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1.
Physiol Rev ; 100(2): 573-602, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-31670611

RESUMO

Parietal cells are responsible for gastric acid secretion, which aids in the digestion of food, absorption of minerals, and control of harmful bacteria. However, a fine balance of activators and inhibitors of parietal cell-mediated acid secretion is required to ensure proper digestion of food, while preventing damage to the gastric and duodenal mucosa. As a result, parietal cell secretion is highly regulated through numerous mechanisms including the vagus nerve, gastrin, histamine, ghrelin, somatostatin, glucagon-like peptide 1, and other agonists and antagonists. The tight regulation of parietal cells ensures the proper secretion of HCl. The H+-K+-ATPase enzyme expressed in parietal cells regulates the exchange of cytoplasmic H+ for extracellular K+. The H+ secreted into the gastric lumen by the H+-K+-ATPase combines with luminal Cl- to form gastric acid, HCl. Inhibition of the H+-K+-ATPase is the most efficacious method of preventing harmful gastric acid secretion. Proton pump inhibitors and potassium competitive acid blockers are widely used therapeutically to inhibit acid secretion. Stimulated delivery of the H+-K+-ATPase to the parietal cell apical surface requires the fusion of intracellular tubulovesicles with the overlying secretory canaliculus, a process that represents the most prominent example of apical membrane recycling. In addition to their unique ability to secrete gastric acid, parietal cells also play an important role in gastric mucosal homeostasis through the secretion of multiple growth factor molecules. The gastric parietal cell therefore plays multiple roles in gastric secretion and protection as well as coordination of physiological repair.


Assuntos
Ácido Gástrico/metabolismo , ATPase Trocadora de Hidrogênio-Potássio/metabolismo , Células Parietais Gástricas/metabolismo , Animais , Forma Celular , Homeostase , Humanos , Células Parietais Gástricas/efeitos dos fármacos , Potássio/metabolismo , Inibidores da Bomba de Prótons/farmacologia , Via Secretória , Transdução de Sinais
2.
Bull Math Biol ; 86(7): 77, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38775877

RESUMO

Several recent theoretical studies have indicated that a relatively simple secretion control mechanism in the epithelial cells lining the stomach may be responsible for maintaining a neutral (healthy) pH adjacent to the stomach wall, even in the face of enormous electrodiffusive acid transport from the interior of the stomach. Subsequent work used Sobol' Indices (SIs) to quantify the degree to which this secretion mechanism is "self-regulating" i.e. the degree to which the wall pH is held neutral as mathematical parameters vary. However, questions remain regarding the nature of the control that specific parameters exert over the maintenance of a healthy stomach wall pH. Studying the sensitivity of higher moments of the statistical distribution of a model output can provide useful information, for example, how one parameter may skew the distribution towards or away from a physiologically advantageous regime. In this work, we prove a relationship between SIs and the higher moments and show how it can potentially reduce the cost of computing sensitivity of said moments. We define γ -indices to quantify sensitivity of variance, skewness, and kurtosis to the choice of value of a parameter, and we propose an efficient strategy that uses both SIs and γ -indices for a more comprehensive sensitivity analysis. Our analysis uncovers a control parameter which governs the "tightness of control" that the secretion mechanism exerts on wall pH. Finally, we discuss how uncertainty in this parameter can be reduced using expert information about higher moments, and speculate about the physiological advantage conferred by this control mechanism.


Assuntos
Mucosa Gástrica , Conceitos Matemáticos , Modelos Biológicos , Concentração de Íons de Hidrogênio , Mucosa Gástrica/metabolismo , Humanos , Ácido Gástrico/metabolismo , Simulação por Computador
3.
Int J Mol Sci ; 25(10)2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38791497

RESUMO

Proton pump inhibitors (PPIs) are widely used in the long-term treatment of gastroesophageal reflux disease (GERD) and other upper gastrointestinal disorders, such as the healing of peptic ulcers and/or prophylactic treatment of peptic ulcers. PPIs are also widely used as symptomatic treatment in patients with functional dyspepsia. One of the adverse effects of the long-term use of PPI is rebound acid hypersecretion (RAHS), which can occur after the withdrawal of PPI therapy due to a compensatory increase in gastric acid production. Mechanisms of the RAHS have been well established. Studies have shown that pentagastrin-stimulated acid secretion after the discontinuation of PPIs increased significantly compared to that before treatment. In healthy volunteers treated with PPIs, the latter induced gastrointestinal symptoms in 40-50% of subjects after the discontinuation of PPI therapy but after stopping the placebo. It is important for practicing physicians to be aware and understand the underlying mechanisms and inform patients about potential RAHS before discontinuing PPIs in order to avoid continuing unnecessary PPI therapy. This is important because RAHS may lead patients to reuptake PPIs as symptoms are incorrectly thought to originate from the recurrence of underlying conditions, such as GERD. Mechanisms of RAHS have been well established; however, clinical implications and the risk factors for RAHS are not fully understood. Further research is needed to facilitate appropriate management of RAHS in the future.


Assuntos
Ácido Gástrico , Refluxo Gastroesofágico , Inibidores da Bomba de Prótons , Humanos , Inibidores da Bomba de Prótons/efeitos adversos , Inibidores da Bomba de Prótons/uso terapêutico , Refluxo Gastroesofágico/tratamento farmacológico , Refluxo Gastroesofágico/metabolismo , Ácido Gástrico/metabolismo , Animais
4.
Bioorg Chem ; 137: 106588, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37167705

RESUMO

H+, K+-ATPase, as the most critical enzyme in gastric acid secretion, has long been an attractive target for the treatment of acid-related diseases. In this study, a series of benzimidazole derivatives were designed and synthesized through conformational restriction and skeleton hopping strategies by using vonoprazan as the lead compound. Among them, compounds A12 (IC50 = 9.32 µM) and A18 (IC50 = 5.83 µM) showed better inhibition at the enzyme level. In addition, gastric acid secretion inhibition was assessed in vivo, and the results showed that A12 and A18 significantly inhibited basal gastric acid secretion, 2-deoxy-d-glucose (2DG) stimulated gastric acid secretion and histamine-stimulated gastric acid secretion. In further in vitro metabolic experiments, A12 and A18 demonstrated excellent stability and low toxicity. Pharmacokinetic studies showed that the p.o. and i.v. half-lives of A18 were 3.21 h and 8.67 ± 1.15 h, respectively. In summary, A18 might be a novel and effective potassium-competitive acid blocker, and this study provides strong support for it use in the treatment of acid-related diseases.


Assuntos
Ácido Gástrico , Inibidores da Bomba de Prótons , Inibidores da Bomba de Prótons/farmacologia , Ácido Gástrico/metabolismo , Potássio , Histamina/metabolismo , Benzimidazóis/farmacologia , Benzimidazóis/metabolismo , ATPase Trocadora de Hidrogênio-Potássio/metabolismo
5.
Clin Oral Investig ; 27(11): 6865-6877, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37821653

RESUMO

OBJECTIVES: To investigate the impact of simulated gastric acid on the surface properties of lithium disilicate-reinforced glass-ceramics and zirconia-reinforced lithium silicate glass-ceramic after certain polishing and glazing procedures. MATERIALS AND METHODS: Four different types of square-shaped specimens (10 × 10 × 2 mm3, n = 13) were manufactured: lithium disilicate-reinforced glass-ceramic milled and polished (LDS-P); milled, polished, and glazed (LDS-PG); milled, glazed, and no polishing (LDS-G); and milled and polished zirconia-reinforced lithium silicate glass-ceramic (ZR-LS). Specimens were immersed in hydrochloride acid (HCl 0.06 M, pH 1.2) to simulate gastric acid irritation and stored in the acid for 96 h in 37 °C. Specimen weight, surface gloss, Vickers surface microhardness and surface roughness (Ra, Rq, with optical profilometer), and surface roughness on nanometer level (Sq, Sal, Sq/Sal, Sdr, Sds with atomic force microscope) were measured before and after the acid immersion. RESULTS: ZR-LS specimens lost significantly more weight after acid immersion (p = 0.001), also surface microhardness of ZR-LS was significantly reduced (p = 0.001). LDS-G and LDS-PG showed significantly lower surface roughness (Sa, Sq) values compared to LDS-P before (p ≤ 0.99) and after (p ≤ 0.99) acid immersion and ZR-LS after acid immersion (p ≤ 0.99). CONCLUSIONS: Gastric acid challenge affects the surface properties of lithium disilicate-reinforced glass-ceramic and zirconia-reinforced lithium silicate glass-ceramic. Glazing layer provides lower surface roughness, and the glazed surface tends to smoothen after the gastric acid challenge. CLINICAL RELEVANCE: Surface finish of lithium disilicate-reinforced glass-ceramic and zirconia-reinforced lithium silicate glass-ceramic has a clear impact on material's surface properties. Gastric acidic challenge changes surface properties but glazing seems to function as a protective barrier. Nevertheless, also glazing tends to smoothen after heavy gastric acid challenge. Glazing can be highly recommended to all glass-ceramic restorations but especially in patients with gastroesophageal reflux disease (GERD) and eating disorders like bulimia nervosa.


Assuntos
Ácido Gástrico , Lítio , Humanos , Teste de Materiais , Desenho Assistido por Computador , Porcelana Dentária/química , Cerâmica/química , Zircônio/química , Silicatos , Propriedades de Superfície
6.
J Prosthet Dent ; 129(2): 364.e1-364.e9, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36604260

RESUMO

STATEMENT OF PROBLEM: The effect of gastric acid on the surface properties of denture base acrylic resin is unknown. PURPOSE: The purpose of this in vitro study was to evaluate changes in the surface roughness and hardness of denture base acrylic resins after immersion in simulated gastric acid. MATERIAL AND METHODS: Acrylic resin specimens (n=10) were prepared with 3 different processing techniques (compression-molded, injection-molded, and computer-aided design and computer-aided manufacturing [CAD-CAM] milled) and exposed to either gastric acid or artificial saliva (control). Surface roughness and hardness were measured at baseline (T0) and after 24-hour (T24) and 96-hour (T96) immersion in the solutions. The surface roughness and hardness data were analyzed by 3-way ANOVA and the Tukey HSD test (α=.05). RESULTS: At T24, the greatest change in surface hardness was observed for compression-molded specimens in gastric acid (P<.05). At T96, changes in hardness values were higher in compression-molded specimens than those in milled specimens (P<.05). Regarding surface roughness, at T24, compression-molded and injection-molded specimens showed higher values than milled specimens in gastric acid (P<.05). Concerning specimens in artificial saliva, compression-molded specimens showed significantly higher changes in roughness than those of the others (P<.05). At T96, injection-molded specimens had the greatest roughness values (P<.05). Among specimens immersed in artificial saliva, milled specimens showed lower roughness values than the injection-molded or compression-molded specimens (P<.05). CONCLUSIONS: Gastric acid exposure adversely affected the roughness and hardness of all the acrylic resins evaluated. CAD-CAM milled specimens showed better resistance to acid exposure after 24 and 96 hours in terms of roughness and hardness.


Assuntos
Resinas Acrílicas , Bases de Dentadura , Saliva Artificial , Dureza , Ácido Gástrico , Imersão , Teste de Materiais , Propriedades de Superfície
7.
J Clin Pediatr Dent ; 47(5): 145-151, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37732448

RESUMO

In this study, we aimed to demonstrate changes in the surface roughness and microhardness of three different restorative materials routinely used in pediatric dentistry (composite, compomer and resin-modified glass ionomer cement (RMCIS)) in response to continuous daily exposure to gastric acid. Twelve samples of each of type of restorative material were prepared. Eleven of the specimens were included in the gastric acid cycle. The microhardness and surface roughness of ten samples were measured before and after the cycle. Another sample included in the cycle was compared with the sample not included in the cycle by scanning electron microscopy (SEM). There was a significant difference between the groups in terms of roughness scores following gastric acid cycle (p = 0.039). RMCIS material possessed the highest roughness value. A significant difference was identified in terms of microhardness levels before and after the gastric acid cycle (p = 0.001). The most significant change was observed in the compomer material. SEM analysis, performed after the gastric acid cycle, revealed that most cracks were identified in RMCIS material; this was followed by compomer and composite materials, respectively. Our analysis indicates that the restorative materials used frequently in pediatric dental procedures, show increased surface roughness and reduced microhardness when exposed to gastric acid.


Assuntos
Compômeros , Ácido Gástrico , Humanos , Criança , Microscopia Eletrônica de Varredura , Materiais Dentários , Cimentos de Ionômeros de Vidro
8.
Niger J Clin Pract ; 26(10): 1505-1511, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37929527

RESUMO

Background: Gastric acid, which is among erosive substances, gradually rises to the mouth in individuals with reflux and bulimia nervosa disorders, and this causes various effects on dental restorations. Aim: The objective of this study is in vitro investigation of gastric acid's effect on flexural strength and hardness on aesthetic restorative computer-aided design and computer-aided manufacturing (CAD-CAM) materials. Materials and Methods: For this study, four materials have been used, namely Enamic (Vita), Superfect Zir (Aidite) Zirconia, IPS e.max CAD (Ivoclar Vivadent), and Mark II (Vita). From these four different materials, 24 samples with 14 × 4 × 1 dimensions in rectangular prism form are used, which makes a total of 96 samples. One group was separated as the control group, while the rest was allowed to wait at 37°C, 5 ml gastric acid for 96 hours. Hardness value and flexural strengths were measured as pre-exposure and post-exposure to gastric acid. Results: There is a statistically significant difference between the groups in terms of the amount of decrease in the mean hardness after exposure to gastric acid compared to pre-exposure values (p: 0,000; P < 0,05). There was no statistically significant difference between the groups in terms of the amount of decrease in the post-exposure average flexural strength compared to the pre-exposure value (p: 0.063; P > 0.05). There is a statistically significant difference between the groups in terms of the average flexural strength after exposure to the acid. Conclusions: According to the data obtained, it was concluded that exposure to gastric acid affects the hardness and flexural strength properties of dental restorative ceramic materials.


Assuntos
Resistência à Flexão , Ácido Gástrico , Humanos , Teste de Materiais , Dureza , Cerâmica , Desenho Assistido por Computador , Propriedades de Superfície , Materiais Dentários
9.
PLoS Pathog ; 16(12): e1008686, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33370399

RESUMO

Helicobacter pylori chronically infects the stomach of approximately half of the world's population. Manifestation of clinical diseases associated with H. pylori infection, including cancer, is driven by strain properties and host responses; and as chronic infection persists, both are subject to change. Previous studies have documented frequent and extensive within-host bacterial genetic variation. To define how within-host diversity contributes to phenotypes related to H. pylori pathogenesis, this project leverages a collection of 39 clinical isolates acquired prospectively from a single subject at two time points and from multiple gastric sites. During the six years separating collection of these isolates, this individual, initially harboring a duodenal ulcer, progressed to gastric atrophy and concomitant loss of acid secretion. Whole genome sequence analysis identified 1,767 unique single nucleotide polymorphisms (SNPs) across isolates and a nucleotide substitution rate of 1.3x10-4 substitutions/site/year. Gene ontology analysis identified cell envelope genes among the genes with excess accumulation of nonsynonymous SNPs (nSNPs). A maximum likelihood tree based on genetic similarity clusters isolates from each time point separately. Within time points, there is segregation of subgroups with phenotypic differences in bacterial morphology, ability to induce inflammatory cytokines, and mouse colonization. Higher inflammatory cytokine induction in recent isolates maps to shared polymorphisms in the Cag PAI protein, CagY, while rod morphology in a subgroup of recent isolates mapped to eight mutations in three distinct helical cell shape determining (csd) genes. The presence of subgroups with unique genetic and phenotypic properties suggest complex selective forces and multiple niches within the stomach during chronic infection.


Assuntos
Úlcera Duodenal/microbiologia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/genética , Helicobacter pylori/genética , Gastropatias/microbiologia , Animais , Atrofia/microbiologia , Doença Crônica , Ácido Gástrico , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Fenótipo , Polimorfismo de Nucleotídeo Único , Gastropatias/patologia
10.
Br J Clin Pharmacol ; 88(7): 3288-3296, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35146797

RESUMO

AIMS: Nocturnal acid breakthrough has been considered an unmet need of proton-pump inhibitors. Tegoprazan, a novel potassium-competitive acid blocker, is expected to show improved properties for this unmet need. This study was aimed to compare night-time acid suppression by tegoprazan with that by vonoprazan or esomeprazole, and to explore the effect of CYP2C19 phenotypes on acid-suppressive effects. METHODS: A randomized, open-label, 3-period, 6-sequence crossover study was conducted. A single oral dose of tegoprazan 50 mg, vonoprazan 20 mg or esomeprazole 40 mg was administered at night in each period. Continuous intragastric pH was monitored at baseline and after each dosing. RESULTS: Sixteen healthy subjects (6 CYP2C19 extensive metabolizers, 5 intermediate metabolizers, 5 poor metabolizers) completed the study. After a single dose of tegoprazan, intragastric pH increased more rapidly to over 4 at approximately 1 hour compared to the other treatments, and elevated intragastric pH was maintained stably at night. Tegoprazan exhibited night-time acid suppression for slightly but not significantly longer than vonoprazan, and greater than esomeprazole; % time at pH ≥ 4 at night was 66.0%, 60.5% and 36.1% for tegoprazan, vonoprazan and esomeprazole, respectively. Night-time acid suppression by tegoprazan and vonoprazan was not dependent on CYP2C19 phenotypes, while that by esomeprazole tended to be influenced by CYP2C19 phenotypes. CONCLUSION: Tegoprazan produced more rapid, potent and well sustained night-time acid suppression vs. vonoprazan or esomeprazole when administered at night. Furthermore, tegoprazan showed no CYP2C19 phenotype dependency in acid suppression. It suggests the potential of tegoprazan, especially in preventing nocturnal acid breakthrough.


Assuntos
Esomeprazol , Ácido Gástrico , Derivados de Benzeno , Estudos Cross-Over , Citocromo P-450 CYP2C19/genética , Esomeprazol/farmacologia , Humanos , Concentração de Íons de Hidrogênio , Imidazóis , Inibidores da Bomba de Prótons/farmacologia , Pirróis , Sulfonamidas
11.
J Clin Gastroenterol ; 56(6): 512-517, 2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34049376

RESUMO

GOAL: The aim of this study was to investigate the pepsin values and pH results of gastric juice among the subtypes of gastroesophageal reflux disease (GERD) and functional heartburn. BACKGROUND: The major destructive agents of GERD on the esophageal epithelium are gastric acid and pepsin. No precise information about pepsin concentration in gastric juice exists. STUDY: Ninety patients with GERD, 39 erosive reflux disease (ERD) Los Angeles (LA) grade A/B, 13 ERD LA grade C/D, 19 nonerosive reflux disease (NERD), 8 esophageal hypersensitivity, 11 functional heartburn, and 24 healthy controls were included in the study. During endoscopy gastric juices from the patients were aspirated and their pH readings immediately recorded. Gastric juice samples were analyzed using Peptest, a lateral flow device containing 2 unique human monoclonal antibodies to detect any pepsin present in the gastric juice sample. RESULTS: The highest mean gastric pepsin concentration (0.865 mg/mL) and the lowest median gastric pH (1.4) was observed in the LA grade C/D group compared with the lowest mean gastric pepsin concentration (0.576 mg/mL) and the highest median gastric pH (2.5) seen in the NERD group. Comparing pH, the NERD patient group was significantly higher (P=0.0018 to P=0.0233) when compared with all other GERD patient groups. CONCLUSIONS: The basal gastric pepsin level in the healthy control group was comparable to literature values. There was good correlation and a significant linear relationship between the gastric pepsin level and gastric pH within the patient groups. The severity of the GERD disease is related to the lowest pH and the highest pepsin concentration in gastric juice.


Assuntos
Esofagite Péptica , Refluxo Gastroesofágico , Endoscopia Gastrointestinal , Monitoramento do pH Esofágico , Ácido Gástrico , Refluxo Gastroesofágico/diagnóstico , Azia , Humanos , Concentração de Íons de Hidrogênio , Pepsina A
12.
Bioorg Med Chem ; 64: 116765, 2022 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-35477061

RESUMO

With the aim to discover a novel potent potassium-competitive acid blocker (P-CAB) agent, a series of 5-methyl-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole derivatives were synthesized, and their H+/K+-ATPase inhibitory activities and inhibitory action on histamine-stimulated gastric acid secretion in rats were evaluated. Among the compounds synthesized, compound 3'-((3-(2-fluorophenyl)-5-methyl-5,6-dihydropyrrolo[3,4-c]pyrazol-2(4H)-yl)methyl)-[1,1'-biphenyl]-3-carboxamide not only exhibited potent H+/K+-ATPase inhibitory activity but olso showed potent inhibitory action in vivo on histamine-stimulated gastric acid secretion. In addition, the lead compound displayed favourable oral pharmacokinetic properties in rats, which was worthy of further study as a novel P-CAB agent.


Assuntos
Ácido Gástrico , ATPase Trocadora de Hidrogênio-Potássio , Animais , Ácido Gástrico/metabolismo , ATPase Trocadora de Hidrogênio-Potássio/metabolismo , Histamina , Potássio/metabolismo , Inibidores da Bomba de Prótons/farmacologia , Pirazóis/farmacologia , Pirróis/farmacologia , Ratos
13.
J Gastroenterol Hepatol ; 37(12): 2217-2228, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36181401

RESUMO

BACKGROUND AND AIM: Potassium-competitive acid blocker (PCAB) is a recent alternative to proton pump inhibitor (PPI) for potent acid suppression. The current systematic review and meta-analysis aimed to compare the efficacy and safety of PCAB versus PPI in treating gastric acid-related diseases. METHODS: We searched up to June 5, 2022, for randomized controlled trials of gastric acid-related diseases that included erosive esophagitis, symptomatic gastroesophageal reflux disease (GERD), peptic ulcers, and Helicobacter pylori infection. The pooled risk ratio (RR) was evaluated for the efficacy outcome and treatment-emergent adverse events (TEAEs) as the safety outcome. Sensitivity analyses were performed to test the robustness of the study findings. RESULTS: Of the 710 screened studies, 19 studies including 7023 participants were analyzed. The RRs for the healing of erosive esophagitis with Vonoprazan versus PPI were 1.09 (95% confidence interval [CI] 1.03-1.14), 1.03 (95% CI 1.00-1.07), and 1.02 (95% CI 1.00-1.05) in Weeks 2, 4, and 8, respectively. There were no differences in the improvement of GERD symptoms and healing of gastric and duodenal ulcers between PCAB and PPI. The pooled eradication rates of H. pylori were significantly higher in Vonoprazan versus PPI first-line treatment (RR 1.13; 95% CI 1.04-1.22). The overall RR of TEAEs with Vonoprazan versus PPI was 1.08 (95% CI 0.89-1.31). Overall, the risk of bias was low to some concerns. Furthermore, sensitivity analyses confirmed the robustness of the study's conclusion. CONCLUSION: Vonoprazan is superior to PPI in first-line H. pylori eradication and erosive esophagitis but non-inferior in other gastric acid-related diseases. Likewise, short-term safety is comparable in both treatment groups.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Humanos , Ácido Gástrico , Inibidores da Bomba de Prótons/efeitos adversos , Potássio , Infecções por Helicobacter/tratamento farmacológico
14.
Pharmacoepidemiol Drug Saf ; 31(3): 314-321, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34738287

RESUMO

BACKGROUND: Controversies exist about excessive use of gastric acid-suppressing agents or lack of adequate indications, especially when co-prescribed with analgesics for gastroprotection. We aimed to analyze the nationwide trend of gastric acid-suppressing agents and analgesics. METHODS: We obtained nationwide consumption data of analgesics (nonsteroidal anti-inflammatory drugs [NSAIDs], opioids, others) and gastric acid-suppressing agents (proton pump inhibitors [PPI] and histamine-2 receptor antagonists [H2RAs]) between years of 2014-2018 from IQVIA Turkey. Drug utilization was measured by defined daily dose (DDD)/1000 inhabitants/day (DID) unit. Drug sales data were further used to test the correlation of PPIs and H2RAs to analgesics. RESULTS: During the study period, analgesic utilization increased from 65.7 to 67.4 DID. NSAIDs constituted 82.7%-84.9% of all analgesic utilization. The consumption of NSAIDs increased by 3.1%, and the most commonly consumed analgesic was diclofenac (18.5 ± 1.5 DID), constituting 25.4%-29.0% of all analgesics. PPI utilization was found to regularly raise from 52.1 DID in 2014 to 72.0 DID in 2018 with an overall increment of 38.2%. Use of H2RAs was found to increase from 11.4 DID in 2014 to 14.0 DID in 2018. The physician visit-adjusted utilization of both antirheumatic NSAIDs and non-antirheumatic analgesics showed significantly moderate-strong positive correlations with PPIs (r: 0.63, 0.48-0.76 and r: 0.63, 0.47-0.75, respectively) and H2RAs (r: 0.61, 0.44-0.73 and r: 0.57, 0.41-0.71, respectively). CONCLUSION: The utilization trend exhibited a dramatic increase of the gastric acid-suppressing agents -more pronounced for PPIs, with a modest increase in analgesics. Excessive utilization of PPIs does not seem to imply a tendency toward only NSAID-related gastroprotection.


Assuntos
Ácido Gástrico , Fármacos Gastrointestinais , Anti-Inflamatórios não Esteroides/uso terapêutico , Antagonistas dos Receptores H2 da Histamina/uso terapêutico , Humanos , Inibidores da Bomba de Prótons/uso terapêutico
15.
Int J Clin Pract ; 2022: 3102641, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35685507

RESUMO

Background: The influence of concomitant use of gastric acid suppressants (AS) on survival of patients with non-small-cell lung cancer (NSCLC) treated with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) is inconsistent according to previous studies. We performed a meta-analysis to evaluate the effect of additional AS in patients with NSCLC taking TKIs. Methods: Relevant observational studies were identified by a search of Medline, Embase, and Web of Science databases. Only studies with multivariate analyses were included. A random-effect model was used to combine the results. Results: Thirteen retrospective studies with 12259 patients were included. Pooled results showed that concomitant use of AS was associated with worse progression-free survival (PFS, adjusted hazard ratio (HR): 1.57, 95% confidence interval (CI): 1.31 to 1.89, P < 0.001; I 2 = 65%) and overall survival (OS, adjusted HR: 1.38, 95% CI: 1.19 to 1.61, P < 0.001; I 2 = 70%) in NSCLC patients taking TKIs. Sensitivity analysis limited to studies including NSCLC with EGFR mutation showed consistent results (HR for PFS: 1.53, P=0.003; HR for OS: 1.43, P=0.001). Subgroup analyses indicated that the association between concomitant use of AS and poor survival was not significantly affected by the category of AS used (proton pump inhibitors or histamine type-2 receptor antagonists) or the country of the study (Asian or non-Asian, P for subgroup analysis all >0.05). Conclusions: Concomitant use of AS in patients with NSCLC taking TKIs may be associated with poor survival outcomes.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/induzido quimicamente , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/genética , Receptores ErbB/metabolismo , Ácido Gástrico/metabolismo , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Estudos Retrospectivos
16.
Dysphagia ; 37(2): 350-355, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33905046

RESUMO

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).


Assuntos
Cáusticos , Estenose Esofágica , Adulto , Cáusticos/toxicidade , Estenose Esofágica/induzido quimicamente , Feminino , Ácido Gástrico , Humanos , Masculino , Estudos Prospectivos , Adulto Jovem
17.
Acta Chir Belg ; 122(5): 321-327, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33534655

RESUMO

Background: Although medical treatment is the best approach for treating gastroesophageal reflux disease (GERD), surgery has a significant role to play not only in cases of failure of medical treatment but also as in a long-term approach, specifically in young patient. On the other hand, alarming reports have been published concerning the outcomes and usefulness of antireflux surgery (ARS). The aim of this study was to evaluate medium and long-term functional outcomes following ARS performed in our institution over a 10 year period.Methods: This was a retrospective review of patients in our department who underwent primary or redo laparoscopic fundoplication between 2005 and 2015. Evaluation of the outcomes was made using a validated questionnaire specifically dedicated to GERD (the Gastroesophageal Reflux Disease - Health-Related Quality of Life (GERD-HRQL) questionnaire) and by investigation about the continued use of proton-pump inhibitors (PPIs). Exclusion criteria were patients treated for GERD with Roux-en-Y gastric bypass, emergency reduction of hiatal hernia, patients missing from follow-up and patients deceased from unrelated causes.Results: 296 patients out of 309 met the inclusion criteria. Primary procedures included 214 Nissen, 35 Toupet, and 23 Collis gastroplasty; there were additionally 62 redo operations. Neither postoperative mortality nor conversion was observed. The mean follow-up was 8 years post-surgery, and contact was made with 96% of the original group. 85% of the patients had stopped PPI use since their operation (86% after Nissen, 73% after Toupet, 94% after Collis and 82% after redos). 90% of the patients had good to excellent functional results as reported by their GERD-HRQL score, and independent of the type of previous procedure. 31 patients were dissatisfied due to dysphagia in 7 and GERD recurrence in 24. Again 75% were extremely satisfied and 15% satisfied. Our own incidence of redo procedures was 11% but the functional result and satisfaction index were comparable between redo and primary procedures. The addition of Collis gastroplasty in cases of real short oesophagus did not alter the final result.Conclusions: Laparoscopic ARS presents a superior alternative to lifetime medication use and can provide long-term control of GERD symptoms in the majority of patients if it is performed skillfully and in carefully evaluated patients. Based on the present study, we believed that significant improvement in GERD health-related quality of life can be attained following both primary and reoperative ARS.


Assuntos
Refluxo Gastroesofágico , Laparoscopia , Fundoplicatura/métodos , Ácido Gástrico , Refluxo Gastroesofágico/tratamento farmacológico , Refluxo Gastroesofágico/etiologia , Refluxo Gastroesofágico/cirurgia , Humanos , Laparoscopia/métodos , Inibidores da Bomba de Prótons , Qualidade de Vida , Estudos Retrospectivos , Resultado do Tratamento
18.
Medicina (Kaunas) ; 58(9)2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36143960

RESUMO

Background and Objectives: The aim of this in vitro study was to evaluate the effect of gastric acid associated with the effect of toothbrushing on the surface roughness of different types of composite resin used for direct restorations. Materials and Methods: The materials used in this study were two microhybrid (Filtek Z250, Herculite XRV) and two nanohybrid (Filtek Z550, Herculite XRV Ultra) composite resins. Two hundred and forty cylindrical samples with a height of 2 mm and a diameter of 6 mm were divided into four groups (groups A, B, C and D) corresponding to each tested material (n = 60). Each group was divided in two subgroups: subgroup I-the samples were submersed in hydrochloric acid and immediately submitted to toothbrushing; subgroup II-the samples were submitted only to toothbrushing. The simulation of the acid attack was performed by immersing the samples in a 0.01 M hydrochloric acid solution for 90 min. This procedure was followed immediately by toothbrushing simulation with 10,000 cycles. The acid attack and toothbrushing simulation were performed for two times. The surface roughness evaluation was performed with a Proscan 2100 profilometer. Repeated Measures ANOVA and Bonferroni post-hoc tests were used to perform the statistical analysis. Results: Simulation of one year of toothbrushing associated or not to hydrochloric acid exposure increases the surface roughness of microhybrid and nanohybrid composite resins. Six months of toothbrushing associated to six months of hydrochloric acid exposure increase the surface roughness of nanohybrid composite resins. Conclusions: Microhybrid composite resins surface becomes rougher after toothbrush and acid submersion when comparing to nanohybrid composite resins.


Assuntos
Ácido Clorídrico , Escovação Dentária , Resinas Compostas , Ácido Gástrico , Humanos , Propriedades de Superfície
19.
Medicina (Kaunas) ; 58(9)2022 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-36143826

RESUMO

Background and Objectives: The aim of this in vitro study was to evaluate the effect of simulated gastric acid associated with toothbrushing on the surface condition of three resin-modified glass-ionomer cements (RMGIC). Materials and Methods: One hundred and sixty samples of each material were obtained and included in three study groups according to the tested material: Group I (Ionolux, VOCO GmbH, Cuxhaven, Germany); Group II (Vitremer, 3 M-ESPE, St. Paul, MN, USA); and Group III (Fuji II LC, GC Corporation, Tokyo, Japan). The samples were submersed in hydrochloric acid 0.01 M (pH 3.8) for 3 h and exposed to a toothbrushing procedure at a frequency of 10,000 cycles with medium and hard bristles immediately or 30 min after the acid attack. Profilometric measurements were performed by using a non-contact profilometer (Dektak XT, Bruker, Billerica, MA, USA) in order to assess the surface roughness. ANOVA and Bonferroni post hoc tests were used for the statistical analysis at a significance level of p < 0.05. Results: Exposure of RMGICs to the erosive effect of hydrochloric acid in association with toothbrushing 30 min after the chemical attack increased the surface roughness of all three RMGICs. Exposure of the three tested materials exclusively to the action of hydrochloric acid did not affect the surface roughness. Conclusions: One year of hydrochloric acid challenge associated with one year of toothbrushing with medium-hardness bristles performed 30 min after the acid attack increase the surface roughness of two of the three types of RMGIC tested (Ionolux and Fuji II LC).


Assuntos
Ácido Clorídrico , Escovação Dentária , Ácido Gástrico , Cimentos de Ionômeros de Vidro , Humanos , Teste de Materiais , Propriedades de Superfície
20.
Rev Gastroenterol Peru ; 42(4): 242-247, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36746464

RESUMO

Gastric-acid suppressants are one of the most frequently used classes of drugs worldwide. Several studies about their overprescribing have been carried out in recent years. The aim of the study was to assess the appropriateness of these drugs at an internal medicine service of a tertiary hospital in Venezuela. A retrospective record review of patients admitted to the internal medicine service from January 2020 to February 2021 was performed. Data about indications for gastric-acid suppressants, the type used, and their continuation at discharge were collected. The prescribing was grouped into two categories, appropriate or inappropriate, according to current clinical guidelines. Of the 1203 patients who were newly prescribed gastric-acid suppressants in hospital during the study period, 993 (82.5%) had an inappropriate prescription. Prophylaxis of peptic ulcers in low-risk patients was the most frequent no evidence-based indication (20.24%). Seven hundred sixty-two patients were discharged on gastric-acid suppressants. Of these, 74.7% did not have an acceptable indication to continue this treatment on an outpatient basis. Many hospitalized patients in a Venezuelan academic tertiary healthcare center were given gastric acid suppressants not in accordance with the current clinical practice guidelines.


Assuntos
Ácido Gástrico , Medicina Interna , Humanos , Estudos Retrospectivos , Centros de Atenção Terciária , América Latina
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