RESUMO
BACKGROUND/AIMS: The natural immunomodulator lactoferrin is known to possess anti-inflammatory effects. However, there have been no studies examining the mode of action of lactoferrin in protecting the esophageal mucosa against damage. We investigated the effect of lactoferrin on gastric acid secretion and in protecting against acute acid reflux-induced esophagitis in rats. METHODOLOGY: Male Wistar rats aged 8 weeks, weighing 210-240 g, were used for all the experiments. A gastric perfusion system was installed using the method of Ghosh et al. Lactoferrin was administered once via the caudate vein, starting 24 hours before an acute acid reflux (treatment mode), or saline (control). Statistical comparison of the parameters between the two test conditions was performed. RESULTS: No significant differences in basal or stimulated gastric acid secretion, or in the serum gastrin level were observed between the two test conditions. Esophageal damage was attenuated by lactoferrin in a dose-dependent manner, as reflected by the improvement in the esophageal tissue weight and macroscopic scores. Significant reductions in the histological scores, myeloperoxidase activity and the levels of proinflammatory cytokines, tumor necrosis factor-α and interleukin-1ß were also observed following lactoferrin administration. CONCLUSIONS: We concluded that lactoferrin exerts a protective effect against acute acid reflux-induced esophageal damage in rats.
Assuntos
Esôfago/efeitos dos fármacos , Refluxo Gastroesofágico/tratamento farmacológico , Lactoferrina/farmacologia , Substâncias Protetoras/farmacologia , Animais , Citoproteção , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Esôfago/metabolismo , Esôfago/patologia , Ácido Gástrico/metabolismo , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Gastrinas/sangue , Refluxo Gastroesofágico/metabolismo , Refluxo Gastroesofágico/patologia , Mediadores da Inflamação/metabolismo , Injeções Intravenosas , Lactoferrina/administração & dosagem , Masculino , Mucosa/efeitos dos fármacos , Mucosa/metabolismo , Mucosa/patologia , Substâncias Protetoras/administração & dosagem , Ratos WistarRESUMO
BACKGROUND/AIMS: Nitric oxide (NO) production is elevated in the intestine and may contribute to intestinal injury during inflammation. However, how the expression of inducible NO synthase (iNOS) mRNA and endothelial NO synthase (eNOS) mRNA in the esophageal mucosa contribute to mucosal damage caused by reflux esophagitis remains unknown. Since vascular endothelial growth factor (VEGF) exerts its action on microcirculation, contributing to angiogenesis and inflammation, we examined the role of VEGF together with iNOS and eNOS on development of reflux esophagitis. METHODOLOGY: The mRNA expression levels of iNOS, eNOS and VEGF were measured in biopsy specimens from 25 patients with reflux esophagitis, using TaqMan PCR and reverse transcription PCR. RESULTS: The expression of iNOS mRNA in the esophageal mucosa increased parallel to the severity of the esophagitis. There were no significant differences between both eNOS and VEGF mRNA expression levels and the severity of the esophagitis. The existence of gastric mucosal atrophy, hiatus hernia, therapy and Helicobacter pylori infection did not affect the levels of mRNA expression. CONCLUSIONS: The accumulation of NO, produced by iNOS, was considered to be related to the exacerbation of reflux esophagitis. Therapeutic intervention that reduces NO production may thus be of use in preventing development of esophageal mucosal injury in patients with reflux esophagitis.
Assuntos
Esofagite Péptica/metabolismo , Esôfago/metabolismo , Regulação da Expressão Gênica , Óxido Nítrico Sintase Tipo II/biossíntese , RNA Mensageiro/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Esofagite Péptica/patologia , Esôfago/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa/metabolismo , Mucosa/patologia , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo III/genética , Óxido Nítrico Sintase Tipo III/metabolismo , Estudos Retrospectivos , Índice de Gravidade de Doença , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
BACKGROUND/AIMS: Endoscopic injection sclerotherapy is in widespread use for patients with esophageal varices. It is well known that pleural effusions are among complications following endoscopic sclerotherapy. However, there are few studies regarding the proportion of patients developing pleural effusions after sclerotherapy. METHODOLOGY: Between August 1991 and September 1998, 575 endoscopic injection sclerotherapies were carried out in 128 patients. Chest radiographs were obtained prior to and 24 hours after all procedures. We also obtained other clinical data from all patients. RESULTS: In total, 17.7% of post-sclerotherapy patients were diagnosed as having small amounts of pleural effusions. Logistic regression revealed pleural effusions after sclerotherapy to be associated with ascites, chest pain for 24 hours, total volume of sclerosant and submucosal injection of more than 4mL of sclerosant. In parallel with injection of an increasing amount of submucosal sclerosant, the proportion of patients with pleural effusion increased. CONCLUSIONS: Pleural effusions were related to ascites, chest pain for 24 hours, total sclerosant volume and submucosal injection of sclerosant.
Assuntos
Varizes Esofágicas e Gástricas/terapia , Cirrose Hepática/terapia , Derrame Pleural/etiologia , Escleroterapia/efeitos adversos , Ascite/etiologia , Dor no Peito/etiologia , Endoscopia/efeitos adversos , Feminino , Humanos , Injeções/efeitos adversos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Ácidos Oleicos/administração & dosagem , Ácidos Oleicos/efeitos adversos , Estudos Retrospectivos , Soluções Esclerosantes/administração & dosagem , Soluções Esclerosantes/efeitos adversosRESUMO
BACKGROUND: Medication for the relief of heartburn should have the rapid onset of action required for on-demand use. We studied the inhibition of gastric acid secretion by lafutidine and rabeprazole, given in single doses to fasting and postprandial subjects. METHODS: A total of 22 healthy male, Helicobacter pylori-negative volunteers participated in this randomized, two-way crossover study. They were randomly assigned to receive a single oral dose of 10 mg lafutidine or 20 mg rabeprazole after fasting overnight (12 subjects, fasting study) or after eating a test meal (noodles, 364 kcal; protein, 10.1 g; fat, 16 g; carbohydrates, 44.9 g; NaCl, 1.1 g; 10 subjects, postprandial study). Intragastric pH was monitored continuously for 6 h after treatment. The other drug was given after a washout period of at least 7 days, and intragastric pH was similarly monitored. RESULTS: In the fasting study, lafutidine sustained pH at >3 and >4 during the second, third, fourth, fifth, and sixth hours of the study for significantly longer than rabeprazole. During the first 6 h after treatment, lafutidine sustained pH at more than 2, 3, 3.5, 4, 5, 6, and 7 longer than rabeprazole. In the postprandial study, lafutidine sustained pH >3 and >4 for longer periods than rabeprazole during the third, fourth, fifth, and sixth hours of the study. During the first 6 h after treatment, lafutidine sustained pH at more than 2, 3, 3.5, 4, 5, 6, and 7 longer than rabeprazole. CONCLUSIONS: Lafutidine 10 mg produces a prompter rise in intragastric pH than rabeprazole 20 mg in fasting and postprandial Helicobacter pylori-negative male subjects.
Assuntos
Acetamidas/administração & dosagem , Benzimidazóis/administração & dosagem , Azia/tratamento farmacológico , Omeprazol/análogos & derivados , Piperidinas/administração & dosagem , Período Pós-Prandial/efeitos dos fármacos , Piridinas/administração & dosagem , 2-Piridinilmetilsulfinilbenzimidazóis , Administração Oral , Adulto , Estudos Cross-Over , Esquema de Medicação , Ácido Gástrico/metabolismo , Determinação da Acidez Gástrica , Azia/diagnóstico , Humanos , Concentração de Íons de Hidrogênio , Masculino , Monitorização Fisiológica , Omeprazol/administração & dosagem , Rabeprazol , Valores de Referência , Medição de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND/AIMS: Triple therapy consisting of lansoprazole, amoxicillin, and clarithromycin (LAC regimen) is widely used to eradicate Helicobacter pylori in Japan. However, the need for appropriate treatment after failure of initial therapy to eradicate H. pylori has been increasing. We therefore assessed the efficacy of a combination of rabeprazole, amoxicillin, and faropenem for second-line eradication therapy. METHODOLOGY: The subjects were 116 patients positive for H. pylori infection. Patients initially received lansoprazole 60 mg/day, amoxicillin 1500 mg/day and clarithromycin 400 mg/day in two divided doses for 7 days. Patients in whom eradication treatment failed were given rabeprazole 20 mg/day and amoxicillin 1500 mg/day in two divided doses, and faropenem 600 mg/day in three divided doses (RAF regimen) for 7 consecutive days. H. pylori status was assessed by the 13C-urea breath test combined with rapid urease test or H. pylori culture method 8 weeks after completion of therapy. Susceptibility to clarithromycin was determined by the agar dilution method, and genetic polymorphism of CYP2C19 was analyzed by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: The initial H. pylori eradication rate with the LAC regimen was 76.4% (84/110). Assessment of the CYP2C19 genotypes of the patients in whom eradication therapy failed revealed that homozygous extensive metabolizers accounted for 70.0% (16/23) and heterozygous extensive metabolizers for 30.0% (7/23), with no poor metabolizers. The acquired resistance rate for clarithromycin was 52.0% (12/23). The success rate of re-eradication with the RAF regimen was 91.3% (21/23) with no serious adverse effects. CONCLUSIONS: Triple therapy comprising rabeprazole, amoxicillin, and faropenem is effective for second-line eradication treatment of H. pylori infection, regardless of the genetic polymorphism of CYP2C19 or the presence of resistance to clarithromycin.
Assuntos
Amoxicilina/uso terapêutico , Antibacterianos/uso terapêutico , Benzimidazóis/uso terapêutico , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori , Lactamas/uso terapêutico , Omeprazol/análogos & derivados , Omeprazol/uso terapêutico , 2-Piridinilmetilsulfinilbenzimidazóis , Adulto , Idoso , Idoso de 80 Anos ou mais , Amoxicilina/administração & dosagem , Antibacterianos/administração & dosagem , Benzimidazóis/administração & dosagem , Esquema de Medicação , Quimioterapia Combinada , Humanos , Lactamas/administração & dosagem , Pessoa de Meia-Idade , Omeprazol/administração & dosagem , Rabeprazol , Retratamento , Resultado do Tratamento , beta-LactamasRESUMO
BACKGROUND: The ideal medication for the treatment of acid-related diseases, for example, hemorrhagic ulcers and stress-related gastric bleeding, should have a rapid onset of action to promote hemostasis and alleviate symptoms. The aim of our study was to investigate the inhibitory effects on gastric acid secretion after single intravenous administrations of omeprazole 20mg and famotidine 20 mg. METHODS: Ten healthy Helicobacter pylori-negative male subjects participated in this randomized, double-masked, two-way crossover study. Intragastric pH was monitored continuously for 4 h after a single intravenous administration of omeprazole 20 mg and after a single intravenous administration of famotidine 20 mg. The administration of the two agents was separated by a 7-day washout period. RESULTS: In all ten subjects, the length of time that intragastric pH remained over 3, during the 0- to 3- and 0- to 4-h study periods, was greater after famotidine treatment than after treatment with omeprazole, and famotidine increased the average pH during the 0 to 3- and 0 to 4-h study periods significantly more than omeprazole did. During the 4-h study period, famotidine provided a longer duration of pH of more than 2, 3, 3.5, 4, 5, 6, and 7, compared to omeprazole. CONCLUSIONS: In Helicobacter pylori-negative healthy male subjects, an intravenous dose of 20 mg famotidine increased intragastric pH more rapidly than intravenous omeprazole 20 mg.
Assuntos
Antiulcerosos/farmacologia , Famotidina/farmacologia , Omeprazol/farmacologia , Adulto , Antiulcerosos/administração & dosagem , Estudos Cross-Over , Método Duplo-Cego , Famotidina/administração & dosagem , Ácido Gástrico/metabolismo , Antagonistas dos Receptores H2 da Histamina/administração & dosagem , Antagonistas dos Receptores H2 da Histamina/farmacologia , Humanos , Concentração de Íons de Hidrogênio , Injeções Intravenosas , Masculino , Omeprazol/administração & dosagemAssuntos
Inibidores Enzimáticos/administração & dosagem , Famotidina/administração & dosagem , Ácido Gástrico/metabolismo , Mucosa Gástrica/efeitos dos fármacos , Antagonistas dos Receptores H2 da Histamina/administração & dosagem , Omeprazol/administração & dosagem , Adulto , Esquema de Medicação , Quimioterapia Combinada , Humanos , Concentração de Íons de Hidrogênio , MasculinoRESUMO
BACKGROUND AND AIMS: The natural immunomodulator, lactoferrin, is widespread among various biological fluids and is known to exert an anti-inflammatory effect. However, there has been only one study that examined the mode of action of lactoferrin in reducing intestinal damage. We investigated the therapeutic role of lactoferrin and its effect on the levels of pro-inflammatory and anti-inflammatory cytokines, by using a rat model of dextran sulfate sodium (DSS) induced-colitis. METHODS: Male Sprague-Dawley rats were given distilled drinking water containing 2.5% (wt/vol) synthetic DSS ad libitum. Bovine lactoferrin was given once daily through gavage, starting 3 days before beginning the DSS administration, until death. The whole colon was removed to be examined macroscopically and histologically. Myeloperoxidase activity, and pro-inflammatory and anti-inflammatory cytokines in the colonic tissue were also measured. RESULTS: Dextran sulfate sodium-induced colitis was attenuated by oral administration of lactoferrin in a dose-dependent manner, as reflected by improvement in clinical disease activity index, white blood cell count and hemoglobin concentration, macroscopic and histological scores, and myeloperoxidase activity. Reduced inflammation in response to lactoferrin was correlated with the significant induction of the anti-inflammatory cytokines, interleukin-4 and interleukin-10, and with significant reductions in the pro-inflammatory cytokines, tumor necrosis factor alpha, interleukin-1beta, and interleukin-6. CONCLUSIONS: We concluded that oral administration of lactoferrin exerts a protective effect against the development of colitis in rats via modulation of the immune system and correction of cytokine imbalance. Lactoferrin has potential as a new therapeutic agent for inflammatory bowel disease.
Assuntos
Colite/tratamento farmacológico , Lactoferrina/uso terapêutico , Administração Oral , Animais , Bovinos , Colite/induzido quimicamente , Colo/metabolismo , Citocinas/metabolismo , Sulfato de Dextrana , Relação Dose-Resposta a Droga , Lactoferrina/administração & dosagem , Masculino , Peroxidase/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
Natural immunomodulator lactoferrin is known to exert an anti-inflammatory effect. However, there have been no studies that examine the mode of action of lactoferrin in reducing intestinal damage. We investigated the effect of lactoferrin on a trinitrobenzenesulfonic acid (TNBS)-induced colitis model in rats. Bovine lactoferrin was given once daily through gavage, starting 3 days before (preventive mode) or just after TNBS administration (treatment mode) until death. The distal colon was removed to be examined. Colitis was attenuated by lactoferrin via both modes in a dose-dependent manner, as reflected by improvement in macroscopic and histological scores and myeloperoxidase activity. Lactoferrin caused significant induction of the anti-inflammatory cytokines interleukin (IL)-4 and IL-10, significant reductions in the proinflammatory cytokines tumor necrosis factor-alpha and IL-1beta, and downregulation of the nuclear factor-kappaB pathway. We concluded that lactoferrin exerts a protective effect against colitis in rats via modulation of the immune system and correction of cytokine imbalance. Lactoferrin has potential as a new therapeutic agent for inflammatory bowel disease.
Assuntos
Colite/patologia , Citocinas/metabolismo , Sistema Imunitário/efeitos dos fármacos , Lactoferrina/farmacologia , Animais , Bovinos , Colite/induzido quimicamente , Colite/fisiopatologia , Colo/efeitos dos fármacos , Colo/metabolismo , Relação Dose-Resposta a Droga , Sistema Imunitário/fisiopatologia , Lactoferrina/administração & dosagem , Masculino , NF-kappa B/metabolismo , Ratos , Ratos Sprague-Dawley , Ácido TrinitrobenzenossulfônicoRESUMO
BACKGROUND: Recent studies have shown that the number of patients with reflux esophagitis is increasing in Japan, but the prevalence and risk factors associated with reflux esophagitis in Japanese patients are not well defined. METHODS: By using all endoscopic records in the Katta General Hospital from April through to September 1999, we identified 392 patients. We examined the Los Angeles classification, peptic ulcer, gastric mucosal atrophy, hiatal hernia and other medical variable factors for their contribution to esophagitis in the patients. RESULTS: Patients (13.8%) were diagnosed as having reflux esophagitis with a mucosal break. In a multivariate analysis, reflux esophagitis was associated with hiatal hernia (odds ratio (OR) 2.276, 95% confidence interval (CI) 1.164-4.450), with patients over 65 years of age (OR 2.521, 95% CI 1.238-5.134) and the open type of gastric mucosal atrophy (OR 0.420, 95% CI 0.225-0.785). There was no significant difference between esophagitis and Helicobacter pylori infection and peptic ulcer. CONCLUSIONS: We observed that age, hiatal hernia and a lower rate of gastric mucosal atrophy were associated with the proportion of mucosal breaks accompanying esophagitis.
Assuntos
Envelhecimento/fisiologia , Esofagite Péptica/etiologia , Mucosa Gástrica/patologia , Hérnia Hiatal/complicações , Idoso , Atrofia , Esofagite Péptica/classificação , Esofagoscopia , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Razão de Chances , Análise de Regressão , Fatores de RiscoRESUMO
BACKGROUND AND AIMS: An ideal medication for heartburn should have the rapid onset of action needed for on-demand treatment. However, assessment of the onset of action of proton pump inhibitors has been largely subjective. We compared the inhibitory effect on gastric acid secretion of a single oral dose of omeprazole with that of rabeprazole. METHODS: Fourteen Helicobacter pylori-negative men participated in this randomized, double-masked, two-way cross-over study. Intragastric pH was monitored continuously for 6 h after a single, randomly assigned 20 mg oral dose of either omeprazole or rabeprazole. After a 7-day washout period, the other drug was administered. Each patient's S-mephenytoin 4'-hydroxylase (CYP2C19) genotype was determined by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: Intragastric pH and pH holding time did not differ between treatments when the data were analyzed for the whole group without stratifying for CYP2C19 status. In CYP2C19 homozygous and heterozygous extensive metabolizers (10 subjects), rabeprazole maintained the intragastric at pH > 3 and> 4 for longer than omeprazole during both the 5 and 6 h study periods, and the average pH during the 6 h study period was higher with rabeprazole than with omeprazole. In these extensive metabolizers, rabeprazole maintained the pH > 2,> 3,> 3.5 and> 4 for longer during the 6 h study period than did omeprazole. CONCLUSIONS: In H. pylori-negative men who are CYP2C19 homozygous or heterozygous extensive metabolizers, the intragastric pH after a single dose of 20 mg rabeprazole is higher during first 5-6 h than that after a single dose of 20 mg omeprazole.