory role of subtle vitamin-B12 malabsorption.

    Science.gov (United States)

    Carmel, R

    1978-05-01

    Dietary deficiency of vitamin B-12 has been reported, yet most people ingesting vitamin-B12-deficient diets even for many years appear to achieve a balance that does not lead to overt signs and symptoms of deficiency. I present the case of a vegan of 25 years' duration who developed severe neurologic abnormalities due to vitamin-B12 deficiency. His diet provided 1.2 microgram of vitamin B12 daily at most. Despite normal Schilling test findings, he absorbed subnormal amounts of vitamin B12 given with ovalbumin. This poor absorption appeared to be related to his gastritis, achlorhydria, and subnormal intrinsic-factor secretion. Probably, vitamin-B12 deficiency in this patient resulted from both dietary restriction and the subtle malabsorption, neither of which would have sufficed alone to produce the clinical problem. Possibly such malabsorption may also be present in many of those vegans developing overt vitamin-B12 deficiency in whom Schilling test findings have been normal.

  3. Gastroenterostoma after Billroth antrectomy as a premalignant condition

    Institute of Scientific and Technical Information of China (English)

    Robert Sitarz; Ryszard Maciejewski; Wojciech P Polkowski; G Johan A Offerhaus

    2012-01-01

    Gastric stump carcinoma (GSC) following remote gastric surgery is widely recognized as a separate entity within the group of various types of gastric cancer.Gastrectomy is a well established risk factor for the development of GSC at a long time after the initial surgery.Both exoas well as endogenous factors appear to be involved in the etiopathogenesis of GSC,such as achlorhydria,hypergastrinemia and biliary reflux,Epstein-Barr virus and Helicobacter pylori infection,atrophic gastritis,and also some polymorphisms in interleukin-1β and maybe cyclo-oxygenase-2.This review summarizes the literature of GSC,with special reference to reliable early diagnostics.In particular,dysplasia can be considered as a dependable morphological marker.Therefore,close endoscopic surveillance with multiple biopsies of the gastroenterostomy is recommended.Screening starting at 15 years after the initial ulcer surgery can detect tumors at a curable stage.This approach can be of special interest in Eastern European countries,where surgery for benign gastroduodenal ulcers has remained a practice for a much longer time than in Western Europe,and therefore GSC is found with higher frequency.

  4. Progress of gastric cancer etiology: N-nitrosamides in the 1990s

    Institute of Scientific and Technical Information of China (English)

    Da Jun Deng

    2000-01-01

    Stomach carcinoma is still the leading cause of cancer death in China and the second one in the world. Its possible causes include: A) chemical factors such as intragastric formation of N-nitroso compounds (NOC) and high salt intake; B ) biological factors such as infection of Helicobacter pylori and biotoxins intake; and C ) nutritional factors such as deficiency of vitamin C, selenium, and other antioxidants. Nitrogenous precursors of NOC, e.g., alkylamines, alkylureas, alkylguanidines, and alkylamides, occur widely in nature and potential nitrosating agents, e.g., nitrite (NO2-) and NOx (the gaseous oxides of nitrogen ) are similarly widespread. Relationship between exposure to NOC and causes of human cancer was investigated extensively ten years ago. Results indicated that the exposures of NOC might contribute to the occurrences of malignancy in the upper digestive tracts including stomachs. It was also observed that both high salt intake and deficiency of some micronutrients enhanced NOC-induced carcinogenicity. Recent studies show that infection of H. pylori can lead to atrophic gastritis and achlorhydria, and promote endogenous formation of NOC indirectly[1] . Much attention has been paid to stomach cancer and NOC regarding the characterization of natural N-nitrosamides in human environment in the 1990s.

  5. [Autoimmunity factor in chronic gastritis: incidence of antiparietal cell antibodies and their relation to antral histology and basal blood gastrins].

    Science.gov (United States)

    Schraier, M; Katz, S; Pest, S; Chiocca, J C; Costa, J A

    1983-01-01

    In 118 patients with histological proven chronic gastritis, was performed a study of seric antibodies against parietal cells (ACCP), following the indirect inmuno-fluorescence method. The results were positives in 36 cases (30%). Four positives cases were found in 40 normal controls (10%), two of them were compensated diabetics, one have the thyrohyoid Hashimoto's disease, and the remainder, brother of a patient with chronic gastritis, was a positive ACCP. A major positiveness (44.4%) was obtained in 9 cases of gastric atrophy than in 65 cases with atrophic gastritis (32%) and in 44 cases of superficial gastritis (25%); although due to the few cases of gastric atrophy regarding other histological types, conclusions cannot be obtained about the incidence of ACCP and histological variety of chronic gastritis. If we do group the patients according to their acid secretory debit, 53 achlorhydric patients had a positiveness of ACCP of 45%, while over 63 with decreased secretory capability, only 18.4%, was positive. The distribution by age groups, shows a major incidence of ACCP about the 4th and 5th decade of life. Thirty seven patients with chronic atrophic gastritis and achlorhydria, and seven with chronic superficial gastritis and hypochlorhydria, besides the antibodies study were on a basal dosage of gastrinemia and antral endoscopic biopsy, finding out that, achlorhydric patients (15 on 19) with normal or slightly altered antrus, have gastrinemia (222 +/- 123 Pgo/oo) and the majority of patients with normal gastrinemia (32 +/- 16 pgo/oo) have more important antral lesions. The ratio between antral histology and ACCP in auto--immune gastritis (Type A), conciliates only partially with the observation by Strickland et al., as only 52.4% of achlorhydric patients and ACCP have a normal antrus or al least with mild lesions. Our results suggest the possibility of that on auto--immune gastritis could act other pathogenic factors of antral lesion.

  6. Assessing the risk of pH-dependent absorption for new molecular entities: a novel in vitro dissolution test, physicochemical analysis, and risk assessment strategy.

    Science.gov (United States)

    Mathias, Neil R; Xu, Yan; Patel, Dhaval; Grass, Michael; Caldwell, Brett; Jager, Casey; Mullin, Jim; Hansen, Luke; Crison, John; Saari, Amy; Gesenberg, Christoph; Morrison, John; Vig, Balvinder; Raghavan, Krishnaswamy

    2013-11-04

    Weak base therapeutic agents can show reduced absorption or large pharmacokinetic variability when coadministered with pH-modifying agents, or in achlorhydria disease states, due to reduced dissolution rate and/or solubility at high gastric pH. This is often referred to as pH-effect. The goal of this study was to understand why some drugs exhibit a stronger pH-effect than others. To study this, an API-sparing, two-stage, in vitro microdissolution test was developed to generate drug dissolution, supersaturation, and precipitation kinetic data under conditions that mimic the dynamic pH changes in the gastrointestinal tract. In vitro dissolution was assessed for a chemically diverse set of compounds under high pH and low pH, analogous to elevated and normal gastric pH conditions observed in pH-modifier cotreated and untreated subjects, respectively. Represented as a ratio between the conditions, the in vitro pH-effect correlated linearly with clinical pH-effect based on the Cmax ratio and in a non-linear relationship based on AUC ratio. Additionally, several in silico approaches that use the in vitro dissolution data were found to be reasonably predictive of the clinical pH-effect. To explore the hypothesis that physicochemical properties are predictors of clinical pH-effect, statistical correlation analyses were conducted using linear sequential feature selection and partial least-squares regression. Physicochemical parameters did not show statistically significant linear correlations to clinical pH-effect for this data set, which highlights the complexity and poorly understood nature of the interplay between parameters. Finally, a strategy is proposed for implementation early in clinical development, to systematically assess the risk of clinical pH-effect for new molecular entities that integrates physicochemical analysis and in vitro, in vivo and in silico methods.

  7. Study on histogenesis of enterochromaffin-like carcinoid in autoimmune atrophic gastritis associated with pernicious anemia

    Directory of Open Access Journals (Sweden)

    Mačukanović-Golubović Lana

    2007-01-01

    Full Text Available Background/Aim. Autoimmune atrophic fundic gastritis induces the pernicious anemia (PA, as well as the changes in both epithelium and endocrine cells of gastric mucosa. The most important complications are: achlorhydria, hypergastrinemia, gastric cancer and enterochromaffin-like ( ECL carcinoid. The aim of this study was to examine ECL carcinoid histogenesis in A-gastritis associated with PA. Methods. During the period from 2000−2006, 65 patients with PA and 30 patients of the control group were examined. Histopathological examination was done in endoscopical biopsies of gastric mucosa fixed in 10% formaldehyde. Paraffin sections were stained with classic hematoxylin-eosin (HE; histochemical AB-PAS (pH 2.5, cytochemical argyrophilic Servier-Munger′s and immunocytochemical PAP methods for G cell identification and chromogranin A antibodies - specific marker for neuroendocrine ECL cells. Both G and ECL cells were counted per 20 fields, of surface 0.0245312 mm2 by a field. Basal gastrin serum levels were also examined by using radioimmunoassay (RIA method. The obtained results were statisticaly calculated by using Student΄s t test. Results. Marked antral G cell hyperplasia associated with corporal ECL hyperplasia was found. ECL cell hyperplasia was of simplex, linear, adenomatoid type to the pattern of intramucous ECL cell carcinoid. An average number of G cells was statistically significant in the patients with PA as compared to the control group (p < 0.05 as well as an average number of ECL cells. Conclusion. We concluded that antral G cell hyperplasia accompanied by gastrinemia induces ECL hyperplasia and ECL corporal carcinoid in A-gastritis and that their histogenesis develops trough simple, linear and adenomatoide hyperplasia. .

  8. Early manifestations of gastric autoimmunity in patients with juvenile autoimmune thyroid diseases.

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    Segni, Maria; Borrelli, Osvaldo; Pucarelli, Ida; Delle Fave, Gianfranco; Pasquino, Anna Maria; Annibale, Bruno

    2004-10-01

    Juvenile patients affected with autoimmune thyroid disorders showed a 14-21% prevalence of parietal cell antibodies (PCA) reacting against the H+/K+-ATPase of the gastric parietal cells. PCA are the principal immunological markers of atrophic body gastritis (ABG).ABG is characterized by loss of oxyntic glands, achlorhydria, and hypergastrinemia. The aim of this study was to determine whether PCA positivity could be associated with biochemical and histological manifestations of gastric autoimmunity in juvenile patients with autoimmune thyroid disease (AITD). We studied 129 children (96 females and 33 males) with chronic lymphocytic thyroiditis (n = 115) or Graves' disease (n = 14). Mean age at diagnosis of AITD was 9.7 +/- 3.3 yr, and mean age at sampling was 12.3 +/- 3.7 yr. We determined PCA and Helicobacter pylori antibodies, gastrin, and pepsinogen I plasma levels. Gastroscopy with multiple biopsies was carried out in a subgroup of patients with PCA positivity. We found that 30% of children had detectable PCA. Hypergastrinemia was found in 45% of the PCA-positive children (range, 40-675 pg/ml) vs. 12% of PCA-negative children (range, 35-65 pg/ml; P < 0.001). Eighteen patients with PCA positivity underwent gastroscopy; eight of these children had normogastrinemia, which showed no signs of ABG, and 10 children had hypergastrinemia, of whom five had mild to severe ABG. Our study shows that autoimmune gastritis is an early event in juvenile AITD with detectable PCA. Gastrin plasma level is a reliable marker of gastric atrophy.

  9. Lack of commensal flora in H. pylori-infected INS-GAS mice reduces gastritis and delays intraepithelial neoplasia

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    Lofgren, Jennifer L.; Whary, Mark T.; Ge, Zhongming; Muthupalani, Sureshkumar; Taylor, Nancy S.; Mobley, Melissa; Potter, Amanda; Varro, Andrea; Eibach, Daniel; Suerbaum, Sebastian; Wang, Timothy C.; Fox, James G.

    2010-01-01

    Background & Aims Transgenic, insulin–gastrin (INS–GAS) mice have high circulating levels of gastrin. On a FVB/N background, these mice develop spontaneous atrophic gastritis and gastrointestinal intraepithelial neoplasia (GIN) with 80% prevalence 6 months after Helicobacter pylori infection. GIN is associated with gastric atrophy and achlorhydria, predisposing mice to non-helicobacter microbiota overgrowth. We determined if germ-free INS–GAS mice spontaneously develop GIN and if H. pylori accelerates GIN in gnotobiotic INS–GAS mice. Methods We compared gastric lesions and levels of mRNA, serum inflammatory mediators, antibodies, and gastrin among germ-free and H. pylori-monoinfected INS-GAS mice. Microbiota composition of specific pathogen-free (SPF) INS-GAS mice was quantified by pyro-sequencing. Results Germ-free INS-GAS mice had mild hypergastrinemia but did not develop significant gastric lesions until they were 9 months old; they did not develop GIN through 13 months. H. pylori monoassociation caused progressive gastritis, epithelial defects, oxyntic gland atrophy, marked foveolar hyperplasia and dysplasia, and strong serum and tissue proinflammatory immune responses (particularly in male mice) between 5 and 11 months post infection (P<0.05, compared with germ-free controls). Only 2 of 26 female, whereas 8 of 18 male, H. pylori-infected INS-GAS mice developed low- to high-grade GIN by 11 months post infection. Stomachs of H. pylori-infected SPF male mice had significant reductions in Bacteroidetes and significant increases in Firmicutes. Conclusions Gastric lesions take 13 months longer to develop in germ-free INS–GAS mice than male SPF INS-GAS mice. H. pylori-monoassociation accelerated gastritis and GIN but caused less-severe gastric lesions and delayed onset of GIN compared to H. pylori-infected INS-GAS mice with complex gastric microbiota. Changes of gastric microbiota composition might promote GIN in the achlorhydric stomachs of SPF mice. PMID

  10. Enterococcus faecalis infection causes inflammation, intracellular oxphos-independent ROS production, and DNA damage in human gastric cancer cells.

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    Jesper A B Strickertsson

    Full Text Available BACKGROUND: Achlorhydria caused by e.g. atrophic gastritis allows for bacterial overgrowth, which induces chronic inflammation and damage to the mucosal cells of infected individuals driving gastric malignancies and cancer. Enterococcus faecalis (E. faecalis can colonize achlohydric stomachs and we therefore wanted to study the impact of E. faecalis infection on inflammatory response, reactive oxygen species (ROS formation, mitochondrial respiration, and mitochondrial genetic stability in gastric mucosal cells. METHODS: To separate the changes induced by bacteria from those of the inflammatory cells we established an in vitro E. faecalis infection model system using the gastric carcinoma cell line MKN74. Total ROS and superoxide was measured by fluorescence microscopy. Cellular oxygen consumption was characterized non-invasively using XF24 microplate based respirometry. Gene expression was examined by microarray, and response pathways were identified by Gene Set Analysis (GSA. Selected gene transcripts were verified by quantitative real-time polymerase chain reaction (qRT-PCR. Mitochondrial mutations were determined by sequencing. RESULTS: Infection of MKN74 cells with E. faecalis induced intracellular ROS production through a pathway independent of oxidative phosphorylation (oxphos. Furthermore, E. faecalis infection induced mitochondrial DNA instability. Following infection, genes coding for inflammatory response proteins were transcriptionally up-regulated while DNA damage repair and cell cycle control genes were down-regulated. Cell growth slowed down when infected with viable E. faecalis and responded in a dose dependent manner to E. faecalis lysate. CONCLUSIONS: Infection by E. faecalis induced an oxphos-independent intracellular ROS response and damaged the mitochondrial genome in gastric cell culture. Finally the bacteria induced an NF-κB inflammatory response as well as impaired DNA damage response and cell cycle control gene

  11. Impaired myelination and reduced brain ferric iron in the mouse model of mucolipidosis IV

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    Yulia Grishchuk

    2015-12-01

    Full Text Available Mucolipidosis type IV (MLIV is a lysosomal storage disease caused by mutations in the MCOLN1 gene, which encodes the lysosomal transient receptor potential ion channel mucolipin-1 (TRPML1. MLIV causes impaired motor and cognitive development, progressive loss of vision and gastric achlorhydria. How loss of TRPML1 leads to severe psychomotor retardation is currently unknown, and there is no therapy for MLIV. White matter abnormalities and a hypoplastic corpus callosum are the major hallmarks of MLIV brain pathology. Here, we report that loss of TRPML1 in mice results in developmental aberrations of brain myelination as a result of deficient maturation and loss of oligodendrocytes. Defective myelination is evident in Mcoln1−/− mice at postnatal day 10, an active stage of postnatal myelination in the mouse brain. Expression of mature oligodendrocyte markers is reduced in Mcoln1−/− mice at postnatal day 10 and remains lower throughout the course of the disease. We observed reduced Perls' staining in Mcoln1−/− brain, indicating lower levels of ferric iron. Total iron content in unperfused brain is not significantly different between Mcoln1−/− and wild-type littermate mice, suggesting that the observed maturation delay or loss of oligodendrocytes might be caused by impaired iron handling, rather than by global iron deficiency. Overall, these data emphasize a developmental rather than a degenerative disease course in MLIV, and suggest that there should be a stronger focus on oligodendrocyte maturation and survival to better understand MLIV pathogenesis and aid treatment development.

  12. Netazepide, a gastrin receptor antagonist, normalises tumour biomarkers and causes regression of type 1 gastric neuroendocrine tumours in a nonrandomised trial of patients with chronic atrophic gastritis.

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    Andrew R Moore

    Full Text Available INTRODUCTION: Autoimmune chronic atrophic gastritis (CAG causes hypochlorhydria and hypergastrinaemia, which can lead to enterochromaffin-like (ECL cell hyperplasia and gastric neuroendocrine tumours (type 1 gastric NETs. Most behave indolently, but some larger tumours metastasise. Antrectomy, which removes the source of the hypergastrinaemia, usually causes tumour regression. Non-clinical and healthy-subject studies have shown that netazepide (YF476 is a potent, highly selective and orally-active gastrin/CCK-2 receptor antagonist. Also, it is effective in animal models of ECL-cell tumours induced by hypergastrinaemia. AIM: To assess the effect of netazepide on tumour biomarkers, number and size in patients with type I gastric NETs. METHODS: We studied 8 patients with multiple tumours and raised circulating gastrin and chromogranin A (CgA concentrations in an open trial of oral netazepide for 12 weeks, with follow-up 12 weeks later. At 0, 6, 12 and 24 weeks, we carried out gastroscopy, counted and measured tumours, and took biopsies to assess abundances of several ECL-cell constituents. At 0, 3, 6, 9, 12 and 24 weeks, we measured circulating gastrin and CgA and assessed safety and tolerability. RESULTS: Netazepide was safe and well tolerated. Abundances of CgA (p<0.05, histidine decarboxylase (p<0.05 and matrix metalloproteinase-7(p<0.10 were reduced at 6 and 12 weeks, but were raised again at follow-up. Likewise, plasma CgA was reduced at 3 weeks (p<0.01, remained so until 12 weeks, but was raised again at follow-up. Tumours were fewer and the size of the largest one was smaller (p<0.05 at 12 weeks, and remained so at follow-up. Serum gastrin was unaffected. CONCLUSION: The reduction in abundances, plasma CgA, and tumour number and size by netazepide show that type 1 NETs are gastrin-dependent tumours. Failure of netazepide to increase serum gastrin further is consistent with achlorhydria. Netazepide is a potential new treatment for type 1 NETs

  13. Contribuição ao estudo das doenças hereditárias

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    Ernani Martins da Silva

    1945-08-01

    -Marie's disease, epilepsy, keratosis follicularis or Darier's disease, brachy-dactyly and gastric cancer have been described individuals whose behavior with reference to heredity is very similar to the siclemic in sicle cell anemia. These individuals by means of special proofs are identified because they present very early (in some cases congenital some of the clinical signs of the disease. These observations shows: a that it is possible to identify the heirs of a pathological condition before the development of the disease and consequently, also the carriers; b that the presence of identificable carriers is a characteristic of hereditary diseases, perhaps excepting congenital anomalies. They also suggest that the skipping phenomenon should be related with the carriers. It is suggested a census and periodical examinations of these individuals with a view to get some data about the factors responsible for the development of the disease. Perhaps these data might contribute to establish the basis of eventual prophylactic measures against the above mentioned diseases. In Biermer's pernicious anemia the hepathotherapy should be applied to the individuals with gastric achlorhydria, as it it was advised by Askey, as a preventive.

  14. [Clinical studies of pediatric malabsorption syndromes].

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    Hosoyamada, Takashi

    2006-11-01

    not maintain normal serum zinc ranges. Light microscopic studies of the intestinal villous architecture showed a normal pattern. However, ultrastructual examination of several epithelial cells revealed numerous intracellular vesicles. After zinc therapy, these changes were decreased. The lesions were postulated as the secondary result of zinc deficiency. 8. A 12-year-old girl presented with hypogammaglobulinemia, recurrent infections, chronic diarrhea and intestinal NLH. A barium meal and follow-through examination showed multiple nodules throughout the stomach and intestine. The nodules, all uniform in size, were 2 mm diameter. The barium enema did not show NLH in the colon. Mucosal biopsy of the stomach and jejunum revealed the typical histology of NLH in the lamina propria. Also, achlorhydria was present in this patient and her serum gastrin levels were very high; 315-775 pg/ml. 9. In 4 cases of intractable diarrhea in early infancy (by Avery G B), a jejunal biopsy showed shortening villi and nonspecific enterocolitis. Some patients were found with only low lactase or low lactase and sucrase levels. An electron microscope analysis of the small bowel in 2 cases showed alterations: increased pinocytosis in microvillus membranes and lysosomes by endocytosis of undigested macromolecular substances. I postulated that the stated evidence was causative of this clinical profile. 10. I frequently observed diarrhea as a clinical manifestation in glycogenosis type Ia and lipid malabsorption in one case. The light and electron photomicrographs showed intestinal absorption cells with the glycogen deposits in the inferior devision of nuclei.

  15. Sensibilidade vibratória: valor semiótico em algumas afecções do sistema nervoso

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    Horacio Martins Canelas

    1958-12-01

    bears a close relation to the severeness of the whole neurologic picture. 5. In cases of herniated nucleus pulposus the test of vibration sense can cooperate in the diagnosis of the side of the protrusion. However, it must be emphasized that the changes in pallesthesia have not, in such cases, the semiotic significance which some authors have assigned to them. 6. In the subacute combined degenerations of the spinal cord, with constitutional or acquired achlorhydria, the test of vibration sense is imperative, owing to the early and marked impairment of this form of sensation. The quantitative method can disclose, in several cases, the existence of pallesthesic changes not shown by routine procedures, particularly those involving the upper limbs. 7. In poliradiculoneuritis the vibration sense is deeply impaired, even in the upper limbs, where other forms of sensation can be normal by routine examination. 8. In trigeminal nerve lesions the quantitative test of vibration sense is of little semiotic significance, owing to the great variability of the thresholds in the head and to the frequent confusion between vibration and auditory senses. In the four cases tested the increase of the thresholds was slight, even in two cases with associated facial palsy. 9. In cases of parietal lobe injuries, including two cases of hemisphe-rectomy, the impairment of vibration sense is remarkable and coincident or not with changes in the joint sense. 10. In other diseases of the nervous system, the quantitative test of vibration sense has proved worthful for the diagnosis, either as a positive or sometimes as a negative finding.