RESUMO
GOALS: The aim was to systematically evaluate risks and benefits of proton pump inhibitor (PPI) use for stress ulcer prophylaxis in the critically ill patient. BACKGROUND: Whether PPIs increase mortality in the critically ill patient remains controversial. STUDY: Systematic review and meta-analysis of randomized controlled trials (RCTs) and cohort studies with trial sequential analysis, Bayesian sensitivity analysis, and fragility index analysis. RESULTS: A total of 31 studies in 78,009 critically ill adults receiving PPIs versus any comparator were included. PPI use was associated with an increased mortality risk in all studies [19.6% PPI vs. 17.5% comparator; RR: 1.10; 95% confidence interval (CI): 1.02-1.20; P =0.01], in the subgroup of RCTs (19.4% vs. 18.7%; RR: 1.05; 95% CI: 1.0-1.09, P =0.04), but not cohort studies (19.9% vs. 16.7%; RR: 1.12; 95% CI: 0.98-1.28, P =0.09). Results were maintained with a Bayesian sensitivity analysis (RR: 1.13; 95% credible interval: 1.035-1.227) and a fragility index analysis, but not sequential analysis ( P =0.16). RCTs with a higher baseline severity of illness revealed the greatest mortality risk with PPI use (32.1% PPI vs. 29.4% comparator; RR: 1.09; 95% CI: 1.04-1.14; P <0.001). PPI use reduced clinically important bleeding in RCTs (1.4% PPI vs. 2.1% comparator; RR: 0.67; 95% CI: 0.5-0.9; P =0.009) but increased bleeding in cohort studies (2.7% PPI vs. 1.2% comparator; RR: 2.05; 95% CI: 1.2-3.52; P =0.009). PPI use was not associated with a lower incidence of clinically important bleeding when compared with histamine-2 receptor antagonists (1.3% vs. 1.9%; RR: 0.59; 95% CI: 0.28-1.25, P =0.09). CONCLUSIONS: This meta-analysis demonstrated an association between PPI use and an increased risk of mortality.
Assuntos
Úlcera Péptica , Úlcera , Adulto , Humanos , Úlcera/complicações , Úlcera/tratamento farmacológico , Inibidores da Bomba de Prótons/efeitos adversos , Estado Terminal , Úlcera Péptica/induzido quimicamente , Úlcera Péptica/prevenção & controle , Úlcera Péptica/complicações , Unidades de Terapia IntensivaAssuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Úlcera Péptica/prevenção & controle , Doenças Cardiovasculares/prevenção & controle , Inibidores da Bomba de Prótons/administração & dosagem , Pantoprazol/administração & dosagem , Hemorragia Gastrointestinal/prevenção & controle , Anticoagulantes/efeitos adversos , Úlcera Péptica/induzido quimicamente , Úlcera Péptica/epidemiologia , Esquema de Medicação , Ensaios Clínicos Controlados Aleatórios como Assunto , Aspirina/administração & dosagem , Aspirina/efeitos adversos , Método Duplo-Cego , Administração Oral , Estudos Multicêntricos como Assunto , Resultado do Tratamento , Relação Dose-Resposta a Droga , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Rivaroxabana/administração & dosagem , Rivaroxabana/efeitos adversos , Hemorragia Gastrointestinal/induzido quimicamente , Hemorragia Gastrointestinal/epidemiologia , Anticoagulantes/administração & dosagemRESUMO
BACKGROUND: Aspirin is one of the most used drugs around the Word, it has wide therapeutic indications. From its original indications, as analgesic and anti-inflammatory and due to its platelet antiaggregate properties, this drug has become in the most employed medicine to prevent cardiovascular disease. Never the less, it is a drug with adverse effects and gastrointestinal toxicity indeed. OBJECTIVES: To identify the reasons of using aspirin, endoscopic findings on gastropathy caused by ASA and the relative risk of developing mucosal lesions. This based on a sample of adult patients in a chosen particular institution. MATERIALS AND METHODS: Prospective study of cases and controls, from January 1 to June 31, 2014, with patients with high digestive endoscopy. In the medical center Endocentro Bogotá D.C. it was selected the people with aspirin consumption on 500 mg per day dose or less taken for more than six months prior the endoscopy. RESULTS: We selected 602 patients, 534 (88%) were women and 168 (12%) were men, with an age range from 17 to 92 years and with an average of 51.8 years. 107 patients were the aspirin users, 59 (55%) were women and 48 (45%) were men, with an range from 23 to 85 years and with an average of 58 years. The follow relative risks were found: gastroduodenal erosions RR=4.9 (95%IC 3.87-8.37), gastric ulcer RR=2.4 (95%IC 1.3-9.0), duodenal ulcer RR=2.8 (95%IC 1.3-7.0) any kind of gastrointestinal injury RR=5.5 (95%IC 4.1-7.2) aspirin users without any indication to the risk of develop any mucosa injury RR=2.0 (95%IC 1.4-3.0). CONCLUSIONS: This study showed an important proportion (18%) of dispatched aspirin users adults to digestive endoscopy, the 13.8% of them have a clear indication to use it, a substantial percent (13%) cannot inform any medical reason; the aspirin usage for more than six months in doses lower than 500 mg per day increases the mucosal gastroduodenal injury prevalence (58%)and relative risk of suffering these injuries are high.
Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Aspirina/efeitos adversos , Duodeno/efeitos dos fármacos , Mucosa Gástrica/efeitos dos fármacos , Conhecimentos, Atitudes e Prática em Saúde , Úlcera Péptica/induzido quimicamente , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Colômbia , Duodeno/diagnóstico por imagem , Duodeno/patologia , Endoscopia Gastrointestinal , Feminino , Mucosa Gástrica/diagnóstico por imagem , Mucosa Gástrica/patologia , Humanos , Mucosa Intestinal/diagnóstico por imagem , Mucosa Intestinal/patologia , Masculino , Pessoa de Meia-Idade , Úlcera Péptica/diagnóstico por imagem , Úlcera Péptica/patologia , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Adulto JovemRESUMO
BACKGROUND: Peptic ulcer etiology has been changing because of H. pylori decline. OBJECTIVES: To estimate peptic ulcer prevalence in 10 years-interval and compare the association with H. pylori and use of non-steroidal anti-inflammatory drugs. Methods Records assessment in two periods: A (1997-2000) and B (2007-2010), searching for peptic ulcer, H. pylori infection and non-steroidal anti-inflammatory drugs use. RESULTS: Peptic ulcer occurred in 30.35% in A and in 20.19% in B. H. pylori infection occurred in 73.3% cases in A and in 46.4% in B. Non-steroidal anti-inflammatory drugs use was 3.5% in A and 13.3% in B. Neither condition occurred in 10.4% and 20.5% in A and B respectively. Comparing both periods, we observed reduction of peptic ulcer associated to H. pylori (P=0.000), increase of peptic ulcer related to non-steroidal anti-inflammatory drugs (P=0.000) and idiopathic peptic ulcer (P=0.002). The concurrent association of H. pylori and non-steroidal anti-inflammatory drugs was also higher in B (P=0.002). Rates of gastric ulcer were higher and duodenal ulcer lower in the second period. CONCLUSIONS: After 10 years, the prevalence of peptic ulcer decreased, as well as ulcers related to H. pylori whereas ulcers associated to non-steroidal anti-inflammatory drugs increased. There was an inversion in the pattern of gastric and duodenal ulcer and a rise of idiopathic peptic ulcer.
Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Infecções por Helicobacter/complicações , Helicobacter pylori , Úlcera Péptica/induzido quimicamente , Úlcera Péptica/microbiologia , Brasil/epidemiologia , Estudos Transversais , Infecções por Helicobacter/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Úlcera Péptica/epidemiologia , Prevalência , Fatores de RiscoRESUMO
Background Peptic ulcer etiology has been changing because of H. pylori decline. Objectives To estimate peptic ulcer prevalence in 10 years-interval and compare the association with H. pylori and use of non-steroidal anti-inflammatory drugs. Methods Records assessment in two periods: A (1997-2000) and B (2007-2010), searching for peptic ulcer, H. pylori infection and non-steroidal anti-inflammatory drugs use. Results Peptic ulcer occurred in 30.35% in A and in 20.19% in B. H. pylori infection occurred in 73.3% cases in A and in 46.4% in B. Non-steroidal anti-inflammatory drugs use was 3.5% in A and 13.3% in B. Neither condition occurred in 10.4% and 20.5% in A and B respectively. Comparing both periods, we observed reduction of peptic ulcer associated to H. pylori (P=0.000), increase of peptic ulcer related to non-steroidal anti-inflammatory drugs (P=0.000) and idiopathic peptic ulcer (P=0.002). The concurrent association of H. pylori and non-steroidal anti-inflammatory drugs was also higher in B (P=0.002). Rates of gastric ulcer were higher and duodenal ulcer lower in the second period. Conclusions After 10 years, the prevalence of peptic ulcer decreased, as well as ulcers related to H. pylori whereas ulcers associated to non-steroidal anti-inflammatory drugs increased. There was an inversion in the pattern of gastric and duodenal ulcer and a rise of idiopathic peptic ulcer. .
Contexto A etiologia da úcera péptica vem apresentando mudanças devido à redução da infecção pelo H. pylori. Objetivos Estimar a prevalência da úlcera péptica em dois períodos com intervalo de 10 anos e comparar a associação com a infecção pelo H. pylori com o uso de anti-inflamatórios não esteroides. Métodos Revisão de prontuários em dois períodos: A (1997-2000) e B (2007-2010), com busca por úlcera péptica, H. pylori e uso de anti-inflamatórios não esteroides (AINE). Resultados Úcera péptica apresentou frequência de 30,35% em A e 20,19% em B. Infecção por H. pylori ocorreu em 73,3% em A e em 46,4% em B. Uso de anti-inflamatórios não esteroides ocorreu em 3,5% em A e em 13,3% em B. Nenhuma dessas condições esteve associada em 10,4% e 20,5% das úlceras em A e B, respectivamente. Comparando os dois períodos, houve redução da úlcera péptica associada à H. pylori (P=0,000), aumento das úlceras associadas ao uso de anti-inflamatórios não esteroides (P=0,000) e aumento de úlceras idiopáticas (P=0,002). A associação concomitante de H. pylori e anti-inflamatórios não esteroides foi também mais alta em B (P=0,002). Úlceras gástricas aumentaram e úlceras duodenais diminuíram em B. Conclusões No intervalo de 10 anos, a prevalência de úlcera péptica diminuiu assim como as úlceras relacionadas com H. pylori e houve um aumento das úlceras associadas ao uso de anti-inflamatórios não esteroides. Houve inversão na frequência das lesões gástricas e duodenais e aumento da prevalência da úlcera idiopática. .
Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Anti-Inflamatórios não Esteroides/efeitos adversos , Helicobacter pylori , Infecções por Helicobacter/complicações , Úlcera Péptica/induzido quimicamente , Úlcera Péptica/microbiologia , Brasil/epidemiologia , Estudos Transversais , Infecções por Helicobacter/epidemiologia , Prevalência , Úlcera Péptica/epidemiologia , Fatores de RiscoRESUMO
OBJECTIVES: The objective of this work was to investigate the antiulcerogenic and anti-inflammatory activities of the essential oil from Pterodon emarginatus seeds. METHODS: The following tests were used: ulcers induced by ethanol, indometacin and HCl/ethanol, and pleurisy induced by carrageenan in Swiss albino rats. The rats were treated by the oral route with essential oil of P. emarginatus seeds. KEY FINDINGS: The essential oil at 100, 300 and 500 mg/kg exhibited significant protection against ulcers induced by ethanol, indometacin and HCl/ethanol (P < 0.001). The essential oil caused a marked reduction in the exudate volume and inhibited leucocyte and neutrophil influx (P < 0.05) in carrageenan-induced pleurisy. Moreover, the essential oil significantly decreased nitric oxide (NO) and interleukin-1 (IL-1) levels, without affecting tumour necrosis factor-alpha production. CONCLUSIONS: The results demonstrated the marked antiulcerogenic and anti-inflammatory effects of the essential oil from P. emarginatus, which are, at least in part, a consequence of NO and IL-1 modulation. P. emarginatus or its constituents might represent new therapeutic options to treat gastric ulcers and inflammatory diseases.
Assuntos
Anti-Inflamatórios/uso terapêutico , Antiulcerosos/uso terapêutico , Etanol/toxicidade , Fabaceae/química , Óleos Voláteis/química , Administração Oral , Alquil e Aril Transferases/química , Alquil e Aril Transferases/farmacologia , Alquil e Aril Transferases/uso terapêutico , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Antiulcerosos/química , Antiulcerosos/farmacologia , Brasil , Carragenina/toxicidade , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Etanol/antagonistas & inibidores , Indometacina/toxicidade , Interleucina-1alfa/antagonistas & inibidores , Interleucina-1alfa/metabolismo , Masculino , Medicina Tradicional , Camundongos , Sesquiterpenos Monocíclicos , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/metabolismo , Óleos Voláteis/isolamento & purificação , Óleos Voláteis/farmacologia , Óleos Voláteis/uso terapêutico , Omeprazol/farmacologia , Omeprazol/uso terapêutico , Úlcera Péptica/induzido quimicamente , Pleurisia/induzido quimicamente , Sesquiterpenos Policíclicos , Ranitidina/farmacologia , Ranitidina/uso terapêutico , Sementes/química , Sesquiterpenos/química , Sesquiterpenos/farmacologia , Sesquiterpenos/uso terapêutico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/metabolismoRESUMO
The aim of the present study is to investigate the antiulcerogenic effects of the essential oil (EO) of Croton cajucara Benth in rats fed with a normal protein (NP) and low-protein diet (MN). NP and MN rats were treated with the essential oil for 15 days after chronic ulceration was induced. The EO accelerated healing of acetic acid-induced gastric lesions in NP and MN rats (p<0.05). In a similar experiment on chronic ulceration, Epidermal Growth Factor (EGF) mRNA expression increased in NP rats but not in MN rats. In assays of acute antiulcerogenic activity, C. cajucara increased somatostatin plasma levels and decreased gastrin plasma levels in both animal groups. The EO significantly prevented ethanol-induced gastric ulcers in NP and MN rats (p<0.001). Histological examination showed initial regeneration, formation of inflammatory infiltrate and angiogenesis in the epithelium surface of acetic acid-induced ulcers in NP and MN rats. C. cajucara prevented gastric lesions in both animal groups when ethanol methodology was used. We concluded that the EO showed an antiulcerogenic activity mediated by increased somatostatin secretion and EGF mRNA expression.
Assuntos
Antiulcerosos/farmacologia , Croton/química , Desnutrição/complicações , Ácido Acético/toxicidade , Animais , Sequência de Bases , Primers do DNA , Proteínas Alimentares/administração & dosagem , Fator de Crescimento Epidérmico/genética , Feminino , Gastrinas/sangue , Úlcera Péptica/induzido quimicamente , Úlcera Péptica/complicações , Úlcera Péptica/prevenção & controle , RNA Mensageiro/genética , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Somatostatina/sangueRESUMO
OBJECTIVES: This study examined the association between exposure to nonselective NSAIDs and hospitalization for peptic ulcer disease (PUD) among older adults in Argentina. METHODS: This was a case-control study based on the medical records of 5 hospitals in Buenos Aires. Cases were patients aged > or =50 years and hospitalized with PUD between 1997 and 2002 who were identified by mode of presentation (acute abdominal pain, vomiting, hematemesis, melena, shock, and asymptomatic anemia, or admission for an unknown reason and a discharge diagnosis related to upper gastrointestinal complications). Controls were hospitalized patients without PUD and were matched to cases (1:1) by age, sex, and admission date. NSAID exposure was defined as the use of NSAIDs during the year before admission. Conditional logistic regression analysis was used to examine the association between exposure to nonselective NSAIDs and hospitalizations for PUD, after adjusting for predictors. Subgroup analyses were conducted on patients with severe PUD, moderate PUD, and those whose PUD was confirmed by endoscopy. RESULTS: The study included 324 cases and 324 matched controls. The mean patient age was 74 years. The discharge diagnoses indicated severe PUD in 46.3% (150/324), moderate PUD in 49.4% (160/324), and mild PUD in 4.3% (14/324) of cases. NSAID exposure was associated with an increased risk of hospitalization for PUD (odds ratio [OR], 5.20; 95% CI, 3.31-8.15). Risk was also increased for severe PUD (OR, 4.24; 95% CI, 2.29-7.87) and moderate PUD (OR, 6.08; 95% CI, 3.09-11.96). A history of upper gastrointestinal complications was independently associated with hospitalization for PUD (OR, 14.62; 95% CI, 6.70-31.91). CONCLUSIONS: Use of nonselective NSAIDs is a significant risk factor for PUD-related hospitalizations among older adults in Argentina. The magnitude of the risk ratio resembles that reported for developed countries.
Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Hospitalização/estatística & dados numéricos , Úlcera Péptica/induzido quimicamente , Fatores Etários , Idoso , Anti-Inflamatórios não Esteroides/administração & dosagem , Argentina/epidemiologia , Estudos de Casos e Controles , Doença Crônica , Comorbidade , Uso de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , RiscoAssuntos
Úlcera Péptica/tratamento farmacológico , Úlcera Péptica/microbiologia , Anti-Inflamatórios não Esteroides/efeitos adversos , Ásia/epidemiologia , Austrália/epidemiologia , Reações Falso-Negativas , Helicobacter pylori , Humanos , Úlcera Péptica/induzido quimicamente , Estados Unidos/epidemiologiaRESUMO
Nonsteroidal anti-inflammatory drug (NSAID) use is associated with both upper and lower gastrointestinal tract complications in 1 to 2% of patients using these drugs for 6 to 12 months. Gastroduodenal ulcers are also present in 30 to 50% of patients using NSAID. Dyspepsia is another frequent side effect that may or may not be associated with mucosal lesions. Main risk factors for NSAID-associated gastrointestinal complications include age > 60 years, ulcer history, high dose of NSAID, and concomitant use of anticoagulants, aspirin, or corticosteroids. Patients with risk factors that need NSAIDs should receive gastroprotection with proton pump inhibitors or misoprostol. Another gastrointestinal safer option is use of COX-2 selective NSAIDs (coxibs). Increased cardiovascular risk observed with long-term use of rofecoxib should be compared with other COX-2 selective and non-selective NSAID. In patients at very high risk, co-prescription of coxib with proton pump inhibitors has been recommended. In patients at risk, all these strategies are cost-effective.
Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Úlcera Péptica/induzido quimicamente , Úlcera Péptica/prevenção & controle , Antiulcerosos/uso terapêutico , Inibidores de Ciclo-Oxigenase/uso terapêutico , Humanos , Inibidores da Bomba de Prótons , Fatores de RiscoRESUMO
The aim of this work was to evaluate markers of oxidative stress in ethanol-induced gastric ulcers and the protective antioxidant activity in-vivo of Artemisia douglasiana Besser extracts in ethanol-treated rats. Ethanol-induced oxidative damage is believed to be associated with generation of reactive oxygen molecules, which leads to oxidative stress. A. douglasiana is used in folk medicine as a cytoprotective agent against peptic ulcer. Different bioassays were performed: in-vivo stomach chemiluminescence, tert-butyl hydroperoxide initiated chemiluminescence (in-vitro chemiluminescence), total antioxidant capacity (TRAP) and catalase, superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity in stomach homogenates. When ethanol (3 g kg(-1)) was administered, the in-vivo chemiluminescence increased by 107%, in-vitro chemiluminescence by 108%, SOD by 130% (P < 0.001), and catalase and TRAP decreased by 43 and 59% (P < 0.05 and 0.001, respectively). A. douglasiana (400 mg kg(-1)) pretreatment decreased in-vivo chemiluminescence by 41% (P < 0.05), in-vitro chemiluminescence by 66% (P < 0.001) and SOD by 56% (P < 0.001) and increased catalase by 14% and TRAP by 168% (P < 0.001, respectively) but GPx activity was not significantly different from the ethanol group. These results illustrate the significant antioxidant activity of A. douglasiana extract in-vivo and in-vitro.
Assuntos
Antiulcerosos/farmacologia , Antioxidantes/farmacologia , Artemisia , Úlcera Péptica/metabolismo , Fitoterapia , Extratos Vegetais/farmacologia , Animais , Antiulcerosos/administração & dosagem , Antiulcerosos/uso terapêutico , Antioxidantes/administração & dosagem , Antioxidantes/uso terapêutico , Etanol , Feminino , Medições Luminescentes , Estresse Oxidativo , Úlcera Péptica/induzido quimicamente , Úlcera Péptica/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Extratos Vegetais/uso terapêutico , Folhas de Planta , Ratos , Ratos WistarRESUMO
Oral administration of tenoxicam or zinc-tenoxicam complex inhibited to a similar extent carrageenin-induced paw oedema and granulomatous tissue formation in rats as well as the acetic acid induced writhing response in mice. Gastric lesions induced by oral administration of zinc-tenoxicam were reduced in number and severity when compared with those induced by tenoxicam or the co-administration of tenoxicam and zinc acetate. However, after intraperitoneal administration, both zinc-tenoxicam and tenoxicam plus zinc acetate induced a reduced number of gastric lesions as compared with tenoxicam.
Assuntos
Anti-Inflamatórios não Esteroides/toxicidade , Edema/induzido quimicamente , Úlcera Péptica/induzido quimicamente , Piroxicam/análogos & derivados , Piroxicam/toxicidade , Acetato de Zinco/uso terapêutico , Animais , Anti-Inflamatórios não Esteroides/antagonistas & inibidores , Carragenina , Edema/prevenção & controle , Masculino , Camundongos , Úlcera Péptica/prevenção & controle , Piroxicam/antagonistas & inibidores , Ratos , Ratos WistarRESUMO
Davilla rugosa Poiret ("Cipó- Caboclo") is commonly used in Brazilian folk medicine. The hydroalcoholic extract of the stems (HE) was fractionated with chloroform (CF), chloroform/ethyl acetate (CAF), ethyl acetate (AF), ethyl acetate/ethanol (AEF), ethanol (EF), and ethanol/water (EWF). The hydroalcoholic extract (HE) and fractions of the stems of D. rugosa Poiret were investigated for possible anti gastric ulcer properties. These extracts were shown to protect rats from developing gastric ulcers induced by two acute models: HCl/ethanol (400 mg/kg i.p.) and immersion-restraint stress (15 and 30 mg/kg of the HE and 15 mg/kg either of the ethanol or the ethanol/water fractions, p.o.). The daily oral dose of 800 mg/kg of HE for 30 consecutive days was tested for possible toxic effects. There were no modifications in body weight, water or food intake or in the external aspect of kidneys, spleen, lungs and liver. The only difference observed was a decrease of liver weight. These results suggest that the D. rugosa Poiret HE has an antiulcer activity in rats and the active components are in the two more polar fractions.
Assuntos
Antiulcerosos/uso terapêutico , Úlcera Péptica/prevenção & controle , Extratos Vegetais/uso terapêutico , Ácido Acético/toxicidade , Análise de Variância , Animais , Antiulcerosos/isolamento & purificação , Peso Corporal/efeitos dos fármacos , Brasil , Cimetidina/uso terapêutico , Etanol/toxicidade , Feminino , Masculino , Tamanho do Órgão/efeitos dos fármacos , Úlcera Péptica/induzido quimicamente , Úlcera Péptica/etiologia , Extratos Vegetais/isolamento & purificação , Ratos , Ratos Wistar , Estresse PsicológicoRESUMO
Aparisthmium cordatum (Juss.) Bail. (Euphorbiaceae), known in the State of Pará, Brazil as "ariquena queimosa", is a medium-sized tree which is native to the North Brazilian coastal region. Previous phytochemical studies of the bark of A. cordatum yielded a furan diterpenoid with a clerodane skeleton, called aparisthman. Recently, we reported the antiulcerogenic activity of trans-dehydrocrotonin (DHC), a furan diterpene isolated from Croton cajucara bark, in different ulcerogenic models in mice and rats. The aim of the present study was to assess the possible antiulcerogenic activity of aparisthman. When previously administered (p.o.) at the dose of 100 mg/kg(-1), aparisthman reduced significantly (p < 0.01) gastric injury induced by the indomethacin/bethanechol (71%), ethanol (71%), pylorus ligature, (59%) and hypothermic restraint-stress models (50%), in mice and rats. In the HCl/ethanol-induced gastric ulcer model in mice, at oral doses of 100 and 250 mg/kg(-1), aparisthman from A. cordatum reduced significantly (p < 0.001) the formation of gastric lesions by 59% and 66%, respectively, as compared with control. In the pylorus-ligature model, aparisthman (p.o.) decreased the volume of gastric juice as compared with control (p < 0.001). When aparisthman (100 mg/kg(-1)) was administered intraduodenally to mice, significant modifications were found, such as a decrease in gastric acidity as compared with control. In the animals pre-treated with aparisthman, free mucus production increased by 19% in the gastric mucosa (p < 0.05). The results suggest that aparisthman from A. cordatum presents a significant anti-ulcer effect when assessed in these induced ulcer models. Although the mechanism underlying this antiulcerogenic effect remains unknown, it seems to be related to an increase of the defensive mechanisms of the stomach such as prostaglandin synthesis and mucus production. The good yield of aparisthman obtained from A. cordatum, as well as its antiulcerogenic activity, suggest that this compound should be submitted to pharmacological research as a potential new antiulcerogenic drug.
Assuntos
Antiulcerosos/farmacologia , Diterpenos/farmacologia , Diterpenos/uso terapêutico , Euphorbiaceae/química , Mucosa Gástrica/efeitos dos fármacos , Úlcera Péptica/prevenção & controle , Árvores/química , 2-Piridinilmetilsulfinilbenzimidazóis , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Brasil , Cimetidina/farmacologia , Modelos Animais de Doenças , Diterpenos/química , Diterpenos/isolamento & purificação , Feminino , Ácido Gástrico/metabolismo , Determinação da Acidez Gástrica , Suco Gástrico/metabolismo , Mucosa Gástrica/metabolismo , Indometacina/farmacologia , Lansoprazol , Masculino , Camundongos , Omeprazol/análogos & derivados , Omeprazol/farmacologia , Úlcera Péptica/induzido quimicamente , Extratos Vegetais/farmacologia , Ratos , Ratos WistarRESUMO
The aim of the present work was to study in vivo COX-2-COX-1 selectivity of 16 nonsteroidal anti-inflammatory drugs (NSAIDs) in equipotent ulcerogenic doses in two in vivo experimental models. Indomethacin, ibuprofen, nimesulide, aceclofenac, aspirin, sodium diclofenac, meloxicam, naproxene, paracetamol, piroxicam, tenoxicam, nabumetone, ketoprofen, mefenamic acid, etodolac, and ketorolac were administered to female Wistar rats (N = 10 each group). In experiment I, solid food plus subcutaneous NSAIDs were given. In experiment II, NSAIDs were given by oral gavage and in bolus. Macroscopic gastric antral ulcer area (30%) and intestinal erosiva area (295 mm2) in experiment I and necrotic gastric fundus area (65%) and erosive intestinal area (182 mm2), "in vivo" the NSAIDs COX-1 was showed. Neutrofilia assessed in gastric intestinal mucosa where also ibuprofen and paracetamol not given neotrophilic infiltration. In conclusion, COX-2-COX-1 selectivity was demonstrated in vivo with the drugs aceclofenac, nabumetone, meloxicam, nimesulide, and paracetamol.
Assuntos
Anti-Inflamatórios não Esteroides , Úlcera Péptica/induzido quimicamente , Administração Oral , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Ciclo-Oxigenase 1 , Ciclo-Oxigenase 2 , Inibidores de Ciclo-Oxigenase 2 , Inibidores de Ciclo-Oxigenase/farmacologia , Ingestão de Alimentos/fisiologia , Jejum/fisiologia , Feminino , Injeções Subcutâneas , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/patologia , Isoenzimas/antagonistas & inibidores , Proteínas de Membrana , Úlcera Péptica/patologia , Prostaglandina-Endoperóxido Sintases , Ratos , Ratos Wistar , Estômago/efeitos dos fármacos , Estômago/patologiaRESUMO
BACKGROUND/AIMS: There are few studies about gastrointestinal abnormalities in patients with juvenile rheumatoid arthritis-probably due to the fact that this association is not frequently recognized. The aim of our study was to observe the prevalence of endoscopic gastroduodenal lesions in these patients. METHODOLOGY: Fourteen patients with juvenile rheumatoid arthritis, all of them using non-steroidal anti-inflammatory drugs associated or not with methotrexate, were assessed clinically and by endoscopy. Gastric antrum biopsy and Helicobacter pylori search were also performed. RESULTS: The mean age of the patients was 10.6 years (7 boys). Abdominal pain was observed in 27% of them. Macroscopic endoscopic lesions were found in 43% and infection by Helicobacter pylori in 57%. The correlation between anemia and endoscopic abnormalities was statistically significant (p < 0.05). CONCLUSIONS: Our data show that patients with juvenile rheumatoid arthritis have considerable susceptibility to gastroduodenal lesions, especially if they are using any drug association and present anemia.