Anti-ulcer & antioxidant activities of Hedranthera barteri {(Hook F.) Pichon} with possible involvement of H+, K+ ATPase inhibitory activity.

Background & objective: Hedranthera barteri (HB) is used in folk medicine as a vermifuge, laxative and an anti-inflammatory agent. The aim of this study was to evaluate the anti-ulcer and antioxidant properties of the dichloromethane fraction of HB root (DMHBR). Methods: Anti-ulcerogenic activity was assessed in cold-restraint (CRU), aspirin (ASP), alcohol (AL), pyloric ligation (PL) induced gastric ulcer models in rats and histamine-induced duodenal ulcer (HST) in guinea pigs. The effect of DMHBR (100 mg/kg) on gastric juice for free and total acidity, peptic activity and mucin secretion, using the pylorus ligated model, were evaluated. The H+, K+-ATPase activity was assayed in gastric microsomes, spectrophotometrically. The in vitro anti-oxidant assays were explored through DPPH, nitric oxide, hydroxyl radical, superoxide anion scavenging assays. Results: DMHBR reduced the incidence of ulcers in CRU (63.3%), PL (58.5%), ASP (52.7%), HST (75.0%) and AL (53.87%). Also, reductions were observed in the free acidity (49.4%), total acidity (45.8%) and peptic activity (32.9%) with increase in the mucin secretion by 81.6 per cent. DMHBR (60-100 μg/ml) inhibited the H+,K+-ATPase activity with IC50 of 89.64 μg/ml compared with omeprazole (10-50 μg/ml ) with IC50 of 32.26 μg/ml. DMHBR showed antioxidant activity with IC50 values of DPPH (397.69 μg/ml), nitric oxide (475.88 μg/ml), hydroxyl radical (244.22 μg/ml) and superoxide anion radical (285.20 μg/ml). Interpretation & conclusion: DMHBR showed anti-ulcer activity against experimentally-induced peptic ulcer models and exhibited both cytoprotective and anti-secretory property. It exhibited a proton pump inhibition activity and its anti-ulcer properties may be partly ascribed to its antioxidant activities.

Gastric atrophy and intestinal metaplasia in a patient on long-term proton pump inhibitor therapy.

We report the case of a patient with gastroesophageal reflux disease who developed gastric atrophy and intestinal metaplasia (IM) while on 20-year treatment with proton pump inhibitors. This is perhaps the first report in human beings. A 74-year-old man, who presented with heartburn, showed abnormally high gastric pH (average 6.57) on 24-hour dual channel pH-metry even after discontinuing acid suppressive drugs for one month. No significant esophageal acid exposure was noted, which may be related to an impairment of the acid secreting capacity of the stomach (percentage time esophageal pH<4 during 24-h period 0.3%). Upper gastrointestinal endoscopy was normal except for the prominent submucosal vessels in the body and fundus suggesting gastric atrophy. Histopathological examination of multiple biopsies from the body and antrum of stomach showed signs of gastric atrophy and IM. Rapid urease test and histopathology of gastric biopsies were negative for Helicobacter pylori. Anti-H.pylori IgG ELISA however, was positive. Patient was asked to stop all anti-secretory drugs and only prokinetics were prescribed following which his symptoms markedly improved. On follow-up, in April 2007, he developed symptoms of peripheral neuropathy; serum vitamin 812 level was low. He responded to parenteral vitamin 812 therapy. 24-h dual channel pH-metry repeated after one and a half years showed persistently high gastric pH (average pH 6.76). The patient remained well after discontinuing proton pump inhibitors and continuing prokinetics and vitamin B12 injections.

Estudio multicéntrico con pantoprazol en el tratamiento de la enfermedad ácido péptica e México / Multicentric study using pantoprazole in the treatment of peptic acid disease in Mexico

Se realizó un estudio prospectivo multicéntrico en diversas ciudades de la República Mexicana utilizando pantoprazol para el tratamiento de la enfermedad ácido-péptica. Se incluyeron 1,696 pacientes con diagnóstico de enfermedad ácido-péptica. Se recabaron datos personales y relacionados con la enfermedad, método de diagnóstico, tratamiento y resultado al final del mismo. Se encontró que la media de edad en los pacientes del sexo masculino fue 43.9 años y en las mujeres 42.4 años (p = 0.041). El porcentaje de hombres y mujeres fue de 49.6 respectivamente. Existe correlación entre el consumo de alcohol, el diagnóstico de úlcera péptica (p = 0.032) y el dolor epigástrico en ayunas (p = 0.004). De los diagnósticos establecidos, la gastritis tuvo la mayor proporción (21.19 por ciento). Al final del tratamiento, 68 por ciento (1.157 casos) reportaron ausencia total de los síntomas que los motivaron a buscar atención médica. El 96.26 por ciento de los tratamientos se ajustaron a la dosis diaria recomendada de 40 mg. La evaluación global sobre el tratamiento con pantoprazol en relación con los casos tratados fue que 96 por ciento de los investigadores lo consideraron excelente o bueno. Los resultados obtenidos demuestran la efectividad del pantoprazol en el tratamiento de la enfermedad ácido-péptica, con la dosis recomedada de 40 mg al día. En sólo dos casos se suspendió el tratamiento por probables reacciones adversas al medicamento

Structure-activity relationship studies of 4-substituted-2-guanidinothiazoles: reversible inhibitors of gastric (H+/K+)-ATPase.

The role of physicochemical factors, electronic and hydrophobic, and a hydrogen donor index in the inhibition of gastric (H+/K+)-ATPase by 4-phenyl-2-guanidinothiazoles and the 4-indolyl-2-guanidinothiazoles has been quantitatively analysed. For the first congeneric series, the resonance effect of the ortho- and para-substituents and hydrogen donor property of the meta-substituent in the phenyl ring play crucial role, whereas for 4-indolyl analogues, the hydrophobicity and electron withdrawing effect of X-substituents in the indolyl ring are shown to be important decisive factors. Also the substitution of the guanidine moiety, e.g. by benzyl, raises the activity of proton pump inhibitors. The substitution at 5-position of thiazole ring does not enhance the potency.