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1.
Yakugaku Zasshi ; 144(1): 99-117, 2024.
Artigo em Japonês | MEDLINE | ID: mdl-38171801

RESUMO

In 1985, I was accepted as postdoc by Professor Forte of UC Berkeley. He discovered H+,K+-ATPase and established the membrane recycling theory as the activation mechanism for acid secretion using whole animals. H+,K+-ATPase is an enzyme that exchanges H+ with K+. In resting state, it locates on the tubulovesicles and the pump does not work because the membrane lacks K+ permeability. Upon stimulation, the tubulovesicles fuse to the apical membrane and acquire K+ permeability, turning the pump on. The main route was known to be protein kinase A (PKA), but its specific targets remained unknown. Right after I joined Forte's lab, I was fortunate enough to reproduce the above mechanism in vitro, and I discovered proteins of molecular weight 120 kDa and 80 kDa that were specifically phosphorylated in stimulated parietal cells. After I returned to Japan, the former was cloned and named as parchorin, which is one of the chloride intracellular channels. Although no progress was made on ezrin, I found out the importance of PIP2 and Arf6 using permeabilized gland models. After I left parietal cell research, the link between ezrin and Arf6 was revealed. PKA phosphorylates S66 of ezrin and also MST4. The former changes the N-terminal structure of ezrin to bind syntaxin3, and the latter phosphorylates ACAP4, an Arf6-GAP, to accelerate binding to ezrin. Subsequently, H+,K+-ATPase, SNAREs, ezrin, and Arf6-GAP are aligned on the apical membrane. However, there are still many unsolved questions and the intracellular mechanism of parietal cells remains an attractive research area.


Assuntos
Ácido Gástrico , Células Parietais Gástricas , Animais , Ácido Gástrico/metabolismo , Fosforilação , Células Parietais Gástricas/metabolismo , Transporte Biológico , ATPase Trocadora de Hidrogênio-Potássio/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo
3.
Int J Biol Macromol ; 258(Pt 1): 128815, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38114010

RESUMO

First-line drugs for peptic ulcer (PU) treatment are typically limited by poor targeting and adverse effects associated with long-term use. Despite recent advancements in novel therapeutic approaches for PU, the development of sustained-release delivery systems tailored to specific pathological characteristics remains challenging. Persistent inflammation, particularly gastric inflammatory microenvironment imbalance, characterizes the PU. In this study, we prepared an in situ gel composed of sodium alginate, deacetylated gellan gum, calcium citrate, and Bletilla striata polysaccharide (BSP) to achieve sustained release of BSP. The BSP in situ gel demonstrated favorable fluidity in vitro and completed self-assembly in vivo in response to the acidic milieu at a pH of 1.5. Furthermore, the shear, extrusion, and deformation properties increased by 26.4 %, 103.7 %, and 46.3 %, respectively, with long-term gastric retention (4 h) and mucosal adaptation. Animal experiments confirmed that the BSP in situ gel could attenuate necrotic injury and inflammatory cell infiltration, maintain mucosal barrier integrity, regulate cytokine imbalance and inflammation-associated hyperapoptosis, thus effectively alleviate the inflammatory microenvironmental imbalance in PU without significant side effects. Overall, our findings demonstrated that the BSP in situ gel is a promising therapeutic strategy for PU and opens avenues for developing self-assembled formulations targeting the pathological features of PUs.


Assuntos
Orchidaceae , Úlcera Péptica , Animais , Alginatos/química , Ácido Gástrico , Polissacarídeos/química , Etanol , Inflamação , Orchidaceae/química
4.
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
6.
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
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.
Indian J Gastroenterol ; 42(4): 525-533, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37266896

RESUMO

BACKGROUND: Current gold standard for the diagnosis of gastroesophageal reflux disease (GERD) is 24-hour pH metry though it fails to detect non-acidic reflux. The sensitivity of 24-hour pH metry alone (both catheter-based and Bravo capsule) is questionable, especially if gastric acid secretion is low due to reduced parietal cell mass, Helicobacter pylori-induced gastric atrophy and antisecretory therapy. Accordingly, we analyzed the diagnostic ability of 24-hour pH metry as compared to impedance monitoring in relation to the gastric pH without antisecretory therapy. METHODS: A retrospective analysis of prospectively collected data from 150 patients with suspected GERD undergoing a 24-hour pH impedance study was done. RESULTS: Among 150 patients with symptoms suggestive of GERD, 106 (70.6%) had confirmed GERD diagnosed either by 24-hour pH metry alone (10 [9.4%]), impedance monitoring alone (49 [46.2%]) or both (47 [44.3%]). Abnormal reflux of acidic and non-acidic gastric contents was detected by 24-hour pH metry and 24-hour impedance monitoring in 57/106 (53.7%) and 96/106 (90.5%) of patients, respectively (p < .00001). Patients with GERD diagnosed by 24-hour impedance monitoring had a higher mean gastric pH (2.9 [median 1.3, IQR 5.3]) than those diagnosed by 24-hour pH metry (2.1 [median 1.4, IQR 2.6]) or both (1.6 [median 1.2, IQR 2.1]) (p = 0.001). CONCLUSION: Twenty-four-hour impedance monitoring detects GERD more often than 24-hour pH metry. Patients with higher mean gastric pH leading to non-acidic reflux were more often diagnosed by 24-hour impedance monitoring than 24-hour pH metry. Thus, 24-hour pH metry alone is inferior to additional impedance monitoring in the diagnosis of GERD, particularly in presence of reduced gastric acid secretion.


Assuntos
Ácido Gástrico , Refluxo Gastroesofágico , Humanos , Estudos Retrospectivos , Impedância Elétrica , Refluxo Gastroesofágico/diagnóstico , Concentração de Íons de Hidrogênio , Monitoramento do pH Esofágico
9.
J Neuroendocrinol ; 35(11): e13305, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37317882

RESUMO

The physiology of gastric acid secretion is one of the earliest subjects in medical literature and has been continuously studied since 1833. Starting with the notion that neural stimulation alone drives acid secretion, progress in understanding the physiology and pathophysiology of this process has led to the development of therapeutic strategies for patients with acid-related diseases. For instance, understanding the physiology of parietal cells led to the developments of histamine 2 receptor blockers, proton pump inhibitors (PPIs), and recently, potassium-competitive acid blockers. Furthermore, understanding the physiology and pathophysiology of gastrin has led to the development of gastrin/CCK2 receptor (CCK2 R) antagonists. The need for refinement of existing drugs in patients have led to second and third generation drugs with better efficacy at blocking acid secretion. Further understanding of the mechanism of acid secretion by gene targeting in mice has enabled us to dissect the unique role for each regulator to leverage and justify the development of new targeted therapeutics for acid-related disorders. Further research on the mechanism of stimulation of gastric acid secretion and the physiological significances of gastric acidity in gut microbiome is needed in the future.


Assuntos
Ácido Gástrico , Gastrinas , Humanos , Animais , Camundongos , Inibidores da Bomba de Prótons/farmacologia , Células Parietais Gástricas , Receptor de Colecistocinina B
11.
Adv Sci (Weinh) ; 10(20): e2206957, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37127895

RESUMO

Helicobacter pylori (H. pylori) has infected more than half of the world's population, and is the major cause of gastric cancer. The efficacy of standard antibiotic-based triple therapy is declining due to drug resistance development. Herein, a pH-responsive reactive oxygen species (ROS) nanogenerator (Fe-HMME@DHA@MPN) composed of acid-responsive metal polyphenol network (MPN) shell and mesoporous metal-organic nanostructure core [Fe-HMME (hematoporphyrin monomethyl ether, sonosensitizer)] loaded with dihydroartemisinin (DHA) is reported. These nanoparticles generate more ROS singlet oxygen than sonosensitizer HMME under ultrasonication, and this sonodynamic process is fueled by oxygen generated through Fenton/Fenton-like reactions of the degraded product in gastric acid Fe (II) and hydrogen peroxide (H2 O2 ) in the infection microenvironment. The encapsulated DHA, as a hydroperoxide source, is found to enhance the peroxidase-like activity of the Fe-HMME@DHA@MPN to generate ROS hydroxyl radical, beneficial for the microenvironment without sufficient H2 O2 . In vitro experiments demonstrate that the ROS nanogenerators are capable of killing multidrug-resistant H. pylori and removing biofilm, and ROS nanogenerators show high therapeutic efficacy in a H. pylori infection mouse model. Unlike the triple therapy, the nanogenerators display negligible side effects toward the normal gut microbiota. Taken together, these self-enhanced ROS nanogenerators have a great potential for treatment of H. pylori infection.


Assuntos
Microbioma Gastrointestinal , Infecções por Helicobacter , Helicobacter pylori , Animais , Camundongos , Infecções por Helicobacter/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Helicobacter pylori/metabolismo , Ácido Gástrico/metabolismo
12.
Pharmacol Res Perspect ; 11(3): e01090, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37147903

RESUMO

The global prevalence of GERD is substantially increasing each year, and GERD is a chronic disease that reduces the quality of life of patients. The efficacy of conventional drugs is diverse, and most require long-term or lifetime administration; thus, the development of more effective therapeutic agents is needed. Herein, a more effective treatment for GERD was tested. We investigated whether JP-1366 affected gastric H+/K+-ATPase activity and used the Na+/K+-ATPase assay to confirm the selectivity of H+/K+-ATPase inhibition. To clarify the mechanism of enzyme inhibition, JP-1366 and TAK-438 were analyzed by Lineweaver-Burk. Also, we investigated the effects of JP-1366 in various models involving reflux esophagitis. We found that JP-1366 mediates strong, selective, and dose-dependent inhibition of H+/K+-ATPase. We found that JP-1366 significantly suppressed gastric acid secretion in histamine-treated pylorus-ligated rats in a dose-dependent manner. Additionally, we confirmed that JP-1366 inhibited histamine-stimulated gastric acid secretion in the HPD model. JP-1366 exhibited a more than 2-fold higher inhibitory effect on esophageal injury than TAK-438 in GERD lesions and had a more potent inhibitory effect in indomethacin- or aspirin-induced gastric ulcer rat models than TAK-438. Additionally, JP-1366 inhibited gastric ulcers. These results support the possibility that JP-1366 is a good candidate drug for treating acid-related diseases.


Assuntos
Refluxo Gastroesofágico , Inibidores da Bomba de Prótons , Ratos , Animais , Inibidores da Bomba de Prótons/farmacologia , Inibidores da Bomba de Prótons/uso terapêutico , Histamina , Potássio/uso terapêutico , Qualidade de Vida , Ácido Gástrico , Refluxo Gastroesofágico/tratamento farmacológico , Adenosina Trifosfatases
13.
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
14.
Food Res Int ; 169: 112828, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37254404

RESUMO

Gastric acid diffusion and penetration constitute an essential process in the structural breakdown and enzymatic hydrolysis of solid food during digestion. This study aimed to quantify the real-time diffusion and spatial distribution of gastric acids in whey protein isolate (WPI) gels in the presence of 0-0.05 M NaCl during simulated digestion using a wide-field fluorescence microscope. For all the gels regardless of NaCl concentration, the outer surface rapidly developed a near-saturated layer, resulting in a higher normalized gastric acid concentration in the outer layer than in the inner layer. The pH decrease was more significant for the gels at a higher NaCl concentration (i.e., 0.05 M) due to the formation of a more discontinuous and looser network structure that would facilitate acid diffusion into the gel matrix and decrease the gel buffering capacity. Consistently, the effective diffusion coefficient (DA) estimated via the Fick diffusion model was 6.19 × 10-10 m2/s for 0.05 M WPI-RITC gels, significantly higher than 0.015 M (4.46 × 10-10 m2/s) and 0 M (3.54 × 10-10 m2/s) gels. The present study has provided a quantitative understanding of the diffusion process and spatial distribution of gastric acids within the WPI gel matrix in real-time during in vitro gastric digestion as influenced by NaCl concentration.


Assuntos
Ácido Gástrico , Cloreto de Sódio , Proteínas do Soro do Leite/química , Ácido Gástrico/metabolismo , Géis/química , Estômago
15.
Drug Des Devel Ther ; 17: 1115-1124, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37077412

RESUMO

Background: Esomeprazole, a proton pump inhibitor (PPI), is widely used to treat acid-related disorders, but it has short plasma half-life which can cause insufficient gastric acid suppression, such as nocturnal acid breakthrough. A new dual delayed-release (DR) formulation of esomeprazole (Esomezol DR), was developed to extend the duration of gastric acid suppression. Purpose: This study aimed to evaluate the pharmacokinetics (PKs) and pharmacodynamics (PDs) of esomeprazole for the DR formulation compared to a conventional enteric-coated (EC) formulation (Nexium) in healthy male subjects. Methods: Two randomized, open-label, multiple-dose, two-way crossover studies with esomeprazole 20 mg and 40 mg were conducted. Subjects received the DR formulation or the EC formulation once daily for 7 days in each period with a 7-day washout. Serial blood samples were collected up to 24 hours after the 1st dose, and 24-hour intragastric pH was continuously monitored before the 1st dose as baseline and after the 1st and the 7th dose. Results: In 20 mg and 40 mg dose groups, 38 and 44 subjects completed the study, respectively. The DR formulation exhibited the dual-release pattern of esomeprazole, resulting in more sustained plasma concentration-time profiles compared to the EC formulation. The systemic exposure of esomeprazole for the DR formulation was comparable to that for the EC formulation, showing the similar area under the plasma concentration-time curve. The 24-hour gastric acid suppression was also similar between the two formulations, while the inhibition during night-time (22:00-06:00) showed a better tendency in the DR formulation. Conclusion: The sustained exposure of esomeprazole in the DR formulation led to well-maintained and higher acid inhibition compared to the EC formulation, especially during the night-time. These results suggest that the DR formulation can be an alternative formulation to the conventional EC formulation, expecting the potential of relieving nocturnal acid-related symptoms.


Assuntos
Antiulcerosos , Esomeprazol , Humanos , Masculino , Antiulcerosos/farmacologia , Estudos Cross-Over , Ácido Gástrico , Voluntários Saudáveis , Concentração de Íons de Hidrogênio , Inibidores da Bomba de Prótons/farmacologia
16.
Microbiol Spectr ; 11(3): e0482022, 2023 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-37070984

RESUMO

The assessment of factors that can promote the transmission of antibiotic resistance genes (ARGs) across bacteria in the gastrointestinal tract is in great demand to understand the occurrence of infections related to antibiotic-resistant bacteria (ARB) in humans. However, whether acid-resistant enteric bacteria can promote ARG transmission in gastric fluid under high-pH conditions remains unknown. This study assessed the effects of simulated gastric fluid (SGF) at different pH levels on the RP4 plasmid-mediated conjugative transfer of ARGs. Moreover, transcriptomic analysis, measurement of reactive oxygen species (ROS) levels, assessment of cell membrane permeability, and real-time quantitative assessment of the expression of key genes were performed to identify the underlying mechanisms. The frequency of conjugative transfer was the highest in SGF at pH 4.5. Antidepressant consumption and certain dietary factors further negatively impacted this situation, with 5.66-fold and 4.26-fold increases in the conjugative transfer frequency being noted upon the addition of sertraline and 10% glucose, respectively, compared with that in the control group without any additives. The induction of ROS generation, the activation of cellular antioxidant systems, increases in cell membrane permeability, and the promotion of adhesive pilus formation were factors potentially contributing to the increased transfer frequency. These findings indicate that conjugative transfer could be enhanced under certain circumstances in SGF at elevated pH levels, thereby facilitating ARG transmission in the gastrointestinal tract. IMPORTANCE The low pH of gastric acid kills unwanted microorganisms, in turn affecting their inhabitation in the intestine. Hence, studies on the factors that influence antibiotic resistance gene (ARG) propagation in the gastrointestinal tract and on the underlying mechanisms are limited. In this study, we constructed a conjugative transfer model in the presence of simulated gastric fluid (SGF) and found that SGF could promote the dissemination of ARGs under high-pH conditions. Furthermore, antidepressant consumption and certain dietary factors could negatively impact this situation. Transcriptomic analysis and a reactive oxygen species assay revealed the overproduction of reactive oxygen species as a potential mechanism by which SGF could promote conjugative transfer. This finding can help provide a comprehensive understanding of the bloom of antibiotic-resistant bacteria in the body and create awareness regarding the risk of ARG transmission due to certain diseases or an improper diet and the subsequent decrease in gastric acid levels.


Assuntos
Antagonistas de Receptores de Angiotensina , Genes MDR , Humanos , Espécies Reativas de Oxigênio , Antagonistas de Receptores de Angiotensina/farmacologia , Ácido Gástrico , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Bactérias/genética , Antibacterianos/farmacologia , Intestinos , Concentração de Íons de Hidrogênio , Transferência Genética Horizontal , Genes Bacterianos , Plasmídeos
17.
Biosens Bioelectron ; 224: 115062, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36646014

RESUMO

Gastric acid is an important functional substance secreted by the stomach of the living organisms, reflecting the gastric physiological condition. The sensing of gastric acid in vivo is of great significance for evaluation of gastric function, diagnosis and treatment of gastric diseases and maintenance of organism health but remains challenging due to the harsh acid and digestive environment of stomach. This study developed an activatable nanoprobe based on Au nanoclusters (Au NCs) for sensitive and real-time noninvasive near-infrared II (NIR-II) fluorescence imaging detection of gastric acid in vivo for the first time. The Au NCs were encapsulated by polydopamine to have enhanced NIR-II luminescence and high stability and combined with methylene blue to possess the pH responsiveness for gastric acid imaging. The developed nanoprobe could not only monitor gastric acid secretion in vivo but also imaging the changes of gastric acid caused by feeding, acid-inhibition drugs and gastric ulcer disease. This study provides a promising avenue for the improvement of the application performance of Au NCs and imaging analysis of gastric acid and related gastric diseases.


Assuntos
Técnicas Biossensoriais , Ácido Gástrico , Imagem Óptica/métodos
18.
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
19.
Int Urol Nephrol ; 55(1): 141-150, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35821366

RESUMO

BACKGROUND: Ferric citrate hydrate (FC), an oral iron product is approved as iron preparation for iron deficiency anemia and phosphate binder for chronic kidney disease (CKD). We investigated whether gastric acid secretion inhibitors (GASI) influenced on iron absorption and phosphate-lowering effects of FC. METHODS: Two phase 3 studies of FC for treatment of hyperphosphatemia in CKD patients (non-dialysis-dependent, 12 weeks, and hemodialysis, 52 weeks), were retrospectively analyzed. Patients were divided into with or without concomitant GASI and levels of iron- and phosphate-related parameters were analyzed. RESULTS: In non-dialysis study (FC, 60 patients; placebo, 30 patients), 14 FC patients and 14 placebo patients used GASI. No significant differences were found between the FC and placebo groups for adjusted mean differences (95% CI) of changes from baseline to end of treatment (EOT) in serum ferritin [104.84 ng/mL (35.97, 173.71) with GASI vs 145.30 ng/mL (96.34, 194.25) without GASI, P = 0.34], and transferrin saturation (TSAT) [12.56% (- 0.83, 25.95) with GASI vs 18.56% (8.15, 28.98) without GASI, P = 0.49]. In hemodialysis study, 95/180 patients used GASI. Mean changes (SD) from baseline to EOT in serum ferritin were 166.32 ng/mL (153.70) with GASI and 155.16 ng/mL (139.47) without GASI, and for TSAT were 16.60% (19.44) with GASI and 16.02% (18.81) without GASI. In both studies, there were no differences in the changes from baseline to EOT in serum phosphate between with and without GASI cohorts. CONCLUSION: GASI did not influence on the changes in serum ferritin, TSAT and serum phosphate by FC administration.


Assuntos
Fosfatos , Insuficiência Renal Crônica , Humanos , Estudos Retrospectivos , Ácido Gástrico/metabolismo , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/terapia , Ferro/metabolismo , Diálise Renal , Ferritinas
20.
ISME J ; 17(1): 36-46, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36153406

RESUMO

The gastrointestinal (GI) environment plays a critical role in shaping enteric infections. Host environmental factors create bottlenecks, restrictive events that reduce the genetic diversity of invading bacterial populations. However, the identity and impact of bottleneck events on bacterial infection are largely unknown. We used Citrobacter rodentium infection of mice, a model of human pathogenic Escherichia coli infections, to examine bacterial population dynamics and quantify bottlenecks to host colonization. Using Sequence Tag-based Analysis of Microbial Populations (STAMP) we characterized the founding population size (Nb') and relatedness of C. rodentium populations at relevant tissue sites during early- and peak-infection. We demonstrate that the GI environment severely restricts the colonizing population, with an average Nb' of only 12-43 lineages (of 2,000+ inoculated) identified regardless of time or biogeographic location. Passage through gastric acid and escape to the systemic circulation were identified as major bottlenecks during C. rodentium colonization. Manipulating such events by increasing gastric pH dramatically increased intestinal Nb'. Importantly, removal of the stomach acid barrier had downstream consequences on host systemic colonization, morbidity, and mortality. These findings highlight the capability of the host GI environment to limit early pathogen colonization, controlling the population of initial founders with consequences for downstream infection outcomes.


Assuntos
Infecções por Enterobacteriaceae , Infecções por Escherichia coli , Camundongos , Humanos , Animais , Citrobacter rodentium/genética , Ácido Gástrico , Infecções por Enterobacteriaceae/microbiologia , Infecções por Enterobacteriaceae/patologia , Trato Gastrointestinal/microbiologia , Camundongos Endogâmicos C57BL
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