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1.
Chemosphere ; 287(Pt 3): 132311, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34560499

RESUMO

A new electrochemical sensor based on Li2FeMn3O8/C-C3N4 (LFMO/CCN)/1-ethyl-3-methylimidazolium chloride modified carbon paste electrode (CPE) has been constructed to measure pantoprazole sodium (PNZS). The electrochemical impedance spectroscopy (EIS) method was employed to evaluate the electrode charge-transfer resistances. Moreover, the differential pulse voltammetry method was used to detect PNZS in phosphate buffer solution (PBS) at pH 7.0. The detection limit of 80.0 × 10-9 M and 10.9 × 10-7 M was obtained under optimal conditions in the linear concentration range of PNZS 0.09-100 µM and 100-900 µM. Chronoampermetry technique was utilized to determine the diffusion coefficient (D) of PNZS on the modified electrode surface. The CCN/LFMO/IL/CPE was successfully used to determine PNZS in various drug formulations such as tablets and vials. Finally, simultaneous determination of PNZS and acetaminophen was accomplished with no interference based on the proposed sensor.


Assuntos
Técnicas Eletroquímicas , Nanocompostos , Carbono , Eletrodos , Pantoprazol
2.
Int J Mol Sci ; 22(19)2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34639009

RESUMO

Ischemia/reperfusion injury (IRI) in the kidney is the most common cause of acute renal dysfunction through different cell damage mechanisms. This study aimed to investigate, on molecular basics for the first time, the effect of pantoprazole on renal IRI in rats. Different biochemical parameters and oxidative stress markers were assessed. ELISA was used to estimate proinflammatory cytokines. qRT-PCR and western blot were used to investigate the gene and protein expression. Renal histopathological examination was also performed. IRI resulted in tissue damage, elevation of serum levels of creatinine, urea nitrogen, malondialdehyde, TNF-α, IL-6, IL-1ß, up-regulation of NF-κB, JNK1/2, ERK1/2, p38, and cleaved caspase-3 proteins. Furthermore, it up-regulated the expression of the Bax gene and down-regulated the expression of the Bcl-2 gene. Treatment of the injured rats with pantoprazole, either single dose or multiple doses, significantly alleviated IRI-induced biochemical and histopathological changes, attenuated the levels of proinflammatory cytokines, down-regulated the expression of NF-κB, JNK1/2, ERK1/2, p38, and cleaved caspase-3 proteins, and the Bax gene, and up-regulated Bcl-2 gene expression. Moreover, treatment with pantoprazole multiple doses has an ameliorative effect that is greater than pantoprazole single-dose. In conclusion, pantoprazole diminished renal IRI via suppression of apoptosis, attenuation of the pro-inflammatory cytokines' levels, and inhibition of the intracellular signaling pathway MAPK (ERK1/2, JNK, p38)-NF-κB.


Assuntos
Apoptose/efeitos dos fármacos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Pantoprazol/farmacologia , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Biomarcadores , Citocinas/sangue , Suscetibilidade a Doenças , Expressão Gênica , Imuno-Histoquímica , Mediadores da Inflamação/sangue , Estresse Oxidativo/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Espécies Reativas de Oxigênio/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/patologia , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo
3.
Int J Pharm ; 605: 120857, 2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34229072

RESUMO

There are many hurdles in the development of generic formulations. In vitro biopredictive dissolution conditions together with alternative in vitro - in vivo relationship (IVIVR) approaches can be a powerful tool to support the development of such formulations. In this study, we hypothesized that the release profile of enteric coated (EC) formulations of pantoprazole in physiologically relevant bicarbonate buffer (BCB) would detect possible performance differences between test and reference formulations resulting in more accurate IVIVR results and predictability when compared to a pharmacopeial dissolution test. We correlated the in vitro performance of test and reference formulations (both in BCB and pharmacopeial phosphate buffer) with the in vivo data from a failed bioequivalence study. Test and reference formulations of EC pantoprazole tablets passed the USP dissolution criteria. However, they failed statistical similarity in vitro both in compendial and BCB. Bicarbonate buffer was additionally more discriminative while being more physiologically relevant. Having BCB as an additional test to evaluate EC products in vitro might improve the comparison of formulations. This can de-risk the development of generic EC formulations.


Assuntos
Química Farmacêutica , Tampões (Química) , Concentração de Íons de Hidrogênio , Pantoprazol , Solubilidade , Comprimidos , Comprimidos com Revestimento Entérico
4.
Calcif Tissue Int ; 109(6): 696-705, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34213594

RESUMO

Proton pump inhibitors (PPIs) have been associated with an increased risk of fragility fractures in pharmaco-epidemiological studies. The mechanism is unclear, but it has been speculated that by neutralising gastric acid, they may reduce intestinal calcium absorption, causing secondary hyperparathyroidism and bone loss. Here we investigated that hypothesis that the skeletal effects of PPI might be mediated by inhibitory effects on the bone-specific phosphatase PHOSPHO1. We found that the all PPIs tested inhibited the activity of PHOSPHO1 with IC50 ranging between 0.73 µM for esomeprazole to 19.27 µM for pantoprazole. In contrast, these PPIs did not inhibit TNAP activity. We also found that mineralisation of bone matrix in primary osteoblast cultures was inhibited by several PPIs in a concentration dependent manner. In contrast, the histamine-2 receptor antagonists (H2RA) nizatidine, famotidine, cimetidine and ranitidine had no inhibitory effects on PHOSPHO1 activity. Our experiments show for the first time that PPIs inhibit PHOSPHO1 activity and matrix mineralisation in vitro revealing a potential mechanism by which these widely used drugs are associated with the risk of fractures.


Assuntos
Antagonistas dos Receptores H2 da Histamina , Inibidores da Bomba de Prótons , Calcificação Fisiológica , Pantoprazol , Monoéster Fosfórico Hidrolases , Inibidores da Bomba de Prótons/farmacologia
5.
Ann Intern Med ; 174(6): 836-843, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34097431

RESUMO

Nonvariceal upper gastrointestinal bleeding is common, morbid, and potentially fatal. Cornerstones of inpatient management include fluid resuscitation; blood transfusion; endoscopy; and initiation of proton-pump inhibitor therapy, which continues in an individualized manner based on risk factors for recurrent bleeding in the outpatient setting. The International Consensus Group released guidelines on the management of nonvariceal upper gastrointestinal bleeding in 2019. These guidelines provide a helpful, evidence-based roadmap for management of gastrointestinal bleeding but leave certain management details to the discretion of the treating physician. Here, 2 gastroenterologists consider the care of a patient with nonvariceal upper gastrointestinal bleeding from a peptic ulcer, specifically debating approaches to blood transfusion and endoscopy timing in the hospital, as well as the recommended duration of proton-pump inhibitor therapy after discharge.


Assuntos
Úlcera Péptica Hemorrágica/terapia , Idoso , Transfusão de Sangue , Endoscopia Gastrointestinal , Feminino , Humanos , Pantoprazol/uso terapêutico , Úlcera Péptica Hemorrágica/diagnóstico , Guias de Prática Clínica como Assunto , Inibidores da Bomba de Prótons/uso terapêutico , Recidiva , Fatores de Risco , Visitas com Preceptor
6.
Am J Physiol Gastrointest Liver Physiol ; 320(6): G1105-G1110, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33949198

RESUMO

Phlebotomies are performed in hereditary hemochromatosis (HH) to maintain normal iron concentrations. Proton-pump inhibitors (PPIs) can reduce the number of phlebotomies in patients with HH. However, in patients without HH, the iron concentrations do not appear to be compromised when using PPIs. Therefore, we aim to explain the differences in iron absorption between patients with and without HH. In 10 p.cysteine282tyrosine (p.C282Y) homozygous HH patients with normalized iron stores and 10 healthy control subjects (HCs), the iron parameters and hepcidin concentrations were determined before ingestion of a pharmacological dose of 50 mg iron [ferric iron (Fe3+)] polymaltose and hourly for 4 h afterward. This was repeated after 7 days of treatment with pantoprazole 40 mg once daily. Serum iron concentrations and transferrin saturation percentages dropped significantly during PPI use in the patients with HH, whereas no changes were observed in the HCs. Hepcidin concentrations were lower in the patients with HH compared with the HCs both before and during PPI use. In both groups, hepcidin levels did not significantly decrease during the treatment. Seven-day PPI use significantly reduces iron absorption in patients with HH but not in HCs. Changes in hepcidin concentrations could not explain these different PPI effects on iron absorption probably due to a small sample size.NEW & NOTEWORTHY This study confirms that lowering gastric acidity by proton pump inhibitors results in a reduction in iron absorption in patients with hemochromatosis and not in healthy control subjects. The presupposition that a decrease in hepcidin concentration in healthy control subjects in response to lowering gastric acidity can explain the difference in iron absorption between these groups could not be confirmed probably because of a small sample size.


Assuntos
Ferritinas/sangue , Hemocromatose/sangue , Hepcidinas/sangue , Ferro/sangue , Adulto , Índice de Massa Corporal , Feminino , Hemocromatose/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Pantoprazol/uso terapêutico , Inibidores da Bomba de Prótons/uso terapêutico
7.
Wiad Lek ; 74(2): 228-235, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33813477

RESUMO

OBJECTIVE: The aim: Was to characterize the morphological peculiarities of the gastric mucosa at early stage of prescription of acetylsalicylic acid (ASA) and clopidogrel as well as to study the impact of pantoprazole on the gastric mucosa to optimize the prophylaxis and treatment of gastropathies induced by ASA and clopidogrel. PATIENTS AND METHODS: Materials and methods: The experiments were performed on 77 non-linear white male rats with the average weight of 150-180 g. Depending on the aim of research, the animals were divided into 7 groups. RESULTS: Results: The administration of pantoprazole in combination with ASA and clopidogrel presented positive trends in neutral glycoproteins amount and contributes to preventing GM necrotic lesions by amplification of protective properties of mucus and stabilization of apoptotic activity of gastric epithelial cells. CONCLUSION: Conclusions: 1. According to our study findings, administration of ASA in combination with clopidogrel results in 2,5 times higher risk of GM erosive lesions. 2. One of the most significant morphological manifestations of gastropathy in ASA and clopidogrel regimen is the development of microerosions, which are poorly diagnosed by macroscopic examination. 3. The use of PAS-reaction makes possible to identify damage to the basal membrane of superficial epitheliocytes, which may be a top-priority morphological criterion of gastropathy induced by ASA or clopidogrel in the absence of an inflammatory reaction. 4. Administration of pantoprazole in combination with ASA and clopidogrel contributes to preventing GM necrotic lesions by amplification of protective properties of mucus and stabilization of apoptotic activity of gastric epithelial cells.


Assuntos
Aspirina , Ticlopidina , Animais , Aspirina/efeitos adversos , Clopidogrel , Mucosa Gástrica , Masculino , Pantoprazol , Ratos
8.
Clin Transl Gastroenterol ; 12(4): e00325, 2021 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-33835078

RESUMO

INTRODUCTION: Proton pump inhibitors (PPIs) and histamine receptor 2 (H2) antagonists are commonly prescribed medications. Association between PPIs and alteration of the gut microbiota has been reported. Blastocystis, the most common intestinal protozoan worldwide, occurs in both healthy and symptomatic people with gastrointestinal or cutaneous disorders, with controversial pathogenicity. The current study was aimed to investigate the influence of PPIs and H2 blockers on the in vitro proliferation of selected intestinal bacteria, fungi, and protozoa. METHODS: Cultures of Lactobacillus rhamnosus, Escherichia coli, Enterococcus faecium, Candida albicans, and Blastocystis subtype 3 were treated with different concentrations of respective medications in vitro, and the numbers of microorganisms were quantified and compared. RESULTS: Pantoprazole and esomeprazole exerted a significant inhibition on Blastocystis and C. albicans, especially at higher concentrations, which were even more effective than metronidazole. On the other hand, treatment with pantoprazole caused an increase in proliferation of L. rhamnosus and E. coli. There was no influence of H2 blockers on the examined microorganisms. DISCUSSION: PPIs, such as pantoprazole, can be a potential treatment in the prophylaxis or eradication of Blastocystis and C. albicans.


Assuntos
Blastocystis/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Antagonistas dos Receptores H2 da Histamina/farmacologia , Inibidores da Bomba de Prótons/farmacologia , Anti-Infecciosos/farmacologia , Candida albicans/efeitos dos fármacos , Enterococcus faecium/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Esomeprazol/farmacologia , Humanos , Concentração de Íons de Hidrogênio , Lactobacillus rhamnosus/efeitos dos fármacos , Metronidazol/farmacologia , Testes de Sensibilidade Microbiana , Pantoprazol/farmacologia
9.
Medicine (Baltimore) ; 100(8): e24808, 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33663099

RESUMO

BACKGROUND: Previous studies have showed that anti-acid therapy with proton pump inhibitors (PPIs) can inhibit pancreatic secretion and it may be used in treating acute pancreatitis (AP). But at present, there is no systematic reviews for the evidence and the therapeutic effectiveness and safety of anti-acid therapy with PPIs in AP were not unclear. Therefore, we will undertake a systematic review of the literature to summarize previous evidence regarding this topic, in order to clarify the effectiveness and safety of anti-acid therapy with PPIs in AP. METHODS: We will search the EMBASE, WANFANG DATA, Web of Knowledge, China National Knowledge Infrastructure, PubMed, ClinicalTrials.gov and Cochrane Library from inception to June 30,2021 to retrieve relevant studies using the search strategy: ("Proton pump inhibitors" OR "PPI" OR "PPIs" OR "Omeprazole" OR "Tenatoprazole" OR "Pantoprazole" OR "acid suppression therapy" OR "acid suppression drugs") AND ("pancreatitis" OR "pancreatitides"). Two authors independently judged study eligibility and extracted data. Heterogeneity will be examined by computing the Q statistic and I2 statistic. RESULTS: This study assessed the efficiency and safety of proton pump inhibitors for treating acute pancreatitis. CONCLUSIONS: This study will provide reliable evidence-based evidence for the clinical application of PPIs for treating AP. ETHICS AND DISSEMINATION: Ethical approval is unnecessary as this protocol is only for systematic review and does not involve privacy data. The findings of this study will be disseminated electronically through a peer-review publication or presented at a relevant conference.


Assuntos
Pancreatite/tratamento farmacológico , Inibidores da Bomba de Prótons/uso terapêutico , 2-Piridinilmetilsulfinilbenzimidazóis/uso terapêutico , Humanos , Omeprazol/uso terapêutico , Pantoprazol/uso terapêutico , Inibidores da Bomba de Prótons/administração & dosagem , Inibidores da Bomba de Prótons/efeitos adversos , Projetos de Pesquisa
10.
Acta Anaesthesiol Scand ; 65(6): 792-800, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33635540

RESUMO

BACKGROUND: In previous studies of predictors of gastrointestinal (GI) bleeding in the intensive care unit (ICU), most patients received pharmacological stress ulcer prophylaxis (SUP). We aimed to assess associations between potential predictors of clinically important GI bleeding (CIB) and overt GI bleeding in adult ICU patients, while considering the effect and potential interaction with use of SUP. METHODS: We included 3291 acutely admitted adult ICU patients with risk factors for GI bleeding randomized to SUP (pantoprazole) or placebo in the SUP-ICU trial. We used logistic regression models adjusted for allocation to SUP to estimate associations between 23 potential predictors and CIB (primary outcome) and overt GI bleeding (secondary outcome). Furthermore, we assessed associations between potential predictors and both outcomes in each allocation group and assessed potential interaction with allocation to SUP. RESULTS: Increasing SAPS II and SOFA scores, use of circulatory support and renal replacement therapy were associated with increased risk of CIB and overt GI bleeding; chronic lung disease was associated with increased risk of overt GI bleeding. Results for the remaining potential predictors were compatible with both no difference or increased and decreased risks. We found no strong evidence for any interaction between treatment allocation and any potential predictors. CONCLUSION: In adult ICU patients at risk of GI bleeding, severity of illness, use of circulatory support and renal replacement therapy were associated with higher odds of CIB, with no strong evidence of interaction with SUP.


Assuntos
Úlcera Péptica , Adulto , Hemorragia Gastrointestinal/epidemiologia , Hemorragia Gastrointestinal/etiologia , Humanos , Unidades de Terapia Intensiva , Pantoprazol , Escala Psicológica Aguda Simplificada
11.
Am J Case Rep ; 22: e928021, 2021 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-33473099

RESUMO

BACKGROUND Cameron lesions are linear erosions and ulcers on the crests of gastric mucosal folds in the neck of a hiatal hernia and can be difficult to diagnose and treat. This report is of a case of chronic iron deficiency in a 61-year-old woman with a late diagnosis of a Cameron lesion, who did not respond to a single treatment with the proton pump inhibitor (PPI) pantoprazole, but was then treated with oral poloxamer 407 with hyaluronic acid and chondroitin sulfate in addition to PPI. CASE REPORT We report the case of a 61-year-old women with recurrent iron-deficiency anemia, first diagnosed 40 years prior to her presentation at our Endoscopy Unit, and an ongoing melena. We discovered an intrahiatal gastric mucosal defect, which we at first treated with proton pump inhibitors and sucralfate. After a follow-up gastroscopy revealed the persistence of the lesion, we decided to incorporate into the treatment a gel-like substance containing, among others, hyaluronic acid and chondroitin sulfate, and observed that the lesion resolved completely. CONCLUSIONS This report highlights that Cameron lesions should be considered in patients with hiatal hernia who have iron-deficiency anemia and can be diagnosed on upper endoscopy. Further clinical studies are required to determine the role of combined poloxamer 407 with hyaluronic acid and chondroitin sulfate in the management of Cameron lesions.


Assuntos
Anemia Ferropriva/tratamento farmacológico , Úlcera Gástrica/complicações , Úlcera Gástrica/tratamento farmacológico , Adjuvantes Imunológicos/uso terapêutico , Sulfatos de Condroitina/uso terapêutico , Doença Crônica , Portadores de Fármacos , Feminino , Gastroscopia , Hérnia Hiatal/complicações , Hérnia Hiatal/diagnóstico , Humanos , Ácido Hialurônico/uso terapêutico , Pessoa de Meia-Idade , Pantoprazol/uso terapêutico , Poloxâmero/uso terapêutico , Inibidores da Bomba de Prótons/uso terapêutico , Úlcera Gástrica/diagnóstico
12.
Am J Emerg Med ; 42: 137-142, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-32081556

RESUMO

OBJECTIVE: We determine how aggregate costs have changed for commonly used emergency department (ED) medications, and assess drivers of cost increases. METHODS: Using the National Hospital Ambulatory Medical Care Survey (NHAMCS), we identified the top 150 ED medications administered and prescribed at discharge in 2015. We used average wholesale prices (AWP) for each year from 2006 to 15 from the Red Book (Truven Health Analytics Inc.). Average wholesale price per patient (AWPP) was calculated by dividing AWP by drug uses. This was then multiplied by the total drug administrations or prescriptions to estimate the total cost in a given the year. All prices were converted to 2015 dollars. RESULTS: Aggregate costs of drugs administered in the ED increased from $688.7 million in 2006 to $882.4 million in 2015. For discharge prescriptions, aggregate costs increased from $2.031 billion in 2006 to $4.572 billion in 2015. AWPP for drugs administered in the ED in 2015 was 14.5% higher than in 2006 and 24.3% higher at discharge. The largest absolute increase in AWPP for drugs administered was for glucagon, which increased from $111 in 2006 to $235 in 2015. The largest AWPP increase at discharge was for epinephrine auto-injector, which increased from $124 in 2006 and to $481 in 2015. CONCLUSION: Over the course of the study period, the aggregate costs of the most common medications administered in the ED increased by 28% while the costs of medications prescribed at discharge increased 125%.


Assuntos
Custos de Medicamentos , Serviço Hospitalar de Emergência/economia , Medicamentos sob Prescrição/economia , Estudos Transversais , Epinefrina/economia , Glucagon/economia , Humanos , Pantoprazol/economia , Alta do Paciente , Pravastatina/economia , Estados Unidos
13.
Cell Mol Neurobiol ; 41(1): 173-183, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32862257

RESUMO

Recent studies have shown that proton pump inhibitors have positive effects on the nervous system. However, its effect on epileptic seizure and neuronal damage are still unclear. In this study, it was aimed to investigate the effect of pantoprazole on pentylenetetrazole-induced epileptic seizures in rats and neurotoxicity in the SH-SY5Y cell line. Animals were divided into three groups: control, saline (1 mL/kg serum physiologic), and pantoprazole (10 mg/kg). Pentylenetetrazole (45 mg/kg) was given to induce a seizure and a passive avoidance test trial was carried out to evaluate memory function. 8-hydroxy-2'-deoxyguanosine (8-OHdG), caspase-3, and brain-derived neurotrophic factor (BDNF) levels were measured in the brain by commercial kits. SH-SY5Y cells were treated with saline or pantoprazole for one hour, and then pentylenetetrazole (30 µm) was added to the medium to induce neurotoxicity. After 24 h, cell viability, total antioxidant, total oxidant status, and apoptosis were measured in SH-SY5Y cells. It was found that pantoprazole treatment postponed epileptic seizure onset, protected memory, reduced 8-OHdG, caspase-3, and also increased BDNF in the brain. In addition, it blocked pentylenetetrazole toxicity, apoptosis, increased antioxidant, and decreased oxidant status in SH-SY5Y cells. Pantoprazole significantly improved seizure, oxidative stress, and apoptosis. Thus, pantoprazole could be used as a supportive therapeutic agent in epilepsy.


Assuntos
Neuroblastoma/patologia , Neurotoxinas/toxicidade , Pantoprazol/uso terapêutico , Inibidores da Bomba de Prótons/uso terapêutico , Convulsões/tratamento farmacológico , 8-Hidroxi-2'-Desoxiguanosina/metabolismo , Animais , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Encéfalo/patologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Caspase 3/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Masculino , Oxidantes/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Pantoprazol/farmacologia , Pentilenotetrazol , Inibidores da Bomba de Prótons/farmacologia , Ratos Wistar , Convulsões/induzido quimicamente , Convulsões/patologia
14.
Chem Biol Drug Des ; 97(2): 305-314, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32854159

RESUMO

Proton pump inhibitors, such as omeprazole, pantoprazole and lansoprazole, are an important group of clinically used drugs. Generally, they are considered safe without direct toxicity. Nevertheless, their long-term use can be associated with a higher risk of some serious pathological states (e.g. amnesia and oncological and neurodegenerative states). It is well known that dysregulation of the metabolism of transition metals (especially iron ions) plays a significant role in these pathological states and that the above drugs can form complexes with metal ions. However, to the best of our knowledge, this phenomenon has not yet been described in water systems. Therefore, we studied the interaction between these drugs and transition metal ions in the surrounding water environment (water/DMSO, 99:1, v/v) by absorption spectroscopy. In the presence of Fe(III), a strong redshift was observed, and more importantly, the affinities of the drugs (represented as binding constants) were strong enough, especially in the case of omeprazole, so that the formation of a metallocomplex cannot be excluded during the explanation of their side effects.


Assuntos
Complexos de Coordenação/química , Lansoprazol , Inibidores da Bomba de Prótons/química , Espectrofotometria , Água/química , Compostos Férricos/química , Lansoprazol/química , Omeprazol/química , Pantoprazol/química , Elementos de Transição/química
15.
Gastroenterology ; 160(5): 1521-1531.e9, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33346007

RESUMO

BACKGROUND & AIMS: Despite the growing recognition of duodenal alterations in the pathophysiology of functional dyspepsia (FD), the effect and mechanism of proton pump inhibitors (PPIs) or first-line therapy remain unclear. We studied duodenal and systemic alterations in relation to PPI therapy in patients with FD and healthy volunteers (HVs). METHODS: We performed a prospective interventional study assessing symptoms (Patient Assessment of Gastrointestinal Symptom Severity Index), duodenal alterations, and systemic factors in patients with FD ("FD-starters") and HVs before and after PPI therapy (pantoprazole 40 mg once daily for 4 weeks). Duodenal mucosal eosinophils, mast cells and permeability were quantified. Luminal pH and bile salts were determined in duodenal aspirates. Procedures were also performed in PPI-refractory patients with FD ("FD-stoppers") before and 8 weeks after PPI withdrawal. Between- and within-group changes from baseline and associations with duodenal or systemic factors were analyzed using linear mixed models. RESULTS: The study was completed by 30 HV, 27 FD-starters, and 18 FD-stoppers. Symptoms and duodenal eosinophils, mast cells (all, P < .0001), and paracellular passage (P = .02) were significantly higher in FD-starters vs HVs and reduced with PPI therapy. Symptoms and duodenal immune cells also decreased in FD-stoppers off PPIs. In contrast, immune cells and permeability increased in HVs on PPIs. Dyspeptic symptoms correlated with eosinophils before and during PPI therapy, and increased eosinophils and permeability in HVs on PPIs were associated with changes in bile salts. CONCLUSIONS: We provide the first prospective evidence for eosinophil-reducing effects as a therapeutic mechanism of PPIs in FD, with differential effects in HVs pointing to a role of luminal changes. ClinicalTrials.gov, Number: NCT03545243.


Assuntos
Duodenopatias/tratamento farmacológico , Duodeno/efeitos dos fármacos , Dispepsia/tratamento farmacológico , Eosinofilia/tratamento farmacológico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Mucosa Intestinal/efeitos dos fármacos , Mastócitos/efeitos dos fármacos , Pantoprazol/uso terapêutico , Inibidores da Bomba de Prótons/uso terapêutico , Adulto , Bélgica , Ácidos e Sais Biliares/metabolismo , Estudos de Casos e Controles , Duodenopatias/diagnóstico , Duodenopatias/imunologia , Duodenopatias/metabolismo , Duodeno/imunologia , Duodeno/metabolismo , Dispepsia/diagnóstico , Dispepsia/imunologia , Dispepsia/metabolismo , Eosinofilia/diagnóstico , Eosinofilia/imunologia , Eosinofilia/metabolismo , Feminino , Humanos , Mediadores da Inflamação/metabolismo , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/imunologia , Doenças Inflamatórias Intestinais/metabolismo , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Masculino , Mastócitos/imunologia , Mastócitos/metabolismo , Pantoprazol/efeitos adversos , Permeabilidade , Estudos Prospectivos , Inibidores da Bomba de Prótons/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
16.
Chemosphere ; 262: 127671, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32805651

RESUMO

In this study, silver molybdate was used as a catalyst in different oxidation processes to degrade pantoprazole (PAN) from aqueous suspension. The catalyst was synthesized using a controlled precipitation method and characterized by XRD, FTIR spectroscopy, BET analysis, Zeta potential, FEG-SEM/EDS, DRS and EPR. The α- and ß-phases of Ag2MoO4 were identified as crystalline structure of the butterfly-shaped particles. The metastable α-phase could be completely converted into ß-Ag2MoO4 by thermal treatment at 300 °C. The band gap energy of ß-Ag2MoO4 (Eg = 3.25 eV) is slightly higher than for as-prepared catalyst (α-Ag2MoO4 + ß-Ag2MoO4) (Eg = 3.09 eV), suggesting that as-prepared catalyst should be active under visible light. PAN is sensible to UV light irradiation, and the addition of H2O2 as electron acceptor enhanced the mineralization rate. In the catalytic UV-based reactions, high PAN oxidation efficiencies were obtained (>85%) but with low mineralization (32-64%). Catalytic peroxidation and photo-catalytic peroxidation under visible light showed the highest PAN oxidation efficiency, leading to its almost complete mineralization (>95%), even under dark conditions (98% in 120 min). Several degradation byproducts were identified and three mechanistic routes of PAN decomposition were proposed. The identified byproducts are less toxic than the parent compound. EPR coupled with the spin trapping method identified •OH radicals as the main ROS species in both photocatalytic and catalytic peroxidation reactions. Ag2MoO4 showed to be a promising catalyst to promote the decomposition of hydrogen peroxide into ROS.1.


Assuntos
Pantoprazol/química , Catálise , Peróxido de Hidrogênio/química , Luz , Molibdênio , Oxirredução , Prata , Soluções , Raios Ultravioleta
18.
Sci Rep ; 10(1): 22376, 2020 12 23.
Artigo em Inglês | MEDLINE | ID: mdl-33361800

RESUMO

Proton pump inhibitors (PPIs) belong to the most common medication in geriatric medicine. They are known to reduce osteoclast activity and to delay fracture healing in young adult mice. Because differentiation and proliferation in fracture healing as well as pharmacologic actions of drugs markedly differ in the elderly compared to the young, we herein studied the effect of the PPI pantoprazole on bone healing in aged mice using a murine fracture model. Bone healing was analyzed by biomechanical, histomorphometric, radiological and protein biochemical analyses. The biomechanical analysis revealed a significantly reduced bending stiffness in pantoprazole-treated animals when compared to controls. This was associated with a decreased amount of bone tissue within the callus, a reduced trabecular thickness and a higher amount of fibrous tissue. Furthermore, the number of osteoclasts in pantoprazole-treated animals was significantly increased at 2 weeks and decreased at 5 weeks after fracture, indicating an acceleration of bone turnover. Western blot analysis showed a lower expression of the bone morphogenetic protein-4 (BMP-4), whereas the expression of the pro-angiogenic parameters was higher when compared to controls. Thus, pantoprazole impairs fracture healing in aged mice by affecting angiogenic and osteogenic growth factor expression, osteoclast activity and bone formation.


Assuntos
Envelhecimento/metabolismo , Consolidação da Fratura/efeitos dos fármacos , Pantoprazol/efeitos adversos , Envelhecimento/patologia , Animais , Proteína Morfogenética Óssea 4/biossíntese , Modelos Animais de Doenças , Camundongos , Neovascularização Fisiológica/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Pantoprazol/farmacologia
19.
Medicine (Baltimore) ; 99(50): e23436, 2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33327272

RESUMO

There is evidence that intake of proton pump inhibitors (PPI) increases the risk for spontaneous bacterial peritonitis (SBP) in patients with liver cirrhosis. However, data regarding the impact of PPI intake on occurrence of infections other than SBP are still lacking.We hypothesized that PPI use is associated with a higher rate of infections other than SBP in patients with liver cirrhosis.The current case-control study sample included patients with liver cirrhosis from the Disease Analyzer database (IQVIA), which compiles data such as risk factors, drug prescriptions and diagnoses obtained from general practitioners and specialists in Germany. In total, 2,823 patients with infections were matched with 2,823 patients without infections by propensity scores. For quantification of PPI use the prescribed quantity of PPI during the past 12 months before index date was analyzed.Frequency of PPI users was significantly higher in patients with infections than in patients without infections (47.9% vs 37.9%). In regression analysis, PPI use was significantly associated with the occurrence of infections overall (OR 1.55, 95% CI 1.39-1.72, P < .001), and associated with the occurrence of lower respiratory tract infections, urinary tract infections and infectious gastroenteritis. There was no association between PPI use and skin infections. Pantoprazole and omeprazole were the most frequently prescribed PPIs and were both independently associated with the occurrence of infections.PPI use may be associated with infections other than SBP in patients with liver cirrhosis. Prescription of PPI should be limited to patients with a clear indication.


Assuntos
Infecções Bacterianas/induzido quimicamente , Cirrose Hepática/tratamento farmacológico , Inibidores da Bomba de Prótons/efeitos adversos , Estudos de Casos e Controles , Bases de Dados Factuais , Feminino , Alemanha , Humanos , Cirrose Hepática/microbiologia , Masculino , Pessoa de Meia-Idade , Omeprazol/efeitos adversos , Pantoprazol/efeitos adversos , Pontuação de Propensão , Análise de Regressão , Fatores de Risco
20.
Drug Des Devel Ther ; 14: 5689-5698, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33380789

RESUMO

Objective: We developed and validated a simple, convenient and reproducible method for simultaneous estimation of six proton-pump inhibitors (PPIs), omeprazole (OPZ), esomeprazole (EOPZ), lansoprazole (LPZ), pantoprazole (PPZ), rabeprazole (RPZ) and ilaprazole (IPZ) in pharmaceutical dosage forms by a single marker. Meanwhile, the stability of the cited PPIs in 0.9% sodium chloride injection stored in polypropylene syringes up to 48 hours for continuous infusion use was investigated. Materials and Methods: The chromatographic separation was achieved on an InterSustain® C18 column (150 × 4.6 mm, 5 µm). The isocratic mobile phase made up of 0.05 M potassium dihydrogen phosphate buffer (pH 4.0): acetonitrile (65:35, v/v) was pumped through the column at a temperature maintained at 30°C and a flow rate of 1.0 mL/min. The relative retention time, UV spectral similarity and relative correction factors between OPZ and the other five PPIs were calculated and investigated using the quantitative analysis of multi-components with a single marker (QAMS) method. The stability study examined physical parameters, pH values and drug concentrations of the PPIs mixtures. Results: Under these conditions, all cited PPIs were separated simultaneously at a retention time of 6.0, 7.3, 7.3, 9.9, 12.5 and 13.9 min for RPZ, OPZ, EOPZ, IPZ, PPZ and LPZ, respectively, with a total run time less than 20.0 min. Comparative analysis results indicated that there were no significant differences observed between the QAMS method and the external standard method. The percentage of initial concentration of each PPI gradually decreased during the storage time. Conclusion: The proposed method, which is selective, economical and accurate, was applied successfully for determination of the cited PPIs in their respective pharmaceutical dosage forms. Admixtures of OPZ, EOPZ, PPZ, IPZ in 0.9% sodium chloride injection were stable for 24 hours and LPZ, RPZ in 0.9% sodium chloride injection were stable for 8 hours in polypropylene syringes.


Assuntos
Drogas em Investigação/análise , Polipropilenos/análise , Inibidores da Bomba de Prótons/análise , 2-Piridinilmetilsulfinilbenzimidazóis/análise , Cromatografia Líquida de Alta Pressão , Esomeprazol/análise , Humanos , Lansoprazol/análise , Estrutura Molecular , Omeprazol/análise , Pantoprazol/análise , Rabeprazol/análise
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