Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.855
Filtrar
1.
Chem Biol Interact ; 321: 108964, 2020 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-32006539

RESUMO

Lupeol (1) was isolated from hexane branch extract of Maytenus salicifolia and the Lupeol stearate (2), Lupeol palmitate (3), Lupeol myristate (4), Lupeol laurate (5) and Lupeol caprylate (6) were obtained reacting 1 with an adequate carboxylic acid. Swiss mice were treated with vehicle, carbenoxolone or Lupeol esters before administration of ethanol/HCl or indomethacin. Additionally, the involvement of nitric oxide (NO), sulfhydryl compounds (NP-SH), α-2 adrenergic receptors (α2-AR) and prostaglandins (PGE) in antiulcer effects was investigated using appropriate inhibitors or antagonist. Oxidative and inflammatory parameters were measured after euthanasia and anti-secretory effects was evaluated in pylorus-ligated rats. Ethanol/HCl ulcerated the gastric mucosa by 64.45 ± 6.58 mm2, which the oral treatment with 1, 4 and 6 (10 mg/kg), and 3 and 5 (30 mg/kg) reduced the lesion area. Interestingly, 2 reduced the gastric ulcer by oral route in a potent and dose-dependent manner (ED50 = 0.40 mg/kg), which was accompanied by the increase in reduced glutathione levels and by the reduction of lipids peroxidation and myeloperoxidase and superoxide dismutase activities. Moreover, 2 (0.1 mg/kg) also prevented the ulcerogenesis by intraperitoneal route. The participation of NO, NP-SH, α2-AR and PGE in 2-mediated gastroprotection was confirmed. In indomethacin-induced ulcer, 2 (1 mg/kg, p.o) also reduced the ulcer area and increased the PGE2 levels. However, 2 did not alter the gastric acid secretion. Therefore, these findings indicate that the obtention of 2 potentiated the antiulcer activity of 1 and that this compound can elicit gastroprotective action due a diversified mode of action.


Assuntos
Antiulcerosos/farmacologia , Triterpenos Pentacíclicos/farmacologia , Úlcera Gástrica/prevenção & controle , Animais , Antiulcerosos/administração & dosagem , Antiulcerosos/química , Modelos Animais de Doenças , Esterificação , Etanol/toxicidade , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Ácido Clorídrico/toxicidade , Indometacina/toxicidade , Camundongos , NG-Nitroarginina Metil Éster/metabolismo , Óxido Nítrico/metabolismo , Triterpenos Pentacíclicos/administração & dosagem , Triterpenos Pentacíclicos/química , Ratos , Ratos Wistar , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/metabolismo , Relação Estrutura-Atividade
2.
Ulus Travma Acil Cerrahi Derg ; 25(6): 585-588, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31701498

RESUMO

BACKGROUND: Perforation is a rare complication of peptic ulcer. Although the most widely accepted treatment for peptic ulcer perforation is surgery, non-operative treatment can be an option in selected patients. In this study, we aimed to present our non-surgical treatment experience in peptic ulcer perforation. METHODS: In this study, the data of the patients who were treated due to peptic ulcer perforation between January 2012 and September 2017 in our clinic were retrospectively reviewed. The diagnosis was reached by physical examination and radiologic findings. After obtaining the informed consent from the patients, non-operative treatment was performed to the selected patients who had normal vital parameters and did not have findings of generalized peritonitis in the abdominal examination. Oral food and fluid intake were stopped and intravenous fluid, antibiotics and pantoprazole were administered to all patients in this study. RESULTS: A total of 41 patients were treated due to the diagnosis of peptic ulcer perforation in our clinic during the study period. Out of 41 patients, while 35 of the patients were operated, six of them were treated non-operatively. There were peritoneal irritation signs and symptoms in the upper quadrants on physical examination in all of the patients. None of them had generalized peritonitis. Abdominal X-ray and computed tomography were obtained from all of the patients. None of the patients in the non-operative group underwent any interventional procedure or surgery during the follow-up period. The median length of hospital stay was four days in this group. All of the patients were discharged uneventfully. CONCLUSION: Standard treatment of peptic ulcer perforation in most of the patients is still surgical repair. Non-surgical treatment should be kept in mind as an option in the selected patients who had normal vital parameters and did not have any findings of generalized peritonitis in the abdominal examination. In this way, it may be possible to avoid unnecessary surgery and reduce the possible morbidity and mortality associated with the operation.


Assuntos
Úlcera Péptica Perfurada , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Antiulcerosos/administração & dosagem , Antiulcerosos/uso terapêutico , Hidratação , Humanos , Tempo de Internação , Pantoprazol/administração & dosagem , Pantoprazol/uso terapêutico , Úlcera Péptica Perfurada/epidemiologia , Úlcera Péptica Perfurada/terapia , Peritonite , Estudos Retrospectivos
3.
Pharm Res ; 36(12): 164, 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31637544

RESUMO

PURPOSE: To describe a stepwise approach to evaluate the pH effect for a weakly basic drug by in vitro, in vivo and in silico techniques and identify a viable mitigation strategy that addresses the risk. METHODS: Clinical studies included assessment of the pH effect with famotidine. In vitro dissolution was evaluated in various biorelevant media and in a pH-shift test. PK studies in dogs were conducted under pentagastrin or famotidine pre-treatment and GastroPlus was employed to model human and dog PK data and simulate the performance in human. RESULTS: Clinical data indicated considerable pH dependent absorption of the drug when dosed in the presence of H2-antagonists. In vitro dissolution and in vivo dog data confirmed that the observed pH effect was due to reduced dissolution rate and lower solubility at increased gastric and intestinal pH. A salt form was identified to overcome the effect by providing fast dissolution and prolonged supersaturation. GastroPlus simulations predicted a mitigation of the pH effect by the salt. CONCLUSIONS: The drug exhibited a strong pH-effect in humans. The in vitro, in vivo and modeling approach provides a systematic workflow to evaluate the risk of a new drug and identify a strategy able to mitigate the risk.


Assuntos
Antiulcerosos/farmacocinética , Simulação por Computador , Composição de Medicamentos/métodos , Famotidina/farmacocinética , Absorção Intestinal , Modelos Biológicos , Administração Oral , Animais , Antiulcerosos/administração & dosagem , Disponibilidade Biológica , Cães , Famotidina/administração & dosagem , Feminino , Humanos , Concentração de Íons de Hidrogênio , Masculino
4.
BMJ ; 366: l5016, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31511230

RESUMO

OBJECTIVE: To assess the effects of Helicobacter pylori treatment, vitamin supplementation, and garlic supplementation in the prevention of gastric cancer. DESIGN: Blinded randomized placebo controlled trial. SETTING: Linqu County, Shandong province, China. PARTICIPANTS: 3365 residents of a high risk region for gastric cancer. 2258 participants seropositive for antibodies to H pylori were randomly assigned to H pylori treatment, vitamin supplementation, garlic supplementation, or their placebos in a 2×2×2 factorial design, and 1107 H pylori seronegative participants were randomly assigned to vitamin supplementation, garlic supplementation, or their placebos in a 2×2 factorial design. INTERVENTIONS: H pylori treatment with amoxicillin and omeprazole for two weeks; vitamin (C, E, and selenium) and garlic (extract and oil) supplementation for 7.3 years (1995-2003). MAIN OUTCOME MEASURES: Primary outcomes were cumulative incidence of gastric cancer identified through scheduled gastroscopies and active clinical follow-up through 2017, and deaths due to gastric cancer ascertained from death certificates and hospital records. Secondary outcomes were associations with other cause specific deaths, including cancers or cardiovascular disease. RESULTS: 151 incident cases of gastric cancer and 94 deaths from gastric cancer were identified during 1995-2017. A protective effect of H pylori treatment on gastric cancer incidence persisted 22 years post-intervention (odds ratio 0.48, 95% confidence interval 0.32 to 0.71). Incidence decreased significantly with vitamin supplementation but not with garlic supplementation (0.64, 0.46 to 0.91 and 0.81, 0.57 to 1.13, respectively). All three interventions showed significant reductions in gastric cancer mortality: fully adjusted hazard ratio for H pylori treatment was 0.62 (95% confidence interval 0.39 to 0.99), for vitamin supplementation was 0.48 (0.31 to 0.75), and for garlic supplementation was 0.66 (0.43 to 1.00). Effects of H pylori treatment on both gastric cancer incidence and mortality and of vitamin supplementation on gastric cancer mortality appeared early, but the effects of vitamin supplementation on gastric cancer incidence and of garlic supplementation only appeared later. No statistically significant associations were found between interventions and other cancers or cardiovascular disease. CONCLUSIONS: H pylori treatment for two weeks and vitamin or garlic supplementation for seven years were associated with a statistically significant reduced risk of death due to gastric cancer for more than 22 years. H pylori treatment and vitamin supplementation were also associated with a statistically significantly reduced incidence of gastric cancer. TRIAL REGISTRATION: ClinicalTrials.gov NCT00339768.


Assuntos
Infecções por Helicobacter/terapia , Lesões Pré-Cancerosas/terapia , Neoplasias Gástricas/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antiulcerosos/administração & dosagem , Biópsia , China/epidemiologia , Suplementos Nutricionais , Quimioterapia Combinada/métodos , Feminino , Seguimentos , Alho/química , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Gastroscopia , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/patologia , Helicobacter pylori/isolamento & purificação , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Extratos Vegetais/administração & dosagem , Lesões Pré-Cancerosas/microbiologia , Lesões Pré-Cancerosas/patologia , Inibidores da Bomba de Prótons/administração & dosagem , Neoplasias Gástricas/patologia , Neoplasias Gástricas/prevenção & controle , Análise de Sobrevida , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Vitaminas/administração & dosagem
5.
BMC Complement Altern Med ; 19(1): 205, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31391093

RESUMO

BACKGROUND: Gastric ulcer is one of the most prevalent diseases worldwide. In Iranian folk medicine, Achillea wilhelmsii (AW) is used as a treatment for gastric ulcer. Previous reports also mentioned Antiulcerogenic properties for this herbal plant. This study investigated the therapeutic effects of Achillea wilhelmsii C. Koch extract on indomethacin-induced gastric lesion in rats, from both proteomic and metabolomic perspectives. METHODS: The rats were divided into 4 groups. Gastric ulceration was induced by a single dose of indomethacin (45 mg/kg) by oral gavage. An amount of 800 mg/kg of AW extract was administered orally. Serum and tissue samples were collected for further investigations. The metabolomic study was performed by 1H-NMR CPMG spectrometry. Proteomic analysis was also executed by using two dimensional gel electrophoresis (2DE) followed by liquid chromatography coupled to tandem mass spectrometry (LC-ESI/MS/MS). Real time PCR was used to confirm some of the genes. RESULTS: The macroscopic and microscopic investigations confirmed the effectiveness of the AW extract. There was a panel of metabolites which showed alteration during gastric lesion development. The levels of some of these metabolite reversed nearly to their control values after the administration of AW extract. There were also changes in the levels of some proteins including Alb, Fabp5, Hspb1, Tagln, Lgals7, Csta and Myl9 which were reversed after AW administration. CONCLUSIONS: Our findings suggested that Achillea wilhelmsii C. Koch extract could be a potential therapy to be used for indomethacin-induced gastric lesion treatment in the future. However, further investigations are needed to confirm the results.


Assuntos
Achillea/química , Antiulcerosos/administração & dosagem , Extratos Vegetais/administração & dosagem , Úlcera Gástrica/tratamento farmacológico , Animais , Antiulcerosos/isolamento & purificação , Humanos , Indometacina/efeitos adversos , Masculino , Metabolômica , Extratos Vegetais/isolamento & purificação , Proteômica , Ratos , Ratos Wistar , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/genética , Úlcera Gástrica/metabolismo
6.
J Vet Intern Med ; 33(5): 1988-1994, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31294879

RESUMO

BACKGROUND: Famotidine is sometimes administered as a continuous rate infusion (CRI) to treat gastrointestinal ulceration in critically ill dogs. However, clinical studies have not evaluated the efficacy of a famotidine CRI in dogs. HYPOTHESIS/OBJECTIVES: To evaluate the efficacy of famotidine at raising intragastric pH when it is administered as a CRI in dogs. We hypothesized that CRI treatment with famotidine would meet clinical goals for raising intragastric pH ≥3 and 4. ANIMALS: Nine healthy Beagle dogs. METHODS: Randomized 2-way crossover. All dogs received 1.0 mg/kg IV q12h famotidine or CRI famotidine at 1.0 mg/kg IV loading dose and 8.0 mg/kg/d for 3 consecutive days. Beginning on day 0 of treatment, intragastric pH monitoring was used to continuously record intragastric pH. Mean percentage times (MPTs) for which intragastric pH was ≥3 and ≥4 were compared between groups using analysis of variance. RESULTS: There was a statistically significant difference (P < .05) in MPT ≥3 and ≥4 between the CRI and IV q12h groups on all treatment days. On days 1, 2, and 3, the MPTs ± SD for which pH was ≥3 were 92.1 ± 8.5, 96.3 ± 6.2, and 90.0 ± 15.7 for the CRI treatment group and 49.3 ± 27.3, 42.2 ± 19.6, and 45.8 ± 10.1, respectively, for the twice-daily group. CONCLUSIONS AND CLINICAL IMPORTANCE: These results suggest that a famotidine CRI, but not standard doses of famotidine, achieves the clinical goals established in people to promote healing of gastric tissue injury and offers an alternative to intravenous treatment with proton pump inhibitors in dogs.


Assuntos
Administração Intravenosa/veterinária , Antiulcerosos/farmacologia , Cães , Famotidina/farmacologia , Animais , Antiulcerosos/administração & dosagem , Estudos Cross-Over , Famotidina/administração & dosagem , Feminino , Determinação da Acidez Gástrica/veterinária , Masculino , Monitorização Fisiológica/veterinária , Estômago/efeitos dos fármacos
7.
Helicobacter ; 24(5): e12615, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31282081

RESUMO

OBJECTIVE: Most therapies for Helicobacter pylori eradication utilize multiple drugs given 2-4 times daily. Patient adherence has been an impediment to reliably achieving high success. This study evaluated a once-daily dosing H pylori eradication regimen. METHODS: A prospective randomized pilot study of H pylori eradication compared once-daily treatment regimen containing levofloxacin (750 mg), clarithromycin-MR (1 g), rabeprazole (60 mg), and bismuth subsalicylate (1,048 mg) for a 7 or 14 days. CYP2C19 genotype and antibiotic susceptibility tests were performed. Successful eradication was defined as negative 13C-urea breath test at least 4 weeks after completion of treatment. RESULTS: 100 subjects were randomized (40 men, 60 women with mean age =54 years). The eradication rates were as follows: 94% (47/50; 95%CI 0.87-1.01) and 84% (42/50; 95%CI 0.73-0.95) with 14-day and 7-day therapy (OR 0.34; 95%CI 0.08-1.35, P = 0.06), respectively. Resistance rates were as follows: 13.0% for clarithromycin, 26.0% for fluoroquinolone, 2.9% for dual clarithromycin-fluoroquinolone resistance, and 62.8% for metronidazole. The 14-day regimen provided 100% eradication in patients with levofloxacin susceptible strain irrespective of the presence of clarithromycin resistance. CYP2C19 genotypes had no effect on cure rates. CONCLUSIONS: The once-daily 14-day rabeprazole-, levofloxacin-, clarithromycin-MR-, and bismuth-containing therapy provided high eradication rate suggested that triple therapies with a PPI, bismuth, and clarithromycin-MR or levofloxacin would be highly effective for once-a-day tailored therapy or as empiric therapy for first-line regimen.


Assuntos
Antibacterianos/administração & dosagem , Antiulcerosos/administração & dosagem , Infecções por Helicobacter/tratamento farmacológico , Rabeprazol/administração & dosagem , Adolescente , Adulto , Idoso , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Distribuição Aleatória , Resultado do Tratamento , Adulto Jovem
8.
Res Vet Sci ; 125: 266-271, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31326702

RESUMO

Clinical signs of syringomyelia and hydrocephalus occur secondary to cerebrospinal fluid (CSF) accumulation within the central nervous system. Omeprazole is recommended to treat these conditions despite little evidence of its capacity to decrease CSF production in the dog. Studies into new treatments are hampered by difficulties in measuring CSF production. The albumin quotient (QAlb), the ratio between CSF and serum albumin concentrations, may reflect CSF production and any decrease in CSF production should be associated with an increase in QAlb. The primary objective of this study was to determine CSF omeprazole concentration after administration of a high intravenous dose of omeprazole and to evaluate its impact on QAlb in the dog. The second aim was to validate QAlb as a surrogate marker of CSF production. Eighteen dogs were included in this prospective crossover placebo-controlled study. Each dog received omeprazole (10 mg/kg), acetazolamide (50 mg/kg) combined with furosemide (1 mg/kg) and saline. Blood and CSF samples were obtained on day 0 and then every 7 days, one hour after drug administration. Omeprazole concentrations (2.0 ±â€¯0.4 µmol/L) reached in CSF after high dose omeprazole were lower than the concentrations previously described as decreasing CSF production in dogs. There was no significant increase in QAlb following administration of acetazolamide/furosemide, prohibiting validation of QAlb as a surrogate marker for CSF production. Several dogs presented transient mild side effects after injection of acetazolamide/furosemide. High dose omeprazole was well tolerated in all dogs.


Assuntos
Antiulcerosos/líquido cefalorraquidiano , Cães , Omeprazol/líquido cefalorraquidiano , Albumina Sérica , Administração Intravenosa , Animais , Antiulcerosos/administração & dosagem , Antiulcerosos/farmacocinética , Biomarcadores/sangue , Estudos Cross-Over , Relação Dose-Resposta a Droga , Feminino , Masculino , Omeprazol/administração & dosagem , Omeprazol/farmacocinética , Estudos Prospectivos , Distribuição Aleatória
9.
Free Radic Res ; 53(6): 596-610, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31215272

RESUMO

The cytoprotective action of the synthetic resveratrol (Resv) congener, E-3,3',5,5'-tetrahydroxystilbene (designated as HST-1) against indomethacin (IND)-induced stomach ulceration has been established using a mice model. HST-1 reversed the adverse effects of IND on several inflammatory (myeloperoxidase, cytokines, adhesion molecules etc.) and ulcer-healing (cyclooxygenases, prostaglandin, growth factors and their receptors etc.) parameters in mice. More importantly, HST-1 down-regulated TNF-α and the TNF-α-mediated activation of NF-κB and JNK/MAPK pathways that are the key determinants in the IND-gastropathy. The effect of HST-1 on all these factors was significantly better than that of Resv, misoprostol, and omeprazole. HST-1 also did not induce small intestinal mucosal injury, unlike some of the proton pump inhibitors. On the other hand, Resv reduced activation of the prosurvival ERK1/2 pathway that may explain its contraindicative property in the gastrointestinal tract.


Assuntos
Antiulcerosos/farmacologia , Proteínas Quinases JNK Ativadas por Mitógeno/antagonistas & inibidores , NF-kappa B/antagonistas & inibidores , Resveratrol/farmacologia , Úlcera Gástrica/prevenção & controle , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Administração Oral , Animais , Antiulcerosos/administração & dosagem , Indometacina , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Camundongos , NF-kappa B/metabolismo , Resveratrol/administração & dosagem , Úlcera Gástrica/induzido quimicamente , Fator de Necrose Tumoral alfa/metabolismo
10.
Helicobacter ; 24(5): e12606, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31168941

RESUMO

BACKGROUND: Several studies have shown that Pylera® (three-in-one capsules containing 140 mg bismuth potassium subcitrate, 125 metronidazole, and tetracycline 125 mg) in association with omeprazole or esomeprazole is a good option in the treatment of Helicobacter pylori infection. In particular, the adjunction of a PPI to Pylera® may be useful to overcome metronidazole resistance. However, omeprazole and its derivatives can promote greater bismuth absorption and enhance its toxicity. The H2 receptor antagonist (H2RA) ranitidine seems to induce less bismuth absorption and as a consequence less systemic toxicity. AIM: To evaluate whether Pylera® in combination with esomeprazole or with ranitidine is equally effective in the treatment of H. pylori infection. MATERIAL AND METHODS: Two separate groups of patients were treated simultaneously. One group was treated with Pylera® three capsules qid plus esomeprazole 40 mg bid for 10 days (group A), and the other group was treated with Pylera® three capsules qid plus ranitidine 300 mg bid for 10 days (group B). H. pylori eradication was defined as a negative result in 13 C urea breath test performed at least 8 weeks after the end of treatment with a delta-over-baseline value less than 5. RESULTS: Thirty-two patients were recruited for group A and thirty-three patients in group B. Eradication rates were 93.7% (30/32) and 90.9% (30/33), respectively, at intention-to-treat analysis, and 96.6% (29/30) and 93.3% (28/30), respectively, at per-protocol analysis. Adverse events occurred in 26 patients and led to the suspension of treatment in one patient in group A and in one patient in group B. CONCLUSION: The results showed that Pylera® plus a PPI or ranitidine were equally effective in the population studied. The high cure rates of bismuth triple therapy (without an antisecretory drug) and the lack of susceptibility testing make it impossible to exclude the possibility that the results would have been similar if neither the PPI nor the ranitidine were given.


Assuntos
Antibacterianos/administração & dosagem , Antiulcerosos/administração & dosagem , Esomeprazol/administração & dosagem , Infecções por Helicobacter/tratamento farmacológico , Ranitidina/administração & dosagem , Adolescente , Adulto , Idoso , Antibacterianos/efeitos adversos , Antiulcerosos/efeitos adversos , Quimioterapia Combinada/métodos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Esomeprazol/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ranitidina/efeitos adversos , Resultado do Tratamento , Adulto Jovem
11.
J Oncol Pharm Pract ; 25(7): 1705-1711, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31081468

RESUMO

BACKGROUND: Capecitabine is a commonly used oral chemotherapy agent. Recent data suggest that concurrent use of proton pump inhibitors may reduce the efficacy of capecitabine by decreasing its absorption through increased gastric pH. Since proton pump inhibitors are widely used, we evaluated the supportive evidence for the probability of occurrence and potential seriousness of this drug interaction. METHODS: The probability of occurrence was evaluated based on the clinical, pharmacokinetic and in vitro evidence using the Drug Interaction Probability Scale. The possibility of seriousness was assessed based on the potential impact on the therapeutic intent of capecitabine therapy. RESULTS: The probability of occurrence of the interaction is doubtful. Clinical findings from two retrospective post hoc analyses showed inconsistent trends towards reduced survival. Pharmacokinetics studies found no significant decrease in systemic capecitabine level with concurrent gastric acid suppression with antacid or food intake. In vitro data do not support the proposed mechanism of reduced capecitabine absorption due to increased gastric pH. The possibility of seriousness varies depending on the treatment intent of capecitabine therapy. The most and least serious possible outcome would be reduced possibility of cure or survival and symptom control, respectively. CONCLUSION: Although the possible outcome may be serious, the probability of interaction between capecitabine and proton pump inhibitors is doubtful. Therefore, we suggest that intervention should be limited to minimal change to existing therapy plan. This may include routinely ascertaining the need for proton pump inhibitor use. Alternate acid suppressing agents may be considered based on the therapeutic intent of capecitabine therapy.


Assuntos
Capecitabina/administração & dosagem , Inibidores da Bomba de Prótons/administração & dosagem , Antiácidos/administração & dosagem , Antiulcerosos/administração & dosagem , Capecitabina/efeitos adversos , Interações de Medicamentos , Ácido Gástrico/metabolismo , Humanos , Inibidores da Bomba de Prótons/efeitos adversos , Estudos Retrospectivos
12.
Medicine (Baltimore) ; 98(22): e15807, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31145312

RESUMO

BACKGROUND: The role of Helicobacter pylori eradication is still not clear in endoscopic submucosal dissection (ESD)-induced artificial ulcer. This study investigates the therapeutic effects of H. pylori eradication on ESD-induced artificial ulcers. METHODS: Eighty-four patients with ESD-induced artificial ulcers were enrolled. H. pylori eradication success subgroup (Group A1) and H. pylori eradication failure subgroups (Group A2) received standard triple therapy orally for 7 days, followed by esomeprazole 20 mg bis in die (bid) orally for the remainder of the treatment period (4 weeks in total). The H. pylori positive (Group B1) and H. pylori negative subgroups (Group B2) received esomeprazole 20 mg bid orally for 4 weeks. Ulcer healing was evaluated by gastroscopy, and H. pylori was identified by a C13 breath test or an Hp-RUT 2 and 6 months after treatment. RESULTS: Successful eradication of H. pylori can promote healing of ESD-induced artificial ulcers. The ESD-induced artificial ulcer healing rate in Group A1 was statistically higher than that in Groups A2, B1, and B2. CONCLUSION: Our results indicated that early H. pylori eradication therapy can promote ESD-induced artificial ulcer healing in H. pylori positive patients with ESD-induced artificial ulcers.


Assuntos
Antiulcerosos/uso terapêutico , Ressecção Endoscópica de Mucosa/efeitos adversos , Esomeprazol/uso terapêutico , Infecções por Helicobacter/tratamento farmacológico , Úlcera Gástrica/etiologia , Adulto , Idoso , Antibacterianos/uso terapêutico , Antiulcerosos/administração & dosagem , Quimioterapia Combinada , Esomeprazol/administração & dosagem , Feminino , Infecções por Helicobacter/complicações , Helicobacter pylori , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Úlcera Gástrica/complicações , Úlcera Gástrica/microbiologia
14.
Medicina (Kaunas) ; 55(3)2019 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-30862060

RESUMO

Background and objectives: Zingerone is an ingredient of ginger (Zingiber officinale) with different pharmacological activities. Several studies have investigated the effect of zingerone on various gastrointestinal diseases, including irritable bowel syndrome and diarrhea. This study is aimed to evaluate the effect of zingerone on ethanol-induced gastric ulcers in rats. Materials and Methods: Gastric ulcers were induced by ethanol (96%, 5 mL/kg, po) in male wistar rats and zingerone (50, 100, and 200 mg/kg) was administrated orally. Normal saline and ranitidine were used as negative and positive control, respectively. In this study, the number and length of ulcers, and malondialdehyde (MDA) and nitric oxide (NO) levels in stomach tissues were determined. Results: The findings showed that the mean number and length of gastric ulcers were significantly lower in zingerone-received groups than ethanol group (P < 0.05). The level of malondialdehyde was decreased in the stomach of zingerone groups (P < 0.05) compared to the ethanol group. In addition, zingerone treatment prevented the decrease of nitric oxide level by ethanol in the stomach tissue. Conclusions: The present study showed that zingerone has a protective effect on the ethanol-induced gastric ulcer, which may be due to its free radical scavenging activity.


Assuntos
Antiulcerosos/uso terapêutico , Gengibre/química , Guaiacol/análogos & derivados , Fitoterapia , Extratos Vegetais/uso terapêutico , Substâncias Protetoras/uso terapêutico , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/patologia , Animais , Antiulcerosos/administração & dosagem , Antiulcerosos/farmacologia , Modelos Animais de Doenças , Etanol/administração & dosagem , Etanol/efeitos adversos , Etanol/farmacologia , Mucosa Gástrica/metabolismo , Guaiacol/administração & dosagem , Guaiacol/farmacologia , Guaiacol/uso terapêutico , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Malondialdeído/análise , Malondialdeído/metabolismo , Necrose , Óxido Nítrico/análise , Óxido Nítrico/metabolismo , Extratos Vegetais/administração & dosagem , Extratos Vegetais/farmacologia , Substâncias Protetoras/administração & dosagem , Substâncias Protetoras/farmacologia , Ratos , Ratos Wistar , Solventes/administração & dosagem , Solventes/efeitos adversos , Solventes/farmacologia , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/prevenção & controle
15.
Invest Ophthalmol Vis Sci ; 60(4): 1076-1087, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30901389

RESUMO

Purpose: The aim of this study was the investigation of the effect of sulglycotide (SOS), a polysulfated glycopeptide derived from porcine duodenal mucin, for the treatment of dry eye disease. Methods: NOD.B10.H2b mice were exposed to an air draft for 10 days, and, simultaneously, scopolamine hydrobromide was injected subcutaneously. The mice were randomly divided into nine groups as follows: four kinds of SOS formulations and three kinds of commercial medicine. After 10 days of treatment, we estimated the effect of treatment on tear production, epithelium stabilization, mucin secretion, and inflammation. Results: The desiccation stress significantly decreased tear production and corneal epithelium stabilization, as well as markedly decreased the numbers of goblet cells and mucin-stained cells in conjunctiva. However, the topical 4% SOS eye drops markedly increased tear production and corneal stabilization, which recovered to baseline levels. In addition, topical 4% SOS significantly induced an increase in the numbers of goblet cells and the expression of membrane-associated mucins including MUC1, MUC4, and MUC16, as well as the gel-forming mucin, MUC5AC. Furthermore, SOS formulations provided anti-inflammatory improvement in a dose-dependent manner. Conclusions: In summary, we suggest that a new ophthalmic pharmaceutical formulation, topical sulglycotide, enhances the ocular mucin secretion in dry eye disease and can be used as a new ophthalmic pharmaceutical material to treat dry eye disease.


Assuntos
Antiulcerosos/uso terapêutico , Síndromes do Olho Seco/tratamento farmacológico , Mucinas/metabolismo , Sialoglicoproteínas/uso terapêutico , Lágrimas/metabolismo , Administração Oftálmica , Animais , Antiulcerosos/administração & dosagem , Dessecação , Modelos Animais de Doenças , Composição de Medicamentos , Síndromes do Olho Seco/induzido quimicamente , Síndromes do Olho Seco/metabolismo , Ensaio de Imunoadsorção Enzimática , Técnica Indireta de Fluorescência para Anticorpo , Células Caliciformes/efeitos dos fármacos , Imuno-Histoquímica , Camundongos , Camundongos Endogâmicos NOD , Antagonistas Muscarínicos/toxicidade , Soluções Oftálmicas , Estresse Oxidativo , Reação em Cadeia da Polimerase em Tempo Real , Escopolamina/toxicidade , Sialoglicoproteínas/administração & dosagem
16.
Equine Vet J ; 51(5): 575-580, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30809869

RESUMO

BACKGROUND: Previous studies have demonstrated a poor response to healing of gastric glandular lesions with oral omeprazole and other medications. OBJECTIVES: To evaluate the efficacy of two novel treatments (misoprostol [M] and combined omeprazole-sucralfate [OS]) in horses for gastric glandular disease. STUDY DESIGN: Prospective, clinical study. METHODS: Sixty-three sports horses with grade >1/4 glandular disease were identified by gastroscopy. Horses received either 5 µg/kg of misoprostol per os BID 1 h prior to feeding or a combination of 4 mg/kg enteric coated omeprazole per os SID and 12 mg/kg sucralfate per os BID where drugs were given 1 h prior to feeding and sucralfate given 60 min after omeprazole; allocation was dependent upon centre. Gastroscopy was repeated at 28-35 days. Evaluators of the gastroscopy images were blinded to the treatments the horses received and images were reviewed independently. RESULTS: The most common presenting sign in both treatment groups was poor performance (Overall - 65.1%; M - 60.5% and OS - 75%). Overall healing (P<0.001; OR = 11 [2.8-45]) and improvement (P = 0.006; OR = 11 [1.9-59]) of lesions were associated with resolution of clinical signs. Misoprostol was shown to be superior to combined omeprazole-sucralfate both for healing (M - 72% [95% CI 43-67] and OS - 20% [95% CI 7-41]; P<0.001) and improvement (M - 98% [95% CI 90-100] and OS - 65% [95% CI 43-83]; P<0.001). MAIN LIMITATIONS: Relatively small, clinical study, reliance on client questionnaire data, clients not blinded to the treatments the horse received, diet could have affected drug pharmacodynamics although mimics clinical practice and no validated scoring system available for glandular lesions. CONCLUSIONS: These results suggest that gastric glandular disease does indeed result in clinical signs. In this population of horses, misoprostol was superior to omeprazole and sucralfate and warrants further evaluation in a large scale, multi-centre trial.


Assuntos
Mucosa Gástrica/patologia , Doenças dos Cavalos/tratamento farmacológico , Misoprostol/uso terapêutico , Omeprazol/uso terapêutico , Gastropatias/veterinária , Sucralfato/uso terapêutico , Animais , Antiulcerosos/administração & dosagem , Antiulcerosos/uso terapêutico , Quimioterapia Combinada , Feminino , Cavalos , Masculino , Razão de Chances , Omeprazol/administração & dosagem , Gastropatias/tratamento farmacológico , Gastropatias/patologia , Sucralfato/administração & dosagem
17.
Clin Transl Gastroenterol ; 10(1): e00008, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30702488

RESUMO

OBJECTIVES: To evaluate the healing efficacy of rebamipide and lansoprazole combination therapy with lansoprazole alone for endoscopic submucosal dissection (ESD)-induced ulcers and clarify the ulcer healing-associated factors. METHODS: Three hundred patients were randomized into control and experimental groups after they underwent ESD. The patients received intravenous pantoprazole (30 mg) every 12 hours and oral rebamipide (100 mg, experimental group) or placebo (control group) 3 times daily on days 1-3. On days 4-56, patients received oral lansoprazole (30 mg daily) and rebamipide (100 mg) or placebo 3 times daily. Endoscopic evaluations were performed at postoperative weeks 4 and 8. RESULTS: At week 4, the ulcer reduction rate was significantly higher in the experimental than in the control group (0.97 ± 0.034 vs. 0.94 ± 0.078; P < 0.001). The ulcer healing (18.2% vs 20.3%; P = 0.669) and ulcer improvement rates (94.2% vs 88.7%; P = 0.109) in the 2 groups were not significantly different. At week 8, the ulcer healing and ulcer improvement rates were 90.6% and 100%, respectively, in both groups. Multivariate analysis showed that the combination treatment was an independent factor associated with ulcer area reduction after ESD. The maximum diameter of the initial ulcer (≥35.5 mm vs <35.5 mm) was an independent factor associated with the ulcer improvement rate after ESD. CONCLUSIONS: The rebamipide and lansoprazole combination therapy can help accelerate the reduction rate of post-ESD ulcer compared with the lansoprazole monotherapy at 4 weeks of therapy.


Assuntos
Alanina/análogos & derivados , Antiulcerosos/administração & dosagem , Ressecção Endoscópica de Mucosa/efeitos adversos , Lansoprazol/administração & dosagem , Quinolonas/administração & dosagem , Úlcera Gástrica/tratamento farmacológico , Administração Oral , Idoso , Alanina/administração & dosagem , Biópsia , Método Duplo-Cego , Quimioterapia Combinada/métodos , Feminino , Mucosa Gástrica/diagnóstico por imagem , Mucosa Gástrica/patologia , Mucosa Gástrica/cirurgia , Gastroscopia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Úlcera Gástrica/diagnóstico por imagem , Úlcera Gástrica/etiologia , Fatores de Tempo , Resultado do Tratamento
18.
J Vet Intern Med ; 33(2): 544-550, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30746763

RESUMO

BACKGROUND: Famotidine is commonly administered to cats. Prolonged famotidine administration results in decreased efficacy in humans, dogs, and cows, but the long-term effects in cats are unknown. OBJECTIVES: To compare the effect of 2 oral administration frequencies of famotidine, twice daily (Group 1) and twice daily every second day (Group 2), on intragastric pH and serum gastrin concentrations in cats. We hypothesized a diminished effect on intragastric pH would be observed over time in Group 1 but not Group 2. ANIMALS: Sixteen healthy cats. METHODS: Randomized, 2-factor repeated measures crossover design. Cats received 0.5-1.24 mg/kg (median, 0.87 mg/kg) famotidine twice daily or twice daily every second day for 14 consecutive days. Intragastric pH monitoring was used to record intragastric pH on treatment days 1-3 and 11-13. Mean pH and mean percentage time (MPT) intragastric pH was ≥3 and 4 were compared between and within treatment groups by analysis of variance. RESULTS: Significant treatment group by time interactions were observed for mean intragastric pH, MPT intragastric pH ≥3 and 4 (P = .009, P = .02, P = .005, respectively). Interaction post hoc tests identified significant decreases in mean intragastric pH (P = .001), MPT ≥3 (P = .001), and MPT ≥4 (P = .001) on day 13 compared to day 1 in Group 1 but not in Group 2. CONCLUSIONS AND CLINICAL IMPORTANCE: Oral famotidine administration results in a diminished effect on intragastric pH in healthy cats when given twice daily every day.


Assuntos
Antiulcerosos/farmacologia , Gatos/metabolismo , Famotidina/farmacologia , Ácido Gástrico/metabolismo , Administração Oral , Animais , Antiulcerosos/administração & dosagem , Estudos Cross-Over , Esquema de Medicação/veterinária , Famotidina/administração & dosagem , Feminino , Determinação da Acidez Gástrica/veterinária , Concentração de Íons de Hidrogênio/efeitos dos fármacos , Masculino , Distribuição Aleatória
19.
Rev Gastroenterol Mex ; 84(3): 317-325, 2019.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-30679027

RESUMO

INTRODUCTION AND AIM: Ulcerative colitis is a chronic condition characterized by inflammation affecting the colon. To objectively and integrally measure disease activity in patients with ulcerative colitis and thus optimize pharmacologic treatment, a novel integral disease index was created that includes the clinical, biochemical, endoscopic, and histologic characteristics necessary for achieving that task. The aim of the present study was to validate the novel integral disease index in patients with ulcerative colitis. MATERIALS AND METHODS: A cohort study on a total of 222 patients with histologic confirmations of ulcerative colitis diagnosis was conducted. The variables included in the disease index were: number of bowel movements per day; values for hemoglobin, high-sensitivity C-reactive protein, and serum albumin; and endoscopic and histologic findings measured through the subscales of the Mayo and Riley scores, respectively. The data analysis was performed utilizing the STATA SE 11.1 statistics program. RESULTS: The correlation of the novel disease index was very good (r=0.817, p <.001 with the Truelove and Witts criteria and r=0.957, p <.0001 with the Mayo score, respectively). Good internal consistency was found with a Cronbach's alpha coefficient of 0.78 and an acceptable mean inter-item correlation (r=0.47, p <.05). The total efficacy of the novel index was 87.2% correctly classified patients, with an AUC according to the three scenarios described of 0.93, 0.92, and 0.96, respectively. CONCLUSIONS: The novel integral disease index (Yamamoto-Furusho Index) provides an integral view of disease activity in patients with ulcerative colitis and is useful for optimizing pharmacologic treatment.


Assuntos
Colite Ulcerativa/diagnóstico , Colite Ulcerativa/patologia , Adulto , Idoso , Antiulcerosos/administração & dosagem , Antiulcerosos/uso terapêutico , Proteína C-Reativa/análise , Estudos de Coortes , Colite Ulcerativa/tratamento farmacológico , Colonoscopia , Defecação , Feminino , Hemoglobinas/análise , Humanos , Masculino , México , Pessoa de Meia-Idade , Estudos Prospectivos , Reprodutibilidade dos Testes , Albumina Sérica/análise
20.
Int J Clin Pharmacol Ther ; 57(4): 197-206, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30663979

RESUMO

OBJECTIVE: Prevalence of guideline adherence for antiulcer drug prescription in patients receiving low-dose aspirin (LDA) therapy was examined and the association of risk factors with the adherence was assessed. MATERIALS AND METHODS: A retrospective cohort study using a population-based longitudinal healthcare database was conducted. Claims data between January 2005 and April 2016 were analyzed. A total of 3,079 patients were included in the study. The selected patients taking LDA were divided into two categories: those taking and those not taking antiulcer drugs in an inpatient setting. Additionally, they were classified into four groups according to the time antiulcer therapy was initiated. The risk factors for ulcer, such as history of gastrointestinal injuries; age ≥ 65 years; and concomitant use of anticoagulants, antiplatelets, oral corticosteroids, and nonsteroidal anti-inflammatory drugs except aspirin, were assessed. RESULTS: A total of 3,079 patients were included in the study. The rate of LDA patients using antiulcer drugs was 65.2%, with the strongest single factor associated with the use of antiulcer drugs being the concomitant use of corticosteroids. Among the LDA patients not taking antiulcer drugs, 66.8% had more than one risk factor. Irrespective of the use of concomitant treatment with antiulcer drug prior to hospital admission, 78.3% of the LDA patients continued their home regimen after hospital admission. CONCLUSION: Our results showed that the requirement of antiulcer therapy is not routinely evaluated at hospital admission, and antiulcer drugs for patients with ulcer risks are under-prescribed. Developing strategies to screen gastrointestinal risk factors at hospital admission is required to improve the guideline adherence for LDA-induced ulcer.


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Antiulcerosos/administração & dosagem , Aspirina/administração & dosagem , Prescrições de Medicamentos/normas , Úlcera Péptica/tratamento farmacológico , Fidelidade a Diretrizes , Humanos , Japão , Estudos Retrospectivos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA