Chronic use of proton pump inhibitors and the quantity of g, d, and ecl cells in the stomach / Uso crônico de inibidores de bomba de prótons e a quantidade de células g, d e ecl no estômago

ABSTRACT Background: Acid inhibition from chronic proton pump inhibitor use and a possible increase in gastrin can lead to changes in the regulation of hydrochloric acid production. However, it has not known whether such chronic use changes the presence of gastrin, delta, and enterochromaffin-like cells in the stomach or the relationship between gastrin and delta cells. Aim: To analyze the number of gastrin-producing gastrin cells, somatostatin-producing cells, and histamine-producing cells in patients who were chronic users of proton pump inhibitor, with or without related Helicobacter pylori infection. Methods: Biopsies from 105 patients, including 81 chronic proton pump inhibitor users (experimental group) and 24 controls, were processed immunohistochemically and subjected to counting of gastrin, delta, and enterochromaffin-like cells in high-magnification microscopic fields and in 10 glands. Results: Gastrin cell, delta cell, and enterochromaffin-like cells counts were similar across the groups and appeared to be unaffected by Helicobacter pylori infection. The ratio between gastrin cells and delta cells was higher in the chronic users of proton pump inhibitor group than in controls. Conclusion: Chronic users of proton pump inhibitor does not affect gastrin cell, delta cell, and enterochromaffin-like cell counts significantly, but may alter the ratio between gastrin cells and delta cells.

RESUMO Racional: A inibição ácida pelo uso crônico de inibidores de bomba de prótons e o possível aumento da gastrina podem ser seguidos de alterações na regulação da produção do ácido clorídrico. Ainda não está definido se o uso crônico altera a quantidade de células G, D e ECL no estômago ou a razão células G/D. Objetivo: Avaliar o número de células G - produtoras de gastrina -, células D - produtoras de somatostatina - e células ECL - produtoras de histamina -, em pacientes com uso crônico de inibidores de bomba de prótons, com ou sem infecção pelo Helicobacter pylori. Método: Trata-se de estudo retrospectivo avaliando 105 pacientes, 81 usadores crônicos de inibidores de bomba de prótons e 24 controles, através de biópsias com contagem das células G, D e ECL por estudo imunoistoquímico, de forma quantitativa onde havia maior número de células positivas por campo microscópico de grande aumento e em 10 glândulas. Resultados: Não houve diferença estatística comparando-se o número de células G, D e ECL. A razão entre as células G e D foi maior nos pacientes usadores crônicos de inibidores de bomba de prótons. Conclusão: O uso crônico de inibidores de prótons parece não interferir na contagem das células G, D e ECL, porém, interfere na razão entre as células G e D.

Gastric and renal effects of COX-2 selective and non-selective NSAIDs in rats receiving low-dose aspirin therapy

Abstract The consumption of low-dose aspirin (LDA) to prevent cardiovascular disease continues to increase worldwide. Consequently, the number of chronic LDA users seeking dental procedures that require complementary acute anti-inflammatory medication has also grown. Considering the lack of literature evaluating this interaction, we analyzed the gastric and renal effects caused by a selective COX-2 inhibitor (etoricoxib) and a non-selective COX-2 inhibitor (ibuprofen) nonsteroidal anti-inflammatory drug (NSAID) in rats receiving chronic LDA therapy. Male Wistar rats were divided into six experimental groups (carboxymethylcellulose (CMC) - vehicle; LDA; LDA + ibuprofen; ibuprofen; LDA + etoricoxib; and etoricoxib) and submitted to long-term LDA therapy with a subsequent NSAID administration for three days by gavage. After the experimental period, we analyzed gastric and renal tissues and quantified serum creatinine levels. The concomitant use of LDA with either NSAID induced the highest levels of gastric damage when compared to the CMC group (F = 20.26, p < 0.05). Treatment with either LDA or etoricoxib alone was not associated with gastric damage. No significant damage was observed on kidney morphology and function (F = 0.5418, p > 0.05). These results suggest that even the acute use of an NSAID (regardless of COX-2 selectivity) can induce gastric damage when combined with the long-term use of low-dose aspirin in an animal model. Additional studies, including clinical assessments, are thus needed to clarify this interaction, and clinicians should be careful of prescribing NSAIDs to patients using LDA.

The hydrogen sulfide donor, Lawesson's reagent, prevents alendronate-induced gastric damage in rats

Our objective was to investigate the protective effect of Lawesson's reagent, an H2S donor, against alendronate (ALD)-induced gastric damage in rats. Rats were pretreated with saline or Lawesson's reagent (3, 9, or 27 µmol/kg, po) once daily for 4 days. After 30 min, gastric damage was induced by ALD (30 mg/kg) administration by gavage. On the last day of treatment, the animals were killed 4 h after ALD administration. Gastric lesions were measured using a computer planimetry program, and gastric corpus pieces were assayed for malondialdehyde (MDA), glutathione (GSH), proinflammatory cytokines [tumor necrosis factor (TNF)-α and interleukin (IL)-1β], and myeloperoxidase (MPO). Other groups were pretreated with glibenclamide (5 mg/kg, ip) or with glibenclamide (5 mg/kg, ip)+diazoxide (3 mg/kg, ip). After 1 h, 27 µmol/kg Lawesson's reagent was administered. After 30 min, 30 mg/kg ALD was administered. ALD caused gastric damage (63.35±9.8 mm2); increased levels of TNF-α, IL-1β, and MDA (2311±302.3 pg/mL, 901.9±106.2 pg/mL, 121.1±4.3 nmol/g, respectively); increased MPO activity (26.1±3.8 U/mg); and reduced GSH levels (180.3±21.9 µg/g). ALD also increased cystathionine-γ-lyase immunoreactivity in the gastric mucosa. Pretreatment with Lawesson's reagent (27 µmol/kg) attenuated ALD-mediated gastric damage (15.77±5.3 mm2); reduced TNF-α, IL-1β, and MDA formation (1502±150.2 pg/mL, 632.3±43.4 pg/mL, 78.4±7.6 nmol/g, respectively); lowered MPO activity (11.7±2.8 U/mg); and increased the level of GSH in the gastric tissue (397.9±40.2 µg/g). Glibenclamide alone reversed the gastric protective effect of Lawesson's reagent. However, glibenclamide plus diazoxide did not alter the effects of Lawesson's reagent. Our results suggest that Lawesson's reagent plays a protective role against ALD-induced gastric damage through mechanisms that depend at least in part on activation of ATP-sensitive potassium (KATP) channels.

Hind limb ischemic preconditioning induces an anti-inflammatory response by remote organs in rats

Ischemic preconditioning (IPC), a strategy used to attenuate ischemia-reperfusion injury, consists of brief ischemic periods, each followed by reperfusion, prior to a sustained ischemic insult. The purpose of the present study was to evaluate the local and systemic anti-inflammatory effects of hind limb IPC in male Wistar rat (200-250 g) models of acute inflammation. IPC was induced with right hind limb ischemia for 10 min by placing an elastic rubber band tourniquet on the proximal part of the limb followed by 30 min of reperfusion. Groups (N = 6-8) were submitted to right or left paw edema (PE) with carrageenan (100 µg) or Dextran (200 µg), hemorrhagic cystitis with ifosfamide (200 mg/kg, ip) or gastric injury (GI) with indomethacin (20 mg/kg, vo). Controls received similar treatments, without IPC (Sham-IPC). PE is reported as variation of paw volume (mL), vesical edema (VE) as vesical wet weight (mg), vascular permeability (VP) with Evans blue extravasation (µg), GI with the gastric lesion index (GLI; total length of all erosions, mm), and neutrophil migration (NM) from myeloperoxidase activity. The statistical significance (P < 0.05) was determined by ANOVA, followed by the Tukey test. Carrageenan or Dextran-induced PE and VP in either paw were reduced by IPC (42-58.7 percent). IPC inhibited VE (38.8 percent) and VP (54 percent) in ifosfamide-induced hemorrhagic cystitis. GI and NM induced by indomethacin were inhibited by IPC (GLI: 90.3 percent; NM: 64 percent). This study shows for the first time that IPC produces local and systemic anti-inflammatory effects in models of acute inflammation other than ischemia-reperfusion injury.

Importance of Age and Other Risk Factors in NSAID-induced Gastropathy / 대한소화기학회지

BACKGROUND/AIMS: It is clinically important to analyze the risk factors of NSAID-induced gastropathy because there could be no symptoms. Age is the most important risk factor according to previous reports. The aim of this study was to find risk factors of NSAID-induced gastropathy and to confirm the association between NSAID-induced gastropathy and age. METHODS: We retrospectively assessed 300 patients who conducted an upper gastroscopy during the course of chronic NSAID treatment. RESULTS: Median age of patients group is 51.4 +/- 12.2 years. In multivariate analysis, age and ulcer history are two significant risk factors. Median age is 46.7 +/- 10.7 years for the patients with nonspecific gastroscopic finding, 53.0 +/- 12.5 for those with erosion, 57.6 +/- 10.0 for those with ulcer, and 63.2 +/- 8.9 for those with hemorrhage. The proportion of ulcer patients is as follows: 6% in the patients of under 40 years old, 14.9% in patients of the 40s, 20% in patients of the 50s, 30.9% in patients of the 60s, 33.3% in patients over 70 years. The proportion of nonspecific findings is 62.2% in patients of the 40s, 37.8% in patients of the 50s, and 29% in patients over 60 years. CONCLUSIONS: Age is the most important risk factor of the NSAID-induced gastrointestinal mucosal injury. A larger randomized prospective control study will be required in the future for more conclusive results.

Lesäo aguda esôfago-gástrica causada por agente químico / Chemically induced esophagogastric acute injury

O tratamento da ingestão de agentes químicos corrosivos continua controverso. A incidência desses episódios tem aumentado nas últimas décadas por várias razões. OBJETIVO: Analisar a ocorrência, as complicações e os resultados do tratamento da lesão esôfago - gástrica causada por agentes químicos. MÉTODOS: Foram estudados retrospectivamente 21 pacientes adultos com lesão esôfago-gástrica, causada por ingestão de substância química, admitidos até 23 dias após o episódio, no Serviço de Emergência da Santa Casa de Misericórdia de São Paulo num período de 12 anos. A média de idade foi 32,1 anos e 11 doentes pertenciam ao sexo feminino, as quais mais freqüentemente tinham intenções suicidas. A soda cáustica foi o produto mais ingerido (76,2 por cento), ingestão de ácido muriático ocorreu em três casos (14,3 por cento), amoníaco e ácido sulfúrico em um caso (4,8 por cento) cada. RESULTADOS: As lesões faríngeas e laríngeas estiveram freqüentemente associadas às lesões de esôfago, presentes em 18 casos (85,7 por cento). As lesões esofágicas, gástricas e duodenais foram avaliadas e classificadas por endoscopia. Lesões graves esofágicas ou gástricas estiveram presentes em cinco casos cada. CONCLUSÃO: O tratamento e os resultados foram variados, mas sugeriram que a sondagem esofágica foi prejudicial. A mortalidade global foi 28,6 por cento, mais elevada na lesão esofágica grau 3.

Ketotifen in prevention of indomethacin-induced gastropathy.

BACKGROUND: Therapeutic benefits of nonsteroidal anti-inflammatory drugs (NSAIDs) are offset by their gastrointestinal side effects. We evaluated whether oral ketotifen, which prevents experimental NSAID-induced gastric mucosal injury, is superior to placebo in preventing NSAID-induced gastropathy. DESIGN: Prospective, randomized, double-blind, placebo-controlled clinical trial. SETTING: Rheumatology clinic in a tertiary care hospital. PARTICIPANTS: A majority of the 53 subjects had rheumatoid arthritis (n = 36) or osteoarthritis (12). Those with comorbidity, gastrointestinal (GI) symptoms or abnormal endoscopic findings at entry were excluded. Persons on steroids or NSAIDs in the previous month were also excluded. The subjects were started on indomethacin 25 mg thrice daily. INTERVENTION: Subjects were randomly allocated to receive 2 mg ketotifen or placebo tablets. Compliance was measured by tablet count. OUTCOME MEASURE: At the end of every week a questionnaire was administered to elicit GI symptoms or adverse effects. Every patient underwent endoscopy after four weeks. RESULTS: Of 53 patients recruited (27 drug, 26 placebo), three (2 drug, 1 placebo) dropped out. The age, sex, NSAID use and clinical conditions were similar in the two groups. Eight in the drug group and 16 in the placebo group developed GI symptoms and/or endoscopic lesions (relative risk 0.51, 95% CI 0.27-0.95). The difference was significant on intention-to-treat analysis. CONCLUSIONS: Ketotifen significantly reduced the risk of GI side effects in patients on indomethacin.

Gastropatía por anti-inflamatorios no esteroideos / Nonsteroidal anti-inflammatory drug-induced gastropathy

Los anti-inflamatorios no esteroideos son fármacos ampliamente utilizados en la práctica clínica. Debido a la extensa gama de efectos secundarios asociados a su uso en este artículo nos enfocamos a describir las lesiones gástricas, revisando su fisiopatogenia, su prevalencia e incidencia, así como sus manifestaciones clínicas, factores predisponentes, tratamiento y profilaxis

Efeitos dos pontos de acupuntura E-36 (Zusanli), E-25 (Tianshu) e VC-12 (Zhongwan), estimulados por eletroacupuntura, nas lesöes agudas da mucosa gástrica, produzidas pela indometacina, em ratos Wistar / Effect of acupuncture points E-36 (Zusanli), E-25 (Tianshu) and VC-12 (Zhongwan) in acute injuries of the gastric mucosa produced by indometacin in Wistar rats

O presente estudo tem por objetivo avaliar o efeito da acupuntura na prevençäo de lesöes agudas da mucosa gástrica, produzidas pela indometacina, em ratos Wistar. Material - Foram estudados 48 ratos Wistar, sendo 21 machos e 27, fêmeas, com peso variando de 165 a 375g. Método - Os animais foram mantidos em jejum, com acesso livre à água, por 24h e aleatoriamente divididos em 3 grupos: GRUPO INDO - 16 ratos submetidos à administraçäo de indometacina (20mg/kg peso, V.O.); GRUPO ACP/SHAM - 16 ratos submetidos à anestesia superficial com éter e administraçäo de indometacina (20mg/kg peso, V.O.), seguidas de estimulaçäo por eletroacupuntura (2Hz/30min.), intensidade de 1mV, em pontos aleatórios, distantes 1,5cm dos verdadeiros pontos, e GRUPO ACP-16 ratos submetidos à anestesia superficial com éter e administraçäo de indometacina (20mg/kg peso V.O.), seguidas de estimulaçäo por eletroacupuntura (2Hz/30min.), nos pontos E-36 (Zusanli), E-25 (Tianshu) e VC-12 (Zhongwan). Após 6 horas todos os ratos foram submetidos à anestesia superficial com éter, para retirada cirúrgica do estômago, seguida de sacrifício dos animais. Os estômagos foram fixados em formol e examinados macroscopicamente, para contagem do número de lesöes (petéquias e ulceras e/ou erosöes com até 1mm e com mais de 1mm de extensäo). Resultados - Os resultados, submetidos ao teste estatístico análise de variância por postos de KRUSKAL-WALLIS, complemetado pelo teste de comparaçöes múltiplas, mostraram que o grupo ACP apresentou 61,3 por cento menos lesoes que o grupo INDO, comprovando, estatisticamente, a eficácia da acupuntura na prevençäo de lesoes agudas da mucosa gástrica, produzidas pela indometacina, em ratos. O grupo SHAM apresentou 34,8 por cento menos lesöes que o grupo INDO, demonstrando que a acupuntura em näo pontos também tem algum efeito, embora muito reduzido, em comparaçäo com a acupuntura em pontos certos.

Thioctic acid protection against ethanol and indomethacin induced gastric mucosal lesions in rats

Background/Aims: The gastric protective effect of thioctic acid, a sulfhydryl compund, against chemically induced mucosal lesions has not been reported. Methods: Fasted Wistar rats (24 h) were treated (gavage administration) with graded doses of thiotic acid (12.5, 25, 37.5, 50 mg/kg) followed 0.5 h later by the gavage administration of 1 ml 96 per cent ethanol or intraperitoneal administered indomethacin. The gastric mucosa was examined grossly and histologically for an evaluation of the lesions. Results: Pretreatment of rats with thotic acid has shown a significant decline in the mean number, size, incidence and severity of mucosal lesions induced by both ethanol and indomethacin. Conclusions: This is the first evidence that thiotic acid protects the rat gastric mucosa against chemically induced damage. Its is speculated that this finding may prove to be important in the development of improved therapies for the prevention and treatment of gastric ulcers in humans.

Effect of antihypertensive drugs on ethanol induced gastric lesions: is there a correlation with mucosal blood flow?

We studied the effect of five antihypertensive drugs on ethanol-induced gastric haemorrhagic lesions in rats. While hydralazine aggravates these lesions, nifedipine and propranolol have a protective action. On the other hand, enalapril and prazosin have no effect. Thus the effects of antihypertensive drugs on ethanol-induced lesions do not always correlate with their reported actions on gastric mucosal blood flow.

Aggravating action of hydralazine on ethanol-induced gastric lesions.

Endogenous nitric oxide has been proposed as one of the mediators of gastric cytoprotection. We studied the effect of the vasodilator hydralazine which acts via nitric oxide and thus is expected to have a gastroprotective action. However, hydralazine aggravates ethanol-induced gastric lesions. This effect is not influenced by pretreatment with the selective alpha 1 adrenergic antagonist prazosin but is abolished by the angiotensin converting enzyme inhibitor, captopril suggesting the involvement of the renin-angiotensin system.

Protective effect of propranolol on ethanol-induced gastric lesions in rats: probable mechanism of action.

The non-selective beta-adrenoceptor antagonist, propranolol, has been reported to protect against gastric injury in mice, an effect only partly due to prostaglandin release. This study was designed to confirm the gastric cytoprotective effect of propranolol in another species of animal, the rat, and investigate further its mechanism of action. Our results show that propranolol prevents both ethanol-induced gastric lesions as well as ethanol-induced contraction of the circular muscle of rat fundic strip. The local anaesthetic, lignocaine also inhibited the effect of ethanol on circular muscle. However, timolol, another non-selective beta-adrenoceptor antagonist, failed to produce such an action. The effect of propranolol was abolished by the cyclooxygenase inhibitor, indomethacin and a high dose of the guanylate cyclase inhibitor, methylene blue. The results suggest that in addition to prostaglandins, endogenous nitric oxide and the membrane stabilising action of propranolol may also be involved in its gastroprotective action.

Effect of acute ingestion of tobacco on gastric mucosa. An endoscopic study.

One hundred patients with non ulcer dyspepsia with history of chronic tobacco chewing were examined endoscopically to assess the effect of tobacco ingestion on the gastric mucosa. Gastric erosions were seen in 20 patients in the fasting state. The remaining 80 patients in whom gastroscopy did not reveal erosions were subjected to repeat gastroscopy after tobacco ingestion. In 40 patients, endoscopy was repeated 30 minutes after 200 mg of tobacco ingestion (Group I) and in another 40 patients endoscopy was repeated 1 hour after 400 mg of tobacco ingestion (Group II). Eleven patients (27.5%) in Group I and 19 (47.5%) in Group II developed gastric erosions. Erosions were observed mainly along the lesser curvature, and in the fundus and the body of stomach. Gastric pH, determined after tobacco ingestion, was 2.4 +/- 0.43 in patients with erosions and 3.0 +/- 0.67 in patients without erosions. It is concluded that tobacco ingestion produces dose-dependent damage to the gastric mucosa as seen on endoscopy. Hence, history of tobacco ingestion should always be asked for in patients with gastric erosions.

Pyloric obstruction following the ingestion of corrosive acid.

Pyloric obstruction is a well documented end result of ingestion of corrosive acid. Whereas the oesophageal mucosa is resistant to damage, the pyloric spasm and the resultant pooling of acid in the pre-pyloric region, causes injury to this area. The fibrosis of the gastric wall with motility disturbances, and the diminution of acid and pepsin production from damage to the glandular elements, would weigh against the addition of a vagotomy to the drainage procedure. A case of ingestion of concentrated sulphuric acid and the management of its late sequelae, are discussed.

Efecto citoprotector de enprostil sobre la mucosa gástrica dañada con etanol en la rata. Estudio con citoquímica de alta resolución y microscopía electrónica de barrido / Protective effect of enprostil on the cells of gastric mucosa demaged by ethanol in the rat. High resolution cytochemical scanning elelctron microscopy study

El objeto de este trabajo fue analizar la partcipación de la capa de glicoproteínas de la membrana plasmática en el efecto citoprotector de un análogo de la PGE, utilizando como modelo el estómago de la rata irritado con etanol. A un grupo de ratas Long-Evans previamente tratadas con Enprostil se les instiló 0.5 ml. de etanol absoluto por vía oral. Los animales fueron sacrificados a los 0,30 y 60 minutos y los estómagos fueron estudiados con microscopía de luz, electrónica de transmisión utilizando rojo de Rutenio como marcador y microscopía electrónica de barrido. Un grupo de ratas sólo recibió etanol. La mucosa gástrica de este último grupo reveló hiperhemia y necrosis con disociación y ausencia de la capa glicoproteica. Estos cambios no se observaron en los estómagos del grupo tratado cocn el análogo de la prostaglandina en donde estacó la capa de rojo de Rutenio. Parece ser que el efecto citoprotector de estas sustancias incluye un efecto inductor sobre la producción o secreción de glicocproteínas que se correlacionó con la microscopía electrónica de barrido