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1.
Auris Nasus Larynx ; 51(3): 548-552, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38537558

RESUMO

OBJECTIVES: We aimed to evaluate the treatment outcomes of proton-pump inhibitors (PPIs) in patients with contact granuloma (CG) and to investigate the parameters of 24 h combined dual channel pH/impedance (24 h pH/MII) monitoring, which are reliable for predicting the response to PPI of CG patients. METHODS: We reviewed the medical records of patients with CG who had been treated with PPIs and had completed more than 6 months of follow-up. We classified the patients into two groups (cured vs. persistent), according to their PPI treatment outcomes. Reflux events were categorized into three groups based on pharyngeal pH during reflux: 1) acid reflux (pH < 4), 2) weak acid reflux (4 < pH < 7), and 3) weak alkaline reflux (pH >7), as detected by a proximal probe. We compared the results of 24h-pH/MII between the two groups and used receiver operating characteristic curve (ROC) analysis to determine the cutoff values of significant parameters for predicting responses to PPIs. RESULTS: Among 22 patients who completed at least 6 months of PPI treatment and follow-up, weak acid reflux events were more frequently observed in persistent group than in the cured group (p = 0.046), and the proportion of weak acid reflux was also higher in the persistent group (p = 0.031) than in the cured group. Reliable parameters predictive of a poor response to PPIs were a number of weak acid reflux events ≥ 11 (area under the curve [AUC], 0.775; p = 0.03) and a proportion of weak acid reflux events ≥ 56.7 % (AUC, 0.763; p = 0.038) in ROC analyses. CONCLUSION: Weak acid reflux was identified as a significant factor associated with the treatment outcomes of PPIs in patients with CG. A number of weak acid reflux events ≥ 11 is considered to be the most reliable predictor of a poor response to PPIs in patients with CG.


Assuntos
Impedância Elétrica , Inibidores da Bomba de Prótons , Curva ROC , Humanos , Inibidores da Bomba de Prótons/uso terapêutico , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Idoso , Monitoramento do pH Esofágico , Resultado do Tratamento , Estudos Retrospectivos , Granuloma Laríngeo/tratamento farmacológico , Concentração de Íons de Hidrogênio , Refluxo Gastroesofágico/tratamento farmacológico , Refluxo Laringofaríngeo/tratamento farmacológico , Omeprazol/uso terapêutico
2.
J Mol Med (Berl) ; 102(5): 679-692, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38453697

RESUMO

Chronic kidney disease (CKD) is the 16th leading cause of mortality worldwide. Clinical studies have raised that long-term use of omeprazole (OME) is associated with the morbidity of CKD. OME is commonly used in clinical practice to treat peptic ulcers and gastroesophageal reflux disease. However, the mechanism underlying renal failure following OME treatment remains mostly unknown and the rodent model of OME-induced CKD is yet to be established. We described the process of renal injury after exposure to OME in mice; the early renal injury markers were increased in renal tubular epithelial cells (RTECs). And after long-term OME treatment, the OME-induced CKD mice model was established. Herein, aryl hydrocarbon receptor (AHR) translocation appeared after exposure to OME in HK-2 cells. Then for both in vivo and in vitro, we found that Ahr-knockout (KO) and AHR small interfering RNA (siRNA) substantially alleviated the OME-induced renal function impairment and tubular cell damage. Furthermore, our data demonstrate that antagonists of AHR and CYP1A1 could attenuate OME-induced tubular cell impairment in HK-2 cells. Taken together, these data indicate that OME induces CKD through the activation of the AHR-CYP axis in RTECs. Our findings suggest that blocking the AHR-CYP1A1 pathway acts as a potential strategy for the treatment of CKD caused by OME. KEY MESSAGES: We provide an omeprazole-induced chronic kidney disease (CKD) mice model. AHR activation and translocation process was involved in renal tubular damage and promoted the occurrence of CKD. The process of omeprazole nephrotoxicity can be ameliorated by blockade of the AHR-CYP1A1 axis.


Assuntos
Citocromo P-450 CYP1A1 , Camundongos Endogâmicos C57BL , Camundongos Knockout , Omeprazol , Receptores de Hidrocarboneto Arílico , Insuficiência Renal Crônica , Omeprazol/farmacologia , Omeprazol/uso terapêutico , Receptores de Hidrocarboneto Arílico/metabolismo , Receptores de Hidrocarboneto Arílico/genética , Animais , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/etiologia , Insuficiência Renal Crônica/induzido quimicamente , Citocromo P-450 CYP1A1/metabolismo , Citocromo P-450 CYP1A1/genética , Humanos , Camundongos , Linhagem Celular , Masculino , Modelos Animais de Doenças , Células Epiteliais/metabolismo , Células Epiteliais/efeitos dos fármacos , RNA Interferente Pequeno/metabolismo , RNA Interferente Pequeno/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Túbulos Renais/patologia , Túbulos Renais/metabolismo , Túbulos Renais/efeitos dos fármacos
3.
J Ethnopharmacol ; 327: 117970, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38428660

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Solenostemma argel is widely distributed in Africa & Asia with traditional usage in alleviating abdominal colic, aches, & cramps. This plant is rich in phytochemicals, which must be explored for its pharmacological effects. PURPOSE: Peptic Ulcer Disease (PUD) is the digestion of the digestive tube. PUD not only interferes with food digestion & nutrient absorption, damages one of the largest defensive barriers against pathogenic micro-organisms, but also impedes drug absorption & bioavailability, rendering the oral route, the most convenient way, ineffective. Omeprazole, one of the indispensable cost-effective proton-pump inhibitors (PPIs) extensively prescribed to control PUD, is showing growing apprehensions toward multiple drug interactions & side effects. Hence, finding a natural alternative with Omeprazole-like activity & limited side effects is a medical concern. STUDY DESIGN: Therefore, we present Stemmoside C as a new gastroprotective phytochemical agent isolated from Solenostemma argel to be tested in upgrading doses against ethanol-induced gastric ulcers in mice compared to negative, positive, & reference Omeprazole groups. METHODS: We carried out in-depth pharmacological & histopathological studies to determine the possible mechanistic pathway. RESULTS: Our results showed that Stemmoside C protected the stomach against ethanol-induced gastric ulcers parallel to Omeprazole. Furthermore, the mechanistic studies revealed that Stemmoside C produced its effect using an orchestrated array of different mechanisms. Stemmoside C stimulates stomach defense by increasing COX-2, PGE-2, NO, & TFF-1 healing factors, IL-10 anti-inflammatory cytokine, & Nrf-2 & HO-1 anti-oxidant pathways. It also suppresses stomach ulceration by inhibiting leucocyte recruitment, especially neutrophils, leading to subsequent inhibition of NF-κBp65, TNF-α, IL-1ß, & iNOS pro-inflammatory cytokines & JAK-1/STAT-3 inflammation-induced carcinogenicity cascade in addition to MMP-9 responsible for tissue degradation. CONCLUSION: These findings cast light on Stemmoside C's clinical application against gastric ulcer progression, recurrence, & tumorigenicity & concurrently with chemotherapy.


Assuntos
Antiulcerosos , Úlcera Gástrica , Camundongos , Animais , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/patologia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Extratos Vegetais/metabolismo , Antiulcerosos/farmacologia , Antiulcerosos/uso terapêutico , Omeprazol/farmacologia , Omeprazol/uso terapêutico , Etanol/farmacologia , Citocinas/metabolismo , Mucosa Gástrica
4.
Obes Surg ; 34(4): 1196-1206, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38400943

RESUMO

PURPOSE: To assess the effects of Helicobacter pylori (HP) eradication with an omeprazole, clarithromycin, amoxicillin, and metronidazole (OCAM) regimen on the metabolic profile and weight loss 12 months after bariatric surgery (BS). METHODS: Retrospective analysis of a prospective cohort of patients with morbid obesity undergoing BS. HP presence was tested preoperatively by gastric biopsy and treated with OCAM when positive. Short-term metabolic outcomes and weight loss were evaluated. RESULTS: HP infection was detected in 75 (45.7%) of the 164 patients included. OCAM effectiveness was 90.1%. HP-negative patients had a greater reduction in glucose levels at 3 (-14.6 ± 27.5 mg/dL HP-treated vs -22.0 ± 37.1 mg/dL HP-negative, p=0.045) and 6 months (-13.7 ± 29.4 mg/dL HP-treated vs -26.4 ± 42.6 mg/dL HP-negative, p= 0.021) and greater total weight loss (%TWL) at 6 (28.7 ± 6.7% HP-treated vs 30.45 ± 6.48% HP-negative, p= 0.04) and 12 months (32.21 ± 8.11% HP-treated vs 35.14 ± 8.63% HP-negative, p= 0.023). CONCLUSIONS: Preoperative treatment with OCAM has been associated to poorer glycemic and weight loss outcomes after BS. More research is needed on the influence of OCAM on gut microbiota, and in turn, the effect of the latter on metabolic and weight loss outcomes after BS.


Assuntos
Cirurgia Bariátrica , Infecções por Helicobacter , Helicobacter pylori , Obesidade Mórbida , Humanos , Estudos Retrospectivos , Estudos Prospectivos , Obesidade Mórbida/cirurgia , Infecções por Helicobacter/tratamento farmacológico , Amoxicilina/uso terapêutico , Claritromicina/uso terapêutico , Omeprazol/uso terapêutico , Metronidazol/farmacologia , Metronidazol/uso terapêutico , Redução de Peso , Quimioterapia Combinada , Antibacterianos/uso terapêutico
5.
Inflammopharmacology ; 32(2): 1519-1529, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38227096

RESUMO

AIMS: Putative beneficial effects of neuropeptide W (NPW) in the early phase of gastric ulcer healing process and the involvement of cyclooxygenase (COX) enzymes were investigated in an acetic acid-induced gastric ulcer model. MAIN METHODS: In anesthetized male Sprague-Dawley rats, acetic acid was applied surgically on the serosa and then a COX-inhibitor (COX-2-selective NS-398, COX-1-selective ketorolac, or non-selective indomethacin; 2 mg/kg/day, 3 mg/kg/day or 5 mg/kg/day; respectively) or saline was injected intraperitoneally. One h after ulcer induction, omeprazole (20 mg/kg/day), NPW (0.1 µg/kg/day) or saline was intraperitoneally administered. Injections of NPW, COX-inhibitors, omeprazole or saline were continued for the following 2 days until rats were decapitated at the end of the third day. KEY FINDINGS: NPW treatment depressed gastric prostaglandin (PG) I2 level, but not PGE2 level. Similar to omeprazole, NPW treatment significantly reduced gastric and serum tumor necrosis factor-alpha and interleukin-1 beta levels and depressed the upregulation of nuclear factor kappa B (NF-κB) and COX-2 expressions due to ulcer. In parallel with the histopathological findings, treatment with NPW suppressed ulcer-induced increases in myeloperoxidase activity and malondialdehyde level and replenished glutathione level. However, the inhibitory effect of NPW on myeloperoxidase activity and NPW-induced increase in glutathione were not observed in the presence of COX-1 inhibitor ketorolac or the non-selective COX-inhibitor indomethacin. SIGNIFICANCE: In conclusion, NPW facilitated the healing of gastric injury in rats via the inhibition of pro-inflammatory cytokine production, oxidative stress and neutrophil infiltration as well as the downregulation of COX-2 protein and NF-κB gene expressions.


Assuntos
Neuropeptídeos , Transdução de Sinais , Úlcera Gástrica , Animais , Masculino , Ratos , Acetatos/farmacologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Ciclo-Oxigenase 1/metabolismo , Ciclo-Oxigenase 2/metabolismo , Inibidores de Ciclo-Oxigenase/uso terapêutico , Mucosa Gástrica , Glutationa/metabolismo , Indometacina/uso terapêutico , Cetorolaco/efeitos adversos , Neuropeptídeos/uso terapêutico , NF-kappa B/metabolismo , Omeprazol/farmacologia , Omeprazol/uso terapêutico , Peroxidase/metabolismo , Ratos Sprague-Dawley , Úlcera Gástrica/tratamento farmacológico , Úlcera/metabolismo , Úlcera/patologia
6.
J Equine Vet Sci ; 133: 105015, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38281606

RESUMO

Feedstuffs are often recommended to mitigate potential damage from acid associated with equine squamous gastric disease (ESGD). In acidic conditions, pectin alters its structure to one like mucus and binds the stomach mucosa, whilst alfalfa has a strong intrinsic acid buffering capacity. The study aimed to determine whether feeding a commercial beet pulp/alfalfa/oat fibre mix aids ESGD healing and/or prevention of recurrence. Ten adult horses with naturally occurring ESGD were included. All animals were treated with omeprazole as per the attending veterinarian's recommendation and randomly allocated to also be fed a commercial beet pulp/alfalfa/oat fibre mix (1Kg/horse divided into 2 meals/day; n=5) or no additional feed (n=5) for one month. Gastroscopy was then repeated to assess response to therapy. If the ESGD had healed, omeprazole therapy was discontinued, and the commercial feed given to all horses for a further month. Gastroscopy was repeated to determine ESGD recurrence. The mean (±SD) age of the horses was 11.6 (±3.8) years; 4 mares and 6 geldings; various breeds were represented; and the median (range) initial ESGD grade was 2 (2-4). ESGD had healed (grade 0/4) in all animals after one month. After a further month, ESGD had recurred in significantly (p=0.04) more animals that did not receive the commercial feed initially (3/5; 60%; mean [range] ESGD grade 3 [0,4]) compared to those that did (0/5; 0%; mean [range] ESGD grade 0 [0,0]). Thus, the commercial beet pulp/alfalfa/oat fibre mix aided prevention of ESGD recurrence when fed during the healing and prevention phases.


Assuntos
Carcinoma de Células Escamosas , Doenças dos Cavalos , Gastropatias , Cavalos , Animais , Feminino , Masculino , Melhoramento Vegetal , Gastropatias/veterinária , Omeprazol/farmacologia , Omeprazol/uso terapêutico , Doenças dos Cavalos/tratamento farmacológico , Doenças dos Cavalos/prevenção & controle , Medicago sativa , Carcinoma de Células Escamosas/veterinária
7.
J Matern Fetal Neonatal Med ; 36(2): 2272577, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37884440

RESUMO

OBJECTIVE: To investigate the correlation between the aryl hydrocarbon receptor (AhR) and reactive oxygen species (ROS) in peripheral blood mononuclear cells (PBMCs) of premature infants, to demonstrate the protective role of AhR against hyperoxia-induced oxidative stress in premature infants and to provide a rational basis for the use of omeprazole (OM) as a new treatment for bronchopulmonary dysplasia (BPD). METHODS: From January 2021 to June 2021, 1-3 ml of discarded peripheral blood was collected from premature infants of gestational age less than 32 weeks who were not taking inhaled oxygen and were admitted to the Department of Neonatology of the Affiliated Hospital of Southwest Medical University. Using a random number table, the PBMCs were randomly assigned to each of the following groups: the control group, air + OM group, hyperoxia group, and hyperoxia + OM group. After 48 h of in vitro modeling and culture, PBMCs and the culture medium of each group were collected. Immunofluorescence analysis was used to examine ROS levels in PBMCs. A full-spectrum spectrophotometer was used to examine malondialdehyde (MDA) levels in the culture medium. Enzyme-linked immunosorbent assay (ELISA) was used to examine monocyte chemotactic protein 1 (MCP-1) levels in culture medium. Immunofluorescence analysis was used to examine the intracellular localization of AhR. Western blotting was used to examine the expression level of AhR in PBMCs. RESULTS: Compared with those in the control group, the levels of ROS, MDA, and MCP-1 and the cytoplasm-nuclear translocation rate of AhR in the air + OM group did not change significantly (p > 0.05), but the expression level of AhR increased significantly (p < 0.05). The levels of ROS, MDA, and MCP-1 and the cytoplasm-nuclear translocation rate of AhR significantly increased in the hyperoxia group (p < 0.05), and the expression level of AhR was significantly reduced (p < 0.05). Compared with those in the hyperoxia group, the levels of ROS, MDA, and MCP-1 in the hyperoxia + OM group were significantly reduced (p < 0.05), and the cytoplasm-nuclear translocation rate of AhR and the expression level of AhR were significantly increased (p < 0.05), but did not reach the level of the control group (p < 0.05). CONCLUSION: OM can activate AhR to inhibit hyperoxia-induced oxidative stress in the PBMCs from premature infants.


Assuntos
Hiperóxia , Humanos , Recém-Nascido , Lactente , Hiperóxia/complicações , Espécies Reativas de Oxigênio/metabolismo , Omeprazol/farmacologia , Omeprazol/uso terapêutico , Receptores de Hidrocarboneto Arílico/metabolismo , Leucócitos Mononucleares/metabolismo , Recém-Nascido Prematuro , Estresse Oxidativo , Pulmão/metabolismo
8.
J Feline Med Surg ; 25(10): 1098612X231201769, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37874311

RESUMO

OBJECTIVES: The primary objective of this study was to evaluate the prescription patterns and appropriateness of the use of gastroprotectant medication in cats. METHODS: Pharmacy dispensation logs from an academic tertiary referral center were reviewed between 1 January 2018 and 31 December 2018. Cats that were administered proton pump inhibitors (PPIs), histamine-2 receptor antagonists (H2RAs), sucralfate, misoprostol, antacids or a combination were included. Data regarding medication, dosage, formulation, duration of administration, completeness of discharge instructions and clinical rationales for administration were obtained from medical records. The appropriateness of gastroprotectant use was assessed according to the American College of Veterinary Internal Medicine consensus statement guidelines. RESULTS: Of the 110 cases, 67 (60.9%) were prescribed a gastroprotectant medication without an appropriate indication. The most common reason for prescription was acute kidney injury in 26/67 (38.8%). PPIs were the most common gastroprotectant medication administered in 95/110 (86.3%) cats, followed by sucralfate in 18/110 (16.4%) and H2RAs in 11/110 (10%). Of the 35 cases in which gastroprotectant therapy was indicated, the medication chosen or dosage administered was considered suboptimal in 16 (45.7%). Instructions regarding the duration of administration, potential adverse effects and timing of administration in relation to meals or other medications were inconsistently provided in discharge instructions to pet owners. Of the 29 cases discharged with omeprazole, only 13 (44.8%) instructions included a duration of administration, while 6 (20.7%) recommended continuing gastroprotectants indefinitely until further notice, 16 (55.2%) discussed the timing of the administration in relation to a meal and six (20.7%) mentioned potential adverse effects; none advised tapering of omeprazole before discontinuation. CONCLUSIONS AND RELEVANCE: When prescribed, gastroprotectant medications were frequently prescribed injudiciously to cats in this referral population over a 12-month period. Discharge instructions to pet owners also often lacked information and recommendations regarding optimal administration, potential adverse effects, and tapering or discontinuation of the medications.


Assuntos
Inibidores da Bomba de Prótons , Sucralfato , Humanos , Gatos , Estados Unidos , Animais , Sucralfato/uso terapêutico , Centros de Atenção Terciária , Inibidores da Bomba de Prótons/uso terapêutico , Omeprazol/uso terapêutico , Antagonistas dos Receptores H2 da Histamina
9.
J Assoc Physicians India ; 71(8): 11-12, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37651247

RESUMO

BACKGROUND: In the last 3 decades, omeprazole has proved its mettle in managing acid peptic diseases (APDs). It has established itself as the first line of therapy for duodenal and gastric ulcers, gastroesophageal reflux disease (GERD), ulcers due to nonsteroidal anti-inflammatory drugs (NSAID), and Zollinger-Ellison syndrome (ZES). OBJECTIVES: The purpose of this literature review is to assess the effectiveness of omeprazole as compared to the other proton pump inhibitors (PPIs) currently in use and its safety and efficacy in special populations, including the pediatric and geriatric populations. RESULTS: Omeprazole was found to be the most effective PPI in the management of APDs due to its rapid action, good antioxidant effects, and effectiveness against nocturnal acid breakthroughs. Its safety and tolerance have been proved in various randomized controlled trials. CONCLUSION: Omeprazole is the prototypical drug in the management of APDs and has withstood the test of time. After 3 decades, omeprazole remains the drug of choice in managing APD.


Assuntos
Refluxo Gastroesofágico , Úlcera Gástrica , Humanos , Criança , Idoso , Omeprazol/uso terapêutico , Inibidores da Bomba de Prótons/uso terapêutico , Refluxo Gastroesofágico/tratamento farmacológico , Anti-Inflamatórios não Esteroides
10.
Int Immunopharmacol ; 120: 110335, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37201406

RESUMO

This study aimed to elucidate the gastro-protective effect of fucoidan against ethanol-induced gastric ulcer mediated via NLRP3-induced pyroptosis as an underlying mechanism, not yet assessed in prior research. Forty-eight male Albino mice were divided into six groups: Group I (normal control), group II (Ulcer/ethanol control), group III (Omeprazole + ethanol), group IV (fucoidan 25 mg + ethanol), group V (fucoidan 50 mg + ethanol) and group VI (fucoidan only). Fucoidan was administered orally for seven consecutive days followed by ulcer induction by a single oral dose of ethanol. Using colorimetric analysis, ELISA, qRT-PCR, histological assessment, and immunohistochemical studies, the results revealed that ethanol-induced ulcer exhibited an ulcer score of 42.5 ± 5.1 and a significant increase (p < 0.05) in malondialdehyde (MDA), nuclear factor kappa B (NF-κB), and interleukin 6 (IL-6) with a significant decrease in the gastro-protective mediators, prostaglandin E2 (PGE2), superoxide dismutase (SOD) and glutathione (GSH), accompanied with an increase in NLRP3, interleukin 1ß (IL-1ß), interleukin 18 (IL-18), caspase 1, caspase 11, gasdermin D, and toll-like receptor 4 (TLR4), compared with the normal control. Pre-treatment with fucoidan showed a comparable result with omeprazole. Additionally, pre-treatments elevated the levels of the gastro-protective mediators and lessened oxidative stress, relative to the positive control findings. Conclusively, fucoidan has a promising gastro-protective role by inhibiting inflammation and pyroptosis.


Assuntos
Úlcera Gástrica , Camundongos , Animais , Masculino , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/patologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Úlcera/metabolismo , Piroptose , Mucosa Gástrica , Estresse Oxidativo , Inflamação/metabolismo , Glutationa/metabolismo , Omeprazol/uso terapêutico , Omeprazol/farmacologia , Etanol/metabolismo , NF-kappa B/metabolismo
11.
J Equine Vet Sci ; 126: 104296, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37003396

RESUMO

Equine gastric ulcer syndrome (EGUS) is the most common disease of the stomach in horses and treatment is based on the oral administration of omeprazole for at least 28 days. Aim of this study was to compare the efficacy of two formulations of oral omeprazole-powder paste and gastro-enteric resistant granules-in the treatment of naturally occurring gastric ulcers in racehorses. Thirty-two adult racehorses, aged between 2 and 10 years old, with clinical signs of EGUS were included in this blinded, randomized clinical trial. Two gastroscopies were performed to evaluate gastric lesions in the squamous or glandular mucosa before and after 28 days of treatment. After the first gastroscopy, 2/32 horses were excluded because affected by equine squamous gastric disease (ESGD) 1/4. The remaining horses were divided into 4 groups, and were treated with 2 formulations of omeprazole (gastroenteric resistant granules, group 1, or powder paste, group 3) or with 2 placebo formulations (granules, group 2, or paste, group 4). Treatments were performed in the placebo horses affected by ESGD or equine glandular gastric disease after the T28 gastroscopy control. No differences were found between groups at T0. Differences were found between T0 vs. T28 for granular (P = .002) and powder paste (P = .01) formulations. No differences were detected between the two groups receiving omeprazole formulations at T28 (0.34) and between T0 vs. T28 for either of the groups receiving placebo treatments. For all the variables, the size of the effect was greater than 0.5, proving that the treatments had a considerable effect. Gastro-enteric resistant granules and powder paste omeprazole showed similar efficacy in the treatment of ESGD. The glandular mucosa responded poorly to treatment with omeprazole.


Assuntos
Antiulcerosos , Carcinoma de Células Escamosas , Doenças dos Cavalos , Úlcera Gástrica , Cavalos , Animais , Omeprazol/uso terapêutico , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/veterinária , Antiulcerosos/uso terapêutico , Pós/uso terapêutico , Doenças dos Cavalos/tratamento farmacológico , Carcinoma de Células Escamosas/veterinária
12.
BMJ Open ; 13(4): e066070, 2023 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-37080617

RESUMO

OBJECTIVES: This mixed-methods feasibility study aimed to explore parents' and medical practitioners' views on the acceptability and design of a clinical trial to determine whether routine prophylactic proton pump inhibitors (PPI) reduce the incidence of anastomotic stricture in infants with oesophageal atresia (OA). DESIGN: Semi-structured interviews with UK parents of an infant with OA and an online survey, telephone interviews and focus groups with clinicians. Data were analysed using reflexive thematic analysis and descriptive statistics. PARTICIPANTS AND SETTING: We interviewed 18 parents of infants with OA. Fifty-one clinicians (49 surgeons, 2 neonatologists) from 20/25 (80%) units involved in OA repair completed an online survey and 10 took part in 1 of 2 focus groups. Interviews were conducted with two clinicians whose survey responses indicated they had concerns about the trial. OUTCOME MEASURES: Parents and clinicians ranked the same top four outcomes ('Severity of anastomotic stricture', 'Incidence of anastomotic stricture', 'Need for treatment of reflux' and 'Presence of symptoms of reflux') as important to measure for the proposed trial. RESULTS: All parents and most clinicians found the use, dose and duration of omeprazole as the intervention medication, and the placebo control, as acceptable. Parents stated they would hypothetically consent to their child's participation in the trial. Concerns of a few parents and clinicians about infants suffering with symptomatic reflux, and the impact of this for study retention, appeared to be alleviated through the symptomatic reflux treatment pathway. Hesitant clinician views appeared to change through discussion of parental support for the study and by highlighting existing research that questions current practice of PPI treatment. CONCLUSIONS: Our findings indicate that parents and most clinicians view the proposed Treating Oesophageal Atresia with prophylactic proton pump inhibitors to prevent STricture (TOAST) trial to be feasible and acceptable so long as infants can be given PPI if clinicians deem it clinically necessary. This insight into parent and clinician views and concerns will inform pilot phase trial monitoring, staff training and the development of the trial protocol.


Assuntos
Atresia Esofágica , Estenose Esofágica , Omeprazol , Inibidores da Bomba de Prótons , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Recém-Nascido , Constrição Patológica/etiologia , Constrição Patológica/prevenção & controle , Atresia Esofágica/complicações , Atresia Esofágica/cirurgia , Estudos de Viabilidade , Refluxo Gastroesofágico/etiologia , Refluxo Gastroesofágico/prevenção & controle , Inibidores da Bomba de Prótons/administração & dosagem , Inibidores da Bomba de Prótons/uso terapêutico , Estenose Esofágica/etiologia , Estenose Esofágica/prevenção & controle , Quimioprevenção , Pesquisas sobre Atenção à Saúde , Pais , Médicos , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Omeprazol/administração & dosagem , Omeprazol/uso terapêutico , Aceitação pelo Paciente de Cuidados de Saúde , Atitude do Pessoal de Saúde , Adulto
13.
Aliment Pharmacol Ther ; 58(2): 159-167, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37081832

RESUMO

BACKGROUND: Sustained intragastric antibiotic exposure is important for Helicobacter pylori eradication, yet little is known about gastric pharmacology of commonly used H. pylori regimens. For rifabutin, differing intragastric concentrations based on dosing regimen may account for differences in reported eradication rates. AIM: To compare intragastric rifabutin concentrations between low-dose rifabutin (50 mg three time daily; as in RHB-105) and generically dosed rifabutin 150 mg once daily, 150 mg twice daily, and 300 mg once daily using a validated Physiologically-based pharmacokinetic (PBPK) model. METHODS: We obtained plasma pharmacokinetic data from the RHB-105 clinical development programs and used it to develop and validate a whole-body PBPK model using PK-SIM software. We modified the existing rifabutin model to include the impact of omeprazole on gastric pH and emptying time. Modelled intragastric rifabutin exposure was expressed as the time that each regimen maintained its concentration ≥MIC90 . RESULTS: Rifabutin 50 mg three times daily achieved significantly longer times with intragastric concentration above MIC90 (22.3 ± 1.1 h) than 150 mg once daily (8.3 ± 1.7 h), 150 mg twice daily (16.3 ± 2.3 h), or 300 mg once daily (8.5 ± 1.9 h) while providing the lowest mean maximal plasma concentration and mean area under the plasma concentration-time curve of all regimens studied. CONCLUSIONS: PBPK modelling showed rifabutin 50 mg three times daily had higher intragastric exposure times than 150 mg once daily or twice daily, or 300 mg once daily. This low-dose rifabutin regimen provides the highest potential for H. pylori eradication while minimising systemic rifabutin exposure.


Assuntos
Antiulcerosos , Infecções por Helicobacter , Helicobacter pylori , Humanos , Infecções por Helicobacter/tratamento farmacológico , Rifabutina/uso terapêutico , Omeprazol/uso terapêutico , Antibacterianos/uso terapêutico , Quimioterapia Combinada
14.
Acta méd. costarric ; 65(1): 21-25, ene.-mar. 2023. graf
Artigo em Espanhol | LILACS, SaludCR | ID: biblio-1527609

RESUMO

Resumen Objetivo: Este estudio tiene como objetivo principal determinar la respuesta al esquema de tratamiento de primera línea con triple terapia estándar (amoxicilina, claritromicina, omeprazol), para erradicación de Helicobacter pylori en una determinada población, para determinar si este esquema propuesto en guías internacionales es aún una opción adecuada para pacientes en una determinada región de Costa Rica. Métodos: Se realizó una búsqueda en el servicio de gastroenterología del Hospital San Francisco de Asís, Grecia, Alajuela, Costa Rica; de todos los pacientes con infección por Helicobacter pylori y que recibieron tratamiento de primera línea con triple terapia (amoxicilina, claritromicina y omeprazol) por 14 días, en el periodo comprendido entre febrero 2017 a febrero 2019, incluyendo para el análisis solamente en los que se contaba con una prueba confirmatoria posterior a tratamiento, ya fuera por antígeno fecal de H. pylori o biopsia convencional. Resultados: Se identificaron un total de 369 casos. El diagnóstico se realizó con biopsia en el 96,4% de los pacientes. La respuesta al tratamiento de primera línea se alcanzó en un 90.5% corroborada por antígeno fecal en el 92.1% de los casos. Conclusiones: Este estudio muestra que la terapia triple con amoxicilina, claritromicina e Inhibidor de bomba de protones por 14 días mantiene un adecuado nivel de eficacia. Sin embargo, hay que tomar en cuenta que estos datos son únicamente de un área de atracción determinada y puede que no reflejen la realidad de todo el país.


Abstract Aim: The main objective of this study is to determine the response to the firstline treatment regimen with triple standard therapy (amoxicillin, clarithromycin, omeprazole), to eradicate Helicobacter pylori in a certain population. The goal is to determine if the proposed regimen in international guidelines services is still a suitable option for patients in a certain region of Costa Rica. Methods: The study took place in San Francisco de Asís Hospital, Grecia, Alajuela, Costa Rica. All patients with a Helicobacter pylori infection that were given first- line treatment with triple therapy (amoxicillin, clarithromycin and omeprazole) for its eradication for 14 days, in the period between February of 2017 and February of 2019, were included in the study. Results: A total of 369 cases were identified. The diagnosis was made with biopsy in 96.4% of patients. Response to first-line treatment was achieved in 90.5% corroborated by fecal antigen in 92.1% of all cases. Conclusions: This study shows that triple therapy with amoxicillin, clarithromycin and omeprazole for 14 days maintains an adequate level of efficacy. However, it must be considered that these results are from a specific area and may not reflect the reality of the entire country.


Assuntos
Humanos , Masculino , Feminino , Omeprazol/uso terapêutico , Helicobacter pylori/efeitos dos fármacos , Infecções por Helicobacter/epidemiologia , Claritromicina/uso terapêutico , Amoxicilina/uso terapêutico , Costa Rica , Farmacorresistência Bacteriana
15.
Sci Rep ; 13(1): 1375, 2023 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-36697470

RESUMO

Approximately 36% of the United States (US) population is infected with Helicobacter pylori (HP), a known major risk factor for peptic ulcer disease and gastric cancer. HP eradication reduces the rate of complications; however, the benefits are undermined by rising rates of HP eradication treatment failure. This real-world observational cohort analysis aims to describe HP diagnostic and treatment patterns among insured patients in the US. Using diagnoses, lab results, and treatment patterns, we identified adults (18+) with new diagnoses of HP in the Veradigm Health Insights EHR Database linked to Komodo claims data (1/1/2016-12/31/2019). Patients were required to have ≥ 12 months of data pre-/post-index. We captured patient characteristics, HP-related diagnostic testing, and the use of US guideline-recommended HP eradication regimens. HP eradication rates following first-line eradication treatment were measured among patients with available lab results. Overall, 31.8% of the 60,593 included patients did not receive guideline-recommended treatment. Among the 68.2% (41,340) with first-line treatment, 80.2% received clarithromycin-based triple therapy, and 6.6% received bismuth quadruple therapy. Of the 4569 patients with a repeated course of eradication therapy, 53.4% received the same regimen as their first-line, the majority (90.7%) of whom received two rounds of clarithromycin-based triple therapy. Among the 2455 patients with results of HP non-serology testing following first-line treatment, the 180-day eradication rate was 80.2% overall, with differences based on treatments and demographics. This study highlights gaps between guideline-recommended HP management and real-world patterns, underscoring the need to improve HP testing, treatment, and follow-up practices.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Adulto , Humanos , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/epidemiologia , Claritromicina/uso terapêutico , Antibacterianos/uso terapêutico , Amoxicilina/uso terapêutico , Omeprazol/uso terapêutico , Quimioterapia Combinada , Inibidores da Bomba de Prótons/uso terapêutico
16.
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
17.
Artigo em Português | LILACS, CONASS, ColecionaSUS, SES-GO | ID: biblio-1426235

RESUMO

Tecnologia: Esomeprazol e lansoprazol. Indicação: Tratamento de doença do refluxo gastroesofágico em adultos. Pergunta: Esomeprazol e lansoprazol são mais eficazes e toleráveis que o omeprazol já incorporado ao SUS para o tratamento de Doença do Refluxo Gastroesofágico (DRGE) em adultos? Métodos: Uma revisão rápida de evidências, uma revisão de revisões sistemáticas, com levantamento bibliográfico realizado na base de dados PUBMED, utilizando estratégia estruturada de busca. A qualidade metodológica das revisões sistemáticas foi avaliada com AMSTAR-2 (Assessing the Methodological Quality of Systematic Reviews). Resultados: Foram selecionadas três revisões sistemáticas com meta-análise, que atendiam aos critérios de inclusão. Conclusão: O esomeprazol era mais eficaz para cicatrização da lesão nos casos de esofagite erosiva, prevenção da mucosa do esôfago, maior controle de ácido no tratamento de curto prazo (4 e 8 semanas) de esomeprazol 40mg e tratamento de longo prazo (6 meses) de esomeprazol 20mg. A taxa de resposta no alívio dos sintomas, o esomeprazol 20mg e 40mg apresentou ser mais eficaz, especialmente, na azia e dor epigástrica. Quanto ao perfil de segurança, não houve diferença significativa entre as taxas de eventos adversos, todos medicamentos eram parecidos entre si


Technology: Esomeprazole and Lansoprazole. Indication: Treatment of gastroesophageal reflux disease in adults. Question: Are Esomeprazole and Lansoprazole more effective and tolerable than omeprazole already incorporated into SUS for the treatment of Gastroesophageal Reflux Disease (GERD) in adults? Methods: A rapid review of evidence, an overview of systematic reviews, with bibliographic survey carried out in the PUBMED database, using a structured search strategy. The methodological quality of systematic reviews was assessed using AMSTAR-2 (Assessing the Methodological Quality of Systematic Reviews). Results: Three systematic reviews with meta-analysis were selected, which met the inclusion criteria. Conclusion: Esomeprazole was more effective in achieving wound healing in cases of erosive esophagitis, prevention of esophageal mucosa, greater acid control in short-term treatment (4 and 8 weeks) of esomeprazole 40mg and long-term treatment (6 months) of esomeprazole 20mg. the response rate in symptom relief, esomeprazole 20mg and 40mg proved to be more effective, especially in heartburn and epigastric pain. As for the safety profile, there was no significant difference between the rates of adverse events, all drugs were similar to each other


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Adulto Jovem , Omeprazol/uso terapêutico , Refluxo Gastroesofágico/tratamento farmacológico , Esomeprazol/uso terapêutico , Lansoprazol/uso terapêutico , Esofagite/tratamento farmacológico , Pesquisa Comparativa da Efetividade
18.
Gastroenterol. latinoam ; 34(1): 22-30, 2023. ilus, tab
Artigo em Espanhol | LILACS | ID: biblio-1524575

RESUMO

Heartburn occurs in 75% of patients with digestive discomfort of any origin and is one of the main symptoms of gastroesophageal reflux disease. Treatment focuses on lifestyle modification and symptomatology management with various drugs; when heartburn is moderate to severe, a proton pump inhibitor is more suitable. Omeprazole (OMZ) combined with sodium bicarbonate (BC) has demonstrated significant and sustained suppression of acid secretion. The objective was to compare the effect of sequential OMZ/BC therapy compared to OMZ monotherapy for the improvement of heartburn in Mexican individuals. The study was a double-blind, randomized, controlled, multicenter clinical study including 277 subjects with moderate to severe heartburn. Patients received 7 days of OMZ/BC and 7 days of OMZ (OMZ/BC7) or 14 days of OMZ (OMZ14). The primary endpoint was defined as the change in the number of days a week that the patient has heartburn, it was evaluated at 14 days. Both treatments reduced time (days) with heartburn by less than 4 days (OMZ14 3.9 vs. 4.2 days OMZ/BC7), as well as duration, number of events and intensity of heartburn. The treatments improved the quality of life, and the control of the symptoms. The proportion of adverse events was lower with OMZ/BC. The non-inferiority of OMZ/BC7 with respect to OMZ14 was verified.


La pirosis se presenta en el 75% de los pacientes con molestias digestivas de cualquier origen y es uno de los principales síntomas de la enfermedad por reflujo gastroesofágico. El tratamiento se enfoca en la modificación del estilo de vida y el manejo de la sintomatología con diversos fármacos; cuando la pirosis es moderada a severa, un inhibidor de la bomba de protones es más adecuado. El omeprazol (OMZ) combinado con bicarbonato de sodio (BC) ha demostrado supresión significativa y sostenida de la secreción ácida. El objetivo fue comparar el efecto de la terapia secuencial de OMZ/BC en comparación con el tratamiento continuo de OMZ para la mejoría de la pirosis en individuos mexicanos. Estudio clínico multicéntrico, doble ciego, controlado, aleatorizado que incluyó 277 sujetos con pirosis moderada a severa. Los pacientes recibieron 7 días de OMZ/BC y 7 días de OMZ (OMZ/BC7) o 14 días de OMZ (OMZ14). La variable primaria fue definida como el cambio del número de días a la semana que el paciente presenta pirosis, se evaluó a los 14 días. Ambos tratamientos redujeron los días con pirosis en menos 4 días (OMZ14 3,9 vs. 4,2 días OMZ/BC7), así como la duración, el número de eventos e intensidad de la pirosis. Los tratamientos mejoraron los indicadores de calidad de vida, y el control del padecimiento. La proporción de eventos adversos fue menor con OMZ/BC. Se comprobó la no-inferioridad de OMZ/BC7 respecto OMZ14.


Assuntos
Humanos , Masculino , Feminino , Omeprazol/administração & dosagem , Bicarbonato de Sódio/administração & dosagem , Azia/tratamento farmacológico , Omeprazol/efeitos adversos , Omeprazol/uso terapêutico , Método Duplo-Cego , Resultado do Tratamento , Bicarbonato de Sódio/efeitos adversos , Bicarbonato de Sódio/uso terapêutico , Combinação de Medicamentos
19.
Int J Mol Sci ; 23(16)2022 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-36012136

RESUMO

(1) Background: Oxaliplatin is used as first-line chemotherapy not only for colorectal cancer but also for gastric and pancreatic cancers. However, it induces peripheral neuropathy with high frequency as an adverse event, and there is no effective preventive or therapeutic method. (2) Methods: The effects of omeprazole, a proton pump inhibitor (PPI), on oxaliplatin-induced peripheral neuropathy (OIPN) was investigated using an in vivo model and a real-world database. (3) Results: In a rat model, oxaliplatin (4 mg/kg, i.p., twice a week for 4 weeks) caused mechanical hypersensitivity accompanied by sciatic nerve axonal degeneration and myelin sheath disorder. Repeated injection of omeprazole (5−20 mg/kg, i.p., five times per week for 4 weeks) ameliorated these behavioral and pathological abnormalities. Moreover, omeprazole did not affect the tumor growth inhibition of oxaliplatin in tumor bearing mice. Furthermore, clinical database analysis of the Food and Drug Administration Adverse Event Reporting System (FAERS) suggests that the group using omeprazole has a lower reporting rate of peripheral neuropathy of oxaliplatin-treated patients than the group not using (3.06% vs. 6.48%, p < 0.001, reporting odds ratio 0.44, 95% confidence interval 0.32−0.61). (4) Conclusions: These results show the preventing effect of omeprazole on OIPN.


Assuntos
Antineoplásicos , Neoplasias , Doenças do Sistema Nervoso Periférico , Animais , Antineoplásicos/efeitos adversos , Camundongos , Neoplasias/tratamento farmacológico , Omeprazol/farmacologia , Omeprazol/uso terapêutico , Oxaliplatina/efeitos adversos , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Doenças do Sistema Nervoso Periférico/prevenção & controle , Ratos , Roedores
20.
Chem Biol Interact ; 360: 109933, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35447140

RESUMO

Drug resistance of tumors remains a major barrier in cisplatin (CDDP)-based chemotherapy. Omeprazole (OME) is often utilized during chemotherapy to alleviate gastrointestinal symptoms. In a previous investigation, we demonstrated a protective effect of OME against CDDP-induced kidney injury. To further establish whether OME could enhance chemosensitivity to CDDP and the underlying mechanisms, an in vivo tumor-bearing mouse model with CDDP-resistant A549 non-small cell lung cancer (A549/CDDP) was established in the current study. A high-performance liquid chromatography-time of flight mass spectrometry (HPLC-TOF/MS)-based untargeted metabolomics approach for tumor tissue and serum was employed to explore the mechanisms underlying the enhanced therapeutic effects of co-administration of CDDP and OME. Notably, tumor weights of mice in the CDDP + OME group were significantly decreased compared with those treated with CDDP alone. HE and TUNEL staining revealed more significant apoptosis of tumor cells in the group co-administered CDDP + OME relative to CDDP alone. Overexpression of multidrug resistance-associated protein 2 in CDDP-resistant tumors was significantly reversed upon treatment with CDDP + OME. PCA score plots of the groups co-treated with CDDP + OME were clearly separated from those treated with CDDP alone in metabolomics analysis for tumor and serum samples, clearly suggesting that co-administration of OME enhances the antitumor effect of CDDP. Subsequently, 10 and 7 metabolites in CDDP + OME group with significant changes in tumor and serum compared with CDDP group, respectively, were identified. Pathway analysis both in tumor and serum samples revealed regulation of the metabolism of purines, several amino acids and riboflavin in enhanced chemotherapy with both OME and CDDP. The collective findings provide beneficial novel insights into drug-drug interactions, which could improve the application of CDDP in clinical practice.


Assuntos
Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Neoplasias Pulmonares/patologia , Metabolômica/métodos , Camundongos , Omeprazol/farmacologia , Omeprazol/uso terapêutico
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