RESUMO
AIM: Triple therapy seems more effective in curing Helicobacter pylori infection in patients with peptic ulcer than in those with non-ulcer dyspepsia. It has been suggested that this difference depends on the expression of CagA protein that is more frequent in the former. The objective of this study was to investigate a potential association between serum CagA positivity, severity of gastric mucosal inflammation and eradication success among peptic ulcer and non-ulcer dyspepsia patients. MATERIAL AND METHOD: Patients undergoing upper gastrointestinal endoscopy for investigation of dyspepsia at the Department of Gastroenterology, Hospital Vera Cruz, between March, 2000 and March 2001 were screened. H. pylori positive patients, as diagnosed by rapid urease test and histology were included. Severity of gastric mucosal inflammation was determined and serum CagA positivity was assessed using a commercially available ELISA assay prior to H. pylori 7-day eradication therapy with lansoprazole, clarithromycin and amoxicillin (30 mg, 500 mg and 1 g b.i.d., respectively). Eradication success was determined 8-24 weeks following completion of therapy. RESULTS: Seventy-four patients were included in the study (mean age 40.8, range 18-67, female = 28). CagA positivity was observed in 48% of patients. Gastroduodenal peptic ulceration was found in 54% of patients. Serum CagA positivity was significantly higher among peptic ulcer patients (62.5%), while CagA negativity was significantly higher among non-ulcer dyspepsia patients (67.7%). Lymphocyte and eosinophil infiltration was significantly higher among CagA + patients, despite being comparable when distributed among peptic ulcer and non-ulcer dyspepsia patients. Eradication was successful in 93.2% of patients, regardless of CagA status on a per protocol analysis. Based on a per protocol analysis, eradication success was comparable among peptic ulcer and non-ulcer dyspepsia patients, regardless of CagA status. CONCLUSION: Our results support the concept that CagA positivity is associated to peptic ulcer disease and to a higher severity of lymphocyte and eosinophil infiltration. Efficacy of treatment eradication of H. pylori may not be affected by serum CagA status.
Assuntos
Amoxicilina/uso terapêutico , Antibacterianos/uso terapêutico , Antiulcerosos/uso terapêutico , Antígenos de Bactérias/sangue , Proteínas de Bactérias/sangue , Claritromicina/uso terapêutico , Dispepsia/etiologia , Gastrite/tratamento farmacológico , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/isolamento & purificação , Omeprazol/análogos & derivados , Úlcera Péptica/etiologia , 2-Piridinilmetilsulfinilbenzimidazóis , Adolescente , Adulto , Idoso , Amoxicilina/administração & dosagem , Antibacterianos/administração & dosagem , Antiulcerosos/administração & dosagem , Antígenos de Bactérias/genética , Proteínas de Bactérias/genética , Biomarcadores , Claritromicina/administração & dosagem , Quimioterapia Combinada , Dispepsia/microbiologia , Ensaio de Imunoadsorção Enzimática , Eosinofilia/sangue , Eosinofilia/etiologia , Eosinofilia/patologia , Eosinófilos/patologia , Feminino , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Gastrite/sangue , Gastrite/complicações , Gastrite/microbiologia , Gastrite/patologia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/patologia , Helicobacter pylori/genética , Humanos , Lansoprazol , Linfócitos/patologia , Masculino , Pessoa de Meia-Idade , Omeprazol/administração & dosagem , Omeprazol/uso terapêutico , Úlcera Péptica/sangue , Úlcera Péptica/microbiologia , Úlcera Péptica/patologiaRESUMO
BACKGROUND: The addition of omeprazole to classical triple therapy for eradication of H. pylori may enhance compliance through reducing ulcer symptoms and side-effects. The aim of this study was to investigate the effects of a 5-day administration of omeprazole on metronidazole pharmacokinetics. METHODS: Fourteen healthy male volunteers were selected. The study had an open, randomized, two-period crossover design with a 21-day washout period between the phases. Plasma concentrations of metronidazole and its hydroxy-metabolite were measured by reversed-phase HPLC with ultraviolet detection. RESULTS: Administration of omeprazole did not affect the pharmacokinetic parameters of orally administered metronidazole. CONCLUSION: Our results indicate that short-term treatment with omeprazole in healthy volunteers does not alter the extent or the rate of metronidazole absorption, and does not affect metronidazole clearance.
Assuntos
Antiulcerosos/farmacologia , Antitricômonas/farmacocinética , Ácido Gástrico/metabolismo , Metronidazol/farmacocinética , Omeprazol/farmacologia , Administração Oral , Adulto , Antiulcerosos/administração & dosagem , Antiulcerosos/uso terapêutico , Antitricômonas/efeitos adversos , Antitricômonas/uso terapêutico , Disponibilidade Biológica , Estudos Cross-Over , Interações Medicamentosas , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori , Humanos , Masculino , Metronidazol/efeitos adversos , Metronidazol/uso terapêutico , Omeprazol/administração & dosagem , Omeprazol/uso terapêuticoRESUMO
OBJECTIVE: To evaluate whether the addition of bismuth subnitrate to a dual oral therapy regimen with omeprazole plus amoxycillin could improve Helicobacter pylori eradication. METHODS: Fifty consecutive Helicobacter pylori-positive patients were randomly enrolled to receive either (A) bismuth subnitrate (300 mg q.d.s.), omeprazole (20 mg b.d.) and amoxycillin (500 mg q.d.s.), or (B) omeprazole (20 mg b.d.) and amoxycillin (500 mg q.d.s.). Both groups (n=25 each) received the medication for 14 days. H. pylori status was reassessed 30 days after completion of the therapy in order to evaluate eradication rates. RESULTS: Six patients were lost to follow-up and therefore excluded from the study (three patients from each group). One patient from Group B withdrew from the study because of side-effects. The addition of bismuth subnitrate to omeprazole and amoxycillin significantly improved its efficacy in eradicating H. pylori, with 72% (18/25) eradication in Group A and 52% (13/25) in Group B (P=0.027). The addition of bismuth subnitrate to dual oral therapy was also capable of improving the healing of peptic ulcers when compared with dual oral therapy alone (100%, 8/8 vs. 58%, 4/7; P=0.021). CONCLUSION: Our results demonstrate that the addition of bismuth subnitrate to dual oral therapy enhances H. pylori eradication, and improves healing of peptic ulcers.
Assuntos
Amoxicilina/uso terapêutico , Antiulcerosos/uso terapêutico , Bismuto/uso terapêutico , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori , Omeprazol/uso terapêutico , Penicilinas/uso terapêutico , Ranitidina/análogos & derivados , Úlcera Gástrica/tratamento farmacológico , Adulto , Idoso , Amoxicilina/administração & dosagem , Amoxicilina/efeitos adversos , Antiulcerosos/administração & dosagem , Antiulcerosos/efeitos adversos , Bismuto/administração & dosagem , Bismuto/efeitos adversos , Quimioterapia Combinada , Feminino , Seguimentos , Gastroscopia , Infecções por Helicobacter/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Omeprazol/administração & dosagem , Omeprazol/efeitos adversos , Penicilinas/administração & dosagem , Penicilinas/efeitos adversos , Ranitidina/administração & dosagem , Ranitidina/efeitos adversos , Ranitidina/uso terapêutico , Úlcera Gástrica/microbiologiaRESUMO
AIMS: To evaluate the usefulness of plasma hydroxy-metronidazole/metronidazole (OH-MET/MET) ratios as a dynamic liver function test in ethanol abusers with or without liver cirrhosis. METHODS: Metronidazole was administered intravenously for 20 min to healthy volunteers, and to patients with alcohol-induced, non-cirrhotic hepatopathy and liver cirrhosis. Plasma concentrations of metronidazole and hydroxy-metronidazole were measured by high performance liquid chromatography in samples collected 5, 10, 20 and 30 min after the metronidazole infusion. RESULTS: Patients with non-cirrhotic alcoholic hepatopathy had significantly elevated aminotransferase levels compared to healthy volunteers and Child A patients. Child-Pugh C patients had significantly prolonged prothrombin times when compared to healthy volunteers and patients with non-cirrhotic hepatopathy. Metronidazole metabolism, as measured by the OH-MET/MET ratio following the intravenous administration of 500 mg of the drug, was significantly impaired in all ethanol-abusing individuals, including patients with non-cirrhotic alcoholic hepatopathy. CONCLUSIONS: Metronidazole metabolism was impaired in ethanol abusers, even in the absence of liver cirrhosis, indicating that ethanol was capable of affecting liver function in the early stages of alcohol-induced liver disease.
Assuntos
Consumo de Bebidas Alcoólicas/sangue , Anti-Infecciosos/sangue , Cirrose Hepática Alcoólica/fisiopatologia , Hepatopatias/fisiopatologia , Metronidazol/análogos & derivados , Metronidazol/sangue , Adolescente , Adulto , Idoso , Anti-Infecciosos/administração & dosagem , Cromatografia Líquida de Alta Pressão , Humanos , Cirrose Hepática Alcoólica/sangue , Hepatopatias/sangue , Hepatopatias/etiologia , Testes de Função Hepática , Masculino , Metronidazol/administração & dosagem , Pessoa de Meia-IdadeRESUMO
BACKGROUND: The effects of proton pump inhibitors and Helicobacter pylori infection on the distribution of drugs used for the eradication of the bacteria are poorly understood. AIM: The aim of this study was to investigate the effects of a 7-day administration of 20 mg of omeprazole on the pharmacokinetics of amoxicillin and ampicillin in the plasma, saliva and gastric juice of individuals with and without H. pylori infection. METHODS: Fifty-four healthy volunteers without endoscopic lesions were enrolled. Twenty-six volunteers were included in the amoxicillin study and 28 individuals in the ampicillin study. Each study had an open randomized two-period crossover design and a 21-day washout period between phases. Plasma, saliva and gastric juice concentrations of amoxicillin and ampicillin in subjects with and without omeprazole pre-treatment were measured by reversed-phase HPLC using UV detection. RESULTS: Neither pre-treatment with omeprazole nor H. pylori infection interfered with the plasma bioavailability of amoxicillin or ampicillin, as assessed by the AUC0-2 h. Neither ampicillin nor amoxicillin were detected in saliva or gastric juice in any study phase. CONCLUSION: Short-term treatment with omeprazole does not interfere with the pharmacokinetics of amoxicillin or ampicillin. Our results also exclude the presence of a transfer mechanism for amoxicillin or ampicillin from the plasma to the gastric lumen.
Assuntos
Amoxicilina/farmacocinética , Ampicilina/farmacocinética , Inibidores Enzimáticos/farmacologia , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/patogenicidade , Omeprazol/farmacologia , Penicilinas/farmacocinética , Inibidores da Bomba de Prótons , Adulto , Amoxicilina/administração & dosagem , Ampicilina/administração & dosagem , Área Sob a Curva , Disponibilidade Biológica , Cromatografia Líquida de Alta Pressão , Estudos Cross-Over , Feminino , Suco Gástrico/química , Humanos , Masculino , Penicilinas/administração & dosagem , Saliva/químicaRESUMO
Nitric oxide can exert either protective or damaging effects on the gastric mucosa. To further explore the role of nitric oxide in the modulation of gastric mucosal defense, the effects of intra-arterial administration of the precursor, L-arginine, on susceptibility of the gastric mucosa to damage induced by topically applied 20% ethanol was examined in the rat. L-Arginine administration prior to application of ethanol produced a dose-dependent increase in the extent of damage (P < 0.01 at 300 and P < 0.001 at 500 mg/kg). L-Arginine administration did not increase the extent of damage at a dose of 300 mg/kg, but did at a dose of 500 mg/kg. Pretreatment with NG-nitro-L-arginine-methyl-ester (L-NAME, 25 mg/kg), but not NG-nitro-D-arginine-methyl-ester (D-NAME, 25 mg/kg) significantly attenuated the exacerbation of injury induced by L-arginine (300 mg/kg). L-Arginine significantly reduced gastric blood flow relative to controls, while D-arginine had no effect. L-NAME induced a dose-dependent decrease in gastric blood flow and did not affect the response to L-arginine. These results suggest that L-arginine can significantly increase gastric injury through a mechanism that appears to be partly nitric oxide-dependent and partly nitric oxide-independent. Changes in gastric blood flow do not appear to be the sole mechanism responsible for the augmentation of injury caused by L-arginine.
Assuntos
Arginina/toxicidade , Mucosa Gástrica/efeitos dos fármacos , Animais , Arginina/análogos & derivados , Arginina/antagonistas & inibidores , Arginina/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Etanol/toxicidade , Mucosa Gástrica/irrigação sanguínea , Mucosa Gástrica/patologia , Masculino , NG-Nitroarginina Metil Éster , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/metabolismo , Ratos , Ratos Wistar , Fluxo Sanguíneo Regional/efeitos dos fármacos , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/patologiaRESUMO
We have recently described a novel assay to assess ex vivo the activity and selectivity on cyclooxygenase-1 and -2 (EC 1.14.99.1) of non-steroid anti-inflammatory drugs (NSAID) administered to rats [Br. J. Pharmacol. 126 (1999) 1824.]. Here, we have extended these studies to humans. Healthy male volunteers were given orally one of the following drugs (mg) for 5 days: etodolac (200 or 400 b.i.d.), meloxicam (7.5 or 15 q.d.), nimesulide (100 or 200 b.i.d.), nabumetone (500 or 1000 b.i.d.) or naproxen (500 b.i.d.). Blood samples were withdrawn from the volunteers before and up to 24 h after the last dose. Plasma obtained from the blood was tested for its ability to inhibit prostanoid formation in interleukin-1beta-treated A549 cells (cyclooxygenase-2 system) and human washed platelets (cyclooxygenase-1 system). Plasma from etodolac-treated subjects demonstrated a slight selectivity towards the inhibition of cyclooxygenase-2. This effect was more prominent in plasma from subjects receiving meloxicam or nimesulide. Plasma from nabumetone-treated subjects showed no or little selectivity towards cyclooxygenase-1 depending on the dose of drug administered, while plasma taken from subjects receiving naproxen was more active at inhibiting cyclooxygenase-1 than cyclooxygenase-2. In conclusion, we have demonstrated that this assay can be used to assess ex vivo the relative activity against cyclooxygenase-1 and cyclooxygenase-2 of NSAIDs consumed by human volunteers. It is to be hoped that data from such systems will aid in our understanding of the relationships between the differential inhibition of cyclooxygenase-1 and cyclooxygenase-2 by NSAIDs and their reported efficacies and (gastrointestinal) toxicities.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Prostaglandina-Endoperóxido Sintases/efeitos dos fármacos , Adolescente , Adulto , Butanonas/farmacologia , Ciclo-Oxigenase 1 , Ciclo-Oxigenase 2 , Relação Dose-Resposta a Droga , Etodolac/farmacologia , Humanos , Isoenzimas/efeitos dos fármacos , Isoenzimas/metabolismo , Masculino , Meloxicam , Proteínas de Membrana , Nabumetona , Naproxeno/farmacologia , Prostaglandina-Endoperóxido Sintases/metabolismo , Prostaglandinas/metabolismo , Sulfonamidas/farmacologia , Tiazinas/farmacologia , Tiazóis/farmacologia , Fatores de Tempo , Células Tumorais CultivadasRESUMO
AIM: To investigate the presence of lesions of the upper gastrointestinal tract of asymptomatic, healthy volunteers undergoing clinical pharmacology studies. MATERIAL AND METHODS: A series of 53 volunteers (45 male, 23 Helicobacter pylori negative and 30 Helicobacter pylori positive) underwent upper gastrointestinal endoscopy. Helicobacter pylori status was assessed using two methods (rapid urease test and histology) from antral and corpus biopsies. RESULTS: Peptic lesions were found in 24 (45%) subjects: erosive oesophagitis, gastric/duodenal ulcers and gastric/duodenal erosions were found in 23%, 9% and 36% of these volunteers, respectively. Helicobacter pylori-positive subjects had significantly (p<0.05) more gastroduodenal lesions than Helicobacter pylori negative individuals (12/30 vs 3/23). The presence of peptic ulcers and erosive oesophagitis was similar in Helicobacter pylori-positive and -negative individuals. CONCLUSIONS: The possibility that peptic lesions might exist in otherwise asymptomatic, healthy individuals cannot be ruled out. Helicobacter py lori-positive individuals have a significantly higher incidence of gastric and duodenal lesions than Helicobacter pylori negative subjects.
Assuntos
Úlcera Péptica/microbiologia , Adolescente , Adulto , Feminino , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/etiologia , Helicobacter pylori , Humanos , Masculino , Úlcera Péptica/epidemiologia , PrevalênciaRESUMO
The authors report a case of a 13-year-old girl with Barrett's esophagus who underwent antireflux surgery and was subsequently treated with endoscopic thermal coagulation using bipolar electrocoagulation. Follow-up endoscopy 15 months after completion of the endoscopic therapy showed normal esophageal mucosa without intestinal metaplasia. Longer follow-up is needed to assess the long-term effects of endoscopic treatment of the Barrett's mucosa with thermal coagulation, and this procedure should still be considered under investigation.
Assuntos
Esôfago de Barrett/cirurgia , Eletrocoagulação/métodos , Fundoplicatura , Adolescente , Esôfago de Barrett/patologia , Biópsia por Agulha , Terapia Combinada , Endoscopia/métodos , Feminino , Seguimentos , Humanos , Mucosa/patologia , Mucosa/cirurgia , Indução de RemissãoRESUMO
Cannabis is widely used for treating a number of gastrointestinal ailments, but its use is associated with several adverse effects, particularly when the route of administration is via smoking. In the present study, we tested the effects (in rats) of a simple extract of medicinal cannabis (called "MFF") for its ability to promote resolution of colitis, to prevent gastric damage induced by naproxen, and to reduce gastric distention-induced visceral pain. Intracolonic, but not oral administration of MFF dose-dependently reduced the severity of hapten-induced colitis, an effect not reduced by pretreatment with antagonists of CB1 or CB2 receptors. Significant improvement of symptoms (diarrhea, weight loss) and healing of ulcerated tissue was evident with MFF treatment at doses that did not produce detectable urinary levels of 9-Δ-tetrahydrocannabinol (THC). MFF increased colonic hydrogen sulfide synthesis in healthy rats, but not in rats with colitis, and had no effect on colonic prostaglandin E2 synthesis. Orally, but not systemically administered MFF dose-dependently reduced the severity of naproxen-induced gastric damage, and a CB1 antagonist reversed this effect. MFF prevented gastric distention-induced visceral pain via a CB2-dependent mechanism. These results demonstrate that a simple extract of medicinal cannabis can significantly enhance resolution of inflammation and injury, as well as prevent injury, in the gastrointestinal tract. Interestingly, different cannabinoid receptors were involved in some of the effects. MFF may serve as the basis for a simple preparation of cannabis that would produce beneficial effects in the GI tract with reduced systemic toxicity.
Assuntos
Analgésicos/administração & dosagem , Cannabis , Colite/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Substâncias Protetoras/administração & dosagem , Úlcera Gástrica/tratamento farmacológico , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/efeitos adversos , Colite/metabolismo , Colite/patologia , Trato Gastrointestinal/efeitos dos fármacos , Sulfeto de Hidrogênio/metabolismo , Indóis/farmacologia , Masculino , Naproxeno/efeitos adversos , Piperidinas/farmacologia , Pirazóis/farmacologia , Ratos , Ratos Wistar , Receptor CB1 de Canabinoide/antagonistas & inibidores , Receptor CB1 de Canabinoide/metabolismo , Receptor CB2 de Canabinoide/antagonistas & inibidores , Receptor CB2 de Canabinoide/metabolismo , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/metabolismo , Dor Visceral/tratamento farmacológico , Dor Visceral/metabolismoRESUMO
Dextran sulfate sodium is widely used to induce colitis in rodents. Though given orally in drinking water, this agent is widely believed to produce injury through direct toxic effects on the epithelium, and it has been assumed to produce damage and inflammation only in the colon. Given the apparent toxic effects of dextran sodium sulfate on epithelial cells, its administration orally, and the anticoagulant properties of this agent, we hypothesized that significant damage and inflammation would be produced in regions of the digestive tract proximal to the colon. Groups of rats or mice received DSS (5%) in the drinking water for up to 7 days. Tissues were harvested at various time-points for blind evaluation of damage, and measurement of several markers of inflammation. In both rats and mice given DSS, significant damage and inflammation was produced in the stomach, small intestine and colon. Significant granulocyte infiltration was apparent in all tissues by day 3 of DSS ingestion. Bleeding was evident throughout the small intestine and colon. These studies clearly demonstrate that DSS, when administered orally in drinking water, produces a pan-gastroenteritis, rather than the damage and inflammation being limited to the colon. The damage and inflammation in the stomach and small intestine could contribute to changes in body weight, stool consistency and bleeding, all of which are commonly used as indices of severity of colitis. Beneficial or detrimental effects of therapeutic interventions could be attributable, at least in part, to modulation of injury and inflammation proximal to the colon.
Assuntos
Colite/induzido quimicamente , Sulfato de Dextrana/efeitos adversos , Gastroenterite/induzido quimicamente , Animais , Colite/patologia , Colo/efeitos dos fármacos , Colo/patologia , Gastroenterite/patologia , Hemorragia Gastrointestinal/induzido quimicamente , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Ratos , Ratos Wistar , Estômago/efeitos dos fármacos , Estômago/patologiaRESUMO
Pyoderma gangrenosum (PG) is a neutrophilic dermatosis of unknown etiology characterized by typical skin ulcers. It may be related to systemic disorders but its association with solid tumors is very unusual. In this setting, we describe a patient in whom PG was the first and isolated manifestation of advanced gastric adenocarcinoma.
Assuntos
Adenocarcinoma/complicações , Adenocarcinoma/diagnóstico , Pioderma Gangrenoso/complicações , Pioderma Gangrenoso/diagnóstico , Neoplasias Gástricas/complicações , Neoplasias Gástricas/diagnóstico , Adulto , Diagnóstico Diferencial , Evolução Fatal , Gastroscopia , Humanos , MasculinoRESUMO
Gastric mucosal lesions are frequently observed in patients with liver cirrhosis and portal hypertension. Similar lesions can be observed in experimental portal hypertension. This review summarizes our current knowledge of the pathophysiology of portal hypertensive gastropathy, with a particular focus on the microcirculatory disturbances that characterize this condition. The stomach of cirrhotic patients exhibits an increased susceptibility to injury induced by several irritants. Similarly, the stomach of portal hypertensive animals is less resistant to injury. One of the most important factors contributing to the increased susceptibility to damage is an impaired hyperemic response when the epithelium is exposed to irritants. This appears to be related to a reduction in mucosal prostaglandin production and to altered microcirculatory responsiveness to nitric oxide. Nitric oxide overproduction in portal hypertension may have direct effects on gastric blood flow regulation. Elevated production of tumor necrosis factor-alpha by gastric mucosa in portal hypertensive rats has also been shown to contribute to mucosal injury. A better understanding of the pathogenesis of portal hypertensive gastropathy may lead to development of specific therapeutic interventions for this condition.
Assuntos
Hipertensão Portal/complicações , Gastropatias/etiologia , Animais , Mucosa Gástrica/irrigação sanguínea , Mucosa Gástrica/metabolismo , Humanos , Hipertensão Portal/fisiopatologia , Cirrose Hepática/complicações , Cirrose Hepática/fisiopatologia , Cirrose Hepática Experimental/complicações , Cirrose Hepática Experimental/fisiopatologia , Óxido Nítrico/metabolismo , Prostaglandinas/metabolismo , Ratos , Gastropatias/fisiopatologia , Fator de Necrose Tumoral alfa/metabolismoRESUMO
OBJECTIVES: The most used therapeutic schedule to eradicate Helicobacter pylori is the "triple therapy," which is based on the simultaneous use of a bismuth salt and two antibiotics. Sucralfate, a basic aluminum salt of sucrose sulfate, is supposed to have an antibacterial activity and is said to reduce the bacterial density of H. pylori. This randomized, prospective clinical trial compares the efficacy of an alternative oral triple therapy consisting of sucralfate, tinidazol, and tetracycline with a conventional therapy using ranitidine, with respect to H. pylori eradication and duodenal ulcer healing and recurrence in a 12-month follow-up. METHODS: Forty-three patients with active duodenal ulcers diagnosed at endoscopy were enrolled to receive either 1 g of sucralfate four times daily for 30 days, 500 mg of tetracycline four times daily, and 500 mg of tinidazol three times daily, for 10 days (group A; n = 23) or 150 mg of ranitidine twice daily for 30 days (group B; n = 20). The groups were age- and sex-matched and balanced for tobacco use and H. pylori status. Compliance assessed by post-treatment interviews was considered high (all patients declared that they had ingested at least 80% of the drugs). RESULTS: Both therapies were efficient in healing ulcers (group A, 95%; group B, 90%), the relapse rates were high in both groups (group A, 77%; group B, 89%), and the alternative triple therapy eradicated H. pylori in only 4% of the patients. CONCLUSION: Alternative oral triple therapy presented no significant advantage over ranitidine treatment of active ulcer disease.
Assuntos
Úlcera Duodenal/microbiologia , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/isolamento & purificação , Sucralfato/uso terapêutico , Adulto , Esquema de Medicação , Quimioterapia Combinada , Úlcera Duodenal/tratamento farmacológico , Úlcera Duodenal/epidemiologia , Feminino , Seguimentos , Infecções por Helicobacter/epidemiologia , Humanos , Masculino , Prevalência , Ranitidina/uso terapêutico , Recidiva , Tetraciclina/uso terapêutico , Fatores de Tempo , Tinidazol/uso terapêuticoRESUMO
BACKGROUND/AIMS: The increased susceptibility of the stomach to injury observed in portal hypertension may be related to a defect in the hyperemic response to luminal irritants. The aim of this study was to evaluate the components that mediate this hyperemic response in a rat model of cirrhosis and portal hypertensive gastropathy. METHODS: Cirrhosis was induced by bile duct ligation, whereas controls underwent sham operation. Gastric blood flow responses to topical application of acid, capsaicin, nitrovasodilators, misoprostol, 8-bromo-cyclic guanosine monophosphate, and 8-bromo-cyclic adenosine monophosphate were measured by laser Doppler flowmetry using an ex vivo gastric chamber preparation. Calcitonin gene-related peptide immunoreactivity was used as an index of the anatomic integrity of the sensory afferent neurons of the stomach. RESULTS: Blood flow responses to acid, capsaicin, nitrovasodilators, and 8-bromo-cyclic guanosine monophosphate were significantly depressed in cirrhotic rats, whereas they were augmented after topical application of misoprostol and 8-bromo-cyclic adenosine monophosphate. Calcitonin gene-related peptide immunoreactivity was similar in the stomachs of cirrhotic and control rats. CONCLUSIONS: Gastric vasodilation after stimulation of sensory afferent neurons is impaired in cirrhotic rats despite the normal anatomic distribution of these nerves. This effect seemed to be related to a depressed response of the gastric microcirculation to cyclic guanosine monophosphate-dependent vasodilators. This alteration may contribute to the increased susceptibility to gastric ulceration in cirrhotics.
Assuntos
Cirrose Hepática Biliar/fisiopatologia , Estômago/irrigação sanguínea , Vasodilatação , 8-Bromo Monofosfato de Adenosina Cíclica/farmacologia , Anestesia , Animais , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Capsaicina/farmacologia , GMP Cíclico/análogos & derivados , GMP Cíclico/farmacologia , Modelos Animais de Doenças , Hiperemia/etiologia , Hipertensão Portal/complicações , Fluxometria por Laser-Doppler , Cirrose Hepática Biliar/etiologia , Cirrose Hepática Biliar/metabolismo , Masculino , Microcirculação/efeitos dos fármacos , Microcirculação/fisiopatologia , Misoprostol/farmacologia , Neurônios Aferentes/fisiologia , Nitroprussiato/farmacologia , Ratos , Ratos Sprague-Dawley , Estômago/inervação , Vasodilatação/efeitos dos fármacosRESUMO
Cirrhotic rats exhibit increased susceptibility to ethanol-induced gastric damage, but the underlying mechanism for this phenomenon remains unclear. Abnormalities of the gastric microcirculation have been reported that may contribute to the increased susceptibility to damage. Decreased gastric synthesis of prostaglandins also likely contributes to impaired mucosal defense in cirrhotic rats. Tumor necrosis factor-alpha (TNF-alpha) has been implicated in mucosal injury, and its synthesis can be inhibited by prostaglandins. Therefore, we hypothesized that TNF-alpha synthesis/ release is altered in cirrhotic rats and plays a role in the pathogenesis of ethanol-induced gastric damage. Cirrhosis was induced by bile duct ligation, whereas controls had sham operations. Topical application of 40% ethanol caused four times as much damage in cirrhotic rats than in controls. Basal plasma TNF-alpha levels did not differ between control and cirrhotic rats, although cirrhotic rats exhibited significantly higher levels of gastric TNF-alpha mRNA. Plasma TNF-alpha increased significantly in control and cirrhotic rats after ethanol administration. Inhibition of TNF-alpha synthesis/release with pentoxifylline, thalidomide, dexamethasone, or immunoneutralization of TNF-alpha (with anti-TNF-alpha) was found to significantly reduce the severity of ethanol-induced gastric mucosal damage in cirrhotic rats. We conclude that TNF-alpha contributes to the pathogenesis of ethanol-induced gastric damage in cirrhotic rats.
Assuntos
Etanol , Cirrose Hepática Experimental/fisiopatologia , Gastropatias/induzido quimicamente , Fator de Necrose Tumoral alfa/fisiologia , Animais , Etanol/farmacologia , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Soros Imunes , Masculino , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/genéticaRESUMO
BACKGROUND: Management of Barrett's esophagus requires reduction of gastric acid secretion and screening for the development of adenocarcinoma. However, the current therapeutic options are ineffective in reducing the Barrett's mucosa. The aim of this study was to evaluate the effectiveness of endoscopic thermal coagulation of Barrett's mucosa as an alternative therapeutic approach and the recurrence of the disease in the long term. METHODS: Fourteen patients (11 men, 3 women; mean age 45.7 years) with Barrett's esophagus participated in the study. They underwent laparoscopic fundoplication and were symptom free with no defective fundoplication wraps before therapeutic endoscopy. Endoscopic thermocoagulation was performed with a flexible videoendoscope and a bipolar probe. Mucosal areas were treated once a month until the Barrett's mucosa disappeared. Endoscopy was performed 1 and 7 months after completion of the treatments and once a year thereafter. RESULTS: The mean follow-up period was 21.6 months (range 18 to 30 months). The mean length of Barrett's esophagus was 4.8 cm. Successful ablation of the columnar epithelium was achieved in 3.7 sessions, as defined by demonstration of normal squamous epithelium at histologic examination of biopsy samples collected after completion of the treatments and at follow-up evaluations. Three patients experienced short-term (10 days) odynophagia or dysphagia. All patients were symptom free with no evidence of Barrett's esophagus at the end of the study. CONCLUSIONS: Bipolar electrocoagulation after antireflux operations is effective in promoting regression of Barrett's esophagus and has few complications. Endoscopic thermal coagulation might reduce risk for adenocarcinoma among these patients.
Assuntos
Esôfago de Barrett/cirurgia , Eletrocoagulação , Endoscopia , Esofagite Péptica/cirurgia , Esofagoscopia , Fundoplicatura , Laparoscopia , Adolescente , Adulto , Idoso , Esôfago de Barrett/patologia , Biópsia , Epitélio/patologia , Esofagite Péptica/patologia , Esôfago/patologia , Esôfago/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Reoperação , Resultado do TratamentoRESUMO
AIMS: To evaluate plasma hydroxy-metronidazole/metronidazole ratio as a dynamic liver function test in HCV-infected individuals with/without liver disease, in the absence of liver cirrhosis. METHODS: Metronidazole was administered intravenously in healthy volunteers, asymptomatic anti-HCV-positive blood donors, and in chronic hepatitis C patients. Serology to HCV was determined by a second generation assay and confirmed by gelatin particle agglutination test using recombinant antigens C22-3 and C200. Plasma concentration of metronidazole and hydroxy-metronidazole was measured by high performance liquid chromatography in samples collected 5, 10, 20 and 30 min following the end of metronidazole infusion. RESULTS: Chronic hepatitis C patients had abnormal liver enzymes, while healthy volunteers and anti-HCV-positive blood donors had normal liver biochemistry tests. Plasma metronidazole concentration was similar in all groups studied. Plasma hydroxy-metronidazole/metronidazole ratio was significantly reduced in HCV-infected subjects, an effect observed 10 min after the end of drug infusion. CONCLUSIONS: Metronidazole clearance is impaired in anti-HCV-positive blood donors and chronic hepatitis C patients, indicating that HCV is capable of affecting liver function at early stages of the disease. The metronidazole clearance test can detect impaired liver function in HCV-infected individuals even in the absence of liver cirrhosis.
Assuntos
Hepacivirus , Hepatite C/sangue , Fígado/metabolismo , Metronidazol , Adulto , Feminino , Hepacivirus/imunologia , Hepatite C/diagnóstico , Hepatite C/imunologia , Humanos , Testes de Função Hepática , Masculino , Metronidazol/sangue , Metronidazol/metabolismo , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To evaluate the efficacy of two commonly employed treatments for Helicobacter pylori infection and the impact of bacterial resistance to antibiotics on eradication rate. METHODS: Ninety-two consecutive H. pylori-positive patients with active peptic ulcer disease were randomly enrolled to receive a 7-day treatment with either lansoprazole 30 mg plus amoxicillin 1 g and clarithromycin 500 mg [all twice a day (b.i.d.), Group A, n = 46]; or bismuth subcitrate 125 mg four times a day (q.i.d.) plus tetracycline 500 mg q.i.d and furazolidone 200 mg b.i.d. (Group B, n = 46) H. pylori status was reassessed 30 days after completion of the therapy and bacterial resistance to the antibiotics was investigated using an in vitro assay. RESULTS: Five patients from each study group were lost to follow up. Both treatments resulted in similar H. pylori eradication rate: 66-60% (per protocol), 59-52% (intention-to-treat) in Groups A and B, respectively (non significant). However, eradication improved to 79% in the absence of H. pylori resistance to clarithromycin or amoxicillin. CONCLUSION: Primary resistance to clarithromycin or amoxicillin may underscore a potentially serious problem for the eradication of H. pylori infection. Testing for bacterial resistance may become necessary to improve therapeutic efficacy.
Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Úlcera Péptica/tratamento farmacológico , Adulto , Idoso , Antibacterianos/uso terapêutico , Quimioterapia Combinada , Feminino , Infecções por Helicobacter/microbiologia , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Úlcera Péptica/microbiologia , Falha de TratamentoRESUMO
Metronidazole pharmacokinetics were studied in patients with different degrees of liver cirrhosis, classified according to the Child-Pugh algorithm (A, B or C, as liver disease severity increases) and in schistosomic patients. Metronidazole (500 mg) was administered i.v. as a slow infusion over 20 min, and blood samples were collected at set intervals after the end of the infusion. The plasma concentrations of metronidazole and its main metabolite hydroxy-metronidazole were quantified by reversed-phase h.p.l.c. with u.v. detection. The metronidazole and hydroxy-metronidazole areas under the curve from 0 to 24 h (AUC0,24h), the metronidazole terminal elimination half-life (t1/2), the total clearance (CL), the metronidazole volume of distribution (V) values and the hydroxy-metronidazole/metronidazole concentration ratios as a function of time were calculated for each group. Comparison of the metronidazole AUC0,24h, t1/2 and CL values revealed that metronidazole metabolism is progressively impaired as the severity of liver disease increases. There were no variations in these parameters between the schistosomic and Child-Pugh A groups. In addition, there were no differences in the V and hydroxy-metronidazole AUC0,24h among the various groups studied. However, metronidazole metabolism was delayed in patients with hepatic disease, as illustrated by the hydroxy-metronidazole/metronidazole ratio 10 min after the end of metronidazole infusion. These results indicate that the clinical assessment of liver disease is paralleled by an impairment of metronidazole metabolism. Of the studied variables, we propose the hydroxy-metronidazole/metronidazole ratio 10 min after metronidazole infusion as a suitable and practical index for liver function evaluation.