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Immunopathology
Published in Constantin A. Bona, Francisco A. Bonilla, Textbook of Immunology, 2019
Constantin A. Bona, Francisco A. Bonilla
Pernicious anemia is a syndrome of gastric mucosal dysfunction and atrophy combined with a megaloblastic anemia and neurologic symptoms. A cellular immune reaction to gastric mucosal cells is responsible for gastric atrophy. Two major targets of autoantibodies are the a and β subunits of the gastric hydrogen-potassium ATPase. Symptoms also result from production of antibodies binding intrinsic factor. This is a secretory product of neck cells in the gastric glands, and is required for absorption of vitamin B12, a cofactor essential to a number of biochemical pathways. Antibodies binding intrinsic factor inhibit B12 uptake; deficiency of B12 leads to anemia and mixed neuropathy.
Current and future CFTR therapeutics
Published in Anthony J. Hickey, Heidi M. Mansour, Inhalation Aerosols, 2019
Marne C. Hagemeijer, Gimano D. Amatngalim, Jeffrey M. Beekman
It has also been proposed that impaired antibacterial activity of AMPs contributes to increased microbial susceptibility. It has been demonstrated that antibacterial properties in CF patient-derived airway epithelial cells were reduced, which was not due to impaired expression levels of AMPs but due to altered physiological conditions of the ASL (21). This was also observed in CF newborn pigs (22), with this defect being present already after birth and might therefore be the underlying cause of the onset of CF lung disease (4). Several AMPs display pH-sensitive antibacterial properties (22), and it is assumed that reduced CFTR-mediated bicarbonate secretion impairs the ASL antibacterial activity, which allows for microbial outgrowth on epithelia (4,23). This process is normally regulated by the hydrogen potassium ATPase transporter H+,K+-ATPase ATP12A that prevents acidification of the ASL (22,23). pH reduction may also lead to impaired mucociliary clearance, due to increased mucus viscosity (24) or to ASL dehydration by abrogating ENaC inhibition of the pH-sensitive protein short palate lung and nasal epithelial clone 1 (SPLUNC1) (25).
Stomach and duodenum
Published in Professor Sir Norman Williams, Professor P. Ronan O’Connell, Professor Andrew W. McCaskie, Bailey & Love's Short Practice of Surgery, 2018
Professor Sir Norman Williams, Professor P. Ronan O’Connell, Professor Andrew W. McCaskie
These are in the body (acid-secreting portion) of the stomach and line the gastric crypts, being more abundant distally. They are responsible for the production of hydrogen ions to form hydrochloric acid. The hydrogen ions are actively secreted by the proton pump, a hydrogen-potassium-ATPase (Sachs), which exchanges intraluminal potassium for hydrogen ions. The potassium ions enter the lumen of the crypts passively, but the hydrogen ions are pumped against an immense concentration gradient (1 000 000:1).
Clinical features and natural history of idiopathic peptic ulcers: a retrospective case–control study
Published in Scandinavian Journal of Gastroenterology, 2019
Maria Pina Dore, Sara Soro, Caterina Niolu, Nunzio Pio Longo, Stefano Bibbò, Alessandra Manca, Giovanni Mario Pes
Available data on the natural history of IPUD suggests that they are more prone to bleeding, difficult to cure or refractory to treatment, with a poor prognosis compared with H. pylori-PUD. Nevertheless, the proportion of IPUD that healed in our cohort was remarkably high. Malaty et al. demonstrated a moderate genetic influence on PUD [40]. Similarly, our results may have been affected by the genetic background of the study population. However, changes in the rate of IPUD cured cannot be excluded having the chance to check all patients. For instance, in a multicenter study conducted in Japan, the healing rate, evaluated by endoscopy at the end of treatment with 20 mg/die for 6 or 8 weeks of vonoprazan, was 81.2% [41]. The authors concluded that longer-term vonoprazan may be required for refractory peptic ulcers. Vonoprazan is a potassium-competitive acid blocker that is able to inhibit acid secretion by competitively blocking the availability of potassium to hydrogen-potassium ATPase, and it is more potent and longer acting than traditional PPIs [42]. Because ulcer healing needs a pH ≥3, according to the authors conclusions, longer-term vonoprazan treatment may be required for refractory peptic ulcers [41].
An update on the latest chemical therapies for reflux esophagitis in children
Published in Expert Opinion on Pharmacotherapy, 2019
Marc Bardou, Kyle J. Fortinsky, Nicolas Chapelle, Maxime Luu, Alan Barkun
PPIs, include omeprazole, esomeprazole, pantoprazole, and lansoprazole, and is some countries dexlansoprazole. These medications irreversibly bind to the hydrogen-potassium ATPase pump residing on parietal cell membranes thereby blocking acid secretion. PPIs also have a longer duration of action and are less likely to develop tolerance over time when compared to H2RAs which tend to develop tachyphylaxis within a few weeks with repeat dosing [21]. Although there are several different PPI drugs that have similar efficacy and tolerability, omeprazole, esomeprazole, and lansoprazole have been the most widely studied in children, although pantoprazole can also be used. The latest in the class, dexlansoprazole, has been assessed in adolescent with NERD, in a non-comparative manner [22]. PPI is not approved for children below 1 year of age and 10 kg of body weight.