1,378 results on '"Achlorhydria"'
Search Results
2. Atteinte digestive de la sclérodermie systémique.
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Renaud, A., Jirka, A., Durant, C., Connault, J., Espitia, O., Takoudju, C., and Agard, C.
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SYSTEMIC scleroderma , *GASTROESOPHAGEAL reflux , *MALNUTRITION , *ACHLORHYDRIA , *QUALITY of life - Abstract
L'atteinte digestive de la sclérodermie systémique concerne plus de 90 % des patients mais est d'expression clinique hétérogène. Elle peut potentiellement intéresser tout le tractus intestinal et être responsable à terme d'une malnutrition multifactorielle, fréquente dans cette pathologie. Elle est une source majeure d'altération de la qualité de vie et peut même mettre en jeu le pronostic vital. La prise en charge est complexe et multidisciplinaire, allant de simples mesures hygiénodiététiques, à des procédures interventionnelles endoscopiques ou chirurgicales spécialisées, en passant par des médicaments, notamment inhibiteurs de la pompe à proton et prokinétiques, non dénués d'effets secondaires. Des perspectives de nouveaux outils diagnostiques et thérapeutiques font espérer une amélioration de la prise en charge et du pronostic de ces patients. Gastrointestinal tract involvement in systemic sclerosis concerns more than 90% of patients but is of heterogeneous clinical expression. It can involve the entire intestinal tract and be responsible for multifactorial malnutrition, which is frequent in this disease. It is a major source of deterioration in the quality of life and can even be life-threatening. Management is complex and multidisciplinary, ranging from simple hygienic and dietary measures, to specialized endoscopic or surgical interventional procedures, also including medical treatments, particularly proton pump inhibitors and prokinetics, with potential side effects. Ongoing research for new diagnostic and therapeutic tools promises to improve the management and prognosis of these patients. [ABSTRACT FROM AUTHOR]
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- 2023
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3. Study to Evaluate Effects of Food or Proton Pump Inhibitor on the Pharmacokinetics of Itraconazole in Healthy Volunteers
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SeungHwan Lee, Associate Professor
- Published
- 2021
4. Hypochlorhydria reduces mortality in heart failure caused by Kcne2 gene deletion
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Lisewski, Ulrike, Köhncke, Clemens, Schleussner, Leonhard, Purfürst, Bettina, Lee, Soo Min, De Silva, Angele, Manville, Rían W, Abbott, Geoffrey W, and Roepke, Torsten K
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Microbiology ,Biological Sciences ,Biomedical and Clinical Sciences ,Cardiovascular ,Prevention ,Heart Disease ,Genetics ,2.1 Biological and endogenous factors ,Aetiology ,Good Health and Well Being ,Achlorhydria ,Animals ,Bacteroides ,Cardiomyopathy ,Dilated ,Female ,Gastric Acid ,Gastrointestinal Microbiome ,Gene Deletion ,Heart ,Heart Failure ,Male ,Mice ,Mice ,Inbred C57BL ,Mice ,Knockout ,Potassium Channels ,Voltage-Gated ,Risk Factors ,dilated cardiomyopathy ,heart failure ,KCNE ,microbiome ,potassium channel ,Biochemistry and Cell Biology ,Physiology ,Medical Physiology ,Biochemistry & Molecular Biology ,Biochemistry and cell biology ,Medical physiology - Abstract
Heart failure (HF) is an increasing global health crisis, affecting 40 million people and causing 50% mortality within 5 years of diagnosis. A fuller understanding of the genetic and environmental factors underlying HF, and novel therapeutic approaches to address it, are urgently warranted. Here, we discovered that cardiac-specific germline deletion in mice of potassium channel β subunit-encoding Kcne2 (Kcne2CS-/- ) causes dilated cardiomyopathy and terminal HF (median longevity, 28 weeks). Mice with global Kcne2 deletion (Kcne2Glo-/- ) exhibit multiple HF risk factors, yet, paradoxically survived over twice as long as Kcne2CS-/- mice. Global Kcne2 deletion, which inhibits gastric acid secretion, reduced the relative abundance of species within Bacteroidales, a bacterial order that positively correlates with increased lifetime risk of human cardiovascular disease. Strikingly, the proton-pump inhibitor omeprazole similarly altered the microbiome and delayed terminal HF in Kcne2CS-/- mice, increasing survival 10-fold at 44 weeks. Thus, genetic or pharmacologic induction of hypochlorhydria and decreased gut Bacteroidales species are associated with lifespan extension in a novel HF model.
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- 2020
5. Gastric Parietal Cell Regeneration by Nano-Scaffolding in Hypochlorhydria and Achlorhydria Treatment
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Bukva, Merima, Pulo, Evelina, Omerović, Naida, Škrbo, Selma, Magjarevic, Ratko, Series Editor, Ładyżyński, Piotr, Associate Editor, Ibrahim, Fatimah, Associate Editor, Lackovic, Igor, Associate Editor, Rock, Emilio Sacristan, Associate Editor, Badnjevic, Almir, editor, and Gurbeta Pokvić, Lejla, editor
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- 2021
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6. A Case of Severe Hypocalcemia Caused by Malabsorption Due to Partial Gastrectomy and Small Bowel Resection
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John O. Knight, MD, Lucia F. Cotten, MD, Thomas R. Ziegler, MD, and Priyathama Vellanki, MD
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achlorhydria ,gastrectomy ,hypocalcemia ,malabsorption ,small bowel resection ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
Objective: Calcium is an essential mineral involved in the functioning of nearly every human cell. Calcium levels are regulated by dietary absorption, vitamin D status, and parathyroid hormone (PTH). This report describes a patient in whom childhood bowel resection and partial gastrectomy resulted in malabsorptive hypocalcemia in adulthood. Case Report: A 21-year-old man presented with syncope and a fall resulting in a right femoral neck fracture. His medical history included small bowel obstructions at age 9 requiring bowel resection, and at age 12 with gastric perforation and partial gastrectomy. Laboratory values showed calcium level of 4.9 mg/dL (8.9-10.3 mg/dL). PTH level was 273 pg/mL (12.0-88.0 pg/mL), 25-hydroxy-vitamin D was 28 ng/dL (30-100 ng/mL), and 1,25-dihydroxy-vitamin D was 54 pg/dL (18-72 pg/mL). Furthermore, magnesium and phosphorus levels were 2.1 mg/dL (1.5-2.6 mg/dL) and 4.4 mg/dL (2.4-4.7 mg/dL), respectively. Calcium levels improved to 9.5 mg/dL on 10% calcium gluconate drip but could not be maintained above 7 mg/dL on oral calcium carbonate supplementation, despite doses as high as 3750 mg three times daily with calcitriol 0.75 mcg twice daily. After switching from calcium carbonate to calcium citrate 3500 mg three times daily, the calcium level improved and was maintained between 8.3 and 9.0 mg/dL. Discussion: High calcium needs, other nutrient deficiencies, and response to calcium citrate versus calcium carbonate suggest malabsorption from achlorhydria and small bowel resection. Conclusion: This case emphasizes the gastrointestinal physiology in calcium homeostasis and highlights the recognition of hypocalcemia as a complication of gastric and bowel resection.
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- 2021
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7. Meal Effects Confound Attempts to Counteract Rabeprazole-Induced Hypochlorhydria Decreases in Atazanavir Absorption
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Faber, Kathleen Panter, Wu, Hsin-Fang, Yago, Marc R, Xu, Xiaohui, Kadiyala, Pathanjali, Frassetto, Lynda A, and Benet, Leslie Z
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Pharmacology and Pharmaceutical Sciences ,Biomedical and Clinical Sciences ,Clinical Trials and Supportive Activities ,Clinical Research ,Infectious Diseases ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Absorption ,Physiological ,Achlorhydria ,Administration ,Oral ,Adult ,Atazanavir Sulfate ,Betaine ,Cross-Over Studies ,Drug Interactions ,Female ,Food-Drug Interactions ,HIV Protease Inhibitors ,Humans ,Male ,Middle Aged ,Proton Pump Inhibitors ,Rabeprazole ,Ritonavir ,Young Adult ,absorption ,atazanavir ,food effects ,PPIs ,weakly basic drugs ,Pharmacology & Pharmacy ,Pharmacology and pharmaceutical sciences - Abstract
PurposeClinically relevant pharmacokinetic interactions exist between gastric acid-reducing agents and certain weakly basic drugs that rely on acidic environments for optimal oral absorption. In this study, we examine whether the administration of betaine hydrochloride under fed conditions can enhance the absorption of atazanavir, an HIV-1 protease inhibitor, during pharmacologically-induced hypochlorhydria.MethodsIn this randomized, single-dose, 3 period, crossover study healthy volunteers received ritonavir-boosted atazanavir (atazanavir/ritonavir 300/100 mg) alone, following pretreatment with the proton pump inhibitor rabeprazole (20 mg twice daily), and with 1500 mg of betaine HCl after rabeprazole pretreatment. Atazanavir was administered with a light meal and gastric pH was monitored using the Heidelberg Capsule.ResultsPretreatment with rabeprazole resulted in significant reductions in atazanavir Cmax (p
- Published
- 2017
8. In vitro digestion mimicking conditions in adults and elderly reveals digestive characteristics of pork from different cooking ways.
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Cao, Xiangyue, Zhao, Fan, Lin, Ziyi, Sun, Xiaomei, Zeng, Xianming, Liu, Haoxi, Li, Yutong, Yuan, Zihang, Su, Yuan, Wang, Chong, and Zhou, Guanghong
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DIGESTION , *ADULTS , *OLDER people , *PROTEOLYSIS , *PORK processing , *PORK , *ZETA potential - Abstract
[Display omitted] • Changes of gastrointestinal conditions affect protein digestibility. • Differences between control and EA condition diminished between two phases. • The digestive characteristics of pork cooked by different ways were different. • Sous vide is more recommendable to enhance protein digestibility for the elderly. This study aimed to investigate the impact of three cooking ways (sous vide (SV), frying (FR) and roasting (RO)) on pork protein digestion characteristics under conditions simulating healthy adult (control, C) and elderly individuals with achlorhydria (EA). Changes in degree of hydrolysis (DH), SDS-PAGE profiles, zeta potential, particle size and secondary structure during digestion were evaluated. Our results revealed the EA condition markedly affected the protein digestion process of pork with different cooking ways. The DH values of SV (25.62%), FR (21.38%) and RO (19.40%) under the EA condition were significantly lower than those of under the control condition (38.32%, 33.00% and 30.86%, respectively). Moreover, differences were also observed among three cooking ways under the EA condition. For a given cooking way, the differences between control and EA conditions gradually diminished from the gastric to the intestinal phase. Under a certain digestion condition, SV maintained the highest degree of digestion throughout the process, particularly under the EA condition. Therefore, we conclude that pork cooked by sous vide is more recommendable for the elderly considering protein digestibility. [ABSTRACT FROM AUTHOR]
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- 2024
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9. Sham Feeding Induced Gastric Acid Secretion in Patients with Caustic Induced Esophageal Stricture.
- Author
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Shah, Jimil, Bush, Nikhil, Mahesh, T., Nain, C. K., and Kochhar, Rakesh
- Abstract
Caustic ingestion can lead to structural changes in the upper gastro-intestinal tract. However, there is limited data on the effect of caustic ingestion on gastric secretion. This study was planned to determine changes in gastric acid output after sham feeding in patients with caustic induced esophageal stricture and to compare it with healthy controls. It was a prospective study done at tertiary care center in North India. Consecutive patients with caustic induced esophageal stricture were evaluated for the study. Gastric secretory function was estimated in the basal state and after modified sham feeding. These results were compared with age-matched controls. The mean age of the included patients (n = 18) was 30.11 ± 9.19 years and 13 patients were male. 16 (88%) patients had history of acid ingestion. Patients with caustic sequelae had significantly lower basal and stimulated acid secretion compared to controls (n = 10) (5.84 ± 2.44 mmol/hr; p < 0.01 and 17.16 ± 7.53 mmol/hr; p < 0.01; respectively). Patients with lower esophageal stricture (n = 8) had significantly lower increase in acid output compared to patients with stricture elsewhere in esophagus (0.20 ± 0.3 vs. 2.31 ± 1.74 mmol/hr, p < 0.01). Patients with lower esophageal involvement had significantly lower stimulated acid secretion and increase in acid secretion compared to controls (4.74 ± 4.67 vs. 17.16 ± 7.53 mmol/hr; p < 0.01 and 20 ± 0.3 vs. 2.09 ± 0.88 mmol/hr; p < 0.01; respectively). [ABSTRACT FROM AUTHOR]
- Published
- 2022
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10. The Use of Betaine HCl to Enhance Dasatinib Absorption in Healthy Volunteers with Rabeprazole-Induced Hypochlorhydria
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Yago, Marc R, Frymoyer, Adam, Benet, Leslie Z, Smelick, Gillian S, Frassetto, Lynda A, Ding, Xiao, Dean, Brian, Salphati, Laurent, Budha, Nageshwar, Jin, Jin Y, Dresser, Mark J, and Ware, Joseph A
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Clinical Research ,5.1 Pharmaceuticals ,Development of treatments and therapeutic interventions ,Absorption ,Physiological ,Achlorhydria ,Adult ,Antineoplastic Agents ,Area Under Curve ,Betaine ,Cross-Over Studies ,Dasatinib ,Drug Interactions ,Female ,Gastric Acid ,Healthy Volunteers ,Humans ,Hydrogen-Ion Concentration ,Male ,Middle Aged ,Proton Pump Inhibitors ,Pyrimidines ,Rabeprazole ,Thiazoles ,Young Adult ,betaine hydrochloride ,dasatinib ,drug-drug interactions ,pH-dependent solubility ,proton pump inhibitors ,Pharmacology and Pharmaceutical Sciences ,Pharmacology & Pharmacy - Abstract
Many orally administered, small-molecule, targeted anticancer drugs, such as dasatinib, exhibit pH-dependent solubility and reduced drug exposure when given with acid-reducing agents. We previously demonstrated that betaine hydrochloride (BHCl) can transiently re-acidify gastric pH in healthy volunteers with drug-induced hypochlorhydria. In this randomized, single-dose, three-way crossover study, healthy volunteers received dasatinib (100 mg) alone, after pretreatment with rabeprazole, and with 1500 mg BHCl after rabeprazole pretreatment, to determine if BHCl can enhance dasatinib absorption in hypochlorhydric conditions. Rabeprazole (20 mg b.i.d.) significantly reduced dasatinib Cmax and AUC0-∞ by 92 and 78%, respectively. However, coadministration of BHCl significantly increased dasatinib Cmax and AUC0-∞ by 15- and 6.7-fold, restoring them to 105 and 121%, respectively, of the control (dasatinib alone). Therefore, BHCl reversed the impact of hypochlorhydria on dasatinib drug exposure and may be an effective strategy to mitigate potential drug-drug interactions for drugs that exhibit pH-dependent solubility and are administered orally under hypochlorhydric conditions.
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- 2014
11. Clinical Experiment of Helicobacter Pylori Transmission
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Julie Parsonnet, Principle Investigator
- Published
- 2016
12. Gastric Reacidification with Betaine HCl in Healthy Volunteers with Rabeprazole-Induced Hypochlorhydria
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Yago, Marc R, Frymoyer, Adam R, Smelick, Gillian S, Frassetto, Lynda A, Budha, Nageshwar R, Dresser, Mark J, Ware, Joseph A, and Benet, Leslie Z
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Digestive Diseases ,Clinical Research ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Achlorhydria ,Adult ,Anti-Ulcer Agents ,Betaine ,Female ,Healthy Volunteers ,Humans ,Hydrogen-Ion Concentration ,Male ,Middle Aged ,Proton Pump Inhibitors ,Rabeprazole ,betaine hydrochloride ,gastric reacidification ,hypochlorhydria ,pH-dependent solubility ,proton pump inhibitor ,drug-drug interaction ,Macromolecular and Materials Chemistry ,Pharmacology and Pharmaceutical Sciences ,Pharmacology & Pharmacy - Abstract
Previous studies have demonstrated that increased gastric pH from the use of acid-reducing agents, such as proton-pump inhibitors or H2-receptor antagonists, can significantly impact the absorption of weakly basic drugs that exhibit pH-dependent solubility. Clinically practical strategies to mitigate this interaction have not been developed. This pilot study evaluated the extent and time course of gastric reacidification after a solid oral dosage form of anhydrous betaine HCl in healthy volunteers with pharmacologically induced hypochlorhydria. Six healthy volunteers with baseline normochlorhydria (fasting gastric pH < 4) were enrolled in this single period study. Hypochlorhydria was induced via 20 mg oral rabeprazole twice daily for four days. On the fifth day, an additional 20 mg dose of oral rabeprazole was given and gastric pH was monitored continuously using the Heidelberg pH capsule. After gastric pH > 4 was confirmed for 15 min, 1500 mg of betaine HCl was given orally with 90 mL of water and gastric pH was continuously monitored for 2 h. Betaine HCl significantly lowered gastric pH by 4.5 (± 0.5) units from 5.2 (± 0.5) to 0.6 (± 0.2) (P < 0.001) during the 30 min interval after administration. The onset of effect of betaine HCl was rapid, with a mean time to pH < 3 of 6.3 (± 4.3) min. The reacidification period was temporary with a gastric pH < 3 and < 4 lasting 73 (± 33) and 77 (± 30) min, respectively. Betaine HCl was well tolerated by all subjects. In healthy volunteers with pharmacologically induced hypochlorhydria, betaine HCl was effective at temporarily lowering gastric pH. The rapid onset and relatively short duration of gastric pH reduction gives betaine HCl the potential to aid the absorption of orally administered weakly basic drugs that exhibit pH-dependent solubility when administered under hypochlorhydric conditions.
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- 2013
13. Gastric secretion in patients with caustic ingestion: A prospective study.
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Shah, Jimil, Bush, Nikhil, Rajan, K., Nain, C. K., Singh, Kartar, and Kochhar, Rakesh
- Abstract
Background: Caustic ingestion can lead to structural changes in the upper gastrointestinal tract. However, there are limited data on the effect of caustic ingestion on gastric secretion. This study was planned to determine the changes in gastric acid output in patients with caustic ingestion. Methods: It was a prospective study done at a tertiary care center in northern India. Twenty consecutive patients in chronic phase of caustic ingestion were evaluated for the study. The gastric secretory function was estimated in the basal state and following pentagastrin stimulation. These results were compared with normal values for our laboratory. Results: The mean age of the included patients (n = 20) was 27.35 ± 2.96 years and 14 patients were male. Sixteen (80%) patients had a history of acid ingestion. Patients with caustic ingestion had significantly lower mean gastric acid secretion (0.8 ± 0.4 mEq/h vs. 4 ± 0.4 mEq/h; p < 0.001) compared to controls. After pentagastrin stimulation, the mean gastric juice volume (31.8 ± 6 mL/h vs. 62.3 ± 11.7 mL/h; p < 0.01) and acidity (15.3 ± 5.1 mEq/L vs. 39.6 ± 9.3 mEq/L; p < 0.001) increased in patients with caustic ingestion, but were lower than those in control subjects. Patients with a lower esophageal stricture (n = 6) had decreased maximum acid output (0.62 ± 0.32 mEq/h vs. 6.05 ± 0.55 mEq/h; p < 0.05) compared to patients with stricture in the upper or middle esophagus. Conclusion: Caustic ingestion is associated with reduced gastric juice volume and acid output. Patients with stricture in the lower one third of the esophagus are at a higher risk of hypochlorhydria compared to patients with stricture in either the upper or middle esophagus. [ABSTRACT FROM AUTHOR]
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- 2021
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14. Creating a Framework for Treating Autoimmune Gastritis-The Case for Replacing Lost Acid.
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Taylor L, McCaddon A, and Wolffenbuttel BHR
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- Humans, Gastric Mucosa, Nitroso Compounds, Stomach Neoplasms complications, Achlorhydria, Gastritis, Gastritis, Atrophic complications, Gastritis, Atrophic diagnosis, Autoimmune Diseases
- Abstract
Autoimmune gastritis (AIG) is characterized by the destruction of gastric parietal cells, resulting in hypochlorhydria and eventual achlorhydria, as oxyntic glands in the corpus are destroyed and become atrophic. The permanent loss of gastric acid has many impacts-both theoretical and documented. The most concerning of these are hypergastrinemia and increased N-nitroso compounds, both of which increase the risk of gastric cancers. While known deficiencies of B12 and iron are often replaced in AIG, acid is not. Moreover, patients with AIG are often prescribed acid suppression for a stomach that is decidedly no longer acidic, worsening the sequelae of gastric atrophy. Betaine hydrochloride (BHCL) is a short-acting acidifying agent, available over the counter in capsule form. Mealtime acid supplementation has an historic basis and could ameliorate many AIG-related gastrointestinal symptoms. Theoretically, acidification could also reduce the potential for hypergastrinemia and the production of N-nitroso compounds, consequently reducing the risk of gastric cancers. Supplemental vitamin C may also help in preventing gastric N-nitroso formation, regardless of the gastric pH. This narrative review describes the functions of gastric acid in gastrointestinal and immune health, documents the effects of hypochlorhydria in AIG, and proposes potential options for safely re-establishing the acid milieu of the stomach for patients with AIG.
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- 2024
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15. Alterations in SLC4A2, SLC26A7 and SLC26A9 Drive Acid–Base Imbalance in Gastric Neuroendocrine Tumors and Uncover a Novel Mechanism for a Co-Occurring Polyautoimmune Scenario
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Oriol Calvete, José Reyes, Hernán Valdés-Socin, Paloma Martin, Mónica Marazuela, Alicia Barroso, Javier Escalada, Antoni Castells, Raúl Torres-Ruiz, Sandra Rodríguez-Perales, María Currás-Freixes, and Javier Benítez
- Subjects
gastric neuroendocrine tumors (gNETS) ,autoimmune thyrogastric syndrome ,autoimmune polyendocrine syndrome (APS) ,achlorhydria ,solute carriers (SLCs) ,immunodeficiencies ,Cytology ,QH573-671 - Abstract
Autoimmune polyendocrine syndrome (APS) is assumed to involve an immune system malfunction and entails several autoimmune diseases co-occurring in different tissues of the same patient; however, they are orphans of its accurate diagnosis, as its genetic basis and pathogenic mechanism are not understood. Our previous studies uncovered alterations in the ATPase H+/K+ Transporting Subunit Alpha (ATP4A) proton pump that triggered an internal cell acid–base imbalance, offering an autoimmune scenario for atrophic gastritis and gastric neuroendocrine tumors with secondary autoimmune pathologies. Here, we propose the genetic exploration of APS involving gastric disease to understand the underlying pathogenic mechanism of the polyautoimmune scenario. The whole exome sequencing (WES) study of five autoimmune thyrogastric families uncovered different pathogenic variants in SLC4A2, SLC26A7 and SLC26A9, which cotransport together with ATP4A. Exploratory in vitro studies suggested that the uncovered genes were involved in a pathogenic mechanism based on the alteration of the acid–base balance. Thus, we built a custom gene panel with 12 genes based on the suggested mechanism to evaluate a new series of 69 APS patients. In total, 64 filtered putatively damaging variants in the 12 genes of the panel were found in 54.17% of the studied patients and none of the healthy controls. Our studies reveal a constellation of solute carriers that co-express in the tissues affected with different autoimmune diseases, proposing a unique genetic origin for co-occurring pathologies. These results settle a new-fangled genetics-based mechanism for polyautoimmunity that explains not only gastric disease, but also thyrogastric pathology and disease co-occurrence in APS that are different from clinical incidental findings. This opens a new window leading to the prediction and diagnosis of co-occurring autoimmune diseases and clinical management of patients.
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- 2021
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16. Neuroendocrine Neoplasms of the Stomach
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Henderson-Jackson, Evita, Sheikh, Ujalla, Muhammad, Jalil, Coppola, Domenico, Nasir, Aejaz, Nasir, Aejaz, editor, and Coppola, Domenico, editor
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- 2016
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17. Gastric Acid Secretions, Treatments, and Nutritional Consequences
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Zilberboim, Ronit, Bendich, Adrianne, Bendich, Adrianne, Series editor, and Deckelbaum, Richard J., editor
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- 2015
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18. Cobalamin Absorption From Fortified Food (FL-72)
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- 2013
19. Does Omeprazole Decrease Intestinal Calcium Absorption?
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- 2013
20. A case of intestinal myiasis - fact or fiction?
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Bradbury, Richard S
- Published
- 2010
21. Deterioration of apatite orientation in the cholecystokinin B receptor gene (Cckbr)-deficient mouse femurs.
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Mihara Y, Ishimoto T, Ozasa R, Omura T, Yamato Y, Yamada T, Okamoto A, Matsuyama Y, and Nakano T
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- Mice, Animals, Apatites, Bone and Bones, Bone Density, Femur diagnostic imaging, Receptor, Cholecystokinin B, Achlorhydria
- Abstract
Introduction: The discrepancy between bone mineral density (BMD), the gold standard for bone assessment, and bone strength is a constraint in diagnosing bone function and determining treatment strategies for several bone diseases. Gastric hypochlorhydria induced by clinically used proton pump inhibitor (PPI) therapy indicates a discordance between changes in BMD and bone strength. Here, we used Cckbr-deficient mice with gastric hypochlorhydria to examine the effect of gastric hypochlorhydria on bone mass, BMD, and preferential orientation of the apatite crystallites, which is a strong indicator of bone strength., Materials and Methods: Cckbr-deficient mice were created, and their femurs were analyzed for BMD and preferential orientation of the apatite c-axis along the femoral long axis., Results: Cckbr-deficient mouse femurs displayed a slight osteoporotic bone loss at 18 weeks of age; however, BMD was comparable to that of wild-type mice. In contrast, apatite orientation in the femur mid-shaft significantly decreased from 9 to 18 weeks. To the best of our knowledge, this is the first report demonstrating the deterioration of apatite orientation in the bones of Cckbr-deficient mice., Conclusion: Lesions in Cckbr-deficient mice occurred earlier in apatite orientation than in bone mass. Hence, bone apatite orientation may be a promising method for detecting hypochlorhydria-induced osteoporosis caused by PPI treatment and warrants urgent clinical applications., (© 2023. The Japanese Society Bone and Mineral Research.)
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- 2023
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22. An efficient proteome-wide strategy for discovery and characterization of cellular nucleotide-protein interactions.
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Lim, Yan Ting, Prabhu, Nayana, Dai, Lingyun, Go, Ka Diam, Chen, Dan, Sreekumar, Lekshmy, Egeblad, Louise, Eriksson, Staffan, Chen, Liyan, Veerappan, Saranya, Teo, Hsiang Ling, Tan, Chris Soon Heng, Lengqvist, Johan, Larsson, Andreas, Sobota, Radoslaw M., and Nordlund, Pär
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- *
METABOLITES , *PROTEINS , *METABOLIC disorders , *ACHLORHYDRIA , *DISEASES - Abstract
Metabolite-protein interactions define the output of metabolic pathways and regulate many cellular processes. Although diseases are often characterized by distortions in metabolic processes, efficient means to discover and study such interactions directly in cells have been lacking. A stringent implementation of proteome-wide Cellular Thermal Shift Assay (CETSA) was developed and applied to key cellular nucleotides, where previously experimentally confirmed protein-nucleotide interactions were well recaptured. Many predicted, but never experimentally confirmed, as well as novel protein-nucleotide interactions were discovered. Interactions included a range of different protein families where nucleotides serve as substrates, products, co-factors or regulators. In cells exposed to thymidine, a limiting precursor for DNA synthesis, both dose- and time-dependence of the intracellular binding events for sequentially generated thymidine metabolites were revealed. Interactions included known cancer targets in deoxyribonucleotide metabolism as well as novel interacting proteins. This stringent CETSA based strategy will be applicable for a wide range of metabolites and will therefore greatly facilitate the discovery and studies of interactions and specificities of the many metabolites in human cells that remain uncharacterized. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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23. Evaluating Patients With Abnormal Levels of Gastric Acid
- Published
- 2008
24. 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
- Author
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Oriol Calvete, Andrea Varro, D. Mark Pritchard, Alicia Barroso, Marta Oteo, Miguel Ángel Morcillo, Pierfrancesco Vargiu, Steven Dodd, Miriam Garcia, José Reyes, Sagrario Ortega, and Javier Benitez
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ATP4a ,Gastric carcinoids ,Achlorhydria ,Hypergastrinemia ,Oxyntic glands ,Medicine ,Pathology ,RB1-214 - Abstract
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.
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- 2016
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25. Associations of atrophic gastritis and proton-pump inhibitor drug use with vitamin B-12 status, and the impact of fortified foods, in older adults
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M. Clements, Anne M. Molloy, Mary Ward, Miriam Casey, Liadhan McAnena, Eamon Laird, Catherine F Hughes, Fergal Tracey, Leane Hoey, Helene McNulty, James J. Strain, Conal Cunningham, Kevin McCarroll, Maurice O'Kane, K. Porter, and Kristina Pentieva
- Subjects
Gastritis, Atrophic ,Male ,Drug ,Vitamin ,Aging ,medicine.medical_specialty ,Atrophic gastritis ,medicine.drug_class ,media_common.quotation_subject ,Nutritional Status ,Medicine (miscellaneous) ,Proton-pump inhibitor ,proton pump inhibitor drugs ,Gastroenterology ,AcademicSubjects/MED00160 ,AcademicSubjects/MED00060 ,chemistry.chemical_compound ,food-bound malabsorption ,atrophic gastritis ,Internal medicine ,Prevalence ,medicine ,Humans ,Vitamin B12 ,Fortified Food ,older adults ,Aged ,fortified foods ,media_common ,Nutrition and Dietetics ,Pepsinogens ,business.industry ,Achlorhydria ,hypochlorhydria ,Proton Pump Inhibitors ,Vitamin B 12 Deficiency ,medicine.disease ,Vitamin B 12 ,Original Research Communications ,chemistry ,Food, Fortified ,Vitamin B Complex ,Cohort ,vitamin B-12 biomarkers ,Gastric acid ,Female ,business ,Biomarkers - Abstract
Background Atrophic gastritis (AG) and use of proton pump inhibitors (PPIs) result in gastric acid suppression that can impair the absorption of vitamin B-12 from foods. The crystalline vitamin B-12 form, found in fortified foods, does not require gastric acid for its absorption and could thus be beneficial for older adults with hypochlorhydria, but evidence is lacking. Objectives To investigate associations of AG and PPI use with vitamin B-12 status, and the potential protective role of fortified foods, in older adults. Methods Eligible participants (n = 3299) not using vitamin B-12 supplements were drawn from the Trinity-Ulster and Department of Agriculture cohort, a study of noninstitutionalized adults aged ≥60 y and recruited in 2008–2012. Vitamin B-12 status was measured using 4 biomarkers, and vitamin B-12 deficiency was defined as a combined indicator value
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- 2021
26. A Case of Severe Hypocalcemia Caused by Malabsorption Due to Partial Gastrectomy and Small Bowel Resection
- Author
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Lucia Cotten, Priyathama Vellanki, Thomas R. Ziegler, and John O’Connell Knight
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medicine.medical_specialty ,Malabsorption ,malabsorption ,Calcitriol ,medicine.medical_treatment ,Perforation (oil well) ,achlorhydria ,Parathyroid hormone ,chemistry.chemical_element ,Case Report ,030209 endocrinology & metabolism ,Calcium ,hypocalcemia ,Gastroenterology ,Diseases of the endocrine glands. Clinical endocrinology ,03 medical and health sciences ,0302 clinical medicine ,ECF, extracellular fluid ,Internal medicine ,medicine ,D[1,25(OH)2D], 1,25-hydroxy vitamin D ,PTH, parathyroid hormone ,Calcium metabolism ,business.industry ,General Medicine ,Bowel resection ,RC648-665 ,medicine.disease ,gastrectomy ,chemistry ,small bowel resection ,030220 oncology & carcinogenesis ,D[25(OH)D], 25-hydroxy vitamin D ,Gastrectomy ,business ,medicine.drug - Abstract
Objective Calcium is an essential mineral involved in the functioning of nearly every human cell. Calcium levels are regulated by dietary absorption, vitamin D status, and parathyroid hormone (PTH). This report describes a patient in whom childhood bowel resection and partial gastrectomy resulted in malabsorptive hypocalcemia in adulthood. Case Report A 21-year-old man presented with syncope and a fall resulting in a right femoral neck fracture. His medical history included small bowel obstructions at age 9 requiring bowel resection, and at age 12 with gastric perforation and partial gastrectomy. Laboratory values showed calcium level of 4.9 mg/dL (8.9-10.3 mg/dL). PTH level was 273 pg/mL (12.0-88.0 pg/mL), 25-hydroxy-vitamin D was 28 ng/dL (30-100 ng/mL), and 1,25-dihydroxy-vitamin D was 54 pg/dL (18-72 pg/mL). Furthermore, magnesium and phosphorus levels were 2.1 mg/dL (1.5-2.6 mg/dL) and 4.4 mg/dL (2.4-4.7 mg/dL), respectively. Calcium levels improved to 9.5 mg/dL on 10% calcium gluconate drip but could not be maintained above 7 mg/dL on oral calcium carbonate supplementation, despite doses as high as 3750 mg three times daily with calcitriol 0.75 mcg twice daily. After switching from calcium carbonate to calcium citrate 3500 mg three times daily, the calcium level improved and was maintained between 8.3 and 9.0 mg/dL. Discussion High calcium needs, other nutrient deficiencies, and response to calcium citrate versus calcium carbonate suggest malabsorption from achlorhydria and small bowel resection. Conclusion This case emphasizes the gastrointestinal physiology in calcium homeostasis and highlights the recognition of hypocalcemia as a complication of gastric and bowel resection.
- Published
- 2021
27. The occurrence, progression and development of four types of gastric mucosal atrophic lesions and their histopathological characteristics.
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Wang Y, Zhou J, Meng N, Yang B, Zhu C, Jiang B, Wang S, and Chen X
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- Humans, Hyperplasia pathology, Atrophy, Gastric Mucosa pathology, Metaplasia, Stomach Neoplasms pathology, Achlorhydria, Gastritis, Atrophic pathology, Helicobacter pylori, Helicobacter Infections epidemiology
- Abstract
Objective: To investigate the occurrence and development of gastric mucosal atrophic lesions and their histopathological characteristics., Methods: Histopathological diagnosis and immunohistochemical staining using the EnVision two-step method were conducted on 1969 gastric mucosal atrophic lesions obtained from gastroscopic biopsy specimens. A total of 48-month three-stage endoscopic biopsy follow-ups were performed., Results: When the gastric mucosal epithelium was affected by infection, chemical irritation, or immune or genetic factors, the gastric mucosal epithelium glands atrophied, the mucosa became thinner, the number of glands decreased, the intestinal epithelium progressed to metaplasia and smooth muscle fibre became hyperplasia. Such changes may lead to the proliferation and dysplasia of epithelial cells of the gastric mucosa and neoplastic hyperplasia in nature; this is referred to as gastric mucosal atrophic lesions in this study. According to this definition, the present study divided gastric mucosal atrophy into four types: (1) glandular atrophy of the lamina propria; (2) compensatory proliferative atrophy; (3) intestinal metaplasia atrophy; and (4) smooth muscle proliferative atrophy. The incidence rates of the above were 40.1% (789/1969), 14.3% (281/1969), 27.8% (547/1969) and 17.9% (352/1969), respectively. One- to 4-year follow-ups found that the changes were not significant and that the percentages of patients with disease exacerbation were 85.7% (1688/1969) and 9.8% (192/1969). The percentages of patients who developed low-grade intraepithelial neoplasia and high-grade intraepithelial neoplasia were 2.8% (55/1969) and 1.1% (21/1969), respectively; 0.7% (13/1969) of patients developed intramucosal cancer., Conclusion: Gastric mucosal atrophic lesions and histopathological staging are based on the morphological characteristics of gastric mucosal atrophy and the hypothesis of malignant transformation of cells during the occurrence and development of mucosal atrophy. Mastering pathological staging is beneficial to clinicians for enacting precise treatment and is important for reducing the incidence of gastric cancer., (© 2023. The Author(s).)
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- 2023
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28. Gastric Acid Secretions, Treatments, and Nutritional Consequences
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Zilberboim, Ronit, Bendich, Adrianne, Bendich, Adrianne, editor, and Deckelbaum, Richard J., editor
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- 2010
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29. Physiologically based pharmacokinetic modelling to guide drug delivery in older people.
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Chetty, Manoranjenni, Johnson, Trevor N., Polak, Sebastian, Salem, Farzaneh, Doki, Kosuke, and Rostami-Hodjegan, Amin
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- *
PHARMACOKINETICS , *CLINICAL trials , *DRUG absorption , *THERAPEUTIC equivalency in drugs , *ACHLORHYDRIA - Abstract
Abstract Older patients are generally not included in Phase 1 clinical trials despite being the population group who use the largest number of prescription medicines. Physiologically based pharmacokinetic (PBPK) modelling provides an understanding of the absorption and disposition of drugs in older patients. In this review, PBPK models used for the prediction of absorption and exposure of drugs after parenteral, oral and transdermal administration are discussed. Comparisons between predicted drug pharmacokinetics (PK) and observed PK are presented to illustrate the accuracy of the predictions by the PBPK models and their potential use in informing clinical trial design and dosage adjustments in older patients. In addition, a case of PBPK modelling of a bioequivalence study on two controlled release products is described, where PBPK predictions reproduced the study showing bioequivalence in healthy volunteers but not in older subjects with achlorhydria, indicating further utility in prospectively identifying challenges in bioequivalence studies. Graphical abstract Unlabelled Image [ABSTRACT FROM AUTHOR]
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- 2018
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30. Physiologically Based Absorption Modeling of Salts of Weak Bases Based on Data in Hypochlorhydric and Achlorhydric Biorelevant Media.
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Kesisoglou, Filippos, Vertzoni, Maria, and Reppas, Christos
- Abstract
Physiologically based absorption modeling has been attracting increased attention to study the interactions of weakly basic drug compounds with acid-reducing agents like proton-pump inhibitors and H2 blockers. Recently, standardized gastric and intestinal biorelevant media to simulate the achlorhydric and hypochlorhydric stomach were proposed and solubility and dissolution data for two model compounds were generated. In the current manuscript, for the first time, we report the utility of these recently proposed biorelevant media as input into physiologically based absorption modeling. Where needed, data collected with the biorelevant gastrointestinal transfer (BioGIT) system were used for informing the simulations in regard to the precipitation kinetics. Using two model compounds, a HCl salt and a semi-fumarate co-crystal which as expected dissolve to a greater extent in these media (and in gastric and intestinal human aspirates) compared to what the pH-solubility profile of the free form would suggest, we demonstrate successful description of the plasma concentration profiles and correctly predicted the lack of significant interaction after administration with pantoprazole or famotidine, respectively. Thus, the data reported in this manuscript represent an initial step towards defining biorelevant input for such simulations on interactions with acid-reducing agents. [ABSTRACT FROM AUTHOR]
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- 2018
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31. Application of an In Vitro Dissolution/Permeation System to Early Screening of Oral Formulations of Poorly Soluble, Weakly Basic Drugs Containing an Acidic pH-Modifier.
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Mizoguchi, Masashi, Kataoka, Makoto, Yokoyama, Kazutoshi, Aihara, Risa, Wada, Koichi, and Yamashita, Shinji
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- *
DRUG solubility , *DRUG use testing , *DIPYRIDAMOLE , *PERMEATION tubes , *ACHLORHYDRIA , *FUMARATES - Abstract
This study aimed to evaluate the usefulness of the dissolution/permeation system (D/P system) as an in vitro tool for early screening of oral formulations of weakly basic drugs containing an acidic pH-modifier. Dipyridamole, having a prominent pH-dependent solubility, was used as a model drug, and various granules containing different amounts of fumaric acid were prepared. Prepared granules were administered orally to hypochlorhydria model rats. It was confirmed that fumaric acid improved the absorption of dipyridamole depending on its amount in the granules. Separately, dissolution and permeation of dipyridamole were observed in vitro in the D/P system. When using a medium with a low buffer capacity which mimicked the human intestinal fluid, rank order of the permeated amount of dipyridamole from various granules in the D/P system did not correlate with its absorption in hypochlorhydric rats. In contrast, when applying a medium with high buffer capacity, the permeated amount in the D/P system well reflected the effects of fumaric acid on the in vivo absorption of dipyridamole. In conclusion, by setting appropriate experimental protocols according to the properties of test compounds and formulations, D/P system can be a potent in vitro tool to predict in vivo performance of oral formulations. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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32. High incidence of autoimmune gastritis in patients misdiagnosed with two or more failures of H. pylori eradication.
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Furuta, T., Baba, S., Yamade, M., Uotani, T., Kagami, T., Suzuki, T., Tani, S., Hamaya, Y., Iwaizumi, M., Osawa, S., and Sugimoto, K.
- Subjects
- *
AUTOIMMUNE diseases , *PYLORIC spasms , *HELICOBACTER diseases , *GASTROSCOPY , *ACHLORHYDRIA - Abstract
Summary: Background: Although autoimmune gastritis (AIG) is generally considered relatively rare, we frequently encounter AIG among patients at to our hospital who have experienced at least two episodes of Helicobacter pylori eradication failure. Aims: We investigated the incidence of AIG in consecutive patients who consulted our department for H. pylori eradication with reference to eradication history. Methods: A total of 404 consecutive patients who visited the H. pylori‐specific out‐patient unit of our hospital from June 2015 to June 2017 were enrolled. Of these, 137 were treatment‐naive, 47 had failed treatment once (single failure), and 220 had failed treatment twice or more (multiple failures) by 13C‐UBT. Gastroscopy was performed in all patients. Culture tests of gastric mucosal samples were performed for H. pylori and other bacteria positive for urease activity. Anti‐parietal cell antibody (APCA) was measured. Patients with severe atrophy in the gastric corpus and positivity for APCA were diagnosed as having AIG. Results: A total of 43 patients were diagnosed as having AIG, of whom two were treatment‐naive (1.5%, 2/137), 1 failed eradication once (2.1% 1/47), and 40 failed treatment at least twice (18.2%, 40/220). The incidence of AIG was significantly higher in the multiple failure group than in the single failure or treatment‐naive groups. Urease‐positive bacteria, such as Klebsiella pneumoniae and alpha‐streptococcus, were identified in 33 of the 35 AIG patients who underwent culture testing. Conclusion: AIG patients were often misdiagnosed as refractory to eradication therapy, probably because achlorhydria in AIG might allow urease‐positive bacteria other than H. pylori to colonise the stomach, causing positive 13C‐UBT results. [ABSTRACT FROM AUTHOR]
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- 2018
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33. A Study on Immediate Effect of Cold Abdominal Pack on Blood Glucose Level and Cardiovascular Functions in Patients with Type 2 Diabetes Mellitus.
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DAS, SUVITH V., MOOVENTHAN, A., and MANJUNATH, N. K.
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- *
DIABETES , *METABOLIC disorders , *ACHLORHYDRIA , *BLOOD sugar , *STATISTICS , *PATIENTS - Abstract
Introduction: Diabetes mellitus is one of the metabolic disorders which is characterised by chronic hyperglycaemia due to insulin resistance or deficiency or both. Though a hydrotherapy text reported the use of Cold Abdominal Pack (CAP) for various metabolic disorders, there is a lack of scientific evidence for the use of CAP in a metabolic disorder like Type 2 Diabetes Mellitus (T2DM). Aim: To evaluate the immediate effect of CAP on blood glucose level and cardiovascular functions in patients with T2DM. Materials and Methods: In this prospective single group pretest and post-test study, a total of 20 male T2DM subjects with the mean age of 51.75±7.71 years were recruited from June 2016 to December 2016. Study was conducted in SVYASA University, Bengaluru, Karnataka, India. All the subjects underwent CAP for 20 minutes. Assessments were taken before and immediately after the intervention using standard methods. Statistical analysis was performed using Student's paired samples t-test with the use of Statistical Package for the Social Sciences (SPSS), version 16.0. Results: Results of this study showed a significant reduction in random blood glucose level (p=0.011), pulse rate/heart rate (p=0.028), systolic blood pressure (p=0.023), mean arterial pressure (p=0.010), rate pressure product (p=0.006), and double product (p=0.003) compared to its respective pre test and no such significant changes were observed in diastolic blood pressure (p=0.095) and pulse pressure (p=0.306). Conclusion: Results of this study suggest that 20 minutes of CAP might be effective in improving blood glucose level and cardiovascular functions of patients with T2DM. [ABSTRACT FROM AUTHOR]
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- 2018
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34. Effects of miR-200a and FH535 combined with taxol on proliferation and invasion of gastric cancer.
- Author
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Liu, Xi, Du, Ping, Han, Lei, Zhang, Anling, Jiang, Kui, and Zhang, Qingyu
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- *
GASTRIC diseases , *BIOLOGICAL invasions , *PACLITAXEL , *CANCER chemotherapy , *ACHLORHYDRIA - Abstract
Gastric cancer is one of the most common cancers in the world; taxol displayed modest efficacy as first-line chemotherapy for gastric cancer, conversely, it has limitations used alone. β-catenin is a multifunctional oncogenic protein and the elevation in expression and activity of β-catenin has been implicated in many cancers. Therefore, we assume that the inhibition of β-catenin can enhanced the efficacy of taxol. The purpose of this study was to investigate the inhibitory effect of miR-200a mimics, FH535 combined with taxol on proliferation and invasion of human gastric cancer cell lines SGC-7901 and BGC-823. In the current study, we identified that the combination of FH535 and miR-200a with taxol had potent growth-inhibitory and pro-apoptotic effects. Further, similar results were also observed in vivo, intratumoral injection of FH535, taxol and miR-200a mimics which also delayed tumor growth in nude mice harboring subcutaneous SGC-7901 xenografts. Collectively, miR-200a and FH535 can enhance the inhibitory effect of taxol on cell proliferation and moderate the invasion of human gastric cancer. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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35. Virtual bioequivalence for achlorhydric subjects: The use of PBPK modelling to assess the formulation-dependent effect of achlorhydria.
- Author
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Doki, Kosuke, Darwich, Adam S., Patel, Nikunjkumar, and Rostami-Hodjegan, Amin
- Subjects
- *
ACHLORHYDRIA , *THERAPEUTIC equivalency in drugs , *PHARMACOKINETICS , *LEVOTHYROXINE , *NIFEDIPINE - Abstract
Majority of bioequivalence studies are conducted in healthy volunteers. It has been argued that bioequivalence may not necessarily hold true in relevant patient populations due to a variety of reasons which affect one formulation more than the other for instance in achlorhydric patients where elevated gastric pH may lead to differential effects on formulations which are pH-sensitive with respect to release or dissolution. We therefore examined achlorhydria-related disparity in bioequivalence of levothyroxine and nifedipine formulations using virtual bioequivalence within a physiologically-based pharmacokinetic (PBPK) modelling framework. The in vitro dissolution profiles at neutral pH were incorporated into PBPK models to mimic the achlorhydria with in vitro – in vivo relationship established using bio-relevant pH media. The PBPK models successfully reproduced the outcome of the bioequivalence studies in healthy volunteers under the normal conditions as well as under proton pump inhibitor-induced achlorhydria. The geometric mean test/reference ratios for C max and AUC between levothyroxine tablet and capsule in patients receiving proton pump inhibitor were 1.21 (90%CI, 1.13–1.29) and 1.09 (90%CI, 1.02–1.17), respectively. Extension of the virtual bioequivalence study to Japanese elderly, who show high incidence of achlorhydria, indicated bio-inequivalence which C max and AUC ratios between nifedipine control-released reference and test formulations were 3.08 (90%CI, 2.81–3.38) and 1.57 (90%CI, 1.43–1.74), respectively. Virtual bioequivalence studies through the PBPK models can highlight the need for conduct of specific studies in elderly Japanese populations where there are discrepancies in pH-sensitivity of dissolution between the test and reference formulations. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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36. Comparison of the human gastric microbiota in hypochlorhydric states arising as a result of Helicobacter pylori-induced atrophic gastritis, autoimmune atrophic gastritis and proton pump inhibitor use.
- Author
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Parsons, Bryony N., Ijaz, Umer Z., D'amore, Rosalinda, Burkitt, Michael D., Eccles, Richard, Lenzi, Luca, Duckworth, Carrie A., Moore, Andrew R., Tiszlavicz, Laszlo, Varro, Andrea, Hall, Neil, and Pritchard, D. Mark
- Subjects
- *
ADENOCARCINOMA , *CANCER-related mortality , *ACHLORHYDRIA , *GASTRIC disease diagnosis , *HELICOBACTER pylori , *PATIENTS - Abstract
Several conditions associated with reduced gastric acid secretion confer an altered risk of developing a gastric malignancy. Helicobacter pylori-induced atrophic gastritis predisposes to gastric adenocarcinoma, autoimmune atrophic gastritis is a precursor of type I gastric neuroendocrine tumours, whereas proton pump inhibitor (PPI) use does not affect stomach cancer risk. We hypothesised that each of these conditions was associated with specific alterations in the gastric microbiota and that this influenced subsequent tumour risk. 95 patients (in groups representing normal stomach, PPI treated, H. pylori gastritis, H. pylori-induced atrophic gastritis and autoimmune atrophic gastritis) were selected from a cohort of 1400. RNA extracted from gastric corpus biopsies was analysed using 16S rRNA sequencing (MiSeq). Samples from normal stomachs and patients treated with PPIs demonstrated similarly high microbial diversity. Patients with autoimmune atrophic gastritis also exhibited relatively high microbial diversity, but with samples dominated by Streptococcus. H. pylori colonisation was associated with decreased microbial diversity and reduced complexity of co-occurrence networks. H. pylori-induced atrophic gastritis resulted in lower bacterial abundances and diversity, whereas autoimmune atrophic gastritis resulted in greater bacterial abundance and equally high diversity compared to normal stomachs. Pathway analysis suggested that glucose-6-phospahte1-dehydrogenase and D-lactate dehydrogenase were over represented in H. pylori-induced atrophic gastritis versus autoimmune atrophic gastritis, and that both these groups showed increases in fumarate reductase. Autoimmune and H. pylori-induced atrophic gastritis were associated with different gastric microbial profiles. PPI treated patients showed relatively few alterations in the gastric microbiota compared to healthy subjects. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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37. Chronic Atrophic Gastritis Presenting as Hemolytic Anemia due to Severe Vitamin B12 Deficiency
- Author
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Madhurima Anne, Gabriella A Conte, Varsha Gupta, Amanda M. Woodford, and Rabhea Chaudhry
- Subjects
Hemolytic anemia ,medicine.medical_specialty ,Thrombotic microangiopathy ,Intrinsic factor ,business.industry ,Atrophic gastritis ,Case Report ,General Medicine ,030204 cardiovascular system & hematology ,medicine.disease ,Achlorhydria ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,Diseases of the blood and blood-forming organs ,Vitamin B12 ,RC633-647.5 ,Gastritis ,medicine.symptom ,business ,pernicious anemia - Abstract
Vitamin B12 is an essential nutrient which plays an important role in neurological function, hematopoiesis, and DNA synthesis. Low levels usually stem from either poor intake or a malabsorptive process. Presently, the most common cause of vitamin B12 deficiency is food-bound cobalamin malabsorption, which occurs when there is impaired release of vitamin B12 from ingested food due to an outstanding factor preventing the release of the nutrient from its transport protein. Such causes include achlorhydria, gastritis, gastrectomy, or the use of PPIs or antacids. A rarer cause is autoimmune chronic atrophic gastritis, resulting in pernicious anemia. In this disease process, there is destruction of parietal cells and thus a reduction in intrinsic factor, which is essential to the absorption of vitamin B12. Deficiency will result in a variety of abnormalities including but not limited to pancytopenia, paresthesias, and neuropsychiatric symptoms. A rare manifestation of vitamin B12 deficiency is hemolytic anemia, which occurs due to intramedullary and extramedullary dysfunction. This case describes a 46-year-old male with no past medical history who presented with chest pain, fatigue, and progressive weakness, found to have hemolytic anemia, ultimately attributed to vitamin B12 deficiency. Antiparietal cell antibodies and intrinsic factor antibodies (IFA) were both negative. Still, the patient underwent an endoscopy with biopsies of the stomach; pathology was consistent with chronic metaplastic atrophic gastritis. The patient improved with intramuscular vitamin B12 supplementation. This case highlights both a rare cause and presentation of vitamin B12 deficiency. Patients with autoimmune chronic atrophic gastritis should have antiparietal cell or intrinsic factor antibodies. Still, seronegative patients have been reported, like this patient. Additionally, hemolytic anemia secondary to vitamin B12 deficiency is uncommon. The presentation will usually mirror that of a thrombotic microangiopathy (TMA), including hemolytic anemia with schistocytes on peripheral blood smear and thrombocytopenia, as it did in this patient. This clinical entity is described as pseudothrombotic microangiopathy and is crucial to identify in order to prevent the initiation of invasive treatment strategies such as plasmapheresis.
- Published
- 2021
38. Enterochromaffin-like Cell Hyperplasia–Associated Gastric Neuroendocrine Tumors May Arise in the Setting of Proton Pump Inhibitor Use
- Author
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Nikolaos A. Trikalinos, Rehan Rais, Jingxia Liu, and Deyali Chatterjee
- Subjects
medicine.medical_specialty ,Enterochromaffin-like Cells ,Atrophic gastritis ,Neuroendocrine tumors ,Achlorhydria ,Gastroenterology ,Pathology and Forensic Medicine ,Stomach Neoplasms ,Internal medicine ,medicine ,Animals ,Humans ,Enterochromaffin-like cell ,Retrospective Studies ,Parietal cell ,Gastrinoma ,Hyperplasia ,business.industry ,Proton Pump Inhibitors ,General Medicine ,medicine.disease ,Neuroendocrine Tumors ,Medical Laboratory Technology ,medicine.anatomical_structure ,Enterochromaffin cell ,business - Abstract
Context.— Hypergastrinemia states such as achlorhydria from gastric mucosal atrophy or a gastrin-producing tumor in humans have been associated with the development of enterochromaffin-like (ECL) cell hyperplasia and gastric neuroendocrine tumors (GNETs). Whether drugs that can elevate serum gastrin levels, such as proton pump inhibitors (PPIs), can produce the same tissue effect is not known, and there is no concrete evidence linking the use of PPIs to GNETs outside animal models and case reports. Objective.— To explore the clinicopathologic association for GNETs of presumed ECL cell origin that cannot be reliably placed into any of the 3 established categories currently recognized by the World Health Organization. Design.— This is a retrospective clinicopathologic study of GNETs in the body/fundus during a period of 15 years (2005–2019). Results.— Of a total of 87 cases, 57 (65.5%) were associated with atrophic gastritis, 2 (2.3%) were associated with Zollinger-Ellison syndrome, and 28 (32.2%) were unclassified. Of the latter, 11 were consistent with true sporadic/type 3 GNETs, while 17 had background mucosal changes of parietal cell and ECL cell hyperplasia but without underlying detectable gastrinoma, and 88.2% (15 of 17) of patients from this group had documented long-term PPI use. This subtype of GNETs was more commonly multifocal and of higher grade (P = .03) than “true” sporadic GNETs. Conclusions.— A subset of GNETs arises in the background of gastric mucosal changes suggestive of hypergastrinemia, but without underlying gastrinoma, and could be linked to long-term PPI use.
- Published
- 2021
39. In vitro digestion mimicking conditions in young and elderly reveals marked differences between profiles and potential bioactivity of peptides from meat and soy proteins
- Author
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Wang, Chong, Zhao, Fan, Bai, Yun, Li, Chunbao, Xu, Xinglian, Kristiansen, Karsten, Zhou, Guanghong, Wang, Chong, Zhao, Fan, Bai, Yun, Li, Chunbao, Xu, Xinglian, Kristiansen, Karsten, and Zhou, Guanghong
- Abstract
We applied in vitro models of gastrointestinal (GI) digestion simulating the conditions of the GI tract of healthy adults and elderly individuals with achlorhydria (EA) to investigate differences in the digestibility of meat (chicken, beef and pork) and soy proteins. Digestibility was significantly affected by EA alterations. Peptidomics analyses revealed significant differences in peptide profiles between control and EA conditions, including number, length distribution, clustering, and differentially abundant peptides (DAPs). Our results revealed that the differences in meat peptide profiles diminished going from the gastric to intestinal phase. For soy protein, the marked differences between control and EA conditions were maintained in the gastric and intestinal phases. Higher numbers of potentially bioactive peptides were generated under the control condition compared to the EA condition. The present study provides insight into the distinct peptide profiles generated by in vitro digestion of meat and soy proteins under adult and EA GI conditions.
- Published
- 2022
40. IDENTIFYING CANCER SPECIFIC METABOLIC SIGNATURES USING CONSTRAINT-BASED MODELS.
- Author
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SCHULTZ, A., MEHTA, S., HU, C. W., HOFF, F. W., HORTON, T. M., KORNBLAU, S. M., and QUTUB, A. A.
- Subjects
METABOLIC disorders ,DISEASES ,ACHLORHYDRIA ,METABOLIC regulation ,BIOINFORMATICS - Published
- 2016
41. Gastric secretion in patients with caustic ingestion: A prospective study
- Author
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K Rajan, Kartar Singh, C K Nain, Rakesh Kochhar, Nikhil Bush, and Jimil Shah
- Subjects
Adult ,Male ,medicine.medical_specialty ,Caustics ,India ,Achlorhydria ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Burns, Chemical ,medicine ,Humans ,Prospective Studies ,Esophagus ,Prospective cohort study ,Gastrin ,Gastric Juice ,business.industry ,digestive, oral, and skin physiology ,Hepatology ,medicine.disease ,Gastrointestinal Tract ,Pentagastrin ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Esophageal stricture ,Esophageal Stenosis ,Gastric acid ,Female ,030211 gastroenterology & hepatology ,business ,medicine.drug - Abstract
Caustic ingestion can lead to structural changes in the upper gastrointestinal tract. However, there are limited data on the effect of caustic ingestion on gastric secretion. This study was planned to determine the changes in gastric acid output in patients with caustic ingestion. It was a prospective study done at a tertiary care center in northern India. Twenty consecutive patients in chronic phase of caustic ingestion were evaluated for the study. The gastric secretory function was estimated in the basal state and following pentagastrin stimulation. These results were compared with normal values for our laboratory. The mean age of the included patients (n = 20) was 27.35 ± 2.96 years and 14 patients were male. Sixteen (80%) patients had a history of acid ingestion. Patients with caustic ingestion had significantly lower mean gastric acid secretion (0.8 ± 0.4 mEq/h vs. 4 ± 0.4 mEq/h; p
- Published
- 2021
42. Different elemental infant formulas show equivalent phosphorus and calcium bioavailability in healthy volunteers
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Monique Visser, Pilou L.H.R. Janssens, Clemens Bergwitz, Thomas O. Carpenter, Simone R.B.M. Eussen, Ardy van Helvoort, RS: NUTRIM - R3 - Respiratory & Age-related Health, and Bedrijfsbureau NTM
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0301 basic medicine ,Blood Glucose ,Male ,Neocate ,Endocrinology, Diabetes and Metabolism ,Urine ,Gastroenterology ,SUPPLEMENTATION ,GLUCOSE ,0302 clinical medicine ,Endocrinology ,Insulin ,Amino Acids ,ACID-BASED FORMULA ,Nutrition and Dietetics ,Cross-Over Studies ,Achlorhydria ,COWS MILK ,cow's milk allergy ,Healthy Volunteers ,Infant Formula ,HYPOALLERGENICITY ,Parathyroid Hormone ,GROWTH ,Female ,HYPOPHOSPHATEMIA ,Hypophosphatemia ,Adult ,medicine.medical_specialty ,Carbohydrates ,chemistry.chemical_element ,Biological Availability ,030209 endocrinology & metabolism ,Phosphate ,Calcium ,Bioequivalence ,Phosphates ,Excretion ,03 medical and health sciences ,Young Adult ,cross-over study ,Double-Blind Method ,Internal medicine ,medicine ,Humans ,TOLERANCE ,030109 nutrition & dietetics ,business.industry ,amino acid-based formula ,Phosphorus ,MILK PROTEIN ALLERGY ,medicine.disease ,Alkaline Phosphatase ,Crossover study ,Dietary Fats ,Bioavailability ,chemistry ,Therapeutic Equivalency ,business - Abstract
Retrospective chart reviews have reported hypophosphatemia associated with elemental formula use in infants and children with systemic disease involving multiple diagnoses. The present study aims to evaluate the bioavailability of phosphorus from 2 commercial elemental formulas and to test our hypothesis of bioequivalence of the 2 products in healthy volunteers receiving gastric acid-suppressive medication. A single-center, double-blind, randomized, cross-over study was conducted in healthy volunteers with esomeprazole-induced hypochlorhydria. After a standardized low phosphorus meal followed by overnight fasting, subjects consumed 1 gram of phosphorus in a single oral dose of 1217 kcal of Product A (Neocate) or Product B (Elecare). The alternate product was given following a 1-week washout period. Blood and urine were collected at baseline and different time-points for up to 6 hours after product consumption. Area-under-the-curve (AUC) and peak values (C-peak) for serum phosphate and calcium and urinary creatinine-corrected phosphate and calcium were assessed for bioequivalence of Products A and B. Results show that the geometric mean ra tio (GMR) and 90% CI for serum phosphate were 1.041 (0.998-1.086) and 1.020 (0.963-1.080) for AUC(0-360) and C-peak, respectively, meeting the predetermined criteria for bioequivalence. Urinary creatinine-corrected phosphate followed a similar pattern after intake of Product A and B, but did not reach bioequivalence criteria (GMR: AUC(70-370) = 1.105 (0.918-1.330); C-peak = 1.182 (1.040-1.343)). Serum calcium concentrations (GMR: AUC(0-360) = 1.002 (0.9961.009); C-peak = 0.991 (0.983-0.999)) and urinary creatinine-corrected calcium excretion (GMR: AUC(70-370) = 1.117 (1.023-1.219); C-peak = 1.157 (1.073-1.247)) demonstrated bioequivalence of the products. In conclusion, both elemental infant formulas showed equivalent serum phosphorus and calcium bioavailability in healthy volunteers even if combined with treatment with acid-suppressive medication. (c) 2020 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/ )
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- 2021
43. Pancreatic VIPoma as a Differential Diagnosis in Chronic Pediatric Diarrhea: A Case Report and Review of the Literature
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Maria Luisa Contreras, Juliana Rusinque, Carolina Bonilla Gonzalez, Ailim Carias, and Camila Uribe
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Pediatric ,Past medical history ,Pediatrics ,medicine.medical_specialty ,Vasoactive intestinal peptide ,business.industry ,Case Report ,medicine.disease ,Achlorhydria ,Hypokalemia ,Diarrhea ,Pancreatic tumor ,medicine ,Pancreatic Vipoma ,medicine.symptom ,Differential diagnosis ,business ,Chronic diarrhea ,VIPoma - Abstract
Chronic diarrhea is a common chief complaint in the pediatric population with a wide range of diagnostic differentials; as such, whilst suspecting common causes, less prevalent conditions tend to be overlooked, such as neuroendocrine tumor pathologies. VIPomas are characterized by hypersecretion of the vasoactive intestinal peptide (VIP), causing watery diarrhea, hypokalemia, and achlorhydria. Nonetheless, its low incidence rate in children makes it an easily unnoticed pathology. Herein, we report a case of a 14-year-old female patient and a review of relevant literature. The patient complained of 7-month history of watery diarrhea, multiple emetic episodes, and relevant past medical history of multiple hospitalizations. Chronic diarrheal disease work-up studies, including a high VIP scintigram, showed a lesion suggestive of a VIPoma-type neuroendocrine pancreatic tumor. A distal pancreatectomy was performed with a complete resolution of the symptoms. When faced with a pediatric patient presenting with chronic secretory diarrhea and whose work-up studies rule out the most common pathologies, the possible presence of a neuroendocrine tumor as VIPoma should be considered. J Med Cases. 2021;12(5):195-201 doi: https://doi.org/10.14740/jmc3535
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- 2021
44. Vitamin C Improves Dasatinib Concentrations Under Hypochlorhydric Conditions of the Simulated Stomach Duodenum Model
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Fouad S, Moghrabi, Aktham, Aburub, and Hala M, Fadda
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Solubility ,Duodenum ,Reducing Agents ,Achlorhydria ,Dasatinib ,Administration, Oral ,Humans ,Ascorbic Acid ,Hydrogen-Ion Concentration ,Lamotrigine ,Protein Kinase Inhibitors - Abstract
pH-dependent drug-drug interactions (DDIs) with poorly soluble, weakly basic drugs may lead to clinical implications. Dasatinib is a tyrosine kinase inhibitor with reduced absorption in patients on acid-reducing agents (ARAs). The objective of this study is to investigate the influence of gastric pH on dasatinib supersaturation and determine if vitamin C (L-ascorbic acid) can improve dasatinib concentrations under simulated hypochlorhydric gastric conditions.A dynamic, in vitro, multi-compartment, simulated stomach duodenum (SSD) model mimicking fluid volumes and transfer rates was used to investigate the concentration of BCS class IIb drugs versus time curves. Dasatinib and lamotrigine were explored under normal, fasted, simulated gastric fluids (pH 2) (FaSGF), hypochlorhydric simulated gastric fluids (pH 4.5) (FaSGFSignificant supersaturation of dasatinib was observed in the duodenum compartment of the SSD model in FaSGF. A 90% reduction in dasatinib AUCThe SSD model serves as a good in vitro tool for assessing the effect of pH-dependent DDIs on bioavailability of weakly basic drugs with solubility/ dissolution limited absorption. Vitamin C provides a promising approach for improving bioavailability of poorly soluble, weakly basic drugs in hypochlorhydric patients.
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- 2022
45. Parietal Cell Dysfunction: A Rare Cause of Gastric Neuroendocrine Neoplasm with Achlorhydria and Extreme Hypergastrinemia
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Yasuaki Abe, Waku Hatta, Sho Asonuma, Tomoyuki Koike, Hiroko Abe, Yohei Ogata, Masahiro Saito, Xiaoyi Jin, Takeshi Kanno, Kaname Uno, Naoki Asano, Akira Imatani, Fumiyoshi Fujishima, Hironobu Sasano, and Atsushi Masamune
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Gastritis, Atrophic ,Neuroendocrine Tumors ,Parietal Cells, Gastric ,Gastric Mucosa ,Stomach Neoplasms ,Achlorhydria ,Internal Medicine ,Humans ,Female ,General Medicine ,Atrophy ,Aged - Abstract
A 69-year-old woman with multiple neuroendocrine neoplasms (NENs) was referred to our hospital. Although she had extreme hypergastrinemia (11,675 pg/mL), no findings that indicated types I to III gastric NENs were found. Although gastric corpus atrophy was suspected on conventional white-light imaging, findings on magnifying endoscopy with narrow-band imaging indicated no severe atrophy. A biopsy from the background fundic gland mucosa revealed no atrophic changes, parietal cells with vacuolated cytoplasm and negative findings for H
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- 2022
46. The impact of reduced gastric acid secretion on dissolution of salts of weak bases in the fasted upper gastrointestinal lumen: Data in biorelevant media and in human aspirates.
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Litou, Chara, Vertzoni, Maria, Xu, Wei, Kesisoglou, Filippos, and Reppas, Christos
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GASTRIC acid , *GASTROINTESTINAL diseases , *ACHLORHYDRIA , *ASPIRATORS , *BICARBONATE ions - Abstract
Purpose To propose media for simulating the intragastric environment under reduced gastric acid secretion in the fasted state at three levels of simulation of the gastric environment and evaluate their usefulness in evaluating the intragastric dissolution of salts of weak bases. To evaluate the importance of bicarbonate buffer in biorelevant in vitro dissolution testing when using Level II biorelevant media simulating the environment in the fasted upper small intestine, regardless of gastric acid secretions. Methods Media for simulating the hypochlorhydric and achlorhydric conditions in stomach were proposed using phosphates, maleates and bicarbonates buffers. The impact of bicarbonates in Level II biorelevant media simulating the environment in upper small intestine was evaluated so that pH and bulk buffer capacity were maintained. Dissolution data were collected using two model compounds, pioglitazone hydrochloride and semifumarate cocrystal of Compound B, and the mini-paddle dissolution apparatus in biorelevant media and in human aspirates. Results Simulated gastric fluids proposed in this study were in line with pH, buffer capacity, pepsin content, total bile salt/lecithin content and osmolality of the fasted stomach under partial and under complete inhibition of gastric acid secretion. Fluids simulating the conditions under partial inhibition of acid secretion were useful in simulating concentrations of both model compounds in gastric aspirates. Bicarbonates in Level III biorelevant gastric media and in Level II biorelevant media simulating the composition in the upper intestinal lumen did not improve simulation of concentrations in human aspirates. Conclusions Level III biorelevant media for simulating the intragastric environment under hypochlorhydric conditions were proposed and their usefulness in the evaluation of concentrations of two model salts of weak bases in gastric aspirates was shown. Level II biorelevant media for simulating the environment in upper intestinal lumen led to underestimation of concentrations in aspirates, even when bicarbonate buffer was used. [ABSTRACT FROM AUTHOR]
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- 2017
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47. Exposure to chlorantraniliprole affects the energy metabolism of the caddisfly Sericostoma vittatum.
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Rodrigues, Andreia C.M., Gravato, Carlos, Quintaneiro, Carla, Bordalo, Maria D., Golovko, Oksana, Žlábek, Vladimír, Barata, Carlos, Soares, Amadeu M.V.M., and Pestana, João L.T.
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ENERGY metabolism , *OXIDATIVE addition , *METABOLIC disorders , *ACHLORHYDRIA , *ALCOHOL intolerance - Abstract
Caddisflies have been included in ecotoxicological studies because of their sensitivity and ecological relevance. The present study aimed to assess the sublethal effects of an anthranilic diamide insecticide, chlorantraniliprole (CAP), to Sericostoma vittatum. Used worldwide, CAP is a persistent compound that has been found in surface waters at concentrations from 0.1 μg/L to 9.7 μg/L. It targets the ryanodine receptors, and the present ecotoxicological assessment focused on biomarkers related to neurotransmission, biotransformation, oxidative stress damage, and endpoints related to energy processing (feeding, energy reserves, and cellular metabolism). Six days of exposure trials revealed that feeding activity was significantly decreased in S. vittatum larvae exposed to 0.9 μg/L CAP. Concomitantly, a reduction in cellular metabolism and a significant decrease in protein content were also observed in caddisfly larvae exposed to CAP, suggesting metabolic depression. The results show that sublethal concentrations of CAP can cause detrimental sublethal effects on S. vittatum total glutathione content at concentrations as low as 0.2 μg/L. Bioenergetics can be used to assess physiological effects of contaminants, and the present results show that exposure to low, environmentally relevant, concentrations of CAP alter energy acquisition and metabolism in nontarget aquatic insects with potential population level effects. Environ Toxicol Chem 2017;36:1584-1591. © 2016 SETAC [ABSTRACT FROM AUTHOR]
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- 2017
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48. Assessment of Bioequivalence of Weak Base Formulations Under Various Dosing Conditions Using Physiologically Based Pharmacokinetic Simulations in Virtual Populations. Case Examples: Ketoconazole and Posaconazole.
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Cristofoletti, Rodrigo, Patel, Nikunjkumar, and Dressman, Jennifer B.
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KETOCONAZOLE , *ACHLORHYDRIA , *ABSORPTION , *PHARMACOKINETICS , *PRECIPITATION (Chemistry) - Abstract
Postabsorptive factors which can affect systemic drug exposure are assumed to be dependent on the active pharmaceutical ingredient (API), and thus independent of formulation. In contrast, preabsorptive factors, for example, hypochlorhydria, might affect systemic exposure in both an API and a formulation-dependent way. The aim of this study was to evaluate whether the oral absorption of 2 poorly soluble, weakly basic APIs, ketoconazole (KETO) and posaconazole (POSA), would be equally sensitive to changes in dissolution rate under the following dosing conditions—coadministration with water, with food, with carbonated drinks, and in drug-induced hypochlorhydria. The systems-components of validated absorption and PBPK models for KETO and POSA were modified to simulate the above-mentioned clinical scenarios. Virtual bioequivalence studies were then carried out to investigate whether formulation effects on the plasma profile vary with the dosing conditions. The slow precipitation of KETO upon reaching the upper part of the small intestine renders its absorption more sensitive to the completeness of gastric dissolution and thus to the gastric environment than POSA, which is subject to extensive precipitation in response to a pH shift. The virtual bioequivalence studies showed that hypothetical test and reference formulations containing KETO would be bioequivalent only if the microenvironment in the stomach enables complete gastric dissolution. We conclude that physiologically based pharmacokinetic modeling and simulation has excellent potential to address issues close to bedside such as optimizing dosing conditions. By studying virtual populations adapted to various clinical situations, clinical strategies to reduce therapeutic failures can be identified. [ABSTRACT FROM AUTHOR]
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- 2017
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49. Improved oral absorption profile of itraconazole in hypochlorhydria by self-micellizing solid dispersion approach.
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Kojo, Yoshiki, Matsunaga, Saori, Suzuki, Hiroki, Sato, Hideyuki, Seto, Yoshiki, and Onoue, Satomi
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ITRACONAZOLE , *ACHLORHYDRIA , *PARTICLE size determination , *PHARMACOKINETICS , *CRYSTALLINITY , *THERAPEUTICS - Abstract
The present study was aimed to evaluate the applicability of a self-micellizing solid dispersion (SMSD) system of itraconazole (ITZ) with the use of Soluplus ® to achieve improved dissolution and stable oral absorption of ITZ under hypochlorhydric conditions. The SMSD of ITZ (SMSD/ITZ) was prepared by the freeze-drying method. Physicochemical properties of SMSD/ITZ were assessed in terms of morphology, crystallinity, particle size, thermal behavior, dissolution profile, and stability. The pharmacokinetic profile of SMSD/ITZ was evaluated in both normal rats and omeprazole-treated rats as a hypochlorhydric model. From the crystallinity assessment, ITZ in SMSD/ITZ might exist in an amorphous state. The dissolution behavior of SMSD/ITZ was markedly improved under both acidic and neutral conditions through the formation of nano-micelles with a diameter of 127 nm. The degradation of ITZ in SMSD/ITZ was negligible after storage under accelerated conditions at 40 °C or 40 °C/75%RH for 4 weeks. Under light exposure, ca. 33% of ITZ in SMSD/ITZ was degraded, suggesting the need for protection from light. Although the oral absorption of crystalline ITZ was negligible, SMSD/ITZ showed an improved pharmacokinetic profile in normal rats, with an absolute bioavailability (BA) of 2.9%, and even 6.3% in the hypochlorhydric model. From these findings, SMSD technology could be beneficial for improving the absorption profiles of weak basic drugs, even in hypochlorhydric patients. [ABSTRACT FROM AUTHOR]
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- 2017
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50. Metabolism of Intraoperatively Administered Histidine in the Context of Bretschneider Cardioplegia.
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Teloh, J.K., Waack, I.N., Petersen, M., Jakob, H., and Dohle, D.S.
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METABOLIC regulation , *METABOLIC disorders , *ACHLORHYDRIA , *HISTIDINE , *AMINO acids - Published
- 2017
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