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1.
Mol Pharm ; 21(3): 1390-1401, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38329458

RESUMO

Sucralfate, which is a sucrose octasulfate aluminum complex, is an active pharmaceutical ingredient (API) falling in the category of cytoprotective agents which are very effective for gastric and duodenal ulcers. On interaction with stomach acid, it ionizes into aluminum and sucrose octasulfate ions to form a protective layer over the ulcerated region inhibiting further attack from acid. The mechanism of action of sucralfate in the context of its structure is not well understood. Considering that at least two forms of this API are available in the market, there are no reports on the various forms of sucralfate and differences in their pharmacological action. We characterized the two forms of sucralfate using multinuclear, multidimensional solid-state NMR, and the results show significant structural differences between them arising from variation in the aluminum environment and the level of hydration. The impact of structural differences on pharmacological action was examined by studying acid-induced Al release by 27Al liquid-state NMR. The sucralfate, European pharmaceutical standard, Form I, undergoes faster disruption in acid compared to Form II. The difference is explained on the basis of structural differences in the two forms which gives significant insights into the action of sucralfate in relation to its structure.


Assuntos
Antiulcerosos , Úlcera Duodenal , Humanos , Sucralfato/uso terapêutico , Sucralfato/química , Sucralfato/farmacologia , Alumínio/farmacologia , Úlcera Duodenal/tratamento farmacológico , Espectroscopia de Ressonância Magnética , Imageamento por Ressonância Magnética , Antiulcerosos/uso terapêutico
2.
Br J Nutr ; 131(11): 1844-1851, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38443203

RESUMO

The primary goal of the investigation was to analyse the anti-inflammatory and antioxidant properties of Gamma-linolenic acid (GLA) on rats with indomethacin (IND)-induced gastric ulcers. Thirty rats were divided into five groups: Control, IND (50 mg/kg, p.o.), IND pretreated with GLA 100 mg/kg (p.o. for 14 d), IND pretreated with GLA 150 mg/kg (p.o. for 14 d) and IND pretreated with omeprazole (20 mg/kg, p.o. for 14 d). The stomach tissues were examined to calculate the ulcer index and pH and analyse biochemical markers (prostaglandin E2 (PGE2), cyclooxygenase 1 (COX1), TNF-1, IL-6 and intercellular adhesion molecule-1 (ICAM1)) and oxidative stress parameters (malondialdehyde: (MDA), superoxide dismutase (SOD), glutathione (GSH) and CAT (catalase)) as well as undergo histopathological assessment. GLA 100 and 150 mg/kg showed a protective effect against IND-induced gastric damage. It reduced levels of COX1, TNF-1, IL-6 and ICAM and increased PGE2 levels. GLA also normalised antioxidant function by modulating MDA, SOD, GSH and CAT. GLA intervention protects against IND-induced gastric ulcers by restoring oxidant/antioxidant balance and reducing inflammation.


Assuntos
Antioxidantes , Dinoprostona , Indometacina , Estresse Oxidativo , Ratos Wistar , Úlcera Gástrica , Ácido gama-Linolênico , Animais , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/prevenção & controle , Úlcera Gástrica/tratamento farmacológico , Indometacina/efeitos adversos , Antioxidantes/farmacologia , Ratos , Estresse Oxidativo/efeitos dos fármacos , Ácido gama-Linolênico/farmacologia , Masculino , Dinoprostona/metabolismo , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/patologia , Mucosa Gástrica/metabolismo , Interleucina-6/metabolismo , Molécula 1 de Adesão Intercelular/metabolismo , Superóxido Dismutase/metabolismo , Antiulcerosos/farmacologia , Antiulcerosos/uso terapêutico , Glutationa/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Anti-Inflamatórios/farmacologia , Ciclo-Oxigenase 1/metabolismo , Malondialdeído/metabolismo , Omeprazol/farmacologia
3.
BMC Med Res Methodol ; 24(1): 109, 2024 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-38704520

RESUMO

BACKGROUND: During the COVID-19 pandemic, many intensive care units (ICUs) halted research to focus on COVID-19-specific studies. OBJECTIVE: To describe the conduct of an international randomized trial of stress ulcer prophylaxis (Re-Evaluating the Inhibition of Stress Erosions in the ICU [REVISE]) during the pandemic, addressing enrolment patterns, center engagement, informed consent processes, data collection, a COVID-specific substudy, patient transfers, and data monitoring. METHODS: REVISE is a randomized trial among mechanically ventilated patients, comparing pantoprazole 40 mg IV to placebo on the primary efficacy outcome of clinically important upper gastrointestinal bleeding and the primary safety outcome of 90-day mortality. We documented protocol implementation status from March 11th 2020-August 30th 2022. RESULTS: The Steering Committee did not change the scientific protocol. From the first enrolment on July 9th 2019 to March 10th 2020 (8 months preceding the pandemic), 267 patients were enrolled in 18 centers. From March 11th 2020-August 30th 2022 (30 months thereafter), 41 new centers joined; 59 were participating by August 30th 2022 which enrolled 2961 patients. During a total of 1235 enrolment-months in the pandemic phase, enrolment paused for 106 (8.6%) months in aggregate (median 3 months, interquartile range 2;6). Protocol implementation involved a shift from the a priori consent model pre-pandemic (188, 58.8%) to the consent to continue model (1615, 54.1%, p < 0.01). In one new center, an opt-out model was approved. The informed consent rate increased slightly (80.7% to 85.0%, p = 0.05). Telephone consent encounters increased (16.6% to 68.2%, p < 0.001). Surge capacity necessitated intra-institutional transfers; receiving centers continued protocol implementation whenever possible. We developed a nested COVID-19 substudy. The Methods Centers continued central statistical monitoring of trial metrics. Site monitoring was initially remote, then in-person when restrictions lifted. CONCLUSION: Protocol implementation adaptations during the pandemic included a shift in the consent model, a sustained high consent rate, and launch of a COVID-19 substudy. Recruitment increased as new centers joined, patient transfers were optimized, and monitoring methods were adapted.


Assuntos
COVID-19 , Humanos , COVID-19/prevenção & controle , COVID-19/epidemiologia , Pantoprazol/uso terapêutico , SARS-CoV-2 , Unidades de Terapia Intensiva/estatística & dados numéricos , Pandemias/prevenção & controle , Feminino , Respiração Artificial/estatística & dados numéricos , Masculino , Protocolos Clínicos , Pessoa de Meia-Idade , Hemorragia Gastrointestinal/prevenção & controle , Antiulcerosos/uso terapêutico , Antiulcerosos/administração & dosagem
4.
Drug Dev Ind Pharm ; 50(5): 460-469, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38602337

RESUMO

OBJECTIVE: Ferulic acid (FA) is a promising nutraceutical molecule which exhibits antioxidant and anti-inflammatory properties, but it suffers from poor solubility and bioavailability. In the presented study, FA nanoemulsions were prepared to potentiate the therapeutic efficacy of FA in prevention of gastric ulcer. METHODS: FA nanoemulsions were prepared, pharmaceutically characterized, and the selected nanoemusion was tested for its ulcer-ameliorative properties in rats after induction of gastric ulcer using ethanol, by examination of stomach tissues, assessment of serum IL-1ß and TNF-α, assessment of nitric oxide, prostaglandin E2, glutathione, catalase and thiobarbituric acid reactive substance in stomach homogenates, as well as histological and immunohistochemical evaluation. RESULTS: Results revealed that the selected FA nanoemulsion showed a particle size of 90.43 nm, sustained release of FA for 8 h, and better in vitro anti-inflammatory properties than FA. Moreover, FA nanoemulsion exhibited significantly better anti-inflammatory and antioxidant properties in vivo, and the gastric tissue treated with FA nanoemulsion was comparable to the normal control upon histological and immunohistochemical evaluation. CONCLUSION: Findings suggest that the prepared ferulic acid nanoemulsion is an ideal anti-ulcer system, which is worthy of further investigations.


Assuntos
Antiulcerosos , Antioxidantes , Ácidos Cumáricos , Emulsões , Nanopartículas , Úlcera Gástrica , Animais , Ácidos Cumáricos/farmacologia , Ácidos Cumáricos/química , Emulsões/química , Úlcera Gástrica/tratamento farmacológico , Ratos , Antioxidantes/farmacologia , Antioxidantes/química , Masculino , Antiulcerosos/farmacologia , Antiulcerosos/administração & dosagem , Antiulcerosos/química , Antiulcerosos/farmacocinética , Nanopartículas/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/administração & dosagem , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Ratos Wistar , Tamanho da Partícula , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-1beta/metabolismo , Solubilidade , Óxido Nítrico/metabolismo
5.
Inflammopharmacology ; 32(3): 1961-1982, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38652367

RESUMO

Gastric ulcer (GU) is one of the most common diseases of the upper gastrointestinal tract that affects millions of people worldwide. This study aimed to investigate the possible alleviating effect of a combined treatment of pantoprazole (PANTO) and adipose tissue-derived mesenchymal stem cells (ADSCs) in comparison with each treatment alone on the healing process of the experimentally induced GU in rats, and to uncover the involved pathways. Rats were divided into five groups: (1) Control, (2) GU, (3) PANTO, (4) ADSCs and (5) ADSCs + PANTO. Markers of oxidative stress, inflammation and apoptosis were assessed. The current data indicated that PANTO-, ADSCs- and ADSCs + PANTO-treated groups showed significant drop (p < 0.05) in serum advanced oxidation protein products (AOPPs) and advanced glycation end products (AGEPs) along with significant elevation (p < 0.05) in serum TAC versus the untreated GU group. Moreover, the treated groups (PANTO, ADSCs and ADSCs + PANTO) displayed significant down-regulation (p < 0.05) in gastric nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), tumor necrosis factor alpha (TNF-α), cyclooxygenase-2 (COX-2), intercellular adhesion molecule-1 (ICAM-1), matrix metallopeptidase 9 (MMP-9) and caspase-3 along with significant up-regulation (p < 0.05) in vascular endothelial growth factor (VEGF) and peroxisome proliferator-activated receptor gamma (PPARγ) genes expression compared to the untreated GU group. Immunohistochemical examination of gastric tissue for transforming growth factor ß1 (TGF-ß1), epidermal growth factor (EGF) and proliferating cell nuclear antigen (PCNA) showed moderate to mild and weak immune reactions, respectively in the PANTO-, ADSCs- and ADSCs + PANTO-treated rat. Histopathological investigation of gastric tissue revealed moderate to slight histopathological alterations and almost normal histological features of the epithelial cells, gastric mucosal layer, muscularis mucosa and submucosa in PANTO-, ADSCs- and ADSCs + PANTO-treated rats, respectively. Conclusively, the co-treatment with ADSCs and PANTO evidenced sententious physiological protection against GU by suppressing oxidative stress, inhibiting inflammation and reducing apoptosis with consequent acceleration of gastric tissue healing process.


Assuntos
Apoptose , Inflamação , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Estresse Oxidativo , Pantoprazol , Úlcera Gástrica , Animais , Estresse Oxidativo/efeitos dos fármacos , Úlcera Gástrica/induzido quimicamente , Ratos , Apoptose/efeitos dos fármacos , Pantoprazol/farmacologia , Inflamação/metabolismo , Inflamação/tratamento farmacológico , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Masculino , Transplante de Células-Tronco Mesenquimais/métodos , Ratos Wistar , Antiulcerosos/farmacologia , Antiulcerosos/administração & dosagem , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Terapia Combinada
6.
Int J Environ Health Res ; 34(2): 1088-1099, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37015007

RESUMO

The goal of this study was to determine for the first time the polyphenol content, antioxidant, and gastroprotective properties of the roots and leaves of Reichardia picroides. TPC considerably varied as a function of organs and solvent nature and ranged from 50 to 284.80 mg GAE/g DW. Leaves exhibited the highest amount of phenolics by using acetone 70%, the same tendency was observed for antioxidant activity. Besides, in vivo gastro-protective effects following HCl/EtOH-induced ulcer models displayed that roots extract at a high dose (500 mg) seemed to be the best performing extract with a decrease of ulceration index (UI) and an increase in the percentage of protection (PP), SOD, CAT, and GPX activities. All these data have been proved with principal component analysis (PCA). Overall, the results indicated that R. picroides could be considered a valuable source of natural compounds, which are beneficial for human health.


Assuntos
Antiulcerosos , Úlcera Gástrica , Tabernaemontana , Humanos , Ratos , Animais , Antioxidantes/uso terapêutico , Antioxidantes/toxicidade , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/prevenção & controle , Etanol/toxicidade , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Antiulcerosos/uso terapêutico , Antiulcerosos/toxicidade
7.
J Sci Food Agric ; 104(3): 1723-1731, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37851602

RESUMO

BACKGROUND: In the present work, acute gastric ulcer models were constructed by administering hydrochloric acid/ethanol. The mice ingested white jade snail secretion (WJSS) through gastric infusion. Ulcer areas in gastric tissue were recorded, and malondialdehyde (MDA) and superoxide dismutase (SOD) were also measured. Notably, high-throughput 16S rDNA analysis of intestinal flora and determination of amino acid composition in feces were performed to understand the effect of WJSS on model mice. RESULTS: Compared with the control group, the ulcer area in the WJSS low-, medium- and high-concentration groups declined by 28.02%, 39.57% and 77.85%, respectively. MDA content decreased by 24.71%, 49.58% and 64.25%, and SOD relative enzyme activity fell by 28.19%, 43.37% and 9.60%, respectively. The amounts of amino acids in the low-, medium- and high-concentration groups were slightly lower, and probiotic bacteria such as Bacteroidetes and Lactobacillales increased in different-concentration WJSS groups. Adding WJSS contributes to the establishment of beneficial intestinal flora and the absorption of amino acids. CONCLUSION: Our results showed that WJSS has a beneficial effect on inhibiting hydrochloric acid-ethanolic gastric ulcers, suggesting that WJSS has excellent potential as a novel anti-ulcer agent. Combined with ulcer area, MDA content, SOD content, gut probiotics and other indicators, a high concentration of WJSS had the best protective effect on acute gastric ulcer. © 2023 Society of Chemical Industry.


Assuntos
Antiulcerosos , Úlcera Gástrica , Camundongos , Animais , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/metabolismo , Antioxidantes/metabolismo , Ácido Clorídrico , Úlcera/tratamento farmacológico , Úlcera/metabolismo , Antiulcerosos/metabolismo , Antiulcerosos/farmacologia , Antiulcerosos/uso terapêutico , Etanol/metabolismo , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Extratos Vegetais/metabolismo , Aminoácidos/metabolismo , Mucosa Gástrica/metabolismo
8.
Pak J Pharm Sci ; 37(2): 315-320, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38767098

RESUMO

The present study was designed to assess Tradescantia spathacea's antidiabetic ability, as well as the antiulcer activity of the entire plant extract. The diabetic condition was evaluated using Streptozotocin's oral glucose tolerance test, diabetes-alloxan and diabetes-models. Antiulcer activities were observed in rats where gastric ulcers were either caused by oral administration of ethanol, or pyloric ligation. Standards include ranitidine, glibenclamide and sucralfate. In all models, the blood glucose levels of animals treated with the test extract were found to be significantly lower compared to diabetic care. Similarly, in all models, the ulcer index in the animals treated with the test extract was found to be significantly lower relative to the animals under vehicle supervision. Our findings say T. Spathacea extract has essential anti-diabetic properties, as well as antiulcer properties.


Assuntos
Antiulcerosos , Glicemia , Diabetes Mellitus Experimental , Hipoglicemiantes , Extratos Vegetais , Ratos Wistar , Úlcera Gástrica , Animais , Hipoglicemiantes/farmacologia , Hipoglicemiantes/isolamento & purificação , Extratos Vegetais/farmacologia , Extratos Vegetais/isolamento & purificação , Antiulcerosos/farmacologia , Antiulcerosos/isolamento & purificação , Diabetes Mellitus Experimental/tratamento farmacológico , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/prevenção & controle , Úlcera Gástrica/patologia , Úlcera Gástrica/induzido quimicamente , Masculino , Ratos , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Metanol/química , Teste de Tolerância a Glucose , Solventes/química , Fitoterapia
9.
Georgian Med News ; (348): 151-153, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38807409

RESUMO

Rebamipide contributes to the improvement of blood supply of the GI mucosa, activates its barrier function, activates alkaline secretion of the stomach, increases proliferation and metabolism of epithelial cells of the GI tract, cleanses the mucosa from hydroxyl radicals and suppresses superoxides, produced by polymorphonuclear leukocytes and neutrophils in the presence of Helicobacter pylori, protects the GI mucosa from bacterial invasion and the damaging effects of non-steroidal anti-inflammatory drugs (NSAIDs) on the mucosa. Rebamipide, originally developed as a treatment for gastric ulcers, has attracted the attention of researchers as a potential drug for the treatment of UC due to its ability to stimulate mucus production, reduce oxidative stress, and decrease inflammation. Due to the presence of these properties, it is hypothesized that rebamipide may have a protective effect on the intestinal mucosa during prolonged inflammation, making it a promising candidate for inclusion in therapeutic strategies for ulcerative colitis. The results of this study suggest that rebamipide holds potential therapeutic benefits for the treatment of ulcerative colitis.


Assuntos
Alanina , Colite Ulcerativa , Quinolonas , Quinolonas/uso terapêutico , Quinolonas/farmacologia , Alanina/análogos & derivados , Alanina/uso terapêutico , Alanina/farmacologia , Animais , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/patologia , Ratos , Antiulcerosos/uso terapêutico , Antiulcerosos/farmacologia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Mucosa Intestinal/metabolismo , Masculino , Progressão da Doença , Modelos Animais de Doenças , Ratos Wistar
10.
Antimicrob Agents Chemother ; 67(4): e0149522, 2023 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-36943038

RESUMO

Tebipenem pivoxil hydrobromide (TBP-PI-HBr) is a novel oral carbapenem prodrug being developed for the treatment of serious bacterial infections. This open-label, 3-period, fixed sequence study evaluated the effect of gastric acid-reducing agents, aluminum hydroxide/magnesium hydroxide/simethicone, and omeprazole on the pharmacokinetics (PK) of tebipenem (TBP), the active moiety, following coadministration with immediate release TBP-PI-HBr during fasting. In Period 1, subjects received a single oral dose of TBP-PI-HBr 600 mg (2 × 300 mg tablets). In Period 2, subjects received a single oral dose of aluminum hydroxide 800 mg/magnesium hydroxide 800 mg/simethicone 80 mg suspension co-administered with a single dose of TBP-PI-HBr 600 mg. In Period 3, subjects received a single oral dose of omeprazole 40 mg once daily over 5 days, followed by single dose administration of TBP-PI-HBr 600 mg on day 5. In each period, whole blood samples were obtained prior to, and up to 24 h, following TBP-PI-HBr dose administration in order to characterize TBP PK. A 7-day washout was required between periods. Twenty subjects were enrolled and completed the study. Following co-administration of TBP-PI-HBr with either aluminum hydroxide/magnesium hydroxide/simethicone or omeprazole, total TBP exposure (area under the curve [AUC]) was approximately 11% (geometric mean ratio 89.2, 90% confidence interval: 83,2, 95.7) lower, and Cmax was 22% (geometric mean ratio 78.4, 90% confidence interval: 67.9, 90.6) and 43% (geometric mean ratio 56.9, 90% confidence interval: 49.2, 65.8) lower, respectively, compared to administration of TBP-PI-HBr alone. Mean TBP elimination half-life (t1/2) was generally comparable across treatments (range: 1.0 to 1.5 h). Concomitant administration of TBP-PI-HBr with omeprazole or aluminum hydroxide/magnesium hydroxide/simethicone is not expected to impact the efficacy of TBP-PI-HBr, as there is minimal impact on TBP plasma AUC, which is the pharmacodynamic driver of efficacy. Co-administration was generally safe and well tolerated.


Assuntos
Antiácidos , Antiulcerosos , Adulto , Humanos , Administração Oral , Hidróxido de Alumínio/farmacologia , Antiácidos/farmacologia , Estudos Cross-Over , Interações Medicamentosas , Hidróxido de Magnésio/farmacologia , Omeprazol/farmacologia , Inibidores da Bomba de Prótons/farmacologia , Simeticone
11.
Annu Rev Med ; 72: 199-213, 2021 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-33502898

RESUMO

Ulcerative colitis (UC) is a relapsing and remitting inflammatory disease of the colon with a variable course. Despite advances in treatment, only approximately 40% of patients achieve clinical remission at the end of a year, prompting the exploration of new treatment modalities. This review explores novel therapeutic approaches to UC, including promising drugs in various stages of development, efforts to maximize the efficacy of currently available treatment options, and non-medication-based modalities. Treatment approaches which show promise in impacting the future of UC management are highlighted.


Assuntos
Antiulcerosos/uso terapêutico , Colite Ulcerativa/terapia , Transplante de Microbiota Fecal/métodos , Oxigenoterapia Hiperbárica/métodos , Fatores Imunológicos/uso terapêutico , Inibidores de Janus Quinases/uso terapêutico , Moduladores do Receptor de Esfingosina 1 Fosfato/uso terapêutico , Humanos
12.
Am J Gastroenterol ; 118(11): 2014-2024, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37307528

RESUMO

INTRODUCTION: In the treatment of upper GI endoscopy-negative patients with heartburn and epigastric pain or burning, antacids, antireflux agents, and mucosal protective agents are widely used, alone or as add-on treatment, to increase response to proton-pump inhibitors, which are not indicated in infancy and pregnancy and account for significant cost expenditure. METHODS: In this randomized, controlled, double-blind, double-dummy, multicenter trial assessing the efficacy and safety of mucosal protective agent Poliprotect (neoBianacid, Sansepolcro, Italy) vs omeprazole in the relief of heartburn and epigastric pain/burning, 275 endoscopy-negative outpatients were given a 4-week treatment with omeprazole (20 mg q.d.) or Poliprotect (5 times a day for the initial 2 weeks and on demand thereafter), followed by an open-label 4-week treatment period with Poliprotect on-demand. Gut microbiota change was assessed. RESULTS: A 2-week treatment with Poliprotect proved noninferior to omeprazole for symptom relief (between-group difference in the change in visual analog scale symptom score: [mean, 95% confidence interval] -5.4, -9.9 to -0.1; -6.2, -10.8 to -1.6; intention-to-treat and per-protocol populations, respectively). Poliprotect's benefit remained unaltered after shifting to on-demand intake, with no gut microbiota variation. The initial benefit of omeprazole was maintained against significantly higher use of rescue medicine sachets (mean, 95% confidence interval: Poliprotect 3.9, 2.8-5.0; omeprazole 8.2, 4.8-11.6) and associated with an increased abundance of oral cavity genera in the intestinal microbiota. No relevant adverse events were reported in either treatment arm. DISCUSSION: Poliprotect proved noninferior to standard-dose omeprazole in symptomatic patients with heartburn/epigastric burning without erosive esophagitis and gastroduodenal lesions. Gut microbiota was not affected by Poliprotect treatment. The study is registered in Clinicaltrial.gov (NCT03238534) and the EudraCT database (2015-005216-15).


Assuntos
Antiulcerosos , Dispepsia , Esofagite , Úlcera Péptica , Humanos , Omeprazol/uso terapêutico , Azia/tratamento farmacológico , Azia/etiologia , Antiulcerosos/uso terapêutico , Esofagite/induzido quimicamente , Inibidores da Bomba de Prótons/uso terapêutico , Dispepsia/tratamento farmacológico , Úlcera Péptica/complicações , Dor Abdominal/tratamento farmacológico , Resultado do Tratamento , Método Duplo-Cego
13.
Helicobacter ; 28(2): e12952, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36897573

RESUMO

BACKGROUND: Affecting between 20% and 90% of the world's population depending on the geo-socio-economic conditions, Helicobacter pylori (Hp) infection requires an adapted management because of the medico-economic stakes it generates. Also responsible for dyspepsia, the management of Hp infection differs in this context between international guidelines. OBJECTIVES: The primary outcome of the study was assessing the quality of current guidelines for HP eradication in dyspepsia. The secondary was defining the best therapeutic strategy for patients consulting with dyspepsia in the outpatient setting. METHODS: Clinical practice guidelines (CPG) published between January 2000 and May 2021 were retrieved from various databases (PubMed; Guidelines International Network; websites of scientific societies that issued the guidelines). Their quality was assessed using the AGREE II evaluation grid. To provide decision support for healthcare practitioners, particularly in primary care, a summary of the main points of interest for management was made for each guideline. RESULTS: Fourteen guidelines were included. Only four (28.6%) could be validated according to AGREE II? Most of the non-validated guidelines had low ratings in the "Rigour of development" and "Applicability" domains with means of 40% [8%-71%] and 14% [0%-25%], respectively. Three out of four validated guidelines (75%) advocated a "test and treat" strategy for dyspepsia based on the national prevalence of Hp. Gastroscopy was the 1st line examination method in case of warning signs or high risk of gastric cancer. Triple therapy (Proton pomp inhibitor, amoxicillin, and clarithromycin) was favored for Hp eradication but required a study of the sensitivity to clarithromycin in the validated guidelines. Antibiotic resistance also had an impact on treatment duration. CONCLUSIONS: Many guidelines were of poor quality, providing few decision-making tools for practical use. Conversely, those of good quality had established a management strategy addressing the current problems associated with the emergence of antibiotic-resistant strains.


Assuntos
Antiulcerosos , Dispepsia , Infecções por Helicobacter , Helicobacter pylori , Humanos , Infecções por Helicobacter/tratamento farmacológico , Claritromicina/uso terapêutico , Dispepsia/diagnóstico , Antibacterianos/uso terapêutico , Amoxicilina/uso terapêutico , Quimioterapia Combinada , Antiulcerosos/uso terapêutico
14.
Biomarkers ; 28(2): 190-205, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36484430

RESUMO

ContextGastric ulcer (GU) a widely distributed ailment is associated with many causes, including alcohol consumption.Materials and MethodsChemical profiling of Symphyotrichum squamatum ethanol extract (SSEE) was established via ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-qTOF-MS) and employed in a silver nano-formulation (SSEE-N-Ag). SSEE and SSEE-N-Ag antiulcer activities were estimated against ethanol-induced rats by biochemical, histological, and metabolomics assessments. Reduced glutathione, total antioxidant capacity and prostaglandin E2 levels and gastric mucosa histopathological examination were analysed. The rats' metabolome changing alongside action pathways were elucidated via metabolite profile coupled to multivariate data analysis.ResultsUPLC-MS profiling of SSEE identified 75 components belonging to various classes. Compared with control, EtOH-treated rats showed decreased of tissue GSH, TAC and PGE2 by 62.32%, 51.85% and 47.03% respectively. SSEE and SSEE-N-Ag administration mitigated biochemical and histopathological alterations. Serum metabolomics analysis revealed for changes in several low molecular weight metabolites with ulcer development. These metabolites levels were restored to normal post-administration of SSEE-N-Ag. SSEE-N-Ag as mediated via modulating numerous metabolic pathways such as lipids, pyrimidine, energy metabolism and phosphatidylinositol signalling. This study provides novel insight for metabolic mechanisms underlying gastric ulcer relieving effect.ConclusionPresent results revealed potential antiulcer effect of SSEE and SSEE-N-Ag by decreasing ulcer-associated syndromes, supporting their anti-ulcerogenic action.


Assuntos
Antiulcerosos , Úlcera Gástrica , Ratos , Animais , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/patologia , Etanol/toxicidade , Antiulcerosos/farmacologia , Antiulcerosos/uso terapêutico , Extratos Vegetais/química , Ratos Wistar , Metabolômica , Mucosa Gástrica
15.
BMC Gastroenterol ; 23(1): 139, 2023 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-37127558

RESUMO

BACKGROUND: VISION is a randomised, phase 4, open-label, parallel-group, multicentre study conducted in 33 centres in Japan. The aim of this study was to assess the long-term safety of vonoprazan for maintenance treatment of healed erosive oesophagitis versus lansoprazole. METHODS: Patients with endoscopically diagnosed erosive oesophagitis were randomised 2:1 to once-daily vonoprazan 20 mg or lansoprazole 30 mg, for a 4- to 8-week healing phase. Patients with endoscopically confirmed healing entered a 260-week maintenance phase with a once-daily starting dose of vonoprazan 10 mg or lansoprazole 15 mg. Primary endpoint was change in gastric mucosal histopathology. RESULTS: Of 208 patients (vonoprazan, n = 139; lansoprazole, n = 69) entering the healing phase, 202 entered the maintenance phase (vonoprazan, n = 135; lansoprazole, n = 67). At 3 years, 109 vonoprazan-treated and 58 lansoprazole-treated patients remained on treatment. Histopathological evaluation of gastric mucosa showed that hyperplasia of parietal, foveolar and G cells was more common with vonoprazan than lansoprazole at week 156 of the maintenance phase. There was no marked increase in the occurrence of parietal, foveolar and G cell hyperplasia among patients in the vonoprazan group from week 48 to week 156. Histopathological evaluation of the gastric mucosa also showed no neoplastic changes in either group. No new safety issues were identified. CONCLUSIONS: In this interim analysis of VISION, no new safety concerns were identified in Japanese patients with healed erosive oesophagitis receiving vonoprazan or lansoprazole as maintenance treatment for 3 years. (CT.gov identifier: NCT02679508; JapicCTI-163153; Japan Registry of Clinical Trials: jRCTs031180040).


Assuntos
Antiulcerosos , Esofagite , Úlcera Péptica , Humanos , Inibidores da Bomba de Prótons/uso terapêutico , Hiperplasia , Lansoprazol/efeitos adversos , Resultado do Tratamento , 2-Piridinilmetilsulfinilbenzimidazóis/uso terapêutico , Antiulcerosos/uso terapêutico , Método Duplo-Cego
16.
Mol Biol Rep ; 50(11): 9085-9098, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37741810

RESUMO

BACKGROUND: A gastric ulcer is a painful lesion of the gastric mucosa that can be debilitating or even fatal. The effectiveness of several plant extracts in the therapy of this illness has been demonstrated in traditional pharmacopoeias. AIM: this study was aimed to see if propolis, ginseng in normal or nano form, and amygdalin might help in preventing the ulcerative effects of absolute ethanol. METHODS: Gastroprotective properties of pretreatments before ethanol gavage in rats were compared to omeprazole. The ulcer and stomach parameters (ulcerated regions) were measured (mm2), ulcer inhibition percentage, the stomachs were assessed macroscopically with gastric biopsy histological examinations. RESULTS: Amygdalin, normal and nano ginseng, nano propolis followed by propolis all showed great efficacy in protecting the cyto-architecture and function of the gastric mucosa. The number of ulcerated sites was greatly reduced, and the percentage of stomach protection was increased. Histopathological examination had confirmed great protective effects of the nanoformulations followed by amygdalin. The protection and healing rate was completed to about 100% in all tested materials while ulcer areas were still partially unhealed in normal propolis and omeprazole. Quantitative assay of the m-RNA levels Enothelin 1(ET-1), leukotriene4 (LT-4), and caspase 3(Cas-3) genes and Histamine were done and revealed significant up-regulations in ethanol group and the maximum protective effect was reported with ginseng nano, moreover the histamine content was significantly decreased with nano- formulated extracts. CONCLUSION: Amygdalin and the nanoformulated ginseng and propolis had exhibited a marked protective effect against the ulcerative toxic effects of ethanol.


Assuntos
Amigdalina , Antiulcerosos , Própole , Úlcera Gástrica , Ratos , Animais , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/patologia , Úlcera/tratamento farmacológico , Úlcera/patologia , Própole/farmacologia , Amigdalina/farmacologia , Histamina/farmacologia , Histamina/uso terapêutico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Antiulcerosos/farmacologia , Antiulcerosos/uso terapêutico , Mucosa Gástrica , Omeprazol/farmacologia , Etanol/efeitos adversos
17.
Altern Ther Health Med ; 29(2): 213-217, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36525356

RESUMO

Background: Helicobacter pylori (Hp) is one of the most prevalent pathogenic microorganisms in the world, which is related to gastric ulcer. Objective: To observe the effect of lansoprazole and omeprazole combined with antibiotics on gastric juice pH and inflammatory factors in elderly patients with Hp positive gastric ulcer. Design: This study was a prospective observation study. Setting: This study was performed in Department of Gastroenterology, First Affiliated Hospital of Soochow University. Participants: One hundred and ten elder patients with Hp positive gastric ulcer admitted to our hospital from January 2019 to May 2020. Intervention: The control group was treated with omeprazole combined with antibiotics, and the observation group was treated with lansoprazole combined with antibiotics. Primary outcome measures: The level of gastric juice pH, interleukin-1 (IL-1), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α) and heat shock protein-70 (HSP-70). Methods: The changes of gastric juice pH value, IL-1, IL-8, TNF-α and HSP-70 levels before and after treatment were detected in the two groups. The total effective rate, Hp eradication rate, mature type of regenerated mucosal tissue surrounding ulcer and adverse reaction rate were statistically analyzed. Results: The total effective rate and Hp eradication rate in the observation group were higher than those in the control group, while the adverse reaction rate in the observation group was lower than that in the control group (P < .05). After treatment, the pH value of gastric juice and HSP-70 in the observation group were higher than those in the control group, while the IL-1, IL-8 and TNF-α were lower than those in the control group (P < .05). The mature type of regenerated mucosal tissue structure around ulcer in the observation group was better than that in the control group (P < .05). Conclusion: The overall effect of lansoprazole combined with antibiotics in the treatment of Hp positive gastric ulcer in the elderly is better than that of omeprazole combined with antibiotics.


Assuntos
Anti-Infecciosos , Antiulcerosos , Infecções por Helicobacter , Helicobacter pylori , Úlcera Gástrica , Humanos , Idoso , Omeprazol/uso terapêutico , Omeprazol/farmacologia , Lansoprazol/uso terapêutico , Lansoprazol/farmacologia , Úlcera Gástrica/tratamento farmacológico , Interleucina-8/farmacologia , Interleucina-8/uso terapêutico , Antiulcerosos/farmacologia , Antiulcerosos/uso terapêutico , Fator de Necrose Tumoral alfa/farmacologia , Fator de Necrose Tumoral alfa/uso terapêutico , Úlcera/tratamento farmacológico , Estudos Prospectivos , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/patologia , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , Suco Gástrico , Anti-Infecciosos/farmacologia , Anti-Infecciosos/uso terapêutico , Interleucina-1/farmacologia , Interleucina-1/uso terapêutico , Concentração de Íons de Hidrogênio , Quimioterapia Combinada
18.
Chem Biodivers ; 20(12): e202301234, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37867394

RESUMO

The genus of Salix is used in food, medicine and nutraceuticals, and standardized by using the single marker compound Salicin only. Stem bark is the official part used for the preparation of various drugs, nutraceuticals and food products, which may lead to overexploitation and damage of tree. There is need to search substitution of the stem bark with leaf of Salix alba L. (SA), which is yet not reported. Comparative phytochemicals viz. Salicin, Procyanidin B1 and Catechin were quantified in the various parts of SA viz. heart wood (SA-HW), stem bark (SA-SB) and leaves (SA-L) of Salix alba L.by using newly developed HPLC method. It was observed that SA-HW and SA-L contained far better amount of Salicin, Procyanidin B and Catechin as compared to SA-SB (SA-HW~SA-L≫SA-SB). Essential and toxic metal ions of all three parts were analysed using newly developed ICP-OES method, where SA-L were founded as a rich source of micronutrients and essential metal ions as compared to SA-SB and SA-HW. GC-MS analysis has shown the presence of fatty acids and volatile compounds. The observed TPC and TFC values for all three parts were ranged from 2.69 to 32.30 mg GAE/g of wt. and 37.57 to 220.76 mg QCE/g of wt. respectively. In DPPH assay the IC50 values of SA-SB, SA-HW, and SA-L were 1.09 (±0.02), 5.42 (±0.08), and 8.82 (±0.10) mg/mL, respectively. The order of antibacterial activities against E. coli, S. aureus, P. aeruginosa, and B. subtilis strains was SA-L>SA-HW>SA-SB with strong antibacterial activities against S. aureus, and B. subtilis strains. The antacid activities order was SA-L>SA-SB>SA-HW. The leaves of SA have shown significant source of nutrients, phytochemicals and medicinal properties than SA-HW and SA-SB. The leaves of SA may be considered as substitute of stem bark to save the environment or to avoid over exploitation, but after the complete pharmacological and toxicological studies.


Assuntos
Anti-Infecciosos , Antiulcerosos , Catequina , Salix , Catequina/farmacologia , Antioxidantes/análise , Antiácidos/análise , Antiácidos/metabolismo , Salix/química , Salix/metabolismo , Madeira , Casca de Planta/química , Escherichia coli , Staphylococcus aureus , Extratos Vegetais/química , Compostos Fitoquímicos/química , Antibacterianos/metabolismo , Folhas de Planta , Anti-Infecciosos/metabolismo
19.
Int J Mol Sci ; 24(24)2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-38139257

RESUMO

Gastric ulcers are often exacerbated by factors such as nonsteroidal anti-inflammatory drugs (NSAIDs) and inflammation, and they have a substantial impact on a significant portion of the population. Notably, indomethacin is recognized as a prominent contributor to ulcers. This study investigated this potential method, with normalization to the anti-inflammatory and antiulcer properties of deep-sea water (DSW)-derived mineral water, using an indomethacin-induced gastric ulcer model in rats. The study involved four groups (n = 6 rats/group): normal control group (CON), indomethacin-only group (IND), indomethacin with trace mineral water group (TM), and indomethacin with high magnesium low sodium water group (HMLS). For three weeks, the CON and IND groups consumed tap water, while the TM and HMLS groups had access to mineral water. Gastric ulcers were induced on the final day using indomethacin, for all groups except the CON group. The results demonstrated that HMLS intake significantly improved gastric mucosal damage, preserved mucin stability, and increased gastric thickness, indicating its potential to prevent and alleviate indomethacin-induced gastric ulcers. Furthermore, HMLS consumption led to the upregulation of key genes associated with inflammation and a reduction in inflammatory cytokines. These findings suggest that DSW-derived mineral water, and particularly its high Mg2+ content, may offer promising health benefits including anti-inflammatory and anti-ulcer properties.


Assuntos
Antiulcerosos , Águas Minerais , Úlcera Gástrica , Ratos , Animais , Indometacina/farmacologia , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/prevenção & controle , Ratos Wistar , Antiulcerosos/farmacologia , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios/efeitos adversos , Mucosa Gástrica , Água do Mar , Inflamação/tratamento farmacológico
20.
Inflammopharmacology ; 31(3): 1423-1436, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36840885

RESUMO

Bioactivity-guided fractionation of F. drupacea Thunb. extract revealed that the water fraction (FDWF) increased pH of the artificial gastric juice from 1.2 to 5.67 ± 0.015. The gastroprotective effect of FDWF against ulcer induced by ethanol was evaluated in rats. In ulcerogenic rats, increase in the gastric juice volume and ulcer lesions, and decrease in the gastric pH were evident. However, pretreatment with FDWF (100 mg/kg b.wt., p.o.) significantly inhibited lesion index, reduced gastric juice volume by 56.09% and increased gastric pH value. When given after ethanol, the same dose of FDWF led to significant healing of the gastric ulcer, with 75.60% reduction of gastric juice volume, and increase in pH value. In both prophylactic and therapeutic-treated groups, the level of superoxide dismutase and reduced glutathione in gastric homogenate were increased, while that of malondialdehyde was decreased. Also, the levels of succinate dehydrogenase and lactate dehydrogenase were increased, while that of acid phosphatase was decreased. In addition, the inflammatory markers; IL-10 and PGE2 were significantly increased. The histopathological results confirmed the above findings and indicated that the antiulcer effect of FDWF is mediated, at least in part, through antioxidant and anti-inflammatory mechanisms. Twenty-three compounds were tentatively identified in FDWF using UPLC-PDA-ESI-MS/MS and most of them were found to be phenolic acid derivatives. FDWF was standardized to contain 23.66 ± 2.62 mg/g and 8.86 ± 0.29 mg/g of quinic acid and chlorogenic acid, respectively. Accordingly, FDWF is a potential natural product that could increase the healing of gastric mucosal injury and prevents the development of ethanol-induced gastric mucosal injury in rats.


Assuntos
Antiulcerosos , Ficus , Ratos , Animais , Etanol/química , Extratos Vegetais/uso terapêutico , Úlcera/tratamento farmacológico , Úlcera/patologia , Espectrometria de Massas em Tandem , Antiulcerosos/farmacologia , Mucosa Gástrica
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